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Since their introduction in the 1960s, drugs categorized as benzodiazepines, which include diazepam (Valium) and alprazolam (Xanax), have been widely prescribed to treat anxiety and insomnia, alcohol withdrawal, and other conditions. Although they are highly effective for their intended uses, these medications must be prescribed with caution because they can be addictive. Now, work by NIDA-funded researchers has established that benzodiazepines cause addiction in a way similar to that of opioids, cannabinoids, and the club drug gamma-hydroxybutyrate (GHB). The discovery opens the door to designing new benzodiazepines that counteract anxiety but are not addictive.

Dr. Christian Lüscher and colleagues at the University of Geneva, Switzerland, studied benzodiazepines as part of a larger project to identify the point of convergence for all neurobiological pathways to drug addiction. Their findings strongly suggest that this juncture occurs when dopamine surges in response to drug taking initiate a change in synaptic plasticity in dopamine-producing cells.

Mechanisms of Benzodiazepine Addiction (Left Image) Both inhibitory interneurons (labeled GABA) and dopaminergic neurons (labeled DA) are subject to the restraining influence of the inhibitory neurotransmitter GABA. A key difference, however, is that GABA influences the inhibitory interneurons largely via the alpha-1 subset of GABA A receptors and the dopaminergic neurons largely via the alpha-3 subtype. (Right Image) Benzodiazepines currently on the market do not interact strongly with alpha-3 GABA A receptors on dopaminergic neurons and so have no direct impact on dopamine release. However, the drugs do interact strongly with alpha-1 GABA A receptors, thereby curtailing inhibitory interneurons' release of GABA into synapses with dopaminergic neurons. The net result is a lessening of GABA restraint on the dopaminergic neurons and an increase in dopamine release.

From Receptor Activation to Dopamine Surge

The pleasurable sensations that make addictive drugs disastrously attractive for vulnerable individuals occur when dopamine levels in the brain's reward area abruptly surge. Researchers had worked out how most addictive drugs, but not benzodiazepines, precipitate these surges. Dr. Lüscher and colleagues have now demonstrated that benzodiazepines weaken the influence of a group of cells, called inhibitory interneurons, in the brain's ventral tegmental area (VTA). These neurons normally help prevent excessive dopamine levels by downregulating the firing rates of dopamine-producing neurons. Two negatives make a positive, so when benzodiazepines limit the interneurons' restraining influence, the dopamine-producing neurons release more dopamine.

The Swiss researchers traced benzodiazepines' effect on VTA interneurons to the drugs' activation of a subset of GABA A (gamma-aminobutyric acid type-A) receptors on the interneurons. Although benzodiazepines typically activate multiple subtypes of GABA A receptors, their activation of the the alpha-1 subtype is decisive for their impact on VTA interneuron behavior. These interneurons are highly sensitive to such activation because they carry abundant numbers of these receptors. By staining brain tissue, the researchers showed that 81 percent of VTA interneurons carry GABA A receptors that contain the alpha-1 subunit.

To prove that activation of alpha-1 GABA A receptors underlies benzodiazepines' dopamine effect, the researchers administered a typical benzodiazepine, midazolam, to two groups of mice. The results supported the researchers' proposed mechanism: In normal animals, the firing rate of interneurons decreased in response to the drug, while that of dopamine-producing neurons increased. In contrast, in animals that were genetically altered to prevent benzodiazepines from potentiating alpha-1 GABA A receptors, the drug had little or no impact on neuron firing.

A behavioral finding completed the chain of proofs linking benzodiazepines' stimulation of alpha-1 GABA A receptors to their rewarding effects. When given the option of drinking sugar water or a sweetened solution of midazolam, normal mice imbibed roughly three times as much drug-laced as drug-free liquid. Mice with altered alpha-1 GABA A receptors, however, drank equal amounts of each, thereby exhibiting no evidence of finding one drink more rewarding than the other.

When benzodiazepines limit the interneurons' restraining influence, the dopamine-producing neurons release more dopamine.

Benzodiazepines' newly discovered mechanism for producing reward is comparable to those of opiates, cannabinoids, and GHB. Each of the four drugs reduces an inhibitory influence on dopamine-producing cells, thereby promoting dopamine spikes.

From Surge to Addiction

Dopamine surges are transient events, but addictive drugs cause long-lasting changes in the reward system. Among the earliest of these along the path from voluntary to compulsive drug use and addiction is the migration of certain AMPA receptors (i.e., GluA2-lacking receptors) from the interior to the surface of the dopamine-producing neurons. These receptors render the cell more susceptible to stimulation by the excitatory neurotransmitter glutamate, and as a result, the cells respond to future drug exposures with larger dopamine surges that produce even more intense pleasure. Scientists also have evidence that these special AMPA receptors initiate a series of changes in neural transmission that cumulatively give rise to the range of addictive symptoms.

Dr. Lüscher and colleagues showed that benzodiazepines induce AMPA receptor migration via the alpha-1 GABA A receptors. In these experiments, brain tissue from normal mice exhibited GluA2-lacking AMPA receptors after a single injection of midazolam, but tissue from mice with benzodiazepine-insensitive alpha-1 GABA A receptors did not. Recordings of intracellular electrical currents confirmed synaptic changes of dopamine-producing neurons in the normal mice and not the altered mice. To pin down the relationship further, the researchers injected mice with two other compounds, one (zolpidem) that preferentially activates only the alpha-1 GABA A receptors, and one (L-838417) that antagonizes these receptors. GluA2-lacking AMPA receptors were expressed in dopamine-producing neurons following a treatment with zolpidem, but not with L-838417.

Conclusive Proof

The Swiss researchers hypothesize that although different addictive drugs produce dopamine surges by various mechanisms, the subsequent chain of effects is the same. Consistent with this idea, they showed that even in the absence of any drug, artificial stimulation of the dopamine-producing neurons is sufficient to induce the appearance of GluA2-lacking AMPA receptors.

In this experiment, the researchers introduced a virus containing a light-activated protein, channelrhodopsin, into the dopamine-producing cells of mice. When exposed to light pulses from an optical fiber inserted into the animals' VTA, the channelrhodopsin stimulated neuron firing in bursts similar to those produced by addictive drugs. The result was an increase in GluA2-lacking AMPA receptors comparable to that seen following exposure to addictive drugs.

"This was a nail-in-the-coffin study to show that activity of dopaminergic neurons leads to synaptic adaptation that is involved in addiction," says Dr. Lüscher. "This is why addiction is so difficult to treat. Even if you clear the drug from the body, there are long-lasting changes in brain architecture."

Toward Better Benzodiazepines

Taken together, the data from the studies show that the activation of alpha-1-containing GABA A receptors by benzodiazepines calms inhibitory interneurons, increasing dopaminergic neuron firing, and leads to the strengthening of excitatory synapses that favor addictions. Dr. Roger Sorensen of NIDA's Functional Neuroscience Research Branch says, "This is the first demonstration that acute benzodiazepine use can increase dopamine release, supporting its addictive potential."

"Now that we know that it's the alpha-1-containing GABA A receptor that is responsible for benzodiazepine addiction, we can design benzodiazepines that do not touch those particular receptors," says Dr. Lüscher. Drugs that bind only to alpha-2-containing GABA A receptors, he adds, might relieve anxiety nonaddictively. "Such substances already exist for research purposes," Dr. Lüscher says. "It's possible that we can also create them for clinical use."

Sources

Brown, M.T.C., et al. Drug-driven AMPA receptor redistribution mimicked by selective dopamine neuron stimulation. PLoS One. 5:12: e15870, 2010. Full Text Available (PDF,2.2MB)

Riegel, A.C., and Kalivas, P.W. Neuroscience: Lack of inhibition leads to abuse. Nature 463: 743-744, 2010. Abstract Available

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Since their introduction in the 1960s, drugs categorized as benzodiazepines, which include diazepam (Valium) and alprazolam (Xanax), have been widely prescribed to treat anxiety and insomnia, alcohol withdrawal, and other conditions. Although they are highly effective for their intended uses, these medications must be prescribed with caution because they can be addictive.

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ice: training for frontline workers: log in to the site

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Ice: Training for Frontline Workers: Log in to the site

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The NICE Clinical Knowledge Summaries (CKS) site is only available to users in the UK, Crown Dependencies and British Overseas Territories. CKS content is produced by Clarity Informatics Limited. It is available to users outside the UK via subscription from the Prodigy website. If you believe you are seeing this page in error please contact us.

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1.1.8 Ask the person to describe how chronic pain affects their life, and that of their family, carers and significant others, and how aspects of their life may affect their chronic pain. This might include:

lifestyle and day-to-day activities, including work and sleep disturbance

physical and psychological wellbeing

stressful life events, including previous or current physical or emotional trauma

current or past history of substance misuse

social interaction and relationships

difficulties with employment, housing, income and other social concerns.

1.1.9 Be sensitive to the person's socioeconomic, cultural and ethnic background, and faith group, and think about how these might influence their symptoms, understanding and choice of management.

1.1.10 Explore a person's strengths as well as the impact of pain on their life. This might include talking about:

their views on living well

the skills they have for managing their pain

what helps when their pain is difficult to control.

1.1.11 Ask the person about their understanding of their condition, and that of their family, carers and significant others. This might include:

their understanding of the causes of their pain

their expectations of what might happen in the future in relation to their pain

their understanding of the outcome of possible treatments.

1.1.12 When assessing chronic pain in people aged 16 to 25 years, take into account:

1.1.13 Recognise that living with pain can be distressing and acknowledge this with the person with chronic pain.

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Chronic pain (primary and secondary) in over 16s: assessment of all chronic pain and management of chronic primary pain

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1.1.8 Ask the person to describe how chronic pain affects their life, and that of their family, carers and significant others, and how aspects of their life may affect their chronic pain.

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AKA: Amphetamine Sulphate: speed, whizz, sulph, billy, phet, pink champagne,
Base Amphetamine: base, base speed, paste
Dexamphetamine Sulphate: Dexedrine, dexies, dex, Adderall
Methamphetamine Sulphate: Methedrine, Crystal Meth, meth, ice, shard, glass, Tina, Shabu, Yabba, crank, Pervitin, Sisa
Benzphetamine: Didrex
The amphetamine "family" contains a number of prescribed and non-prescribed stimulant compounds. Methylphenidate is related to amphetamines (though not strictly an amphetamine.

PROFILE and RELATIVES: Amphetamines are a family of drugs, part of the larger Phenethylamine group. The amphetamines are stimulant drugs. Other relatives in the family include MDMA (Ecstasy) and the cathinones (e.g. mephedrone).
There are a number of molecular variants of amphetamine, such as 4-fluoro-amphetamine.
Although not actually amphetamines, the drug Methylphenidate (Ritalin) has very similar effects to the amphetamines and risks are similar. Analogues of methylphenidate were briefly available on the UK market as they weren't regulated but, in early 2015, they were brought under the Misuse of Drugs Act.

ORIGINS: First synthesised in 1887, amphetamine only started to get prescribed and used from 1934 onwards. It has been used in a variety of settings including:
·Decongestant
·Weight loss
·Depression
·Military settings

SOURCE: SOURCE: Amphetamines are synthetic chemicals. There are a number of production routes. Some amphetamines are synthesised in clandestine labs in the UK, while the bulk of the rest is imported from mainland Europe.

Ritalin is prescribed in the UK for the treatment of ADHD and some diversion does occur.

There is a limited amount of Dexamphetamine prescribing, including to people with history of amphetamine dependency. However, there is minimal leakage from such prescribing to the street.

Historically, in the UK in the 50s, 60s and early 70s, medical diversion of amphetamines was much more widespread. Benzedrine inhalers were broken open and the drug extracted. Dexamphetamine was widely over-prescribed for weight loss and diverted to the streets. Stimulants were also a target for pharmacy thefts. The now-notorious drug methamphetamine was originally a branded pharmaceutical product and was marketed in the UK as "Methedrine." It was briefly and unsuccessfully used in London as a treatment for cocaine dependency.

In Eastern Europe, when the Warsaw Pact was still in place, a brand of methamphetamine called Pervitin was widely sold. As a term, Pervitin is still used in a number of countries including the Czech Republic. A cheap, crude form of methamphetamine, synthesised from ephedrine, has been reported in the media as a cheap street drug in Greece, sold as Sisa.

APPEARANCE: The mainstay of the UK amphetamine market, amphetamine sulphate, is usually sold as a powder. Colour ranges from white, off-white, grey, yellow, and pink. It is usually sold by weight. This was typically in small rectangular wraps of paper, but increasingly now it is sold in self-seal bags. It is a sour-tasting, water soluble salt powder.

Increasingly commonly available is base-speed, a grey paste similar in consistency to putty or marzipan. It is a non-soluble base drug often smelling strongly of ammonia.

Dexedrine tablets are usually circular and are white or yellow. It is also sometimes prescribed as a linctus.
Ritalin in tablet form is prescribed to children with ADHD and some of this is diverted to illicit use.
Methamphetamine comes in the form of white powder or clear crystals, but is also sold in tablet form, though tablets are less common in the UK.

QUALITY AND PURITY: Non-pharmaceutical products are highly variable in quality. Amphetamine sulphate powder in the UK is notorious for its low purity, typically between 5% and 10% pure.

Base speed, which was taken out of production earlier, tended to be higher purity, often around 40%. However, some suppliers made "fake base" by adding oil and ammonia to low quality speed powder to give it the look and smell of base speed.

Crystal meth, made in small batches and sold in crystalline form, is harder to adulterate and tends to be higher quality.

COSTS: Speed is usually sold by weight, at a cost of around £5 per gram. Base is more expensive, typically £20-40 a gram. Methamphetamine: wide range of cited prices, from £50-200/g

DOSE RANGE: Hugely variable, partly influenced by drug of choice, purity, route, tolerance and experience. For amphetamine sulphate, doses of 100-200mg would be typical, but some will use way in excess of this.
ROUTES OF ADMINISTRATION:
Amphetamine sulphate: as a water-soluble drug, it can be readily snorted or rubbed on gums. However, it has a very unpleasant taste and is painful to snort so it is often wrapped in a cigarette paper and swallowed (bombed) to get it in with as little taste as possible. Speed powder is also injected. It requires no heating or acid but should be filtered (though rarely is).
Base speed: insoluble in water, though will melt in hot water. Injectors have caused significant complications by heating base speed in water and injecting it, where it tends to congeal on cooling. It is safer to dissolve base speed in hot water and drink it. But if it is to be injected, it needs to have an acid added to make a solution. It can be smoked.
Methamphetamine: a salt drug, which dissolves readily. It can be snorted, rubbed on gums or injected without heating or addition of acid. Unusually, although a salt, it can also be smoked.
Tablets: should be swallowed; if crushed for injecting should be filtered thoroughly.

ONSET AND DURATION: Different members of the amphetamine family have different profiles in terms of duration of effect, and this will also change according to route.

Amphetamine Sulphate typically has a 2-4 hour duration of effect. Redosing is common, with people dabbing top-ups in the course of the night to prolong effects. Methamphetamine is longer acting.
Smoked and injected drugs will have a faster onset and shorter duration of effects; swallowed drugs will come on more slowly and last longer.

MECHANISM of ACTION: Amphetamines have a number of mechanisms of action. The key effect is to elevate levels of the brain chemicals dopamine, nor-adrenalin (nor-epinephrine) and to a lesser extent serotonin. They do this by:
" pushing brain chemicals out of storage, increasing active levels in the brain
" preventing the reuptake of brain chemicals back in to storage
" inhibiting the enzymes that would normally break down brain chemicals.

EFFECTS: Drug effects are highly variable and can be influenced by the state and expectations of the user, the environment in which the drugs are taken, the drug itself and how it is taken.

Key physical effects include: Reduced appetite, Clenching jaws, Grinding teeth, Elevated heart rate and blood pressure, dilated pupils, Increased perspiration, nsomnia, talkative, repetitive,Restlessness, pacing

Key psychological effects include:euphoria, intense pleasure, confidence, assertiveness, irritability, aggression, anxiety, panic, repetitive behaviours, increased libido (but possibly reduced erectile function), tactile hallucinations ("bugs under skin")

INDICATORS of USE: The physical effects above are key indicators of amphetamine use, but could also be caused by other stimulants.
Heavy prolonged use can result in nasal or tooth damage (depending on route), weight loss, insomnia and mental health problems.

RISKS: Amphetamines can cause significant short, medium term and long term problems.

OD/Death: amphetamines put a significant strain on the cardiovascular system and can cause death through heart failure. Amphetamine was a feature in 120 deaths in the UK in 2013. This is low compared to opiates but the rate has increased year on year since 2010.

Weight loss: heavy prolonged use of amphetamines can cause significant and dangerous weight loss. In turn this can lead to organ damage, and compromised immune system.

Nasal/tooth damage: highly acidic amphetamine erodes and weakens teeth and, when rubbed on gums can cause tooth loss. It also irritates and damages nasal tissue when snorted. Smoked methamphetamine causes significant tooth damage leading to a condition called "meth mouth."

Swallowing amphetamine: although safer than other routes, amphetamine can irritate and damage the stomach lining and may cause stomach damage.

Risk taking behaviour: amphetamines can cause over-confidence, irritability and possible aggression. It can contribute to increased violent episodes, especially in night-time economy settings. Amphetamines can also increase libido and the use of methamphetamine in the "chemsex" scene has caused increasing concern. Chemsex is a term used to refer to drug-related sex activity, especially amongst Gay men, and is associated with the use of methamphetamine, and increased incidence of high-risk sexual activity.

Mental wellbeing: amphetamine causes an unpleasant comedown. Low levels of dopamine post use can cause low mood, depression, craving and dysphoria. Comedown also tends to leave the person feeling tired, run down, irritable and anxious. Even single episodes of use can lead to an unpleasant comedown - amphetamine is generally a drug that leaves the user feeling pretty low the next day. Some people will use other drugs (cannabis, benzos, alcohol) to take the edge off a comedown. Others will use more speed, leading to multi-day speed binges. The crash off extended use is inevitably far worse.

Amphetamines can cause anxiety and paranoia. With extended use, the combination of amphetamine use and sleep deprivation can lead to serious symptoms - hallucinations, delusion, paranoia and panic. The condition, often referred to as "amphetamine psychosis" doesn't usually persist once use stops and the person starts to eat and sleep again. However, symptoms can last for a number of days and possibly weeks, and may require inpatient treatment

DEPENDENCY: Amphetamines can and do lead to dependency. Patterns of dependency in the UK are significantly different to other countries where methamphetamine dependency is a more significant issue. Many drug projects, especially in regions where there is entrenched amphetamine use, will have a small cohort of speed-dependent clients.
Early speed use is euphoric, rewarding and typified by binges. Most people learn to take long breaks from speed use and the unpleasant come-down is a big deterrent.
After sustained, use, the person is liable to be significantly dopamine depleted and feel very tired. At this point speed use is less about reward and more about just being able to function. Speed becomes a tool to help the person get up and do things.
A fair proportion of the dependent speed users attending drug projects are older men, in poor physical health, who have been using for a number of years. Some agencies also report seeing younger people who may have ADHD who are self medicating with amphetamines some of whom have previously been prescribed Ritalin.
Interventions don't usually require medical input, though some research suggests use of anti-depressants to help reduce craving. The key interventions centre on craving management, and interventions to address the low levels of dopamine and the associated cravings.
Substitute prescribing isn't widespread in the UK but is still undertaken on a limited basis.

MIXING: Amphetamine is used extensively alongside alcohol. The stimulant effects of amphetamine significantly reduce the sedating effects of alcohol, allowing for increased alcohol consumption. This increases the risk of alcohol related liver damage. Alcohol continues to disinhibit and the increased confidence and assertiveness of amphetamine with the disinhibition of alcohol makes for a volatile combination.

HARM REDUCTION:
Route specific harm reduction:

-don't share snorting or injecting equipment
-always practice safer injecting techniques
-discontinue application at site getting nose-bleeds or bleeding gums.

General health:
-don't use for extended periods of time - allow time to rest and recover
-don't use in combination with alcohol; if you do drink on speed moderate alcohol intake and ensure adequate water consumption
-maintain diet or use liquid replacement meals
-consider use of vitamin D and calcium supplements
-avoid if you have high blood pressure or any family history of cardiac problems
-be aware of indications of depression worsening mental health; discontinue use and seek help.

TRENDS: According to the Crime Survey for England and Wales for 2014-15, only 1.3% of 16-24 year olds reported speed use in the last year. This was marginally down on the previous year. Back in 1996 reported levels were almost ten times higher, with 11.8% reporting use in the last year.

LAW: Amphetamines Sulphate is a Class B, Schedule 2 drugs. This means that, unless produced, supplied or possessed under Home Office licence, offences would be committed under the Misuse of Drugs Act 1971. Amphetamines, like other class B drugs, are counted as Class A drugs when prepared for injection.
Methamphetamine and other structurally modified Amphetamines (e.g. 4-Fluoroamphetamine) are Class A drugs.

Pharmaceuticals such as Dexamphetamine Sulphate are legal if prescribed and used by the person to whom they were prescribed. A small number of weaker amphetamine-based compounds (e.g. Benzphetamine) are Class C drugs.

OTHER INFORMATION: Amphetamines were once one of the core drugs on the UK drug scene. Recreationally they were popular in lots of music/club/youth scenes and diverted amphetamines were popular with mods, rockers, Northern Soul fans, and then a core feature in the punk scene and amongst some Goths.
Non-recreationally, amphetamines had long been a feature of the diet-pill world. They were also used in a number of workplace settings, including factory and warehouse work, fishing and driving settings, and amongst students and night workers. Ian Fleming's James Bond uses Benzedrine on several occasions in the course of work.
Speed has, in part been displaced by more popular, less harsh and more "glamorous" competitors, most notably Ecstasy and cocaine. The advent of Ecstasy, with a less edgy, more "loved-up" feel, made for a better clubbing experience and contributed to a decline in speed's popularity. Where cocaine was scarce and expensive, speed, although considered "poor man's coke" was an acceptable alternative. As availability of cocaine increased and price dropped, many people would choose to use cocaine over speed.
It had always been recognised that speed was a low purity drug at street levels, and the advent of legal, pure alternatives like mephedrone and later ethylphenidate contributed still further to a drop in speed's popularity.
Having said this, in large parts of the UK, speed remains the stimulant of choice, especially where cocaine is hard to obtain. In an increasingly contaminated "white powder" market, it's hard to know how many of the street blends are, in part, amphetamine.

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KFx Drug Consultancy Initiative - Learning of Substance

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AKA: Amphetamine Sulphate: speed, whizz, sulph, billy, phet, pink champagne, Base Amphetamine: base, base speed, paste Dexamphetamine Sulphate: Dexedrine, dexies, dex, Adderall Methamphetamine Sulphate: Methedrine, Crystal Meth, meth, ice, shard, glass, Tina, Shabu, Yabba, crank, Pervitin, Sisa Benzphetamine: Didrex The amphetamine "family" contains a number of prescribed and non-prescribed stimulant compounds.

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This guidance has been produced to aid clinicians and other practitioners in the use of, and reduction of misuse of benzodiazepines (BZ) aimed at primary care. Other hypnotics and anxiolytics, including the 'Z-drugs' (zopiclone, zolpidem, zaleplon, eszopiclone) are mentioned briefly.

There is a selection of other helpful guidance documents listed in this guidance but these have not been
specifically aimed at primary care.

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Guidance for the use and reduction of misuse of benzodiazepines

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This guidance has been produced to aid clinicians and other practitioners in the use of, and reduction of misuse of benzodiazepines (BZ) aimed at primary care. Other hypnotics and anxiolytics, including the 'Z-drugs' (zopiclone, zolpidem, zaleplon, eszopiclone) are mentioned briefly.

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AKA: Benzos, tranx, sleepers, downers. Specific drugs are referred to by their chemical name, brand name, and some have got slang names.

Drugs with similar effects and risks (though not benzos) include the "Z-drugs" such as Zopiclone and Zimovane.

More common benzodiazepines include:

SOURCE: Benzodiazepines are widely prescribed as sedatives, to combat anxiety, as skeletal muscle relaxants, anti-epileptics and anti-convulsants. However, some benzodiazepines leak onto the street, and are quite widely misused.

In addition to leaked pharmaceuticals, benzos have been illicitly imported in to the UK. Some have been entering from Eastern Europe and sold on the illicit markets. Others have been ordered on line from one of the many Internet Pharmacies. Some of these tablets are fake, or of variable quality.

From 2009, abandoned experimental benzodiazepines and novel ones appeared on the UK drugs market including etizolam, pyrazolam and flubromazepam. Whilst legal, they were sold on-line and via 'head-shops." These novel benzos were almost all brought under the MoDA in May 2017. Any not covered or emerging since then are automatically covered by the Psychoactive Substances Act 2016.

GPs are regularly reminded not to over-prescribe benzodiazepines and those on long term prescriptions are meant to have these reviewed regularly. Despite this, and prohibition of newer benzos, drugs in this family remain a key feature of the UK drugs market.

APPEARANCE:

The appearance of each drug varies widely. Most are distributed as tablets or capsules. A small number of unregulated compounds are sold as powders. A few also come in preparations for injection, such as Valium ampoules, which command a higher street value.

Different brands of drug will vary from company to company. Tablets will vary in colour, shape and markings.

The mainstay of the street benzodiazepine market has, for a number of years, been diazepam. The most widespread and popular strength, a 10mg tablet, is often a scored blue tablet. As a result, people manufacturing tablets to sell as diazepam invariably produce a blue tablet. These can vary massively in consistency and strength. Some are merely white powders, dyed blue and compressed in to tablets.

Alprazolam (Xanax) has become increasingly popular in the UK. As it is not widely prescribed on the NHS, Alprazolam sold in the UK may be from private prescriptions, overseas pharmacies of grey-market tablets batched from raw alprazolam powder. These can vary greatly in strength. Alprazolam is typically sold as white, scored bars with XANAX printed on them.

COST: At a street level, benzodiazepines have a very low value, typically around 50p per tablet. Ampoules can cost a pound or two. Depending on dose and quantity stronger pills like Xanax can sell for between £2-5 depending on claimed dose.

QUALITY: If pills are genuine pharmacy product, quality is assured. However, it is difficult to correctly identify all of the drugs in this family by eye, let alone assay the strength, so mistakes in strength and name are frequent amongst those purchasing non-medical products.

With so many imported, fake, unlicensed and novel products entering the market, the risks with non-pharmacy products will increase. Products could contain something stronger, weaker or different.

Benzodiazepines interact with the GABA system in the brain. The regulatory neurotransmitter gamma-amino butyric acid (GABA) plays a role in moderating electrical activity in the brain. As GABA levels increase, so electrical activity in relevant neurons goes down. METHODS OF USE: Tablets are designed for oral use, though some users crush and inject tablets. As diazepam has very poor solubility in water this is damaging and not very effective. There are some reports of snorting, especially of novel benzodiazepines.

MECHANISM of ACTION:
Some drugs, like GHB and Barbiturates, are GABA agonists (mimics). Benzodiazepines are not thought to be full GABA mimics. Instead, benzodiazepines bind to Benzodiazepine Receptors (BZ receptors) and appear to increase the regulatory effect of GABA. They need GABA, or a GABA-mimic present to work.

Specific benzodiazepines are believed to be more active at different BZ receptors. This may result in different benzos having greater or lesser sleep-inducing, muscle relaxing or anxiolytic effects.

REASONS for USE: Benzodiazepines are still used medically for a range of conditions including: Anti-convulsants, anti-anxiety (anxiolytic), sleep-inducing (hypnotic), muscle relaxant, amnesiac, alcohol detoxification.

Non-medical use follows similar patterns, self-medicating for a range of conditions including anxiety and insomnia. They are also popular as "come-down" drugs following use of stimulants. The sense of intoxication when used with opiates or alcohol is greater, so these combinations are widely used. This brings a bigger risk of overdose.
Benzodiazepines vary significantly in strength. They are generally compared in potency using diazepam (Valium) as a benchmark. So potencies are expressed in relation to 10mg of diazepam. 5mg of Alprazolam (for example) is equivalent to 10mg of diazepam. So Alprazolam is around twenty times the strength of diazepam.

DOSE RANGES: There are a wide range of benzodiazepines available and the lower dose ranges vary according to the potency of the drug, and its duration of effect. Medical guidance specifies upper dose ranges for medical use. In street settings upper dose range will vary massively according to tolerance. Some people will build up dose tolerance far in excess of the therapeutic dose range.

INDICATORS of USE: Aside from physical evidence such as packaging, there are few markers for benzo use. Illicit fake diazepam can cause blue staining to lips and tongue. Otherwise indicators are simply drowsiness, relaxation and possibly appearing drunk, but without the smell of alcohol.
Whilst older benzos will show up on urine tests, some of the newer products such as Etizolam are sufficiently structurally different so won't show up on urine tests.

ONSET and DURATION: As with strength and dose, benzodiazepines vary significantly in terms of how fast they start working, and how long their effects last.
Slow-onset benzodiazepines increase the risk that a person will re-dose before drugs have started working properly.
Some benzodiazepines produce active metabolites, with very long half-lives. Some can last 100-200 hours or longer. These long-acting drugs increase the risk of building up tolerance, and that any later drug use will be taking place on top of residual benzodiazepines. For example, diazepam used on Sunday will probably still be in the system on Tuesday or Wednesday. This means that alcohol use on these days is effectively taking place on top of benzodiazepines.

EFFECTS: Benzos can cause physical relaxation, reduce stress and anxiety. Users may become drowsy or fall asleep. They can have a big impact on memory, causing amnesia. They can also cause slurred speech, clumsiness and confusion. People report euphoria and some people find benzos disinhibiting, in the same way that alcohol is. Some users gain a feeling of invulnerability or invisibility when using benzodiazepines. They may find this useful when, for example, shoplifting. Some users experience depression and, paradoxically, a few users become over-excited or violent.

HEALTH IMPLICATIONS: Dependence: When used within a supervised medical regime, benzodiazepines should not be used for extensive periods as tolerance develops rapidly and withdrawal can be an unpleasant and, in some cases, dangerous process. After a few weeks, and certainly within a few months, they cease to be therapeutic, and use is now primarily to stave off withdrawal symptoms.
For physically dependent users, abrupt withdrawal can cause insomnia, anxiety, tremors and, in severe cases convulsions.
Withdrawal from Benzodiazepines should always be tapered rather than done suddenly.
Where there is evidence of high doses, long-term use, or where the person has a history of illness such as epilepsy, withdrawal should be done under medical supervision. IT IS POSSIBLE TO DIE DUE TO SEVERE BENZODIAZEPINE WITHDRAWAL. However this is unusual and most people are able to withdraw rapidly, through a tapering reduction programme.

Overdose: There is a low risk of fatal overdose when benzodiazepines are used on their own. They have a very high therapeutic index, and while there's a risk of unconsciousness or possible coma, the risk of death is low. This risk is raised through ignorance as to the strength of various tablets.
However, in combination with other drugs, especially alcohol and opiates, the risk of fatal overdose is far higher. A large number of dependent drinkers and people on opiate substitution therapy are also prescribed diazepam, increasing risk of dangerous polydrug use.

Other risks: When tablets are crushed for injection, this brings with it a range of associated health risks. Of specific concern were Temazepam Capsules. These capsules were originally introduced as a response to growing concern over Temazepam tablets being crushed for injection. The capsules contained a viscous jelly that was intended to discourage injecting. However, users found that heating the jelly made it become liquid, and so injected it. However, at lower temperature, such as at body temperature, the gel solidifies, and a large number of gruesome injecting injuries were reported. Gel capsules have not been legitimately available in the UK for over ten years.

LEGAL STATUS: : Most Benzodiazepines are class C drugs. The majority are Schedule 4i drugs, meaning that they can only be supplied, produced and possessed by those authorised to do so. The law on Schedule 4 drugs changed in 2002; prior to that it was not an offence to possess benzodiazepines without prescription.

The penalty for supply of a Class C drug was increased from 5 years to 14 years, so it is a serious criminal offence.

Temazepam and Flunitrazepam (Rohypnol) were rescheduled, and are Schedule 3 drugs.

Formerly unregulated benzodiazepines (such as etizolam) were brought under the MoDA in May 2017. The benzos were added as a list rather than via an "analogue" clause which means that there is scope for developing new benzos that will not be covered by the MoDA. Any such emergent benzos will automatically be covered by the Psychoactive Substances Act 2016.

OTHER INFORMATION:
Benzodiazepines were introduced and have largely supplanted the BARBITURATE group of drugs, which were widely prescribed and widely misused in the seventies. They were seen as preferential to barbiturates as the risks of overdose, dependence and side-effects were thought to be less. They are very widely prescribed; some critics argue that they are over-prescribed, and do not tackle the causes, merely masking symptoms temporarily.

They are used recreationally in a number of settings. Some people combine benzodiazepines with alcohol to enhance and increase intoxication. Some stimulant users take benzodiazepines to alleviate the "come-down" from speed, Ecstasy or cocaine, and to promote sleep.
It is not uncommon for dependent heroin users to use benzodiazepines when heroin is unavailable, or to use them to help offset some of the symptoms of withdrawal. The use of benzos on top of prescribed opiates - such as with methadone or Subutex - is also common as it can make the effects of the opiates feel stronger. Such use increases risk of overdose.

Many people self-medicate with benzodiazepines to alleviate mental discomfort caused by mental health problems, painful memories, or to escape unpleasant circumstances. For such users, where unsupervised use may be long-term and extensive, careful assessment of needs, of underlying reason for the drug use, and comprehensive care plans are likely to be needed to achieve reduction and cessation of drug use.

Prescribers are very aware of benzodiazepine over prescribing, and in many areas greater care is now taken to reduce and monitor prescribing. However, a number of other drugs have been less closely monitored and have increased in popularity.

Initially, the "Z-Drugs" (Zopiclone, Zimovane, Zaleplon) increased and of course started to be misused. The law in relation to some of these has now been tightened and they are now Controlled Drugs.

More recently, Gabapentin and Pregabalin have emerged as the latest of the sedating drugs to shift from medical to non-medical settings. Although not benzodiazepines, they work in the same parts of the brain, with similar risks in terms of tolerance, dependency and overdose.

Whilst the use of prescribed diazepam is undoubtedly lower, levels of benzo-type drugs (including illicit market, novel psychoactives, and similar prescribed drugs) means overall use is probably increasing. Workers have reported people entering treatment with staggeringly high levels of benzodiazepine dependency, built up exclusively using street benzos.

Alongside opiates, alcohol and strong stimulants, benzos remain a core feature of the UK drug scene.

[updated 11.17]

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KFx Drug Consultancy Initiative - Learning of Substance

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AKA: Benzos, tranx, sleepers, downers. Specific drugs are referred to by their chemical name, brand name, and some have got slang names. Drugs with similar effects and risks (though not benzos) include the "Z-drugs" such as Zopiclone and Zimovane. More common benzodiazepines include: SOURCE: Benzodiazepines are widely prescribed as sedatives, to combat anxiety, as skeletal muscle relaxants, anti-epileptics and anti-convulsants.

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Community pharmacists need to be part of the solution for the millions of people across the UK grappling with prescription drug dependence and withdrawal

A quarter of adults in England take one or more prescription medicine(s) that might cause dependence, withdrawal symptoms or both, according to a new report, Dependence and Withdrawal Associated With Some Prescribed Medicines: An Evidence Review, from Public Health England (PHE). ¹

Brendon Jiang, RPS English Pharmacy Board member and NICE medicines and prescribing associate, describes it as a landmark document.

PHE estimates that in 2017-18, 11.5 million adults in England (26 per cent of adults) received one or more prescriptions for anti-depressants, opioid analgesics for chronic non-cancer pain, gabapentin and pregabalin (gabapentinoids), benzo-diazepines and z-drugs such as zopiclone and zolpidem (see Table 1).

"These drugs are vitally important when prescribed properly for the health and well-being of many patients," says Rosanna O'Connor, director of drugs, alcohol, tobacco and justice at PHE.

"We need to address the problems posed by dependence and withdrawal but care needs to be taken not to inapprop-riately limit the use of these medicines as this could cause patients harm and may lead some people to seek medicines from illicit or less-regulated sources."

A comprehensive literature review and an open call for evidence from patients has led PHE to conclude that benzodiazepines, z-drugs, opioid analgesics and gaba-pentinoids are associated with a risk of dependence and withdrawal.

Antidepressants are associated with withdrawal symptoms, such as insomnia, depression, suicidal ideation and physical changes. Patients may mistake the problems they experience stopping treatment for addiction. "It is crucially important to understand the difference between the terms: addiction, dependence, tolerance and withdrawal," Jiang adds (see Table 2).

Polypharmacy and long-term use

To complicate matters further, PHE found that polypharmacy and long-term use were common. About a fifth of patients (19.1 per cent) were taking two of the five classes of drugs, most commonly antidepressants and opioids (9.3 per cent of the total, some 513,000 people). One in 20 (5.2 per cent) received three classes, most commonly anti-depressants, gabapentinoids and opioids (2.8 per cent of the total, about 157,000 people).

Almost one in 100 (0.8 per cent) and one in 1,000 (0.1 per cent) took four and all five drug classes respectively. This means some 48,000 people in England take four or all five classes. The impact of polypharmacy on the potential for dependence and withdrawal is just one of several areas that urgently need further research. About three in 10 of those prescribed one of the classes received the drugs long-term (see Table 1).

Between 2015-16 and 2017-18, for example, prescribing for antidepressants increased from 15.8 to 16.6 per cent of adults and from 2.9 to 3.3 per cent for gabapentinoids. Prescriptions for the other groups showed small decreases.

Despite the well-publicised concerns over at least some of these drugs, PHE identified "large variations" in prescribing across clinical commissioning groups, which demographics and deprivation only partly explain. In general, rates of prescribing were 1.5 times higher among women than men and increased with age.

For all five classes, the proportion of patients who had at least a year of prescriptions increased among people from more deprived backgrounds. That may be justified for antidepressants, given the psychological devastation often wrought by poverty, but it is not in line with guidelines for the other drugs.

"The review makes a number of recommendations related to reducing variations in practice and it is now for the NHS to take these and other activity forward, including examining the data and supporting adherence to guidance," O'Connor says.

Lack of information

Patients told PHE they felt there was a lack of information about medication risks and that doctors did not acknowledge or recognise withdrawal symptoms. Patients also felt that they were not offered non-medicinal options and were unable to access effective management and NHS support services.

In addition, patients felt that their treatment was not reviewed sufficiently. "Patients should meet with their GP to review their prescriptions at least annually but preferably three- or six-monthly," O'Connor advises. "It needs to be a clinical decision, tailored to the patient, their condition and history. Some may need more frequent reviews."

Pharmacists should encourage people with concerns about dependence and withdrawal to seek professional help. "Patients with concerns about their medicines should not stop taking them, but should speak to a healthcare professional. "We must treat the person behind the prescription and discuss these problems professionally and without judgement," Jiang says.

Language matters and emphasises the value of a consistent message from healthcare professionals, he says. "No patient actively seeks treatment with the aim of pharmacological dependence or withdrawal. We must shift the narrative from misuse, abuse or addiction, whereby patients risk feeling blamed or victimised, to a factual discussion about the lack of evidence, their awareness of the risks, their perceptions of benefit and what truly matters to them," he says.

"This does not need to be a sit-down, in-depth consultation. Earlier interventions can be more effective and there is power in consistent messages repeated from all clinicians involved in the care pathway."

Avoiding withdrawal symptoms means slowly tapering the dose but in some cases the formulations may not be available. "Pharmacists can use their specialist knowledge of pharmaceutics and pharmacokinetics to recommend alternatives," Jiang says. "An alternative with a longer half-life reduces the dosing interval and onset of withdrawal symptoms.

"Pharmacists can also use their professional judgement, in conjunction with the available evidence to recommend a course of action appropriate to the patient if no licensed form exists."

Against this background, PHE recommends increasing the availability and use of data on the prescribing of medicines that can cause dependence or withdrawal. This, it argues, would support greater transparency and accountability as well as helping ensure that practice is consistent and in line with guidance. In addition, PHE has called for enhanced clinical guidance and ensuring that healthcare professionals follow the guidelines.

PHE has also suggested improving information for patients and carers on prescribed medicines and other treatments, enhancing informed choice and shared decision-making, and transforming the available support for patients experiencing dependence or withdrawal. Finally, PHE calls for further research on the prevention and treatment of dependence and withdrawal associated with prescribed medicines.

The report notes that there isn't enough evidence to draw robust conclusions about best practice. Nevertheless, current services offer various combinations of primary care involvement, a helpline, counselling, support groups and individualised plans. And it seems community pharmacists have an important role - one that could expand as recognition of the problems posed by dependence and withdrawal rises among patients and professionals.

No patient actively seeks treatment with the aim of pharmacological dependence

Roles for community pharmacists

"Community pharmacists already practise in ways that can reduce dependence. They clinically assess prescriptions and query or intervene with both patients and prescribers if necessary," Jiang says. "They counsel patients when initiating new therapies, outlining the expected duration of treatment, safe use, risks, potential harms and requirement for review.

"There need not be a drastic change in practice, but more can be done to support these patients," he believes.

The continuity of care offered by community pharmacists may be especially helpful when tackling sensitive, contentious issues such as dependence and withdrawal. "Pharmacists and their teams get to know their patients, review any use that strays beyond expected guidelines, and monitor for
and identify signs of misuse or dependency," Jiang says. "This is the responsibility of the entire team - from healthcare assistants through to dispensers, technicians and pharmacists. Their knowledge of the community and the relationships and trust built over time can facilitate having what can be challenging conversations."

In addition, community pharmacists can signpost patients to local services. "Apart from referring to the GP, is there a helpline, talking therapy service, cognitive behavioural therapist, support group, specialist support service, community pain team, social prescriber locally, and what is the referral pathway?

Strategically, the PHE report advises that CCGs work with sustainability and transformation partnerships and integrated care systems. The report makes several recommendations about how community pharmacists and NHS structures can help to address the issues in the report.

"This includes improving training provided to primary care services, clinical and community pharmacists. GPs also need to develop their knowledge of, and competence to identify, assess and respond to dependence or withdrawal associated with some medicines and the support needs of people experiencing problems," O'Connor remarks.

"PrescQIPP audit tools have also been made available to support primary care practices and community pharmacists review and tackle high-dose opioid prescribing. The NHS now needs to take the agenda forward."

It won't be a moment too soon. The PHE report clearly and unambiguously lays out the scale of the problem and what the NHS can and needs to do. There is no longer any excuse for equivocation.

Reference

Dependence and withdrawal associated with some prescribed medicines: an evidence review.

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Tackling prescribed medicine dependence and withdrawal - Pharmacy Magazine

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A quarter of adults in England take one or more prescription medicine(s) that might cause dependence, withdrawal symptoms or both, according to a new report, Dependence and Withdrawal Associated With Some Prescribed Medicines: An Evidence Review, from Public Health England (PHE).

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Inappropriate use of OTC medicines can be termed medicine "misuse" or "abuse". Abuse is considered to be the use of medicines for a non-medical use whilst misuse is the improper use of an OTC medicine for a recognised medical condition. Generally these terms are synonymous and the reason that the medication is being misused does not always need to be known to reduce its incidence. In the context of this module we will be using the term "misuse" when referring to inappropriate use of over the counter medicines.

OBJECTIVES

After reading this module you will be able to:

* Understand the reasons why customers misuse over the counter medicines.

* How to recognise customers who may be misusing medicines.

* Suggest strategies that can be employed to combat or reduce over the counter medicine misuse.

* Identify the categories of medicines most likely to be misused.

Transferring medicines from prescription only control provides advantages to customers by allowing easier access to medication and avoiding the repeated need to visit their GP, but also poses disadvantages by increasing the opportunity for the inappropriate use of the medicine.

It is very hard to quantify the extent of the problem of misuse of OTC medicines, and most research concludes that the majority of community pharmacists acknowledge that misuse occurs but that it represents only a small minority of customers visiting community pharmacy. Medicines perceived to have the biggest misuse problem include opioid containing painkillers, sedative antihistamines and laxatives.

Whilst the incidence of misuse may only affect a small percentage of customers, its effects are important as further research has shown that a high proportion of abusers of illicit drugs have at some point in their drug taking career abused OTC medicines. An increasing number of patients of local substance misuse teams are being supported to combat dependence on OTC medicines.

Reasons why customers may misuse over the counter medicines

Customers misuse medicines for a variety of reasons. These include:

* Inappropriate medical use: this is where a medicine is used incorrectly to treat an appropriate medical condition. This form of misuse would apply when a customer uses a medicine to treat a recognised medical condition but at too high a dose or for too long a period of time, such as codeine containing analgesics being used for longer than three days without consulting a doctor.

* Medication dependence: this occurs where customers start to take a medicine for a medical condition and then either abuse it or become dependent on it. A classic example of this would be the use of codeine containing pain killers initiated for their analgesic effect, customers then experience withdrawal symptoms when trying to stop using them and continuing their use to avoid withdrawal effects.

* Attempt to change body shape: this includes customers trying to lose weight or to increase body muscle. An example of this would be the use of large doses of stimulant laxatives when trying to lose weight or avoid weight gain.

* Unintentional misuse: this can occur when customers take medicines believing that they are using them for an appropriate indication or at an appropriate dose. This may be a consequence of poor advice or advice from people who are not medically trained. An example of this would be the use of over the counter head lice treatments in the belief that it will help to prevent head lice infestation.

* Deliberate abuse for non-medical reasons: such as using decongestants to produce a stimulant effect. Over the counter medicines can be used to supplement the effects of illicit street drugs or to reduce the withdrawal effects when these drugs are not available to the customer.

* To facilitate the use of illegal substances: over the counter products can be used to assist with the abuse of other products without themselves being abused. An example of this would be the use of citric acid or ascorbic acid to convert base heroin, cocaine or amphetamine to soluble forms that can be injected.

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Abuse or Misuse of Over the Counter Medicines

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Inappropriate use of OTC medicines can be termed medicine "misuse" or "abuse". Abuse is considered to be the use of medicines for a non-medical use whilst misuse is the improper use of an OTC medicine for a recognised medical condition.

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Are you living with aches and pains and want to make some positive changes in your life, but don't know where to start?

Living with aches and pain seriously affects our well being. Being active and getting out and about can help reduce the pain caused by muscle, joint and bone problems. It can improve well being and even prevent related conditions from developing. But it can be difficult to get started or know where to go for help.

Right Track is a collaboration between the voluntary sector and health to support you (and your carer if you have one) to become more active. We can link you into support and activity near you which can help improve your health and well being.

We work across Brighton, Hove and West Sussex in partnership with the Sussex MSK Partnership Central.

Contact us

Let us help you get on the right track. Telephone us on 01273 069850 or email right-track@possabilitypeople.org.uk

MSK Partnership is made up of Here (formerly known as Brighton and Hove Integrated Care Service, BICS), Horder Healthcare (HH), Sussex Community NHS Foundation Trust (SCFT) and Sussex Partnership NHS Foundation Trust (SPFT). It also works closely with specialist partner suppliers from patient charities, GP groups, diagnostic providers and local providers of secondary care.

It is a local, not for profit partnership bringing together primary care, specialist musculoskeletal care, community and mental health and well-being experts to deliver the whole musculoskeletal service in central Sussex. It is committed to a truly integrated MSK service that is effective, efficient and compassionate.

You can find out more about them at http://sussexmskpartnershipcentral.co.uk/

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Managing aches and pain - Possability People

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Are you living with aches and pains and want to make some positive changes in your life, but don't know where to start? Living with aches and pain seriously affects our well being. Being active and getting out and about can help reduce the pain caused by muscle, joint and bone problems. It can improve well being and even prevent related conditions from developing.

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Sussex MSK Partnership 4th Floor, 177 Preston Road, Brighton, BN1 6AG

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Advice for healthcare professionals:

opioid medicines (opioids) provide relief from serious short-term pain; however long-term use in non-cancer pain (longer than 3 months) carries an increased risk of dependence and addiction

discuss with patients that prolonged use of opioids may lead to drug dependence and addiction, even at therapeutic doses - warnings have been added to the labels (packaging) of UK opioid medicines to support patient awareness

before starting treatment with opioids, agree with the patient a treatment strategy and plan for end of treatment

explain the risks of tolerance and potentially fatal unintentional overdose, and counsel patients and caregivers on signs and symptoms of opioid overdose to be aware of (see opioids safety information leaflet plus PDF leaflet)

provide regular monitoring and support especially to individuals at increased risk, such as those with current or past history of substance use disorder (including alcohol misuse) or mental health disorder

at the end of treatment, taper dosage slowly to reduce the risk of withdrawal effects associated with sudden cessation of opioids; tapering from a high dose may take weeks or months

consider the possibility of hyperalgesia if a patient on long-term opioid therapy presents with increased sensitivity to pain

consult the latest advice and warnings for opioids during pregnancy in the product information and in clinical resources

report suspected dependence or addiction to any medicine, including to an opioid, via the Yellow Card scheme

National review of benefits and risks of opioid medicines

More than 20 different opioid medicines (opioids) are authorised for use in the treatment of pain in the UK. The relative potency differs between these medicines. Opioids relieve pain but may not remove pain altogether.

Considerable concern has been raised regarding prescribing rates of opioids in the UK and the awareness of healthcare professionals and patients of the risks of dependence and addiction. This includes Public Health England's evidence review of dependence and withdrawal associated with some prescribed medicines.

In 2019, the Commission on Human Medicines (CHM) convened an Expert Working Group to examine the benefits and risks of opioids in the relief of non-cancer pain, including information available to healthcare professionals and patients about the risks of dependence and addiction. Following this review, CHM has made recommendations to improve information for prescribers and patients about these risks to protect public health.

To make it clear that a medicine contains an opioid and that there is a risk of addiction (a recognised term by patients) with prolonged use, CHM recommended that the packaging for all opioid medicines in the UK carries the warnings 'Can cause addiction' and 'Contains opioid'. The CHM also recommended including further information on the risk of tolerance, dependence and addiction in the product information.

The changes apply to the following opioids:

Tolerance, dependence, and addiction

Product information for opioids in the UK will include consistent warnings of the risks of tolerance and dependence and addiction. Patients may find that treatment is less effective with long-term use and express a need to increase the dose to obtain the same level of pain control as initially experienced. This could indicate that the patient is developing tolerance and dependence.

For all patients, prolonged use of opioids may lead to drug dependence (and in some patients addiction/opioid use disorder), even at therapeutic doses (see resources from the Faculty of Pain Medicine). The risks are increased in individuals with current or past history of substance use disorder (including alcohol misuse) or mental health disorder (for example, major depression). Additional support and monitoring may be necessary when prescribing for patients at risk of opioid misuse.

Typical signs of addiction are:

Expression of craving for the drug, even if it is causing adverse effects on overall health

Expression of a need for more, or reporting additional use of other pain-relief medicines

Taking medicines for reasons other than pain relief

Experiencing withdrawal side effects when opioids are stopped suddenly

Withdrawal reactions

Dependence and addiction to opioids are associated with adverse reactions of withdrawal upon sudden cessation of treatment that make it harder to stop taking these medicines. CHM has therefore recommended that before prescribing an opioid a discussion should be held with the patient, to put in place a withdrawal strategy for ending treatment with their opioid medicine.

Withdrawal from an opioid is characterised by shivers, diarrhoea, difficulty sleeping (insomnia), sweating, body aches (myalgia), widespread or increased pain, irritability and agitation, and nausea and vomiting. Other signs and symptoms include restlessness, lacrimation, rhinorrhoea, yawning, mydriasis, palpitations, anxiety, hyperkinesia, tremor, weakness, anorexia, abdominal cramps, and increased blood pressure, respiratory rate, and heart rate.

Tapering doses

To minimise the risk of withdrawal reactions, the dose of opioid should be tapered slowly at the end of treatment. This can take weeks or months, depending on individual response and the dose taken. Healthcare professionals should advise patients not to stop suddenly taking their medicines or try to self-medicate to overcome withdrawal effects. Self-medication with opioids can result in overdose and potentially death.

Hyperalgesia

Some patients can develop hyperalgesia (increased sensitivity to pain) with long-term use of opioids. This might be qualitatively and anatomically distinct from pain related to disease progression or to breakthrough pain resulting from development of opioid tolerance. These symptoms may resolve with a gradual reduction in opioid dose.

Opioids in pregnancy

Opioids readily cross the placenta, therefore if used during pregnancy neonates may become dependent and experience neonatal abstinence syndrome at birth. Extra vigilance is required and appropriate treatment should be made available.

Resources for prescribers and dispensers

We have developed an opioids safety information leaflet on the risks of dependence and addiction (also available as a PDF leaflet). This advice for patients and their families and carers was developed following consultation with a number of stakeholder organisations, charities, and patient groups.

We encourage healthcare professionals to use this information alongside the statutory patient information leaflet supplied with opioid medicines.

Additional guidance is available for healthcare professionals and patients at the following websites:

Report side effects, including dependence

If a patient experiences any side effect related to dependence to a medicine or is recognised by the prescriber to be dependent, CHM encourages prescribers, patients, or carers to report this to the MHRA through the Yellow Card scheme with the term 'dependence'. Use of this specific term will assist the MHRA to monitor the rates reported in the UK and therefore to further protect public health.

Any other suspected adverse drug reactions associated with opioids should also be reported to the MHRA through the Yellow Card scheme. Report via the Yellow Card website, Yellow Card App (download at iTunes Yellow Card for iOS devices or at PlayStore Yellow Card for Android devices), or some clinical IT systems (EMIS/SystmOne/Vision/MiDatabank).

Article citation: Drug Safety Update volume 14, issue 2: September 2020: 1.

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Opioids: risk of dependence and addiction

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New recommendations following a review of the risks of dependence and addiction associated with prolonged use of opioid medicines (opioids) for non-cancer pain. Before prescribing opioids, discuss with the patient the risks and features of tolerance, dependence, and addiction, and agree together a treatment strategy and plan for end of treatment.

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B+H CCG Non-Malignant Chronic Pain Prescribing Guidelines FINAL.pdf

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B+H CCG Non-Malignant Chronic Pain Prescribing Guidelines FINAL.pdf

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It is important to taper or stop the opioid regimen if:

the medication is not providing useful pain relief. The dose above which harms outweigh benefits is 120mg oral morphine equivalent/24hours. Increasing opioid load above this dose is unlikely to yield further benefits but exposes the patient to increased harm

the underlying painful condition resolves

the patient receives a definitive pain relieving intervention (eg, joint replacement)

the patient develops intolerable side effects

there is strong evidence that the patient is diverting his/her medications to others

Preparation for dose reduction includes:

explanation of the rationale for stopping opioids including the potential benefits of opioid reduction (avoidance of long term harms and improvement in ability to engage in self management strategies)

agreeing outcomes of opioid tapering

deciding which patients may need admission for opioid taper/cessation informed by existing opioid dose

physical co-morbidities

mental health co-morbidities including significant emotional trauma

monitoring during taper of pain

symptoms and signs of opioid withdrawal

choice of opioid reduction scheme

incremental taper of existing drug

conversion to methadone or buprenorphine

defining the role of drug and alcohol services to support dose reduction

close collaboration between the patient, his or her carers and all members of the patient's health care team

arrangements for follow-up including agreed prescribing responsibilities

The dose of drug can be tapered by 10% weekly or two weekly.
Points to discuss with patients when de-prescribing:

Remain empathic and focus the discussion on medicines only

Take a full medicines history and ask the patient how well the medicines are working, and reflect that the patient is describing severe pain despite medicines

Share that the experience of many patients is that taking medicines results in no observable benefit for pain

Explain that we have much better ways of working out how helpful medicines really are and we know that a lot of things that we thought were helpful in the past have proved to be disappointing and...

...take responsibility for contributing to where we are now!

Medicines for pain can be associated with significant harm

It matters a lot that the patient has confidence that all their medicines are working well

Usally stopping medicines makes no difference to the pain but can make people feel better

If a tapering trial doesn't work we can think again

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It is important to taper or stop the opioid regimen if: the medication is not providing useful pain relief. The dose above which harms outweigh benefits is 120mg oral morphine equivalent/24hours.

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1. Opioids are very good analgesics for acute pain and for pain at the end of life but there is little evidence that they are helpful for long term pain.

2. A small proportion of people may obtain good pain relief with opioids in the long-term if the dose can be kept low and especially if their use is intermittent (however it is difficult to identify these people at the point of opioid initiation).

3. The risk of harm increases substantially at doses above an oral morphine equivalent of 120mg/day, but there is no increased benefit: tapering or stopping high dose opioids needs careful planning and collaboration.

4. If a patient has pain that remains severe despite opioid treatment it means they are not working and should be stopped, even if no other treatment is available.

5. Chronic pain is very complex and if patients have refractory and disabling symptoms, particularly if they are on high opioid doses, a very detailed assessment of the many emotional influences on their pain experience is essential.

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Opioids Aware: A resource for patients and healthcare professionals to support prescribing of opioid medicines for pain

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1. Opioids are very good analgesics for acute pain and for pain at the end of life but there is little evidence that they are helpful for long term pain. 2.

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The NICE Clinical Knowledge Summaries (CKS) site is only available to users in the UK, Crown Dependencies and British Overseas Territories.

CKS content is produced by Clarity Informatics Limited. It is available to users outside the UK via subscription from the Prodigy website.

If you believe you are seeing this page in error please contact us.

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The NICE Clinical Knowledge Summaries (CKS) site is only available to users in the UK, Crown Dependencies and British Overseas Territories. CKS content is produced by Clarity Informatics Limited. It is available to users outside the UK via subscription from the Prodigy website. If you believe you are seeing this page in error please contact us.

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In a hypercompetitive world, drugs like Adderall offer students, athletes, coders and others a way to do more -- faster and better. But at what cost?

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Edit

Summaries

In this follow-up to his film BIGGER FASTER STRONGER, director Chris Bell turns his camera on the abuse of prescription drugs and, ultimately, himself. As Bell learns more about Big Pharma, an industry he had been brought up to trust, he falls down his own hole of addiction.

In this follow-up to his film Bigger Stronger Faster, director Chris Bell turns his camera on the abuse of prescription drugs and, ultimately, himself. After witnessing friends and relatives face tragedy as they become addicted to prescription drugs, Bell sets out to explore the goals of pharmaceutical companies and doctors in this ever-growing market, and asks how they are any different from back-alley drug-pushers. His journey leads to experts on the nature of addiction in our culture, as well as to pharmaceutical whistleblowers that testify to the solely dollar-driven aims of pharmaceutical companies. Chris meets with WWE legends, such as Matthew "Horshu" Wiese and Chris Leben, along with former California State Senator (now Congressman for California's 33rd District) Ted Lieu, pharmaceutical company whistleblower Gwen Olsen, Cliffside Malibu Rehabilitation Center founder Richard Taite, Professor of Psychiatry David Healy, author of Generation RX Greg Critser, and members of his own family.

PRESCRIPTION THUGS is filmmaker Chris Bell's (Bigger Stronger Faster) hard hitting and thought provoking expose of Big Pharma, its marketing practices and their impact on the staggering level of addiction to prescription drugs in North America. Executive Produced by Vince Vaughn and Peter Billingsley, this documentary is compelling viewing.

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Edit Summaries In this follow-up to his film BIGGER FASTER STRONGER, director Chris Bell turns his camera on the abuse of prescription drugs and, ultimately, himself. As Bell learns more about Big Pharma, an industry he had been brought up to trust, he falls down his own hole of addiction.

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Dose Equivalent and Changing Opioids | The Royal College of Anaesthetists

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In most cases, when switching between different opioids, the calculated dose-equivalent must be reduced to ensure safety. The starting point for dose reduction from the calculated equi-analgesic dose is around 25-50%.

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Toolkit for Chronic Opioid Use in Non-Cancer Pain

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This is the Complete Ashton Manual & Works, combined into a single PDF format. This Manual was written by Chrystal Heather Ashton DM, FRCP, Emeritus Professor of Clinical Psycho-pharmacology at the University of Newcastle upon Tyne, England, for those trying to rationally and scientifically withdraw from a (typically "iatrogenic" = physician-created) Benzodiazepine dependency.

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In a recent pilot scheme in Hastings run jointly by Change Grow Live's East Sussex drug and alcohol recovery service (STAR) with local GP surgeries, 235 patients were assessed and supported to manage their pain and wean them from opiate medications. Sixty were fully weaned and a further 57 reduced to a safe and sustainable level.

The results were startling. Patients who weaned from opiates reported an average 19 per cent improvement in their quality of life, significant reductions in anxiety levels, improved sleep, less constipation - and no increase in pain. Early indications also suggest a further reduction in GP appointments following weaning of as much as 20 per cent - a huge cost saving, especially when added to the £31,000 per annum saved in medications.

In addition a group work programme was developed that supported patients with a range of self-management techniques for pain. The isolation caused by chronic pain leads to a wide range of problems, and the group found it useful to spend time together connecting with others who truly understood their issues. In fact, the core of the group has continued to meet and, with support from Change Grow Live (CGL), is setting up a community-based peer support group for chronic pain sufferers.

Moderate to severe chronic pain - that is, pain that continues for more than 12 weeks - is thought to affect around 18 per cent of the UK population. GPs have traditionally prescribed opiate medications such as morphine, fentanyl, buprenorphine and oxycodone, as it was thought that - provided they did not over-sedate, cause overdose or other severe reactions - it was safe and there was little else that could be done for these patients.

A broad definition of dependence-forming medications encompasses GABAergic medicines, benzodiazepines and Z-drugs such as zopiclone, and the prescribing of these has been increasing (with the exception of benzodiazepines). In 2000, 6 per cent of the UK population were prescribed at least one of these types of medicines, but by 2015 this had risen to 9 per cent.

Hastings and Rother CCG looked at GP surgeries locally and were able to identify those with the highest rates of opiate prescribing. CGL were then contracted to provide a pilot scheme alongside The Station Practice in Hastings for one year from February 2018.

The pilot worked in two phases, with the first half of the year a multi-disciplinary team (MDT) approach, and the second half CGL-led with limited GP support and expansion into a second practice. The MDT approach showed the greatest results, but also used the most resource. The CGL worker engaged patients with an above 120mg morphine daily equivalent, as well as patients prescribed polypharmacy opiates or other DFMs.

Engagement was key - someone listening to patients' stories was an incredibly powerful experience for them, as most clinical staff are usually unable to take the time to do this. Motivational interviewing was used to support movement towards change, both with lifestyle and medication, and mindfulness, TENS machines, sleep hygiene, and referral to other agencies were also key in fully engaging patients.

Once a week for half a day a dedicated GP was available and MDT practice appointments were run alongside the CGL worker - these were 20-minute slots that allowed time for holistic interventions for a wide range of health issues. Patients were provided with a 'Hastings pain toolkit' to assist with self-management of pain and lifestyle, which included links to other useful resources. A surgery pharmacist was also involved to provide follow-up support and discuss medication with patients by telephone. The MDT team has been nominated for this year's BMJ awards in general practice, and has reached the final five.

During the second half of the year the CGL worker was spread across two GP surgeries, carrying out the same interventions without the MDT clinic. This approach was less resource intensive, yet still wielded some promising results.

Future plans - provided appropriate funding can be secured - centre around whole-surgery approaches, with all GPs supporting the programme, referring to a DFM worker for assessment, and most psychosocial and self-management of pain support taking place in a group setting. A similar trial is due to begin soon in Worthing, supported by CGL.

This is an often-neglected cohort of patients, who suffer daily and are often left 'parked' on large doses of opiates that have devastating long-term effects on their life, affecting their memory and digestion, accelerating osteoporosis, and potentially damaging their immune systems or causing fatal overdose.

Long-term prescription of opiates can also lead to a faulty pain system, with the medications starting to 'drive' the pain. But these effects can be reduced or negated through a combination of psychosocial support, a change in pain management techniques and judicious use of pain relief medications. After all, who wouldn't want an 18-20 per cent improvement in their overall quality of life?
Robert Ralph is dependence forming medications lead at Change Grow Live (CGL)

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Less pain, more gain - Drink and Drugs News

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Opiate medications don't work for chronic pain - in fact they often make it worse. In a recent pilot scheme in Hastings run jointly by Change Grow Live's East Sussex drug and alcohol recovery service (STAR) with local GP surgeries, 235 patients were assessed and supported to manage their pain and wean them from opiate ...

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Helpful Materials for Patients | Drug Overdose | CDC Injury Center

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Skip directly to search Skip directly to A to Z list Skip directly to navigation Skip directly to page options Skip directly to site content

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Information for Patients | Drug Overdose | CDC Injury Center

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NEJM.org uses cookies to improve performance by remembering your session ID when you navigate from page to page. This cookie stores just a session ID; no other information is captured. Accepting the NEJM cookie is necessary to use the website.

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Patient Publications | British Pain Society

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The British Pain Society aims to produce contemporary guidance, supported by available evidence, on clinical and other pain matters. Most British Pain Society guidelines have an accompanying information for patient leaflet. Documents are updated three yearly to incorporate relevant new information.

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Brighton and Sussex University Hospitals NHS Trust

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Inpatient services

We advise on and manage more difficult cases of inpatient care involving:

complex surgery on high-risk patients

complex patients, i.e. sufferers from acute and chronic pain, cancer pain (until referred to the Macmillan team), opioid dependence or substance misuse

prevention of chronic pain by good acute pain management

recognition and early treatment of neuropathic pain

non-surgical patients, i.e. medicine, obstetrics, ITU/HDU

specific vulnerable groups: the elderly, pregnancy, paediatrics, patients with liver and renal problems

We also promote competent practice by providing clinical guidelines and regular teaching sessions for staff.

Outpatient services

We provide outpatient services at Hove Polyclinic.

Location

We provide inpatient services in our hospital wards and outpatient services at Hove Polyclinic.

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Pain management - Brighton and Sussex University Hospitals NHS Trust

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We advise on and manage more difficult cases of inpatient care involving: We also promote competent practice by providing clinical guidelines and regular teaching sessions for staff. We provide outpatient services at Hove Polyclinic. We provide inpatient services in our hospital wards and outpatient services at Hove Polyclinic.

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New rules to keep people safe when buying medications from online pharmacies have been described as a "big step forward" by Britain's pharmacy regulator.

It comes after patients and relatives raised concerns, as well as an investigation by BBC Panorama.

The General Pharmaceutical Council has issued guidance for providers.

It will help regulate access to addictive medication, such as strong painkillers.

Duncan Rudkin, the General Pharmaceutical Council's chief executive, told the BBC that he hoped the new rules would "make an important difference to improving standards of safety and care for patients".

The way some online pharmacy websites operate will change, and more checks will be done on medications.

Extra safety measures include:

Sites cannot be set up in a way that allows patients to choose a prescription-only medication before an online consultation with a healthcare professional

More safeguards will be introduced for certain medications, including antibiotics and medicines that need ongoing monitoring or management

For medications that are liable to abuse, overuse or misuse, or when there is a risk of addiction, the prescriber needs to contact the GP in advance of issuing the prescription (and they have confirmed it is appropriate for the patient and the appropriate monitoring is in place)

Online pharmacy websites should be clear about the identity and/or location of the pharmacies issuing prescriptions

Mr Rudkin said the Panorama programme "was really helpful in shining a light on a really important area of public safety".

It revealed how easy it was for patients to buy drugs online that their own GPs would be highly unlikely to prescribe.

Patients contacted Panorama after the programme.

Debbie Headspeath, 41, died in 2017 in Ipswich. Her brother, Kevin Duggan told the BBC that after her death, they found on bank statements that she had bought codeine from 18 online UK pharmacies.

Debbie had started a new job with war veterans and, despite waking up with stomach pains, she did not want to miss work.

"She put her jacket and bag on and then collapsed by the front door. She wasn't found until several hours later when her partner came home from work and it was too late and she had gone. She died."

Debbie had been prescribed the opiate-based painkiller dihydrocodeine by her family doctor in 2008 after developing back pain.

After several years, it was recognised she was addicted. The family doctor tried to wean her off, but she was able to secretly buy medication, prescribed by doctors and dispensed by UK pharmacies, without her GP being informed by the companies.

Kevin said: "There's no justification for what they do, which is exploiting people with an addiction. I would like to invite the companies to try and justify their actions to my mum.

"To look my mum in the eyes and explain why they allowed this to happen."

The inquest, which will decide the cause of death, is next month, but her brother told the BBC he felt the codeine had contributed to her death.

Son born addicted

Another relative of a patient contacted the BBC. His wife had developed back pain after the birth of their first child in 2014.

In 2016, he realised she was addicted to dihydrocodeine - the same drug prescribed to Debbie - and asked her GP to help her get off them.

In 2017, she found out she was pregnant again.

"I think when she fell pregnant she was taking 20 pills a day secretly.

"Then I think she realised, and then the midwife weaned her down to eight to 10 pills a day. And as a consequence of that, you know, my son was born addicted to opiates.

"To see your child in such distress, to see jerky movements; the shaking. It's something that I wouldn't want anybody to ever go through."

His wife managed to come off the codeine, but she has recently relapsed. He says that, so far, the medications have cost them nearly £25,000.

Mr Rudkin told the BBC: "I really want to acknowledge the pain that some families have experienced that's been associated in some cases with online pharmacies.

"It's really important that the stories help to change regulations. We've taken steps to address the risk."
You can watch Panorama: Online Doctors Uncovered on BBC iPlayer.

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New rules to keep people safe when buying medications from online pharmacies have been described as a "big step forward" by Britain's pharmacy regulator. It comes after patients and relatives raised concerns, as well as an investigation by BBC Panorama. The General Pharmaceutical Council has issued guidance for providers.

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Inspired by Soundcloud rap, British teens are developing an appetite for addictive benzos - and the demand is being met by UK-based labs cooking up dangerous counterfeit pills. Jordan Bassett investigates

"You'll have blackouts. You'll wake up on the other side of town not knowing where you are. Last Christmas, lots of young people were turning up at A&E not being able to walk. They'd been at a party, had a few beers, necked Xanax - and shut down. It leaves people very vulnerable."

Nick Hickmott, an Early Intervention Lead for the UK drugs and alcohol charity Addaction, is telling NME about benzodiazepines, or benzos, a group of drugs often used to treat anxiety and which includes the drug Xanax. He's spent 10 years working with young people with drug issues, but had little experience with youth benzodiazepine misuse until the last couple of years, during which time media reports of overdoses rocketed.

From his perspective, it looks like incidents of young people arriving at hospital after a misdose of benzos coincided with the rise of Soundcloud rap, a distinctly DIY music movement epitomised by rappers such as Lil Xan and Lil Peep, young artists who shared nihilistic visions of post-opiate America. Their open discussions about their anxiety, depression and reliance on Xanax resonated with British teens, who got hold of the drug themselves.

Media interest in Xanax as a health issue peaked when Lil Peep, aka Gustav Elijah Åhr, died from an overdose on Xanax and the prescription drug fentanyl, which he took alongside a cocktail of drugs that also included cocaine, marijuana and the painkiller Tramadol. Lil Pump, who once posed proudly on Instagram with a Xanax-shaped cake, vowed that 21-year-old Peep's tragic death had shocked him into quitting Xanax, as did Smokepurrp.

American Xanax headlines spawned others, closer to home. In May 2017 around 20 young people were hospitalised in Wiltshire when they came into contact with benzodiazepines; NHS Grampian and Police Scotland issued a warning last January after 20 benzo-related deaths.

Benzos are particularly dangerous when mixed with other substances, so those hospitalised (or even killed) are most commonly drug users topping up crack or heroin, or - more relevant here - young people who have taken pills with cannabis or alcohol at the kind of party Hickmott described.

It's uncommon for Xanax to be issued by the NHS, so people instead buy counterfeit pills online.

That counterfeit market is the subject of a new BBC documentary, Britain's Black Market: Who Is Selling Fake Stuff?, which will air a week on Monday (February 25). Host Livvy Haydock is an investigative reporter who previously operated behind the scenes, putting journalists in touch with criminals. The documentary is about counterfeit goods in general - think fake designer clothes - but her journey sent her to the fake drugs market.

"I got access to a UK manufacturer," she tells NME. "He had enough product in front of him that, when he turns it into fake Xanax, will be worth a quarter of a million pounds." The manufacturer spends three hours making 42,000 of these tablets, which are worth £100,000.

"I spoke to a dealer who was selling Xanax and she said her customers were getting younger and younger,' Livvy explains. "I said, 'How young?' and she said, 'Well, 14'. When I asked if she felt weird about selling to a 14-year-old, she said, 'No, but i would cut off at about 10 years old'."

According to a BBC Three report, more than 1.5m counterfeit Xanax pills entered Britain's drugs market in the 21 months leading to 2017. Prescription-bought Xanax is between one-and-a-half to four milligrams per pill; counterfeits tend to begin at four milligrams.

"The tolerance builds really, really quickly," says Nick Hickmott. "You can become dependent in five to 10 days - you can start feeling withdrawal when you're in an anxious situation and you haven't got that drug to help you out. And the withdrawal's pretty awful. It's up there with opiate withdrawal. You feel terrible; you can have pains; if you're fully addicted you can have seizures and be fitting."

"Come off benzos and tell me you're going to go back on it. Jesus Christ, it's awful. You feel like you're dying." - The 1975's Matt Healy

Las year, when NME interviewed The 1975's Matt Healy, who had struggled with opiate addiction and been through rehab, he explained that he would sometimes score benzos in the absence of his preferred drug, heroin - and that withdrawing from benzos is harder.

"I would come off heroin 10 times a year instead of coming off benzos once. It's fucking massive over here [in America] and it's fucking horrendous. Come off benzos and tell me you're going to go back on it. Jesus Christ, it's awful. You feel like you're dying."

Initially fake Xannies were mainly sold on the darkweb, but now some dealers sell them on social media. As a result, says Haydock, "a lot of youngsters don't necessarily feel like it's a dangerous thing because you can order it quite blasé online; it arrives at your door, so you don't have to meet some shady dealer." Haydock provided NME with screengrabs of open Instagram accounts claiming to offer benzos and Xanax for sale.

A representative of Instagram told NME: "Buying or selling illegal or prescription drugs is not allowed on Instagram. We encourage anyone who comes across content like this to report it using our in-app tools. We check these reports 24/7 and as soon as we're made aware of violating content, we work quickly to remove it." Instagram has since closed the accounts in question.

According to Hickmott, "Xanax has a close relationship with social media; I think that it's almost the ideal place for it to be sold because of the social issues that represents or aids with."

Last year, a survey from The Royal Society for Public Health and the Young Health Movement concluded what everybody already knows: that image-based apps adversely affect young people's anxiety. Instagram scored the worst. As Haydock puts it: "We're living in a brutal time to be a young person."

The counterfeit Xanax market emerged from the counterfeit steroid market. In 2012 it became illegal to import steroids from overseas, so labs - such as one in Cheetham Hill, Manchester, which Haydock visits in the documentary and which has been dubbed 'the counterfeit capital of the UK', home to fake designer clothes and fake designer drugs - stepped in.

"Once underground labs started popping up," says Haydock, "they realised the capabilities and thought, 'OK, if we're making steroids, why don't we just make all the other meds we want?'"

Joe Casey, who directed Britain's Black Market..., tells NME "it's not as if [dealers and manufacturers] are overly worried about authorities becoming involved." One manufacturer interviewed in the programme, who goes by the pseudonym Phil, reveals that he imports raw materials from China; customs intercept around one in 10 of these packages. "All he gets is a letter saying the package been seized," says Joe. "There's no other follow-up beyond that."

"Police cuts are huge," adds Haydock. "If you look at the cuts to the Border Force you can see [the problem]."

In response, the Home Office told NME: " It is an offence to possess, produce, supply, or import/export alprazolam without the appropriate authority and carries a maximum sentence of 14 years' imprisonment on conviction. Law enforcement agencies continue to work with internet providers to shut down UK-based websites found to be selling these drugs illegally.

"We are increasing total police funding by up to £970m in 2019/20, including precept, and are increasing the headcount of Border Force by around 900 by the end of March 2019."

Benzodiazepines are a Class C drug in the UK, which may be how manufacturers such as 'Phil' - who, says Casey, is "self-taught" and learned to create counterfeit Xanax from YouTube videos - operate relatively openly. Yet as Haydock points out: "If you buy raw products from China, they could easily be counterfeit as well. You're just ordering bags of powders."

Although there is, understandably, potential for panic around counterfeit Xanax, Addaction 's Nick Hickmott praises the way that the UK media has covered the problem.

"It's been quite remarkable to me, honestly," he says. "It's been really pragmatic. Really good, strategic reporting from the media means people can get some decent idea of how to taper off. It's not been a 'zombie drug epidemic'; because it's a prescription med, it feels like the narrative around it in the media and newspapers has been a lot more thoughtful and helpful."

He compares this unfavourably to media coverage of Spice, which was indeed termed a 'zombie drug' when it coursed through city centres - Manchester in particular - in 2017. Spice, an umbrella word that encompasses synthetic cannabinoid drugs, ultra-potent substance with no resemblance to cannabis oil from which it is derived, was largely associated with homeless people. Catatonic users were nicknamed 'The Walking Dead' in local media.

Fake Xanax, on the other hand, has found its way to users in a totally different social sphere. According to Mark Hickmott, a counterfeit pill that costs about 30p on the darkweb could cost around £3 on social media.

"I spoke to a dealer who sells to 14-year-olds" - investigative reporter Livvy Haydock

"Even though Xanax has come from essentially the working class of America through mumble rap and Soundcloud rap," says Hickmott, "it has translated into more of a potentially middle-class issue here. Certainly those that I've spoken to who have had issues around Xanax tend to be grammar school pupils in quite affluent areas. There seems to be something around pressure, stress and mental literacy that means that [benzo addiction] does tend to sit in those more affluent middle- to upper-class areas when it becomes problematic."

Perhaps, then, Xanax has been better reported because journalists in newsrooms relate to young benzo users - who could easily be their own kids - where a homeless Spice addict may seem 'other'. However, the 'mental health literacy' that Hickmott referenced, which implies a certain level of education - or emotional parental support - could be part of the problem.

"We know that his younger generation is often billed as the most anxious generation ever," he explains, "but we've got really poor support for them. What we've done is put in loads and loads of good education around mental health and made them really emotionally literate and being able to talk about feelings - you know, big, strapping seven-foot lads talking about anxiety, paranoia and depression - and then there's no support services for them."

And that's where self-medication with fake Xanax, likely inspired by Soundcloud rap, has come in.

"We're in a pill popping generation, says Hickmott. "There's supposedly a pill for everything - 'We can sort ourselves out.' I think that can easily lead to people going, 'Well, this is a quick fix.'"

Addaction 's Head of Media Mark Byrne confirms that fake Xanax is "definitely a big issue and a growing issue", but says that much of the evidence available is anecdotal. That's because people harmed by knock-off Xanax tend to not to end up working with drugs services, perhaps because they fear the stigma that they feel such an admission would involve.

Of the 47,000 people Addaction helped across the country last year, approximately 250 were dealing with benzo addiction. It's still an emerging issue - remember that Nick Hickmott, with a decade of experience, wasn't aware of adolescent benzodiazepine problems two years ago - so case studies are rare.

"It would be far easier to speak to someone who's been through a heroin recovery service," says Byrne, "because there's an established journey that people go through. It's been around long enough that those people are out there volunteering at the services that we run; they're the people that we go to for first-person stories.

"There are people in our services at the moment getting treated for issues around benzos, but we would never put them forward because they're in the middle of the plan. Mostly they're young, so we can't do anything to jeopardise their recovery."

All drug and alcohol services in the UK, including Addaction, feed information into the National Drug Treatment Monitoring System (NDTMS). In theory, this offers a clear perspective on the substance abuse issues in the country. The problem, says Hickmott, is that the numbers being collected are way behind what's actually happening in the real world: "This information has been added to data sets within the last six months as it has emerged.

"As is kind of typical of the UK, they're trying to play catch-up on it. So, to really get a true reflection and get some hard evidence about people turning up at treatments saying, 'I need support around benzos', or specifically Xanax, you're probably looking at 18 months down the line."

"Tolerance to benzos builds really, really quickly" - Addaction's Nick Hickmott

There are, of course, people who have taken benzos and been absolutely fine. One anonymous person tells NME: "I've only ever taken [Xanax] as part of a cocktail of other drugs - sorry, mum. For example, it's a good thing to take if you've been tripping on psychedelics for a long time and want everything to stop being weird and mellow out. In that situation it gives a sort of warm, drowsy, wrapped-in-cotton-wool sensation. Eventually it'll help you sleep too."

But the problem is the unpredictability of the often very potent pills, and the fact anxious people may be using counterfeit Xanax instead of engaging with mental health services. What advice would Addaction 's Nick Hickmott have for a young person struggling with benzos?

"It's really important to stop gradually - known as 'tapering' - to avoid unpleasant or dangerous side effects," he says. "If someone's struggling with any drug, talking always helps. Excessive or problematic drug use is normally a symptom of a bigger problem in someone's life, which hopefully a good listener could help to solve."

For help and advice on drug and mental health issues

- Britain's Black Market: Who Is Selling Fake Stuff? is available to watch on BBC iPlayer from February 25

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Britain's fake Xanax crisis: how young Brits got hooked on super-strong benzos

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Inspired by Soundcloud rap, British teens are developing an appetite for addictive benzos - and the demand is being met by UK-based labs cooking up dangerous counterfeit pills. Jordan Bassett investigates "You'll have blackouts. You'll wake up on the other side of town not knowing where you are.

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A man - not the author of this article - passed out in a park. Photo: Homer W Sykes / Alamy Stock Photo

"You guys seen my bag of tizzies?"

It's an afternoon in Brighton in 2014. I stumble into the living room and blurt out these words to my housemates. Not, "Hey guys, how's it going?" but, "Where's my pills?" I look at each of them; all their faces are clenched. "You don't remember?" one asks. I don't.

"She's gone home, by the way, in case you were wondering," says another, disdainfully. "She" is my partner who was staying the night after traveling the length of the country to see me. The penny starts to drop: I've blacked out, again. I see a familiar collage of emotions on the faces of my friends; anger, worry, apathy.

My mates tell me that, at about 1AM, my partner had run downstairs scared to death, because I was convulsing violently and sweating profusely in my "sleep". On my bedside table was a bag of red pills, each containing 2mg of etizolam - an extremely potent sedative available legally at the time as a "research chemical". As soon as they mention "those red pills" the fragments of the night return to me. So too does the creeping blackout dread.

Earlier the previous day, the pills had arrived in the post, and after popping two of them the same old mantra that any benzo-head will recognise started going through my mind: "I'm not feeling anything." So it was down the hatch with two more - but clearly something was happening because I'd forgotten the imminent arrival of my partner.

After that, nothing. I have no recollection of the next few hours beyond a thought loop telling me I wasn't not feeling anything, before lurching over my bedside to eat more pills.

My friends had no idea how many I had taken when they found me. I was apparently vaguely responsive enough that they didn't call for help. They put me in the recovery position, while my partner called her sister and left to stay with her.

"We don't want to do this, but we've taken them away from you," my friends told me. Usually I'd flip out at this, but I replied with a solemn nod - they were right. There were 50 pills in that bag at the start of the day.

At that point, it sank in; I came very close to death without realising it, and the first words out of my mouth to the friends who had saved me were, "Where's my pills?"

My name's Dan, I'm 28 and I've been addicted to benzos for about five years. What follows is an attempt to recollect fragments of my past lost to amnesia for my own benefit, and to serve as a cautionary tale, or maybe something someone out there can relate to. I remember how it all began quite well, but it's everything that came after after that's hard to recall.

Benzodiazepines are a class of prescription tranquillisers that were once heavily prescribed in the 1960s for anxiety, depression and insomnia. The most well-known are Valium (a brand name for diazepam) and Xanax (alprazolam), the latter of which has become notorious for its popularity among young people.

These drugs were eventually found to have serious consequences, including reduced inhibitions and delusions of sobriety leading to risky behaviour and compulsive re-dosing; addiction; and an exacerbated return of the treated symptoms after abrupt withdrawal.

Withdrawal from long-term use poses the greatest risk, and if not managed correctly it can lead to potentially fatal seizures. In the wake of these revelations, benzodiazepines became more tightly regulated in the UK and alternative antidepressant medications with less abuse potential were prescribed instead. Benzodiazepines are now primarily only prescribed for short-term use.

When your mind is plagued with a near-constant state of anxiety and riddled with depressive thoughts, it's far too easy to develop a taste for benzodiazepines if you have access to them. It's then just as difficult to stop yourself when lost in their blissful tranquility - unaware that your life is disintegrating around you with every pill you pop.

When I enrolled at university, it dawned on me that something was wrong with my mental health. The doctors tried a number of antidepressants, with limited success. I wasn't depressed, but I also wasn't happy, so I gave them up. I figured it was better to feel awful than feel nothing at all.

One day, in the grip of a horrendous panic attack, someone gave me a small blue pill - which I later learned was called etizolam - and within about 20 minutes everything I'd been worried about just melted away. It was euphoric to feel such a sense of relief, to not care about things I should be caring about. I started to use the pills regularly in social settings, and with my inhibitions destroyed I became more confident and outgoing. Eventually I was given a bag of them with the label still on it. I went home and, with a few mouse clicks, found numerous sources for these wonder pills: 50 etizolam for £20? Ten flubromazepam for £5? I could barely contain myself.

Back then, everything I tried came from the "grey market" - unregulated online shops where you could buy all sorts of chemicals designed to be analogues of illegal drugs. They essentially served as a loophole to drug prohibition laws; change a molecule here and add one there - hey presto! A brand new substance carefully labelled "Not for Human Consumption".

In 2015, thinking that these grey market pills would soon become harder to get, I started to regulate and reduce my use. I found out about the "Ashton Manual" - a guide to withdrawing from long-term benzodiazepine use. I created a rough timetable to reduce my dosage by 10 percent every month to get myself clean within a year, and built up a small stash to avoid the unbearable withdrawal I'd already experienced if I overran.

Ultimately, it was important that I believed I was in control of my problem - and to some extent it worked. In August of 2015, I graduated miraculously with a 2:1, despite being consistently numb to the world around me. I stopped binging and losing countless nights to the fog of synthetic tranquility and began planning where I would go after leaving Brighton. I couldn't afford to stay there without any regular work, and I felt like I needed a fresh start in a new city, so I moved to Bristol.

Before the end of 2015, I started my new life - albeit still carrying my old habits. By sticking rigidly to my withdrawal timetable, two months after the UK government brought in the 2016 Psychoactive Substances Act - which served as a blanket ban for any conceivable substance that had a psychoactive effect - I had fully stopped my abuse of benzodiazepines. At the time I felt a tremendous sense of pride and integrity; I'd overcome a huge weakness within myself.

But then the depression that had been buried all those years returned with full force. I'd forgotten how to cope with that headspace without the help of some chemical crutch to see me along. Roughly three months later, I relapsed.

It's only been in the past year that I've acknowledged this as a problem beyond my control and sought outside help through the services available in Bristol.

I'd managed to keep the extent of my use relatively secret for two-and-a-half years after moving here, maintaining a relatively functional existence and keeping my habit hidden from my new partner. It stopped being recreational and I began to justify it to myself as "self-medicating" my depression and anxiety, while failing to recognise that the pills were only making it worse in the long run.

I'd confided in my partner about my prior use, but I lied that I was no longer using and it was no longer a problem for me. Why? Shame, I suppose; ashamed at being weak-willed, ashamed at not dealing with my problems the way everyone else seemed to be.

Then there's fear. Fear that if I came clean about my use I'd lose her and everyone around me. When you hide a drug problem you convince yourself that you can lie forever about it, that you can keep it hidden as long as you need to.
READ:
My partner found my stash in April of last year and confronted me about it. It finally clicked that I needed to get help, or risked losing everything. I realised how many years had passed since that first tizzy, how many memories I'd lost, how many opportunities I'd squandered, how stupidly oblivious I was that all my friends were well aware of what was going on but had no idea how to help.

After a long talk with my partner, my real recovery began. I spent a few months trying to cut my use again, but with no success, so I searched online for local drug support organisations and found Bristol Drugs Project (BDP).

I spent hours anxiously going over in my head what I would say, to what extent I would tell them about my problem. I was terrified of any negative judgment and being rubber-stamped as another junkie statistic, as I'd never come clean about this before. Fortunately, whoever I spoke to on the phone was very helpful and understanding. They told me they don't have services to help with benzodiazepine use directly, and referred me to another organisation called Battle Against Tranquilisers (BAT), who have been helping me ever since.

They drew up a reduction plan for me to give to my GP, and it was made clear that I shouldn't feel pressured to make any cuts to my dose if I didn't feel ready to do so - and that, by law, I was the one in control of my medication.

I'd like to say I've been attending my group sessions with BAT every week, but holding down a full time job makes it challenging. Not to mention the palpable anxiety I feel when I think about getting that bus to Southmead Hospital every Thursday to sit and confront my demons. It's been at least two months since I last attended, but I can say with confidence that if I hadn't gone at all I'd be in the same place I was in April, if not worse.

Simply knowing that I have a safe space with other people going through those same motions makes this process easier, and I have nothing but gratitude toward BAT and the people who attend those sessions. They give me strength, and strength is a rare resource to find in the depths of withdrawal.

Since seeking help I've kept reducing my use with the help of BAT, and have come clean to my friends and family, who have all supported me in their own way. I'm also now on a waiting list for cognitive behavioural therapy, to address the reasons behind my self-medication.

I count myself extremely lucky to have not faced rejection as a result of my poor decisions. As for the future, it's just a case of taking it all one day at a time and knowing there will be an end to all of this.
Daniel Finn is a pseudonym A version of this article was originally published in the Bristol Cable, a UK-based media co-operative

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A man - not the author of this article - passed out in a park. Photo: Homer W Sykes / Alamy Stock Photo "You guys seen my bag of tizzies?" It's an afternoon in Brighton in 2014. I stumble into the living room and blurt out these words to my housemates.

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Joining us at Outlook on Outcomes this week and next is Dr. Steven Moskowitz, a physical medicine and rehabilitation specialist. As our first guest blogger, Dr. Moskowitz will cover a very important topic in our healthcare system and particularly in workers' compensation. Thanks for sharing your expertise! - Dr. Holt

Dr. Holt asked me to comment on why treating prescription medication addiction is not as simple as a forced referral to a drug and alcohol detoxification or rehabilitation program. I believe chronic pain patients present a greater challenge for several reasons, including maladaptive coping with ongoing pain complaints, fear of activity and debilitation, high incidence of untreated concurrent psychological problems, and, lastly, the availability of community clinicians willing to repeatedly treat subjective pain complaints with opiates without addressing the accompanying psychosocial issues. Such physicians increasingly treat chronic pain patients with escalating or high doses of opiates despite dependence, addiction, the development of complications, and limited overall clinical and functional improvement. To break this pattern, we must consider the unique profile of a chronic pain patient and identify appropriate resources for the management of addiction.

This week, I'll illustrate the main features of iatrogenic addiction in patients with chronic pain and argue that this particular profile requires a comprehensive response. Next week, part two will answer the question of what that methodology for treating iatrogenic addiction looks like.
Defining addiction and dependence
Two major problems with treating chronic pain with opiates are addiction/dependence and side effects. The actual definitions of drug addiction and dependence are very controversial and have been the subject of much debate in the development of the updated criteria for the Diagnostic and Statistical Manual of Mental Disorders, version 5 (DSM-5), due out in 2013. The American Society of Addiction Medicine defines addiction as "a primary, chronic, neurobiologic disease with genetic, psychosocial, and environmental factors influencing its development and manifestations." It is characterized by behaviors that include impaired control over drug use, compulsive use, continued use despite harm, and cravings. The term dependence is often used to denote a physiological dependence composed of tolerance and/or withdrawal symptoms, but sometimes is used to describe psychological dependence on a drug. For our discussion, I'll use these terms interchangeably since the real concept is problem drug use.
What is iatrogenic addiction?
Iatrogenic addiction refers to addiction that is caused by healthcare professionals. The National Institute of Health's MedLine Plus online dictionary defines iatrogenic as "induced inadvertently by a physician or surgeon or by medical treatment or diagnostic procedures." Unlike addiction to non-prescription drugs (e.g. alcohol, cocaine, heroin), addiction to prescription opiates requires a clinician who prescribes the medication. It is tempting to classify those with prescription medication problems as "addicts" and to believe all can be fixed by "detox." This may be true for a small portion of these patients; professionals in the fields of addiction and law enforcement are well aware of illicit drug addicts who find their way into the medical system specifically to acquire prescription drugs. But it is difficult to know exactly what percentage of chronic pain patients is primarily driven by the desire to acquire drugs versus a secondary addiction or psychological dependence as a result of treatment.

Research regarding the chronic pain population suggests that for the majority of cases, addiction or dependence is the result of prescription medication use, not the cause of it. Consider the following:

1. "The prevalence of lifetime substance use disorders ranged from 36% to 56%, and the estimates of the prevalence of current substance use disorders were as high as 43%. Aberrant medication-taking behaviors ranged from 5% to 24%." (The "Systematic Review: Opioid Treatment for Chronic Back Pain: Prevalence, Efficacy, and Association with Addiction (Annals of Internal Medicine, January 16, 2007 vol. 146 no. 2 116-127)

2. Fishbain, et. al, in their article, "Comorbidity Between Psychiatric Disorders and Chronic Pain," estimated that perhaps up to 18.9% of chronic pain patients have issues with abuse, addiction or dependence, but stated that recent studies showed current problems with dependence in up to 34% of chronic pain patients. Up to 12.5 percent were found to use illicit drugs.

3. In my informal discussion with colleagues who run comprehensive pain programs, it was felt that of the patients presenting to their program with problematic prescription drug use, perhaps 20-30% had a primary addiction problem, separate of pain issues.

The chronic pain population includes a wide variety of people who can be vulnerable to addiction to prescription medications. Some have addictive habits, such as smoking, over-eating and alcohol, while others have a past history of addictions. Conversely, others had no prior vulnerability to addiction. One of the most common traits in pain patients with problematic opiate use is maladaptive coping abilities. The Fishbain article noted that 71% of chronic pain patients have adjustment disorders.

It is vital that clinicians recognize pain as a biopsychosocial condition. That means most patients not only have biological factors causing pain, but also significant psychosocial aspects prolonging disability and delaying recovery. This makes treatment a more complicated endeavor than standard drug and alcohol detoxification or rehabilitation.

Return next week to learn how to identify the appropriate resources for treating iatrogenic addiction.

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Treating Iatrogenic Addiction to Narcotics (Part 1) - Outlook on Outcomes

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Joining us at Outlook on Outcomes this week and next is Dr. Steven Moskowitz, a physical medicine and rehabilitation specialist. As our first guest blogger, Dr. Moskowitz will cover a very important topic in our healthcare system and particularly in workers' compensation. Thanks for sharing your expertise!

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The benefits and risks of antidepressants continue to be hotly debated, both in the scientific literature and in the media.

An adverse effect that has been frequently discussed in the past year has been withdrawal symptoms, experienced when stopping antidepressants.

Recognition of these symptoms in the scientific literature is not new; they have been recognised since the early use of tricyclic antidepressants, though there has been debate around their prevalence, severity, and how quickly they resolve.

A recent review, commissioned by the All Party Parliamentary Group for Prescribed Drug Dependence, has addressed a lot of these questions. James Davies and John Read have examined the literature on prevalence of withdrawal symptoms, and severity. This was heavily featured in the media, with statements made such as Antidepressant withdrawal 'hits millions' (BBC) and Now doctors MUST wake-up to the dangers of patients hooked on depression pills (Daily Mail).

Methods

The authors state this is a systematic review, with evidence compiled according to the standard PRISMA guidelines. They used a systematic search of the literature, using Medical Subject Headings to identify relevant papers.

Results

They identified studies of incidence of withdrawal symptoms, from randomised controlled trials, naturalistic studies and surveys

Pooling data together, they found an estimated incidence of 56%. In other words, more than half of people who take antidepressants experience withdrawal

They excluded studies they considered outliers, in terms of reported withdrawal symptoms

They then used survey data to estimate the degree of severity of withdrawal symptoms

They excluded randomised controlled trials and naturalistic studies from this analysis, as they felt they were biased, because they were short-term in nature, funded by the pharmaceutical industry, or the authors had significant conflicts of interest.

Conclusions

The reviewers concluded that:

Over half of people taking antidepressants experience withdrawal symptoms

The severity of these symptoms is severe in over half of cases.

Strengths

A strength of the current study is the attempt to synthesise what is a very heterogeneous set of data, from a number of sources

The questions they address are highly relevant, given the number of people being offered antidepressant medication and have been relatively neglected in high quality studies.

Limitations

However, there are a number of limitations which reduce the utility of this review:

Literature search

The reviewers claim to have conducted a "systematic search" of the literature, looking for relevant studies to include in their review. This consisted of a MeSH search (no freetext searching) of MEDLINE, plus searches of PsychInfo and Google Scholar, as well as some citation searching. Any information scientist worth their salt would suggest other databases that are likely to yield further relevant research (e.g. Embase and the Cochrane Central Register of Controlled Trials). It's highly likely that this "systematic" review does not include all of the published research in the field, and there's no evidence that the reviewers did anything to look for unpublished research.

Inclusion criteria

There is no evidence that the systematic review inclusion criteria was registered in advance (pre-registration is designed to prevent changes to methodology once researchers have had a look at the data). From the paper it is not clear if factors such as length of follow-up, length of antidepressant exposure, or drug company funding were defined as reasons for exclusion before undertaking the search and data extraction.

The authors describe exclusion of "outlier" studies which report withdrawal incidence at 11-12% because they assessed "only 9 withdrawal symptoms", but this outcome measure is not totally at odds with some of the papers they do include. They also exclude a number of studies, summarised by Baldwin and colleagues (Baldwin, 2007), which report withdrawal in the range 6.9% (escitalopram) to 32.7% (paroxetine). Had these studies been included in the analysis, estimates of 11-12% would no longer constitute outliers.

Assessment of study quality

Review articles are notoriously difficult to interpret, and this led to the setting of defined criteria for reviews, which have been called "systematic reviews." This requires the authors to evaluate study quality, based on attempts to control for issues such as selection bias (samples that are not representative of the population of people we wish to examine), or blinding (whether the participant or the observer knows they are receiving the intervention or not). This is part of the PRISMA checklist, subsumed under the heading, "risk of bias". This review does not attempt a traditional assessment of bias in the studies they include. These measures enable study quality to be examined, as lower quality studies will invariably produce biased results.

Though the authors make a point of identifying studies funded by drug companies, and where there are potential conflicts of interest related to pharmaceutical companies, they do not assign measures of study quality across studies, and ignore a number of potential biases, such as selection bias.

Conflict of interest

Whilst identifying conflicts of interest related to drug companies, ideological or intellectual conflicts of interest are not discussed. As Ioannidis (2016) and others have stated, meta-analyses have become a tool for academics with vested interests which might go beyond those tangible conflicts of interest traditionally defined by journals.

Outcome measures

In addressing the first question-incidence/prevalence of withdrawal symptoms, they consider the measure, change in withdrawal symptoms (DESS) as a definitive measure of withdrawal. All measures have weaknesses, and in three of the studies they present, they omit mention that symptoms identified with DESS are also present in those continuing to take antidepressants (Rosenbaum et al., 1998; Zajecka et al., 1998; Montgomery et al., 2005). In the Zajecka randomised, double-blind study it is worth noting that the incidence of withdrawal symptoms as measured by the scale is higher in those continuing to take antidepressants (76%), compared to those stopping (67%). It is also worth noting comments made in a paper cited by the authors on the DESS (Hindmarch et al., 2000), "defining a "discontinuation syndrome" as an increase of four or more symptoms...may lead to an overestimation of symptoms." In fact many of the included studies have an even less stringent cut-off to define "withdrawal". This is not mentioned at all in the Read and Davies article and therefore gives a particularly misleading account of the Zajecka et al. paper.

Furthermore, withdrawal symptoms themselves are not homogeneous; they vary amongst medications and individuals, and no effort is made to unpick this complexity.

Non-representative surveys to measure incidence/prevalence

Using survey data has strengths and weaknesses. A strength is the large numbers of people that fill out online surveys. However, a major concern is whether they are representative of the population of interest (i.e., all people prescribed antidepressants). A standard methodology for online surveys is to assess the completion rate, i.e., those who were offered the survey, and those who completed it (Fincham, 2008). But this is not possible with the internet methodology used in all of the surveys included in this review. A potential bias from online surveys is that they will be filled out by a specific group of people (this is seen frequently with polling surveys). Anyone conversant with UK politics will have seen this phenomena over the last few years.

This does not mean that the views of people who complete online surveys are not relevant (they are) and they provide important information about the qualitative nature of withdrawal symptoms in some individuals. However, they cannot provide a valid estimate of the frequency of withdrawal symptoms in people who stop taking antidepressants. Many journals will not publish surveys if it is impossible to gauge the response rate or response representativeness (Cooke et al., 2000).

When addressing the issue of severity of withdrawal symptoms, the authors only consider survey data. The reason given, is that a lot of the randomised trials and naturalistic studies are short-term, or at risk of potential bias owing to conflicts of interest. However, if they are using these studies for the quantification of withdrawal effects, and the data is valid for that purpose, it is baffling why it would not be valid for reporting severity; scrutiny of these studies commonly shows lower severity compared to survey reports. It would have been legitimate, for example to report withdrawal severity from included studies, and then stratify for type of study.

Data extraction and presentation of results

There are mistakes in their reporting of a number of studies included in the review:

In the Montgomery study, the incidence of withdrawal symptoms following escitalopram treatment is presented as 27%, when it is 16%.

There are 97 people in the Bogetto study, rather than the 95 they report.

There are 8 patients prescribed paroxetine in the Tint et al., study, rather than 9.

The Hindmarch and colleagues paper was published in 2000, rather than 2017.

The total number experiencing withdrawal in the study by Sir and colleagues is 83 rather than 110.

Whilst each of these errors is minor, it does not point to rigorous quality checking by the authors, reviewers or journal editorial staff. Also, where there are errors in reporting the incidence of withdrawal symptoms they are in the direction of symptoms being more frequent; thereby favouring the authors' view.

Mixing study designs

It is questionable how the authors can justify combining data from randomised controlled trials and naturalistic studies, conducted under study conditions, with survey data. All methodologies have their strengths and weaknesses, though combining data from different methodologies is unconventional, and rarely seen in peer-reviewed literature.

In the presentation of the results of the review, there is no measure of how consistent results were between individual studies. We have tried to address this below.

Combining data from different types of antidepressants

Another potential limitation is the combining of antidepressants with different pharmacokinetic properties, i.e., different ways of being metabolised by the body. For example, fluoxetine has a half-life of 4-6 days after chronic use (active metabolite half-life 4-16 days) compared to paroxetine (approximately 21 hours) and venlafaxine (approximately 5 hours). There is fairly strong evidence to suggest that medications with longer half-lives will be associated with less withdrawal effects, so it is puzzling that the results are presented for all antidepressants combined.

Related to this is the lack of any discussion about the pharmacology of antidepressants and mechanisms for withdrawal, which would have been helpful in explaining the results. Particularly, if a large minority of patients are experiencing symptoms for longer than 3 years (as described in Davies et al 2018) the mechanism for this needs to be understood.

Reanalysis

Given the limitations discussed we urge caution in the interpretation of the incidence/prevalence and severity rates presented. However, we reanalysed only the studies included by Davies and Read in their assessment of incidence (whilst incorporating the corrections we note above) to highlight a number of important points. We organised studies by study type and found that reports of withdrawal events were highest in surveys and lowest in RCTs. Also, we can see (from the measure called I ²) that results of individual studies are highly inconstant (I 2 can range from 0%-100% and NICE classes I ² of more than 75% "very serious heterogeneity" and would downgrade the meta-analysis for this because there is no precise estimate of withdrawal occurrence). This suggests that combining study designs does not make statistical sense.

We can do something similar, but this time sorting by antidepressant (though combining studies across different study designs).

Similarly, this shows huge inconsistencies between individual studies. However, it suggests that paroxetine and venlafaxine are associated with withdrawal most commonly, and fluoxetine least commonly. This reflects experience in clinical practice and is useful information "hidden" in this review. Ideally, one would look at drug effects in different study designs, though there are insufficient numbers of studies to do this reliably.

Implications for practice

The headlines that followed the release of this review were very clear. They stated that half of people taking antidepressants would experience withdrawal symptoms, and that most people reporting withdrawal symptoms class them as severe.
Looking carefully at the review, it does not accurately portray the data.
Whilst withdrawal effects are high for certain drugs (paroxetine, venlafaxine), when stopped abruptly, this happens very rarely in clinical practice and guidelines are in placed to address this. Furthermore, if people do experience withdrawal symptoms, there are treatments available, such as cross-titrating to a drug with a longer half-life, less likely to cause withdrawal, such as fluoxetine, followed by tapered withdrawal.

The issue of time course of withdrawal is not addressed in the review, but will merit careful analysis of the trial and study evidence, as well as that reported in surveys, where the length of follow-up may well be longer.

In conclusion, this is a very topical review, and the authors no doubt have the very best of intentions in communicating their analysis of data. However, the non-systematic way in which the review is written, with errors in data extraction and interpretation make it difficult to accept the findings with any confidence. It reflects negatively on the whole of the field of psychiatry that there is not better, clearer evidence from high quality studies on the incidence, severity and duration of any symptoms related to antidepressant cessation.

Conflicts of interest

Joseph Hayes is funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at University College London Hospital and UCL, and the Wellcome Trust. He has never received drug company funding. He is a Consultant Psychiatrist.

Sameer Jauhar is funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London, and a SIM Fellowship from the Royal College of Physicians, Edinburgh. He has never received drug company funding. He is a Consultant Psychiatrist.

Links

Primary paper

Davies J, Read J. (2018) A systematic review into the incidence, severity and duration of antidepressant withdrawal effects: Are guidelines evidence-based? (PDF) Addictive Behaviors. 2018 Sep 4. https://doi.org/10.1016/j.addbeh.2018.08.027

Other references

Baldwin DS, Montgomery SA, Nil R, Lader M. Discontinuation symptoms in depression and anxiety disorders. International Journal of Neuropsychopharmacology. 2007 Feb 1;10(1):73-84.

Cook C, Heath F, Thompson RL. A meta-analysis of response rates in web-or internet-based surveys. Educational and psychological measurement. 2000 Dec;60(6):821-36.

Mayor S. (2016) Five minutes with... John Ioannidis. BMJ

Davies, J et al. (2018) A survey of Antidepressant Withdrawal Reactions and their Management in Primary Care. Report from the All Party Parliamentary Group for Prescribed Drug Dependence.

Fincham, J. E. (2008) Response Rates and Responsiveness for Surveys, Standards, and the Journal. American Journal of Pharmaceutical Education, 72(2).

Montgomery, S. A. et al. (2005) 'A 24-week randomized, double-blind, placebo-controlled study of escitalopram for the prevention of generalized social anxiety disorder', The Journal of Clinical Psychiatry, 66(10), pp. 1270-1278.

Rosenbaum, J. F. et al. (1998) 'Selective serotonin reuptake inhibitor discontinuation syndrome: a randomized clinical trial', Biological Psychiatry, 44(2), pp. 77-87.

Zajecka, J. et al. (1998) 'Safety of Abrupt Discontinuation of Fluoxetine: A Randomized, Placebo-Controlled Study', Journal of Clinical Psychopharmacology, 18(3), p. 193.

de Vrieze J. (2018) Meta-analyses were supposed to end scientific debates. Often, they only cause more controversy. Science, 18 Sep 2018.

Photo credits

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Antidepressant withdrawal: reviewing the paper behind the headlines

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The benefits and risks of antidepressants continue to be hotly debated, both in the scientific literature and in the media. An adverse effect that has been frequently discussed in the past year has been withdrawal symptoms, experienced when stopping antidepressants.

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Whenever a new prescription analgesic or painkiller comes out, people who struggle with prescription painkiller abuse become interested in the potential of the drug. Tramadol, a relatively new prescription analgesic, is no exception.

Because of its status as a painkiller, tramadol developed a following as a target of abuse. And because of recommendations that tramadol is not highly addictive, it has been prescribed more heavily than some other opioid painkillers. However, some individuals may not know the status, addictive potential, or risks that arise from abusing tramadol. Understanding the action that this drug has in the body can help those who do not know much about tramadol become aware of the risks and challenges of using or abusing this drug.

Tramadol is a synthetic opioid painkiller, similar to other opiate or opioid drugs such as morphine, oxycodone, and fentanyl. Because of this, it has many of the same effects as other opiate medications. However, tramadol contains other ingredients as well, and this, plus the low level of opioid content, has made many medical professionals consider it to be safer than traditional opioid drugs, according to an article from Live Science. This can result in a dangerous tendency to prescribe the drug to those who may be more likely to be affected by its addictive potential.

Regardless of the level of opioid content, prescription painkillers based on opiates can be highly addictive and result in abuse and addiction in those who take them for euphoric effect outside of their medical applications. While some consider the addiction potential to be low, those who have a tendency toward opioid addiction can easily become dependent on tramadol and have the same symptoms of addiction that develop with stronger opioid medications.

Tramadol abuse has become relatively common, regardless of the fact that the drug was originally intended to be a less addictive type of opioid analgesic. Research from the World Health Organization has shown that, among opioid abusers, tramadol creates a craving response that is similar to that for oxycodone.

As a result, many people who have become addicted to stronger opioid medications have also become addicted to tramadol. Tramadol can indeed induce drug-seeking behavior, and it has the potential for people to develop tolerance, dependence, and subsequent addiction.

When it was first introduced, tramadol was considered to be a relatively safe alternative for managing pain. Unlike other opioid drugs, it was thought that tramadol's low level of opioid medication would give it a lower addiction potential than other pain medications.

However, as described in an article from Medpage Today, this assumption has proven false in some cases, particularly for those who have a past history of drug abuse, specifically opioid abuse. In some cases, this has resulted in overdose and death for individuals who have developed tolerance and addiction to tramadol. By taking high doses of the drug, these individuals have ended up with similar reactions to more powerful opioids like oxycodone, leading to the potential for fatal overdose.

An article from Drug and Alcohol Dependence demonstrates that tramadol potentially affects the GABA system in the brain, a neurochemical pathway that, when stimulated, decreases neuron activity by decreasing production of dopamine and other neurotransmitters. This system is often implicated in substance abuse and addiction, and it is considered to be one of the potential mechanisms of addiction.

Physical dependence has also been shown through the WHO study, which indicates that, while some studies show only mild effects of dependence on the drug, others have shown a strong tendency toward physical and mental dependence that can lead to addiction to tramadol. Again, prior history of substance abuse often contributes to cases in which tramadol addiction is present.

According to The People's Pharmacy, withdrawal from tramadol can result in an extremely uncomfortable withdrawal syndrome, sometimes referred to as a discontinuation syndrome. Symptoms that arise upon stopping tramadol use may include:

These symptoms have been reported to be extremely uncomfortable and disturbing. However, because tramadol is considered to be safe, some medical professionals do not offer a sound regimen for tapering off the drug or advice on otherwise completing a safe detox that minimizes symptoms.

Substance abuse treatment professionals in reputable rehab programs can provide more experienced support for detox from tramadol. These professionals understand the challenges of detox from addictive substances and are able to provide the medical support required to minimize symptoms of withdrawal.

This support can include pharmacological treatments that assist in reducing the sensations described above. The other advantage of these programs is the ability to begin substance abuse treatment and therapies that can help the individual learn to manage cravings and begin to recover from addiction to tramadol.

As with many substances that are abused for recreational reasons, research-based treatment programs provide therapies and other support that can help the individual learn to recognize triggers for cravings that lead to abuse. This makes it possible for the individual to substitute other behaviors, reducing the likelihood of relapse to tramadol abuse. Therapies include:

Cognitive Behavioral Therapy

Motivation Interviewing

Family and social therapy

Peer support group participation

Experiential therapy to manage mental conditions that contribute to addiction

Exercise, nutrition, and other supportive treatments

Applying these therapies helps the individual learn to understand and cope with the symptoms of addiction, making it possible to stop using tramadol and remain abstinent in the long-term.

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Is Tramadol Addictive? Can It Cause Withdrawal?

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Tramadol is a synthetic opioid painkiller, similar to other opiate or opioid drugs such as morphine, oxycodone, and fentanyl.

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In light of the government's proposals to reclassify pregabalin and gabapentin as Class C controlled drugs due to the risk of misuse, this article examines the extent of the problem of gabapentinoid misuse and its effects, and provides practical advice to prescribers on reducing these harms.
Pregabalin was launched in the UK in 2004 while gabapentin was first authorised in the UK in 1997. Both drugs were originally licensed for seizure disorders but now have multiple licensed indications. In England during 2016, over 12 million prescription items were dispensed for gabapentinoids as a group. ¹ The Advisory Council on the Misuse of Drugs (ACMD) reported that pregabalin prescribing in the UK increased by 350% in the five years to 2012 while gabapentin prescribing increased by 150% during the same period. ²

There has been growing concern about the misuse potential of the gabapentinoids as a group and in particular pregabalin, as reported in the 2016 ACMD review of this class of drugs. ² This concern led to the government launching a consultation on the reclassification of pregabalin and gabapentin as Class C controlled drugs under the Misuse of Drugs Act, which ended on 22 January 2018. ¹

This article discusses both drugs but with a particular emphasis on pregabalin, which presents with a greater misuse potential than gabapentin. It explores the current (licensed and unlicensed) indications and the pharmacology of the two drugs, aspects of their misuse potential and effects of this misuse on the individual. Finally, it provides advice for prescribers on managing the misuse of gabapentinoids and supporting patients who are discontinuing a gabapentinoid.
Licensed uses
The gabapentinoids have a wide range of licensed uses. Pregabalin and gabapentin are both licensed for neuropathic pain and epilepsy. 3,4 Pregabalin also has a licence for the treatment of generalised anxiety disorder (GAD). ³ Pregabalin is recommended by NICE as a second-line pharmacotherapy for GAD if a patient cannot tolerate SSRIs or SNRIs. ⁵ NICE recommends offering a choice of amitriptyline, duloxetine, gabapentin or pregabalin as initial treatment for neuropathic pain (except trigeminal neuralgia). ⁶ Off-label uses for gabapentinoids include the treatment of migraine, alcohol use disorders, mania and bipolar disorder. ⁷

NICE recommends early and regular assessments of patients prescribed pharmacotherapies for neuropathic pain, including the gabapentinoids. The assessment should include dosage titration, tolerability and adverse effects. ⁶ While markers for potential misuse (see Table 1) may emerge later in treatment, prescribers should always be alert to these even at the start of a treatment episode so that misuse can be avoided.

Table 1. Markers for potential misuse of gabapentinoids
Pharmacology
Both gabapentin and pregabalin are structurally similar to the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and rapidly cross the blood-brain barrier. The gabapentinoids bind to the alpha-2-delta subunit of the voltage-dependent calcium channels in the CNS resulting in a decrease in the excitatory neurotransmitters glutamate, noradrenaline, substance P and calcitonin gene-related peptide. Both drugs produce pharmacological effects that are similar in nature to those produced by the inhibitory neurotransmitter GABA, ie they exhibit GABA-mimetic properties.

Pregabalin is rapidly absorbed on an empty stomach with peak plasma concentrations occurring within one hour. It has a high bioavailability (=90%) and a mean elimination half-life of 6.3 hours and undergoes almost no metabolism with the parent drug being largely excreted unchanged in the urine. The linear pharmacokinetics of pregabalin (compared with the non-linear pharmacokinetics of gabapentin) allows straightforward dosing regimens and a predictable response. Pregabalin also has a higher binding efficiency than gabapentin and higher potency (2.5 times greater than gabapentin). The higher potency, quicker absorption and greater availability of pregabalin vs gabapentin makes pregabalin more attractive as a drug of misuse

The absorption of gabapentin following oral administration is less rapid than pregabalin. Peak plasma concentrations are observed within two to three hours with oral bioavailability decreasing with increasing dose. Absolute bioavailability is reported as 60% for a 300mg capsule. ⁴ Gabapentin is also eliminated unchanged through renal excretion with an elimination half-life of between five to seven hours. ⁴
Why are gabapentinoids misused?
Gabapentinoids have been reported to produce alcohol/gamma hydroxybutyrate (GHB)/benzodiazepine-type effects mixed with euphoria. Rates of euphoria have been reported at between 1 and 12% but this has been for therapeutic doses. ⁸ Other reported actions include dissociative effects, improved sociability, relaxation and sense of calm, and psychedelic effects.

Schifano et al. reported that significant psychotropic effects are associated with higher doses and "idiosyncratic ( ie IV, rectal, intranasal) drug intake modalities" but the most common route of misuse remains oral. ⁸

Polydrug misuse remains a significant concern with the cohort of service users that may misuse gabapentinoids and has been implicated in the recent rise in drug-related deaths for the gabapentinoids. A recent review in the journal Addiction suggests that pregabalin is used to enhance the effects of heroin but for some people it may also be used to help support the reduction in use of heroin. ⁷ This synergistic effect can also be used to reduce the amount of heroin needed to provide a similar psychoactive effect. Mixed misuse with antipsychotic drugs can also be a problem - as demonstrated in a case report describing the misuse of gabapentin and quetiapine. ⁹ Pregabalin and gabapentin have also been used to enhance the effects of alcohol and other prescribed and non-prescribed drugs including methadone. 7,8,10 Animal models also support the hypothesis that the effects of morphine and pregabalin are potentiated when taken together.

The onset of action of the gabapentinoids ranges from between 10 minutes, ie quick acting, and two hours depending on the route of administration and both dependent and recreational use has been reported. Rapid development and extinction of tolerance to the effects of gabapentinoids has also been documented. ¹¹

The effects associated with pregabalin at increasing doses, as reported by users, is summarised in Box 1.

Box 1. Online user accounts of pregabalin effects, according to dose ⁸
Evidence for and prevalence of gabapentinoid misuse
There is now a rich source of anecdotal reports that support significant misuse of gabapentinoids both in the UK and internationally, such as the user reports on the Erowid website. ¹² Following the introduction of pregabalin to the UK in 2004, the Medicines and Healthcare products Regulatory Agency (MHRA) received its first report of withdrawal symptoms in 2005. Following this, the first report of drug use disorder was reported in 2006 and drug dependence in 2009. ¹³

Evidence from UK secure settings suggests significant use of gabapentinoids. Prescribing of gabapentin and pregabalin occurs in 2.8% of the prison population, which is twice the rate found in the general population. Category A prisons having the highest rates and 47% of prisoners in this cohort are also prescribed opioid substitution treatments (OST). ¹⁴ The ACMD has also noted that the prescribing of the gabapentinoids in secure environments often does not meet "best practice guidelines". ² The Pain Management Formulary for Prisons classifies the gabapentinoids as drugs for "limited use" and aims to challenge current practice and introduce a framework around the management of pain in secure settings. ¹⁵

The DrugScope 2014 street survey highlighted the problem of misuse quoting "significant use... chiefly among Britain's opiate-using and prison population". ¹⁶ The effects of gabapentinoids are described within the report as "horrendous and life threatening" with one drug worker reporting the prevalence of use in one homeless hostel at 70% of residents. ¹⁶ The manufacturers of both drugs have also warned prescribers of the risk of abuse and dependence, highlighting the need for a careful evaluation of patients with a history of drug or substance abuse. 3,4

International reports from Finland, Germany and the USA suggest a global problem with gabapentinoid misuse. In Finland, a study of toxicology reports of drug-related deaths between 2010 and 2011 suggest a "substantial increase" in drug-related deaths involving pregabalin and opioids, with opioids present in 90% of deaths involving gabapentinoids. The study also reported a seven times greater incidence of pregabalin misuse in drug-related deaths compared with gabapentin. ⁷ In Germany, pregabalin misuse has been reported to the German medical regulatory body with an increasing frequency since 2008, while the USA placed pregabalin under the Controlled Substances Act in 2005, citing that misuse may lead to "limited physical dependence or psychological dependence". ²

The prevalence of gabapentinoid misuse has been assessed in two systematic reviews. An international systematic review of 59 studies indicates a gabapentinoid abuse prevalence of 1.6% in the general population. This prevalence increased to 3-68% among opioid abusers. Risk factors for misuse were identified as a history of substance abuse (particularly opioids) and psychiatric co-morbidities. ¹⁷ Another systematic review looking at gabapentin only reported a 1.1% prevalence of gabapentin misuse in the general population, which increased to 15-22% within "opioid abuse samples". ¹⁸
Drug-related deaths and gabapentinoid misuse
The CNS depressant effects of the gabapentinoids and opioids (drowsiness, respiratory depression and respiratory failure) are a significant risk and have been implicated in drug-related deaths. Deaths where gabapentinoids were mentioned on death certificates in England and Wales have increased from less than one a year before 2009 to 137 deaths in 2015. ⁷ In 79% of these deaths, opioids were also mentioned. This increase in drug-related deaths was also shown to correlate highly with prescribing data, ie increased prescribing of gabapentinoids (see Figure 1).

In summary, we have the "perfect storm" of the summation of CNS effects through polydrug misuse, an increase in prescription numbers, and drug effects that cannot be reversed with an antidote (although naloxone will support the reversal of the opioid element of a drug overdose), which all contribute to the risk of drug-related death.

Figure 1. Gabapentinoid drug-related deaths and correlation with increase in gabapentinoid prescribing in England and Wales ⁷
How can patients be supported to discontinue gabapentinoids safely?
Although there is insufficient evidence to support practitioners in helping patients discontinue gabapentinoids, there are some practical guidelines that provide a framework for the development of an appropriate recovery plan. Harm reduction also remains an important component of the advice practitioners should provide to patients.

Discontinuation symptoms of gabapentinoids are varied and will be dependent on the dose consumed and the route of administration. Table 2 summarises these symptoms for both gabapentin and pregabalin for patients reducing from therapeutic doses, as outlined in the summaries of product characteristics. The manufacturer of pregabalin has noted that the severity of symptoms and their incidence "may be dose-related" ³ and prescribers should take this into account when managing a pharmacological withdrawal episode.

Table 2. Discontinuation symptoms for pregabalin and gabapentin withdrawal, as outlined in the summaries of product characteristics

A more varied presentation of withdrawal symptoms has been reported in the medical literature for both gabapentin and pregabalin. A review of gabapentin misuse case studies by Mersfelder et al. reported withdrawal symptoms beginning between 12 hours and seven days after cessation of use with the majority of cases occurring between 24 and 48 hours. Agitation was reported in more than half of the cases with confusion and disorientation reported in 45% of cases. Other common symptoms included diaphoresis (36%), non-specified GI symptoms (23%), tremor, tachycardia, hypertension (each 18%) and insomnia (14%). Individual cases also presented with akathesia, catatonia and seizures. ¹⁹ Where gabapentin was reintroduced the withdrawal symptoms resolved.

A case study from Grosshans et al. presents the withdrawal symptomology associated with pregabalin at supratherapeutic doses. The authors report the case of a 47-year-old male consuming the equivalent of 7500mg pregabalin daily. On reduction, the patient experienced sweating, unrest, arterial hypertension, tremor and craving for pregabalin. ²⁰ Two reports on withdrawals from pregabalin from the user website Erowid describe the following:
* Insomnia, anxiety and depression
* Suicidal ideation
* Tight chest
* Sweating with alternate chills
* Inability to think or concentrate properly
* "No energy".

Both service users describe their withdrawals from therapeutic doses of pregabalin (450mg and 600mg respectively) as "hellish". ¹²

The summaries of product characteristics suggest that both pregabalin and gabapentin should be discontinued over at least one week. However, this is primarily to minimise the risk of increased seizure frequency where they are being used for patients with a seizure disorder. Public Health England (PHE) recommends a more gradual reduction to reduce withdrawal symptoms. ¹⁴ Considering the link between dose and symptoms suggested by the manufacturers, a collaborative and more conservative approach seems a pragmatic response. Patients on supratherapeutic doses of gabapentinoids should have a reduction plan discussed that allows for an illicit reduction in the community. If the prescriber decides to prescribe above the maximum dose in the summary of product characteristics, this should be for a short period of time with an aim to reduce the patient to below the licensed maximum dose in a short period of time and within the guidance provided by PHE. The maximum reduction rates suggested for the gabapentinoids within the PHE guidelines are:
* 50mg to 100mg a week for pregabalin and
* 300mg every four days for gabapentin.

There is insufficient evidence to suggest what adjuvant medication could be used to support patients, so no recommendations can made. Nevertheless, a reduction in the pharmacological agent used to manage the primary indication should necessitate a review. For example, the treatment of GAD may necessitate a transition to an SSRI. This should also include a review of the psychosocial interventions both to support the patient in managing the withdrawal from the gabapentinoid and to support the patient in managing the presentation of the primary indication. This may include, for example, engagement with cognitive behavioural therapy services for supporting patients in the management of their GAD.
Practical advice for prescribers
To prevent the emergence of problems and to support patients in reducing harm associated with the misuse of gabapentinoids, some practical steps can be employed. These practical advice tips have been brought together from a variety of sources. An excellent document supported by the Northern Ireland Public Health Agency - Pregabalin: Guidance for People Working with Pregabalin Users - is available, ²¹ which provides more comprehensive advice, especially around harm reduction, for patients misusing pregabalin.

* Ensure a robust assessment process is undertaken and careful consideration is given before prescribing gabapentinoids to patients with a history of substance misuse or those who have recently been released from prison. Use an alternative medication when clinically appropriate.

* When gabapentinoids are prescribed, warn patients about the benefits and risks (including dependence) of the medications.

* Review treatment regularly to ensure efficacious prescribing and monitor for potential misuse markers (see Table 1).

* Ensure prescribed doses do not exceed the therapeutic dose ranges (doses will also need to be adjusted in patients with reduced renal function).

* If there is a clinical need to prescribe a gabapentinoid to a service user with a history of drug or alcohol misuse, ensure that it is prescribed as regular short courses, eg every seven days, rather than the standard 28-day prescription to improve monitoring for overuse and to minimise the risk of binge use.

* If a gabapentinoid is used for neuropathic pain, review at eight weeks following initiation and discontinue (gradually) if ineffective.

* Misuse of any psychoactive medication is often linked to either a mental health co-morbidity and/or inadequate management of the primary physical health presentation. Ensure this is reviewed and managed appropriately especially if the gabapentinoid is removed from the pharmacotherapies available.

* Harm reduction advice for illicit users should include advice to take the medication orally and avoid injecting, and to follow the adage of "start low and go slow". The dangers of polydrug use, including the increased risk of drug-related death, should also be discussed.

* Ensure naloxone (Prenoxad injection) is issued to service users who also use opioids (and provide advice on its use as well as basic harm reduction advice). Many drug and alcohol specialist providers now supply this routinely to service users who misuse opioids - contact your local provider for more details.

* When supporting service users with a planned reduction in gabapentinoid use, use the schedules recommended by PHE to plan a collaborative process.

* Be aware of services such as the Battle Against Tranquilisers (BAT), who provide support for service users with pregabalin use disorders in the Bristol area, ²² as well as nationally through their website and national support helpline. UK SMART Recovery® also provides support for individuals who want to seek abstinence from drug misuse through a network of self-help and mutual aid meetings. ²³ If you need support, please speak to your local specialist drug and alcohol provider who can also give practical support and advice on the management of this service user group.

* Improve your knowledge as a prescriber to ensure you can provide appropriate advice and treatment when needed. This article and the associated references should help to support your learning.
Summary
Pregabalin and gabapentin remain important evidence-based treatments for a number of conditions. However, emerging evidence suggests that prescribers should adopt a cautious approach to the assessment and management of patients who are prescribed gabapentinoids. Both misuse and dependence have been reported with gabapentinoids,and they have been widely implicated in a number of drug-related deaths.

Prescribers should make a balanced judgement on prescribing gabapentinoids based on a robust assessment process, especially when prescribing to patients who may be at risk of misusing the medications. Patients should be provided with information about the benefits and risks of taking gabapentinoids and should be supported if they want to undertake a detoxification programme. Harm reduction interventions remain an important approach to this complex phenomenon.
Declaration of interests
Graham Parsons has received funding from Martindale Pharma to provide educational talks at conferences and from Indivior to attend a conference.
Graham Parsons is chielf pharmacist and pharmacist independent prescriber at Turning Point, London References
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6. National Institute for Health and Care Excellence. Neuropathic pain in adults: pharmacological management in non-specialist settings. CG173. November 2013. Available from: https://www.nice.org.uk/guidance/cg173/resources/neuropathic-pain-in-adults-pharmacological-management-in-nonspecialist-settings-pdf-35109750554053 [accessed 13 February 2018].
7. Lyndon A, et al. Risk to heroin users of polydrug use of pregabalin or gabapentin. Addiction 2017;112(9):1580-9.
8. Schifano F, et al. Is there a recreational potential for pregabalin? Analysis of anecdotal online reports in comparison with related gabapentin and clonazepam data. 2011. Available from: https://uhra.herts.ac.uk/bitstream/handle/2299/9328/905139.pdf?sequence=1 [accessed 13 February 2018].
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14. Public Health England, NHS England. Advice for prescribers on the risk of the misuse of pregabalin and gabapentin. December 2014. Available from: https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/385791/PHE-NHS_England_pregabalin_and_gabapentin_advice_Dec_2014.pdf [accessed 3 February 2018].
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17. Evoy KE, et al. Abuse and misuse of pregabalin and gabapentin. Drugs 2017;77(4):403-26.
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23. UK SMART Recovery®. Self-management and recovery training. Available at: https://www.smartrecovery.org.uk/
Guide to the management of gabapentinoid misuse

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Guide to the management of gabapentinoid misuse - Prescriber

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In light of the government's proposals to reclassify pregabalin and gabapentin as Class C controlled drugs due to the risk of misuse, this article examines the extent of the problem of gabapentinoid misuse and its effects, and provides practical advice to prescribers on reducing these harms

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The All Party Parliamentary Group for Prescribed Drug Dependence today publishes two new pieces of research which indicate that many doctors and psychiatrists may be failing to warn patients about the potential risks of antidepressants, and subsequently fail to recognise withdrawal symptoms. Furthermore, sources of NHS support for patients, such as NHS 111, were found to be unhelpful.

The first report, 'Antidepressant Withdrawal: A Survey of Patients' Experience', was authored by researchers at the University of Roehampton on behalf of the APPG, and is based on the results of a survey of 319 UK patients affected by antidepressant withdrawal.

64% of patients surveyed claim not to have received any information from their doctors on the risks or side effects of antidepressants, while only 2.5% of patients found NHS 111 to be a helpful source of support during withdrawal. In addition, responses to the survey make clear that the impact of antidepressant withdrawal can be devastating for some individuals with severe withdrawal reactions, with 30% of respondents reporting being off work indefinitely due to the severity of their symptoms.

The second report, 'Voice of the Patient: Petition Analysis Report', identifies failure points in the health care system based on the testimony of 158 individuals impacted by prescribed drug withdrawal who responded to two petitions lodged with parliamentary Petitions Committees in Scotland (1) and Wales (2) in 2017. The report concludes that the failures encountered by the respondents will require systemic change. Both reports will be submitted to Public Health England as part of its review into prescribed drug dependency and withdrawal, due for publication in spring 2019.

Dr James Davies, of the University of Roehampton, commented: "The majority of the people we surveyed and who responded to the petitions indicated that they were never properly informed about the risks associated with antidepressants, including withdrawal. This undermines the principle of informed consent, which is essential if patients are to make a proper assessment of the harms and benefits. This is very concerning, particularly as the survey shows that severe antidepressant withdrawal can have a devastating effect on patients' lives, including long-term disability. Furthermore, the research suggests that patients who suffer from withdrawal mostly find existing sources of NHS support, such as 111, unhelpful.'

Sir Oliver Letwin MP, chair of the APPG, said: 'These reports indicate that many doctors are unaware of the potential harms of antidepressants, and fail to communicate the risks to their patients. This highlights the need for additional guidance and training in this area, and we hope that Public Health England will consider this as part of their current review into prescribed drug dependence. Furthermore, it suggests that existing NHS sources of support are inadequate, and new dedicated services, including a 24 hour national prescribed drug withdrawal helpline, are therefore urgently needed.'

The report ' Antidepressant Withdrawal: A Survey of Patients' Experience' can be found at this link: http://prescribeddrug.org/wp-content/uploads/2018/10/APPG-PDD-Survey-of-antidepressant-withdrawal-experiences.pdf

The report 'Voice of the Patient: Petition Analysis Report' can be found at this link: http://prescribeddrug.org/wp-content/uploads/2018/10/Voice-of-the-Patient-Petition-Analysis-Report.pdf

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Many doctors may be failing to warn patients about the risks of antidepressants, new APPG research suggests

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The All Party Parliamentary Group for Prescribed Drug Dependence today publishes two new pieces of research which indicate that many doctors and psychiatrists may be failing to warn patients about the potential risks of antidepressants, and subsequently fail to recognise withdrawal symptoms. Furthermore, sources of NHS support for patients, such as NHS 111, were found to be unhelpful.

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Philip A. Yeon, MD, MPH&TM and Helmut Albrecht, MD

Methamphetamine use is already influencing the HIV/AIDS epidemic in the U.S. and could have an even greater impact in coming years.

Crystal methamphetamine (CM) is an extremely addictive stimulant that increases sexual arousal while reducing inhibition and judgment. Its use is associated with a range of high-risk sexual behaviors that increase the likelihood of acquiring or transmitting HIV. Given the relatively high prevalence of CM use among people living with HIV and among men who have sex with men (MSM), there is great concern that this drug is fueling the HIV epidemic. Equally worrisome are the effects that CM use can have on the prognosis and overall health of HIV-infected patients.

Background

Known by various street names (most commonly, "ice" and "glass"), CM can be smoked, snorted, injected, swallowed, or inserted into the rectum. Compared with other illegal drugs, CM is inexpensive, readily available, and provides a stronger, longer-lasting "high" (8-24 hours). 1 Prevalence of use in the U.S. is difficult to pinpoint, but estimates of past-year use from national cross-sectional surveys range from 1.5% to 2.8% among young adults. 2 Estimates of past-year use are even higher among MSM - 9.7%, according to one San Francisco study ( ACC Sep 28 2005) 3 - in part because the drug is now deeply embedded in the MSM "circuit party"culture. 4

Commonly cited reasons for using CM, aside from peer pressure, are increased sexual sensitization, mood enhancement, and disinhibition. However, the drug is also used to provide an escape from stress, depression, alienation, and loneliness, all of which are common among people living with HIV. Furthermore, many HIV-infected MSM report using CM as a way to deal with their illness or with homophobia or prejudice. 4, 5 Consequently, CM use is highly prevalent among people living with HIV. In a San Francisco study, 19% to 39% of HIV-infected people reported using CM during the previous year. 6 This high prevalence is alarming because CM use can increase the risk for HIV transmission and also contribute to poorer health outcomes in HIV-infected users.

Methamphetamine Use and HIV Transmission

CM use increases the risk for HIV transmission and acquisition in a number of ways.

First, the drug lowers sexual inhibitions, impairs judgment, and provides the necessary energy and confidence to engage in sexual activity for long periods of time. As a result, methamphetamine users are more likely than nonusers to engage in unprotected anal sex and to have sex with injection drug users, HIV-positive partners, and those of unknown HIV status; they also tend to report a greater number of sex partners and to have a history of other sexually transmitted diseases (STDs). 3, 7, 8

Second, CM use is a well-documented cause of erectile dysfunction, which can lead users to engage in even higher-risk sexual activities. For example, users who cannot sustain an erection may switch to receptive anal sex ("bottoming"), which carries a higher risk of HIV acquisition than does insertive anal sex. Alternatively, users may take erectile-dysfunction drugs, and the combination of these with CM can lead to longer, more-aggressive periods of sex, potentially resulting in condom breaks or mucosal tears, which can cause bleeding and increased risk of HIV transmission.

Third, CM causes mucosal dryness, which increases the risk for tissue tears. Additional damage to rectal tissues can occur when CM is inserted into the rectum ("keistering," "booty bumping").

Finally, when CM is injected, needle sharing can greatly enhance transmission of HIV and hepatitis viruses.

Numerous cross-sectional studies have demonstrated an association between CM use and increased risk for HIV infection, but only a few studies have prospectively assessed seroincidence. In the largest of these, the Multicenter AIDS Cohort Study, the relative risk for HIV seroconversion was 1.5 among CM users compared with nonusers and was even higher (3.1) among men who used both methamphetamine and poppers ( ACC Apr 13 2007). 9

Methamphetamine Use and Progression of HIV Disease

In addition to facilitating HIV transmission, CM use is associated with detrimental behavior changes that can affect the prognosis and overall health of people living with HIV. For instance, current methamphetamine use decreases adherence to HIV treatment and medical follow-up. 10 Frequent CM use has also been associated with increased risk for antiretroviral resistance, particularly to NNRTIs, with the obvious implications for treatment and transmission risk. 11 For example, CM use is thought to have contributed to the acquisition of triple-class-resistant virus by the New York City patient described in 2005 ( ACC Sep 1 2006). 12 In addition, some patients use CM to treat HIV-associated symptoms, such as fatigue, instead of seeing a physician. Such self-medication may lead to underdiagnosis and undertreatment of HIV and to important complications such as anemia and hypogonadism. 5, 10

CM use may also influence progression and complications of HIV disease more directly. For example, animal studies have shown that CM can impair the immune system 13 and increase HIV replication, 14 and human studies suggests that it can accelerate the progress of HIV-related dementia. 15

Other Consequences of Methamphetamine Use

Other consequences of CM use that are particularly harmful to HIV-infected patients include deterioration of the teeth and gums (a result of dry mouth and grinding of the teeth), reduced appetite, poor eating habits, and weight loss. Furthermore, many users "crash" after using CM for several days straight and are left with little energy and the very feelings they were trying to avoid - depression and isolation.

Other adverse effects of CM use include intense cravings for CM when not taking it; tachyphylaxis; increased risk for heart attack and stroke (because of increases in blood pressure, heart rate, and body temperature); impaired memory, reasoning, and ability to process information; and psychological problems, such as depression, psychosis, aggressive behavior, hallucinations, and paranoia. Chronic use can also cause skin lesions and damage the cardiovascular system, lungs, liver, muscles, and nerve cells in the brain.

Although methamphetamine is not known to affect HIV medications, some PIs increase absorption and decrease metabolism of CM, leading to severe reactions or overdosing. 16, 17

Preventing and Treating Methamphetamine Addiction

Prevention of methamphetamine use is hampered by a relative paucity of epidemiologic data that would enable us to assess the magnitude of the current problem adequately and to evaluate the efficacy of various interventions. Despite federal efforts to restrict pseudoepinephrine imports and a nationwide decline in small methamphetamine laboratories, the drug continues to be widely available. A report from the National Drug Intelligence Center suggests that Mexican drug traders have relocated their labs from the U.S. to Mexico and have expanded distribution to the midwestern and eastern U.S., underscoring the difficulties of drug enforcement in the era of global trade. 18 Developing methamphetamine prevention "task forces" (involving community members and representatives from at-risk groups, STD treatment centers, health departments, and law enforcement) is a reasonable approach, despite a lack of efficacy data. 19 Educational campaigns should be tailored to specific target populations, and care should be taken to help ensure that such campaigns do not increase cravings in CM-addicted patients. 20

Given the high prevalence and dire consequences of CM use among HIV-infected patients, clinicians should be sure to ask patients about past or current use. Drug testing is recommended for all patients who have a history of, or are suspected of, using CM.

Few data are available to recommend any one method of methamphetamine treatment over another. 21 Cognitive behavior-based interventions (Matrix Model), 12-step programs, drug testing, and contingency management interventions have been used by different treatment centers, with varying degrees of success. Nevertheless, treatment of CM addiction can be successful in decreasing risky sexual behaviors and should be an integral part of any HIV prevention effort. 21, 22

Conclusion

All current data underscore the potential of methamphetamine to substantially worsen the current HIV epidemic, with some studies indicating that this potential is already being realized. Methamphetamine use is an important public health problem and is associated with risky sexual behavior; increased rates of transmission of HIV, other STDs, and hepatitis; serious adverse events; and poor adherence to antiretroviral treatment. Prevention efforts not only must encompass traditional education and awareness campaigns but also will require local, national, and international policy changes, including allocation of appropriate resources and funding. Comparative trials of different treatment approaches are needed, as are better evidence-based protocols for treatment.

Citation(s):

1. Centers for Disease Control and Prevention (CDC). Methamphetamine use and risk for HIV/AIDS [fact sheet]. Jan 2007. ( http://www.cdc.gov/hiv/resources/factsheets/meth.htm)

2. Iritani BJ et al. Crystal methamphetamine use among young adults in the USA. Addiction 2007 Jul; 102:1102.

3. Buchacz K et al. Amphetamine use is associated with increased HIV incidence among men who have sex with men in San Francisco. AIDS 2005 Sep 2; 19:1423.

4. Kurtz SP. Post-circuit blues: Motivations and consequences of crystal meth use among gay men in Miami. AIDS Behav 2005 Mar; 9:63.

5. Semple SJ et al. Motivations associated with methamphetamine use among HIV+ men who have sex with men. J Subst Abuse Treat 2002 Apr; 22:149.

6. Mitchell SJ et al. Methamphetamine use and sexual activity among HIV-infected patients in care - San Francisco, 2004. AIDS Patient Care STDS 2006 Jul; 20:502.

7. Frosch D et al. Sexual HIV risk among gay and bisexual male methamphetamine abusers. J Subst Abuse Treat 1996 Nov/Dec; 13:483.

8. Celentano DD et al. Associations between substance use and sexual risk among very young men who have sex with men. Sex Transm Dis 2006 Apr; 33:265.

9. Plankey MW et al. The relationship between methamphetamine and popper use and risk of HIV seroconversion in the Multicenter AIDS Cohort Study. J Acquir Immune Defic Syndr 2007 May 1; 45:85.

10. Reback CJ et al. Methamphetamine abuse as a barrier to HIV medication adherence among gay and bisexual men. AIDS Care 2003 Dec; 15:775.

11. Colfax GN et al. Frequent methamphetamine use is associated with primary non-nucleoside reverse transcriptase inhibitor resistance. AIDS 2007 Jan 11; 21:239.

12. Centers for Disease Control and Prevention (CDC). Investigation of a new diagnosis of multidrug-resistant, dual-tropic HIV-1 infection - New York City, 2005. MMWR Morb Mortal Wkly Rep 2006 Jul 28; 55:793.

13. In SW et al. Methamphetamine administration produces immunomodulation in mice. J Toxicol Environ Health A 2005 Dec 10; 68:2133.

14. Phillips TR et al. Methamphetamine and HIV-1: Potential interactions and the use of the FIV/cat model. J Psychopharmacol 2000; 14:244.

15. Flora G et al. Methamphetamine potentiates HIV-1 Tat protein-mediated activation of redox-sensitive pathways in discrete regions of the brain. Exp Neurol 2003 Jan; 179:60.

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19. Mansergh G et al. CDC consultation on methamphetamine use and sexual risk behavior for HIV/STD infection: Summary and suggestions. Public Health Rep 2006 Mar/Apr; 121:127.

20. Nanín JE et al. Community reactions to campaigns addressing crystal methamphetamine use among gay and bisexual men in New York City. J Drug Educ 2006; 36:297.

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Crystal Meth and HIV/AIDS: The Perfect Storm?

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Philip A. Yeon, MD, MPH&TM and Helmut Albrecht, MD Methamphetamine use is already influencing the HIV/AIDS epidemic in the U.S. and could have an even greater impact in coming years. Crystal methamphetamine (CM) is an extremely addictive stimulant that increases sexual arousal while reducing inhibition and judgment.

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This service is primarily for users who need to use the interaction checker service in an older browser. Ideally, you should try to upgrade your browser to the latest version in order to use our full featured interaction checker.

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Interactions with other drugs | Terrence Higgins Trust

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Some HIV drugs interact with commonly used over-the-counter medication, recreational drugs and even herbal supplements.

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1. 1British Columbia Centre on Substance Use, Vancouver, British Columbia, Canada

2. 2Mailman School of Public Health, Columbia University, New York, USA

3. 3School of Population and Public Health, University of British Columbia, Canada

4. 4Department of Medicine, University of British Columbia, St. Paul's Hospital, Vancouver, British Columbia, Canada

5. 5School of Medicine, University College Dublin, Ireland

A fully validated alternative to DSM-5 is urgently required

Over the past two decades, a steep rise in the number of opioids dispensed for pain treatment has been accompanied by a dramatic rise in overdose deaths in the United States.1 In 2016, up to 32 000 deaths reportedly involved prescription opioids,2 and the economic burden of prescription opioid overdose has been estimated to exceed $78bn (£59bn; €67bn) annually.3 Despite all the evidence of harm, however, it remains unclear exactly how to determine if a patient with chronic pain has opioid addiction, or what criteria should serve as a gold standard in making a diagnosis of opioid use disorder (OUD) in this context. This is an important gap in the literature that hinders both evidence based care and research on the links between prescription opioids and OUD. In this editorial, we discuss the limitations of diagnosing OUD in people with chronic pain, and make several recommendations for further research.

The Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) provides a widely used set of diagnostic criteria for OUD. These criteria, however, do not always apply to patients who are prescribed opioids for chronic pain. According to DSM-5, if a patient presents with two out of nine specific symptoms (box 1), it may indicate ...

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Diagnosing opioid addiction in people with chronic pain

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A fully validated alternative to DSM-5 is urgently required Over the past two decades, a steep rise in the number of opioids dispensed for pain treatment has been accompanied by a dramatic rise in overdose deaths in the United States.1 In 2016, up to 32 000 deaths reportedly involved prescription opioids,2

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This Is What Happens to Your Brain on Opioids | Short Film Showcase

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Prescription opioid use is associated with a higher risk for serious invasive pneumococcal diseases such as meningitis and pneumonia, a study published in Annals of Internal Medicine has found. 1

As opioid use has increased in the United States the safety of prescription opioids has come under scrutiny. But most of the safety concerns have been over the potential for overdose and serious cardiovascular events rather than the risk of infection.

Researchers from Vanderbilt University Medical Centre in Nashville, Tennessee, identified 1233 patients with laboratory confirmed invasive pneumococcal diseases and 24 399 matched control patients from a Tennessee Medicaid database. After adjusting for confounders the researchers found that patients in the pneumococcal disease group were more likely to be current opioid users than those in the control group (adjusted odds ratio 1.62 (95% confidence interval 1.36 to 1.92)).

The study, 1 which was funded by the National Institutes of Health, found that the association was strongest in opioids that were long acting (1.87 (1.24 to 2.82)) or high potency (1.72 (1.32 to 2.25)) or were used at high doses.

The immunosuppressive properties of certain opioids including morphine and fentanyl are well established. In animal models exposure to particular opioids was found to increase the risk for infections due to common pathogens including Streptococcus pneumoniae.

One limitation of the study was that opioid use was based on pharmacy prescription fills, and actual use was not observed. And, although the researchers accounted for evidence of alcohol or substance use disorders in their analysis, they were unable to assess illicit opioid use.

In an accompanying editorial Sascha Dublin and Michael Von Korff, from the Kaiser Permanente Washington Health Research Institute in Seattle, Washington, said that the strengths of the study included laboratory confirmation of infection and adjustment for many potential confounders including markers of frailty.

They wrote, "Before prescribing an opioid, the clinician should carefully consider all reasonable alternative approaches to pain relief. It now seems that decision making also should take into account the risk for serious infections." 2

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Opioid use is linked to risk of serious infections

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Prescription opioid use is associated with a higher risk for serious invasive pneumococcal diseases such as meningitis and pneumonia, a study published in Annals of Internal Medicine has found. 1 As opioid use has increased in the United States the safety of prescription opioids has come under scrutiny.

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Codeine: Signs and symptoms of problematic use; and treatment options available - Drug and Alcohol Information and Support in Ireland - Drugs.ie

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Drug and Alcohol Information and Support for Teenagers, Parents and Carers. Free, Confidential Live Chat. Advice and Support from Drugs.ie

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The number of opioid drugs prescribed in England is steadily rising despite a lack of effectiveness for treating chronic pain and their potentially serious side effects, a study has found.1

Researchers also found that opioid prescriptions by GPs are higher in deprived areas and northern England.

The retrospective observational study, led by Luke Mordecai, a pain research fellow at University College London Hospital, examined official government data on opioids prescribed in primary practice in England from August 2010 to February ...

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Opioid prescriptions rise in England despite poor efficacy and harms, finds study

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The number of opioid drugs prescribed in England is steadily rising despite a lack of effectiveness for treating chronic pain and their potentially serious side effects, a study has found.1 Researchers also found that opioid prescriptions by GPs are higher in deprived areas and northern England.

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Re: What we must learn from the US opioid epidemic

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The excellent article by Makary et al highlights the fact that the current prescribed opioid epidemic that the US is experiencing is multi-factorial in origin. 1 They emphasise that one of the major factors leading to this epidemic was the belief that the risk of addiction/ dependency to opioids prescribed for pain was rare.

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Identification and treatment of Opioid Pa dependence

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The widespread use of opioids to treat pain frequently prompts concerns about addiction and even deaths. So, why are these sometimes dangerous drugs still being given to patients?

Much stronger than many of the other options, opioids are among the world's most commonly prescribed painkillers.

These drugs - including morphine, tramadol and fentanyl - are used to treat pain caused by everything from heart attacks to cancer.

But in the UK they were recently linked to the deaths of hundreds of elderly hospital patients, while the US is battling a well-documented opioid epidemic.

Why not just use other painkillers to avoid the risk of harm?

A worldwide problem

Opioids work by combining with receptors in the brain to reduce the sensation of pain - and they are highly effective.

However, opioid receptors are present in areas of the brain responsible for breath control and high doses can dangerously reduce the rate of breathing - the cause of almost all opioid deaths.

An inquiry into the UK's Gosport War Memorial Hospital said more than 450 people died between 1989 and 2000 from administration of "dangerous" amounts of opioids without medical justification.

In the US, the increasingly widespread prescription of opioids to treat long-term pain has led to an epidemic of addiction. In 2016, a record 11.5 million people in the US misused prescription opioids, and there were 42,249 deaths from overdoses.

In England, GPs prescribed 23.8 million opioid-based painkillers in 2017 - a rise of 10 million prescriptions since 2007. More than 2 million working-age people were thought to have taken a prescription painkiller that was not prescribed for them in 2016-17.

There were more than 2,000 deaths in England related to opioid overdose in 2016, the highest since records began. But unlike the US deaths, these largely related to heroin rather than forms of opioid available on prescription.

What are opioids?

A large group of drugs used mainly to treat pain

Includes naturally occurring chemicals like morphine and codeine, as well as synthetic drugs

Codeine, morphine and methadone are among opioids judged by the World Health Organization as essential for treatment of pain and end-of-life care

Some opioid medications - methadone and buprenorphine - are used to help people break their addictions to stronger opioids like heroin

Consistent relief

One of the reasons opioids are so widely used is that - when used correctly - they are a particularly useful form of painkiller. They can be given to patients in a variety of ways and in many different forms.

Morphine can be given orally or through injection; other opioids can be given through patches, lozenges or under-the-tongue tablets.

The Gosport report focused on syringe drivers, a method of delivering a drug under the skin, to provide a constant dose of an opioid for consistent pain relief.

This can be a useful form of pain relief at the end of someone's life as it means there is no reliance on the patient being able to swallow or absorb the drug. Syringe drivers also help doctors adjust dosage as necessary.

However, at Gosport War Memorial Hospital, syringe drivers were reportedly used when they weren't justified, or to deliver inappropriately high doses of opioid.

A distressing reaction

Despite their benefits, the problems associated with these medicines are clear.

For decades, scientists have tried to develop opioids that work without causing the problems of addiction and misuse.

Some have added extra ingredients deliberately to cause a distressing reaction. For example, added to opioid tablets, the antidote naloxone largely has no side-effects if the medication is taken orally, but causes severe "cold turkey" withdrawal symptoms if the tablet is crushed and injected by a dependent user.

Implants and slow-release injections which wear off over a much longer timeframe have also been investigated.

A particular problem occurs when the need for pain relief is long-term - when the evidence for the benefit of opioids is less clear.

In the US, one cause of the opioid epidemic is over-prescribing, particularly among those with long-term pain.
More like this
For people with acute pain, opioids can be used alongside other drugs - including commonplace painkillers like paracetamol, ibuprofen and aspirin.

When treating patients who are dying, meticulous assessments of the causes of pain are needed to understand the best way to improve it, while minimising potential side-effects.

For example, cancer patients with pain as a result of nerve damage caused by chemotherapy might first be treated with paracetamol and a tricyclic antidepressant.

If that doesn't help, or the patient is in more severe pain, opioids may be introduced - again, this is often in combination with other drugs.

For people who are dying, opioids are very often the most effective way to relieve pain. Anywhere between 30% and 94% of people with advanced cancer are thought to experience pain and about half of cancer patients were prescribed an opioid in the last three months of their life.

If used appropriately, and used in amounts appropriate to patients' symptoms, opioids are not only safe, they are essential for good symptom control.

The events in Gosport and the addiction crisis in the United States have put the medical profession's use of opioids under intense scrutiny.

Better education and training might be one way to make sure they are used appropriately for those who might benefit, so that potential harms are avoided.
About this piece
This analysis piece was commissioned by the BBC from experts working for an outside organisation.

Dr Katherine Sleeman is a National Institute for Health Research clinician scientist and honorary consultant in palliative medicine at the Cicely Saunders Institute, King's College London.

Prof Sir John Strang is director of the National Addiction Centre at King's College London's Institute of Psychiatry, Psychology & Neuroscience. He has worked on ways to improve adherence to treatments and to reduce abuse of opioids, including joint work with the pharmaceutical industry, as well as the development of antidotes for overdoses. More details of his work can be found here.

Edited by Eleanor Lawrie

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Why 'dangerous' drugs are still being used to treat pain

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The widespread use of opioids to treat pain frequently prompts concerns about addiction and even deaths. So, why are these sometimes dangerous drugs still being given to patients? Much stronger than many of the other options, opioids are among the world's most commonly prescribed painkillers.

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Guidance for benzos and anxiolytics 2014

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Helping you protect your health when buying medical products online

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Helping you protect your health when buying medical products online by identifying fake medicines, fake medical devices. Providing advice how to avoid fakemeds.

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Important: Equivalent doses may be inaccurate for larger quantities of benzos with different effect profiles. Please compare the dosages below to see weighted dosage ranges.

Note: It's a good idea to start with a lower dose than the calculator shows, since everybody can react differently to different substances

Please note, these tools were developed and tested to the best possible ability by the TripSit team, and the greatest effort has been made not to produce incorrect or misleading results, though for unforeseen reasons these may occur. Always check your maths, and be careful. If you have any questions, suggestions or error reports on this tool, you can contact us here.

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Important: Equivalent doses may be inaccurate for larger quantities of benzos with different effect profiles. Please compare the dosages below to see weighted dosage ranges.

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One in four older adults prescribed a benzodiazepine goes on to risky long-term use

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They may start as well-intentioned efforts to calm anxiety, improve sleep or ease depression. But prescriptions for sedatives known as benzodiazepines may lead to long-term use among one in four older adults who receive them, ...

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Abstract

Introduction

Non-prescription medicines (NPMs), also known as over-the-counter (OTC) medicines, are used for the management of minor ailments. They are convenient for consumers and can be obtained from community pharmacies and other retail outlets, e.g. petrol stations and supermarkets. NPMs facilitate self-care that brings about benefits for both the individual and the National Health System (NHS) by reducing the burden on other healthcare settings. A recent study estimated that 13 and 5% of general practice and emergency department (ED) consultations, respectively, were for minor ailments suitable for management in community pharmacies. Symptom resolution was shown to be similar for minor ailments irrespective of setting while overall costs are significantly lower for pharmacy consultations compared with general practice and ED consultations. In 2007, there were an estimated 57 million GP consultations per year for minor ailments at a total cost of £2 billion to the NHS.

While NPMs are often perceived by the public as being safer than prescription medicines, they can cause harm. NPMs have the potential to be misused, abused and lead to dependence. Specific NPMs most frequently associated with dependence are those capable of causing tolerance and withdrawal, e.g. codeine-containing analgesics and smoking cessation products containing nicotine. However, the psychological aspects of addiction may occur with any substance, including NPMs. There are other harms associated with NPM including direct physiological or psychological harm, harm from another ingredient and associated social and economic problems. Codeine-containing analgesics are commonly associated with abuse and dependence due to the properties of codeine with studies highlighting the morbidity caused by their additional ingredients, i.e. paracetamol or ibuprofen. In response to these harms, regulation has been applied in the UK to minimize the risk of harm. This includes restricted indications, limits on pack size and warnings on packets, patient information leaflets and advertisements. Codeine-containing products contain an additional specific warning about the risk of addiction.

Despite the drive to encourage and enable self-care in the UK, there is minimal information about the prevalence of NPM misuse, abuse and dependence in the general population. Much of the existing research focuses on pharmacists' perceptions of prevalence. Patient-reported behaviour tends to be highly specific in terms of the population or the outcome measured, e.g. misuse of NPMs in community-dwelling older adults and in people with HIV. Interviews with members of the general public in Northern Ireland found that almost a third of respondents ( n = 298) had personally encountered OTC abuse, although this included personal experience, knowledge or observation, and was solely in relation to abuse.

The current study was designed to estimate the prevalence of and factors associated with self-reported NPM misuse, abuse and dependence in the general UK population. For the purpose of this study, NPM misuse was defined as the use of an NPM for a legitimate medical purpose, but in an incorrect manner, e.g. in terms of dosage or duration of use. Abuse was defined as use for a non-medical purpose, e.g. to achieve mind-altering effects or weight loss. Dependence and addiction were defined as 'the repeated use of an NPM in which the person has a need or desire to use the NPM and has difficulty in voluntarily stopping or altering their use'.

Methods

Study design and participants

This was a cross-sectional postal survey of a random sample of 1000 individuals aged 18 and older drawn from the UK Edited Electoral Register.

Questionnaire development

Questionnaire development was informed by the literature, including previous surveys, and discussion with researchers with expertise in this area. The terms 'misuse' and 'abuse' were not used in the questionnaire to avoid potential stigmatisation and to reduce the likelihood of social desirability and responder bias. Instead, respondents were asked to indicate whether they had ever knowingly used NPMs in specific ways, e.g. 'for a reason that was not recommended by the manufacturer, e.g. for the feeling or effect it caused' (i.e. abuse) or 'at a higher dose than recommended by the manufacturer' (i.e. misuse). The definition of dependence and addiction (above) was provided at the beginning of the relevant section.

Pre-piloting and piloting

Pre-piloting was conducted with an opportunistic sample of 23 academic staff and students. All were asked to complete the questionnaire and provide feedback on clarity and ease of completion. The questionnaire was also reviewed by the Project Director of Over-Count Drugs Information Agency ( http://over-count.weebly.com/), a voluntary organization that provides a telephone helpline and online discussion forum for people dependent on NPMs.

Formal piloting tested both the distribution process and phrasing of the questionnaire. A cover letter, questionnaire, feedback form and reply-paid envelope were posted to a random sample of 100 individuals from the Edited Electoral Register. A pre-notification letter and reminder were used. Questionnaires were returned by 42 of the 100 addressees. Completed questionnaires were examined to identify problems. A list was compiled of feedback from participants and problems identified by examining the completed questionnaires; this informed the refinement of the final questionnaire.

Procedures

In August 2013, a pre-notification letter (to enhance response rate) was sent to a random sample of 1000 individuals aged ≥18 from the UK Edited Electoral Register (provided by an independent commercial marketing company) to notify them of the survey. Two weeks later, addressees were sent a cover letter, questionnaire and reply-paid envelope. Reminders were sent to non-responders at 2 and 4 weeks. Reminder letters included a questionnaire and reply-paid envelope.

Data management and analysis

Data were entered and analysed using SPSS (Version 22). An independent quality assurance check was conducted on data entry by a research secretary for 10% of questionnaires; these were selected using a random sequence generator.

Sample size

An estimated prevalence of 15% for misuse and abuse, and 5% for dependence, was used for the sample size calculation for the current study based on earlier estimates; however, these studies were restrictive in terms of their populations, the NPMs of interest and the type of inappropriate use measured. A respondent group of 300 was required to detect a 5% prevalence of dependence with 2.5% precision (95% confidence interval (CI) 2.5-7.5%) and a 15% prevalence of misuse with 4% precision (95% CI 11.0-19.0%). A minimum expected response rate of 30% ( n = 300) implied this needed to be inflated to an overall sample of 1000.

Statistical methods

Chi-squared tests compared respondents' sex and country of residence with those of non-respondents. A Mann-Whitney U test was used to compare the distribution of year of birth as the data for this variable were not normally distributed. Chi-squared tests compared respondents' age, sex, ethnicity, partnership status and general health with data from the 2011 UK Census to determine the representativeness of respondents compared with the general population.

Chi-squared tests were used to examine univariate associations between categorical characteristics and misuse/abuse status. An independent sample t-test was used for age as the data were roughly normally distributed. Significant associations ( P < 0.05) were entered into a binary logistic regression model using the enter method to produce unadjusted ORs and 95% CIs to determine which characteristics were independently related to self-reported misuse/abuse of NPMs.

Preliminary basic descriptive analysis was undertaken on the full dataset. Where possible and logical and without distortion of findings, aggregations were made to ensure sufficient numbers for analysis and allow comparison with national data.

Results

Participants

The overall response rate was 43.4% (411/946) ( Supplementary data, Figure S1).The pre-notification letter was sent to 1000 addressees. Fifty-four addressees were excluded from the denominator due to death, change of address or asking to be excluded from the research prior to receiving the questionnaire.

Descriptive data

Respondents' age ranged from 19 to 92 years (mean = 60, SD = 15.5). Respondents were similar to national data in terms of gender ( χ ² = 0.026, df = 1, P = 0.87) but not age, country, partnership status, ethnicity or general health (all P < 0.001) (Table 1).

No association was found between response status and country of residence (i.e. England, N. Ireland, Scotland or Wales) (χ ² = 5.3, df = 3, P = 0.15) or gender (χ ² = 0.002, df = 1, P = 0.96). Respondents were significantly older than non-respondents by 10 years (Mann-Whitney U = 86 244.0, P < 0.001).

The majority of respondents who used NPMs indicated that they always read the directions for use when using an NPM that they have never used before (214/343) and follow the directions for use (243/349) (Table 2).

NPM misuse

The lifetime prevalence of any type of self-reported NPM misuse was 19.3% ( n = 76, 95% CI 15.7-23.5%): 11.9% ( n = 47, 95% CI 9.1-15.5%) for using a higher dose than recommended, 10.6% ( n = 42, 95% CI 8.0-14.1%) for using more often than recommended and 10.6% ( n = 42, 95% CI 7.9-14.0%) for using for a longer time than recommended (Table 2). Analgesics, with and without codeine, were the most frequently misused products ( Supplementary data, Table S1).

NPM abuse

The lifetime prevalence of self-reported abuse was 4.1% ( n = 16, 95% CI 2.5-6.5%) (Table 2). The most common reason for abusing an NPM was for sleep or relaxation purposes. Medicines used for these purposes were cold and flu products containing sedative antihistamines ( n = 3), cough remedies ( n = 2), codeine-containing analgesics ( n = 2), analgesics without codeine (n = 1) and an antihistamine (n = 1). A cough remedy was also used by one respondent for another reason: 'When trying to conceive, I read that Benylin help make women more likely to conceive as it made secretions more receptive to sperm'. Haemorrhoid products were reportedly used for facial skin care purposes ( n = 2), and sore throat products were used for the pleasant taste ( n = 1) ( Supplementary data, Table S1).

Characteristics associated with self-reported misuse/abuse

Respondent characteristics associated ( P < 0.05) with misuse/abuse were age; partnership status; level of education; employment status; the presence of a long-standing illness, disability or infirmity that requires the regular use of an NPM; and ever having used illegal drugs or legal highs (hereinafter referred to as illicit drug use) (Table 3). When entered into a logistic regression model, these characteristics correctly predicted 18.1% (15/83) of individuals who had abused/misused NPMs and 95.3% (264/277) who had not abused/missed NPMs. Characteristics that remained significant independent predictors of misuse/abuse were age, the presence of a long-standing illness requiring regular NPM use and illicit drug use status (Table 3).

NPM dependence

Most respondents (71.3%, 281/394) were aware of the potential for NPMs to cause dependence or addiction (Table 4). In total, 12% (47/396) of respondents indicated that they personally knew at least one person (including family members, friends and colleagues) who had been dependent on or addicted to an NPM. The NPMs associated with dependency or addiction in these people were analgesics (without codeine ( n = 14), with codeine ( n = 13), unspecified ( n = 7)), smoking cessations products ( n = 4), laxatives ( n = 3), sleep aids ( n = 3), cough remedies ( n = 2), caffeine tablets ( n = 2) and decongestants ( n = 1).

The lifetime prevalence of NPM dependence was 2% ( n = 8, 95% CI 1.0-3.9%); 0.8% ( n = 3, 95% CI 0.3-2.2%) were currently dependent while 1.3% ( n = 5, 95% CI 0.5-2.9%) had been dependent in the past. For those who had ever been dependent, analgesics containing codeine ( n = 4), analgesics without codeine ( n = 1), a herbal sleep aid ( n = 1) and nicotine gum ( n = 1) were the NPMs of dependence. One individual did not provide a response, but their other data implied dependence associated with analgesic use.

Of the eight respondents ever dependent, six obtained their NPM of dependence from a pharmacy: five used multiple pharmacies and one used one pharmacy. No respondents obtained the NPM of dependence via the internet. Most dependent individuals were rarely or never questioned by pharmacy staff about their medicine needs or health condition when purchasing the NPM of dependence (Table 4). The individual indicating that they were 'usually' questioned by pharmacy staff was dependent on a codeine-containing analgesic. Those 'rarely' questioned were dependent on a codeine-containing analgesic ( n = 1), a smoking cessation product ( n = 1) and a herbal sleep aid ( n = 1). The two respondents who were 'never' questioned were dependent on codeine-containing analgesics. No respondents had ever been refused the sale of the NPM of dependence, or had ever been referred to a GP or substance misuse clinic, by a member of pharmacy staff.

The eight respondents who reported ever being dependent on or addicted to an NPM were asked where they had sought help for their dependence or addiction. The three individuals currently dependent selected 'Nowhere-I haven't sought help'. Of the five whose dependence was in the past, two had not sought help, two sought help from a GP and one from family and friends.

Discussion

Main findings of this study

This is the first study to estimate the prevalence of NPM misuse, abuse and dependence in the UK general population. Lifetime prevalence of any type of misuse was 19.3%. Lifetime prevalence of abuse and dependence was 4.1 and 2%, respectively. The products most commonly misused and abused were codeine-containing analgesics, and cough and cold remedies. Dependence was reported with analgesics (with and without codeine), sleep aids and nicotine products. Being younger, having a long-standing illness requiring regular use of NPMs and ever having used illicit drugs were predictive of misuse or abuse of NPMs.

What is already known on this topic?

There is a drive to encourage and enable self-care in the UK through the use of NPMs for minor ailments. Pharmacy customers who make direct product requests by name are less likely to be questioned by pharmacy staff than customers/patients seeking advice regarding the management of conditions or symptoms. Furthermore, pharmacy users generally report low rates of information disclosure to pharmacy personnel during consultations for NPMs. From a pharmacy perspective, pharmacists suspect that NPMs are sometimes misused. Research has also demonstrated that NPMs can be misused, abused or lead to dependence for some people.

The prevalence of these problems within the UK general population was unknown. Previous surveys have been conducted, but these were limited in either the population studied or type of NPM studied.

What this study adds?

This study identified potential predictors of misuse/abuse as being of younger age, having a long-standing illness that requires regular NPM use and use of illicit drugs. Having a long-standing illness is clinically relevant as it reinforces the need for clinicians to be aware of concurrent use of NPMs by their patients, particularly those with pain and to be mindful of the potential for misuse, abuse and dependence.

Most individuals ever dependent on an NPM had not sought formal help for their dependence. The reasons for this are unknown. Previous qualitative research involving individuals with non-prescription codeine dependence found that attempts at self-treatment were often ineffective; consequently, there is a need for future research to identify the barriers and enablers to seeking treatment for NPM dependence. A qualitative study is ongoing by the research team to address this. There may be a need to clarify sources of treatment/support for NPM dependence and raise awareness of these treatment options.

In our study, individuals who were or had been dependent were generally rarely or never questioned by pharmacy staff about their purchase. More active engagement may be needed by both pharmacy personnel and patients/customers during these consultations, particularly when requests are made for NPMs associated with misuse, abuse and dependence, to explore the need for referral to an appropriate source of support/treatment. However, previous research indicates that there may be difficulties with this due to the difficulty some pharmacists have in challenging customers or raising their concerns with customers, as well as their lack of confidence about signposting customers to potential sources of support.

Respondents' acknowledgement of the potential for NPMs to lead to dependence was high and suggests that there is public awareness that NPMs are associated with risks. However, a considerable proportion of individuals do not always read the directions for use and therefore alternative, or additional, methods of providing important information on medicine risk should be considered, e.g. by pharmacy staff at the time of purchase, through product advertisements or mass media campaigns.

The survey achieved a higher than anticipated response compared with recent studies using the same sampling method. The survey was inclusive with regard to NPMs and was not restricted to a limited selection of NPMs as in previous research. Furthermore, it was conducted on a large, national sample, unlike previous research.

Limitations of this study

There may be some response bias given that respondents differed from non-respondents in various ways; they were older and more likely to be white; married, in a civil partnership or widowed; rate their general health as poorer and reside in Scotland or Wales. A US study indicated that the lifetime prevalence of abuse of non-prescription cough and cold medicines is higher in younger individuals; therefore, the prevalence of lifetime abuse may be underestimated. The same US study reported that lifetime use of a non-prescription cough or cold medicine 'to get high' was 3.0 and 6.6% among those aged 12-17 and 18-25, respectively, while the lowest prevalence rates were among those aged 50-64 and 65 and older, respectively. Consequently, the older age of respondents in our study and the exclusion of individuals <18 years of age may have underestimated the prevalence of abuse in our study. Similarly, groups that are less likely to have registered to vote or to have opted out of the Edited Electoral Register will be under-represented which may have affected the results in unknown ways. Other factors may also serve to under- or over-estimate the prevalence of misuse, abuse and dependence. Social desirability bias and recall bias may result in under-reporting. The explicit use of the terms 'dependence' and 'addiction' may have resulted in under-reporting of dependence due to social desirability bias, although the researchers attempted to minimize the likelihood of this for misuse and abuse by avoiding the use of these terms in the questionnaire. The finding that younger age was predictive of lifetime misuse or abuse of NPMs may be due to recency; it may be that older individuals had simply forgotten about previous use. People may have unknowingly misused NPMs. Our study found that 38% of respondents who used NPMs did not always read the directions for use when using an NPM that they have never used before, which was higher than shown previously.

Authors' contributions

All authors conceived and designed the work. N.F. collected, analysed and interpreted the data. All authors drafted the work or revised it critically for important intellectual content, gave final approval of the version to be published, and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. N.F. and C.M. are the guarantors. N.F. had access to all of the study data and can take responsibility for the integrity of the data and the accuracy of the data analysis.

Supplementary data

Supplementary data are available at PUBMED online.

Conflict of interest statement

N.F. has received financial support for the current work in the form of a PhD studentship from the Society for the Study of Addiction; N.F. is in receipt of funding in the form of a PhD studentship from the Society for the Study of Addiction and C.M. is a member of the Society for the Study of Addiction's executive committee.

Funding

This study was supported by the Society for the Study of Addiction in the form of a PhD studentship awarded to N.F.

Ethical approval

Ethical approval was obtained from University of Aberdeen College Ethics Review Board (reference number CERB/2013/3/874).

Acknowledgements

We thank the survey participants. We also thank Lorna Aucott and Megala Thiruvothiyur (Medical Statistics, University of Aberdeen) for statistical support.

References

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Non-prescription medicine misuse, abuse and dependence: a cross-sectional survey of the UK general population | Journal of Public Health | Oxford Academic

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Non-prescription medicines (NPMs), also known as over-the-counter (OTC) medicines, are used for the management of minor ailments. They are convenient for consumers and can be obtained from community pharmacies and other retail outlets, e.g. petrol stations and supermarkets.

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benzo.org.uk : Benzodiazepine tranquilliser addiction, withdrawal and recovery

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Mind in Camden's REST (Recovery Experience Sleeping Tablets and Tranquilisers) Service, established in 1988, provides support for individuals from who may be experiencing difficulties due to Benzodiazepine dependency.
These individuals include:

Prescribed users of benzodiazepines

Existing, recovering, past and potential users

Carers, friends and relatives of users

People using minor tranquillisers illicitly including benzodiazepine analogues

People using minor tranquillisers in combination with other drugs

How can we help you:

"Being reassured that I could be helped kept me going ... a godsend ... gave me a lifeline. The main psychological benefit was that I was accepted as I am. That makes a great deal of difference when you are ill".

REST Service User

The Project provides a safe and supportive atmosphere for you to discuss the problems of taking and withdrawing from benzodiazepines. You are encouraged to reduce, but never pressurised to do so. Our services are free and confidential.

Support Groups: users and ex-users meet to exchange experiences, discuss problems, gain mutual support and benefit from group therapy

Escorts: we can provide assistance to clients suffering agoraphobia, helping you to attend medical, dental and other types of appointments including our support groups

Home visits: we may be able to provide home visits to clients who are agoraphobic or have physical disabilities

Advocacy: we will write letters of support to various agencies such as GPs, DSS and housing

Outreach: we provide talks and presentations to other community groups and professionals

Information: we highlight issues of concern in the media to promote a better understanding of minor tranquillisers and their effects and offer guidance on withdrawal methods

Counselling: individual and confidential counselling is provided, subject to availability and assessment

Family Support Scheme: a support group is held every month to support carers, friends and relatives of users

Mindfulness: A session is held every month in the support group

Wrap up Video for World Benzodiazepine Day featuring REST
https://www.youtube.com/watch?v=Is8wdwbPezU
Article featuring one of the members of REST:

http://www.mirror.co.uk/news/uk-news/its-parasite-takes-over-your-10417849

Upcoming events:

Christmas party for all REST members on Thursday 15th December 7 PM.

Manager and Donna to speak Camden peer mentoring group at the Margaret Centre on 1.12.2016.

Recent events:

REST represented at the AGM of the APPG for Prescribed Drug Dependence (PDD) followed by a meeting on opioid painkiller dependence (OPD) on October 19th at the House of Lords. Thank you Matthew!

Meeting chair: Harry Shapiro (Opiate Painkiller Dependency Alliance, Director DrugWise, APPG secretariat)

Speakers:
Dr George Ryan - former GP, clinical advisor to PHE England
Dr Jane Quinlan - consultant in pain management Oxford University Hospitals Trust
Dr Farrukh Alam - consultant in addiction psychiatry Central and North West London NHS Foundation Trust
Cathryn Kemp - director Painkiller Addiction Information Network (PAIN) and expert by lived experience

25/10/2016:
Manager spoke at a substance misuse forum at Blenheim CDP

Presentation to Single Homeless Project Recovery Team at the London Irish Centre Camden by Service Manager and Steve.
10/10/16 World Mental Health Day
REST were among the services represented at #worldmentalhealth day held in the Phoenix centre. Thank you for the chats, raffle, yummy food, artwork and poetry recitals. Tim Bleech reading a poem he wrote about serenity. Melanie, Mark and Nicky, Amy and Kate.

Donna represented REST and MIND in Camden at National Minds Equality Improvement leaders Group.

The group aims to bring together the diverse voices of people with lived experiences into Mind work and create an opportunity for local mind service user Reps from diverse background and experience

to also contribute to greater national awareness and learning on what we can do together to make sure
21/09/2016
- National Mind's work is reflective of their diverse needs
Keir Starmer Labour MP
- Contribute to influencing National MINDs wider work to improve mental health support for diverse and marginalised communities

Thank you Donna for being part of shaping conversations to drive positive change.

REST manager Melanie Davis and Lucy spoke to a fibromyalgia support group in South London. Thanks for inviting us Julie!

Offered a surgery at MIND in Camden, spoke to MIC members including REST service users.

7/7/2016:
Frontline
Matthew Follows service user and Manager Melanie Davis spoke at Frontline, the drug user group for Camden. Melanie Davis gave a brief introduction to the service, Matthew told his story and then both took questions. The meeting was well attended by drug service users, some of whom had had experience with benzodiazepines.

The 11 July 2016 was the inaugural World Benzodiazepine Awareness Day, part of a campaign to raise global awareness about the issue of doctor-induced benzodiazepine dependency, which affects millions of people worldwide and can lead to debilitating withdrawal symptoms that may last for weeks, month or even years.

Rest Service User and Manager promoting REST during the World benzo awareness day at the St Pancras Hospital.

Service User Donna speaks about the world benzo awareness day.

John from the REST project loving life in his 83rd year and off benzodiazepines for 22 years. Living proof that a good life after benzodiazepines is possible. He never forgets his severe suffering in protracted withdrawal but wants everyone to know how good things can be on the other side

Other service users looking awesome in
their "world benzo awareness day"T-shirts

30/6/2016:
CRI Margaret Centre - Manager spoke to staff at the Centre and offered a benzo quiz.
"Many thank to Dominic for inviting me to speak and the team were glad to know there is extra support in the borough for benzodiazepine users and hope to refer people to us." (Melanie Davis)

23/6/2016:
Manager and Jilly Moore attended the roundtable event of the Solicitors Regulation Authority:

13/6/2016
REST Project outing to "People, Places and Things" at the Wyndham theatre, London - such a stunning evening!

7/6/2016:
Melanie Davis at the British medical association

Picture 1: Manager Melanie Davis
Picture 2: Beverly Thorpe with Dr James Davies
Picture 3: Luke Montagu
Picture 4: Dr Peter Kinderman

20/5/2016:
REST at the Mental health awareness week - St. Mungo´s Festival in
Camley Gardens Nature Park

11/5/2016: Melanie Davis representing REST at House of Lords and Portcullis House for a meeting of the All Party Parliamentary Group for Prescribed Drug Dependency:
'Rising Prescriptions, Rising Mental Health Disability: Is There a Link?'

Politicians and experts met at parliament to explore link between record antidepressant prescribing and disability. The All-Party Parliamentary Group for Prescribed Drug Dependence met on 11 May 2016 at Westminster to discuss evidence of the link between the rise in disability claimants and the record level of antidepressant prescribing. The event is being hosted by Paul Flynn MP, co-chair of the APPG of PDD.
- Melanie Davis is a member of the APPGPDD. -

(Melanie Davis REST service manager with Robert Whitaker author of "Anatomy of an Epidemic", Lord and Lady Sandwich, Dr James Davies and Dr Alison Tierney).

"The benefits of contacting the service have been excellent. Without this help I don't know where I would have got the support I needed. This helpline is a great help, it made me realise I was not alone."

REST Service User

For more information, please call our REST Project Enquiry Line: 0207 241 8980
mdavis@mindincamden.org.uk

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Mind in Camden's REST (Recovery Experience Sleeping Tablets and Tranquilisers) Service, established in 1988, provides support for individuals from who may be experiencing difficulties due to Benzodiazepine dependency. These individuals include: Prescribed users of benzodiazepines Existing, recovering, past and potential users Carers, friends and relatives of users People using minor tranquillisers illicitly including benzodiazepine analogues People ...

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Information on how it works in the body, its effects, risks and addictive potential (and how you can reduce them), and its potential medical uses

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A pioneering clinic set up to help teenagers addicted to Xanax and other prescription drugs is being sought out by adults who use pills purchased illicitly on the internet.

At the beginning of the year Dr Owen Bowden-Jones opened the Addiction to Online Medicine (Atom) service in London, a free, easy-to-access NHS clinic run by Central North West London NHS Foundation Trust that offers one-to-one meetings and group mindfulness sessions.

The clinic, thought to be the first of its kind in the UK, was established in response to the growing problem of teenagers addicted to prescription drugs, particularly Xanax, bought illegally on the web.

What has surprised Bowden-Jones is that a third of current referrals are over 20. "When we established the clinic we were at the peak in terms of interest in Xanax and we were seeing a lot of young people using it," he says. "But one of the cohorts we have seen are people in their 20s and 30s - people who are prescribed a medicine and then they seek it online, either because the dose they have is not enough or the medicine is stopped by their GP ."

He adds: "Teenagers tend to use [prescription drugs] for the intoxicating effect, to get giddy and drunk, but older people tend to use it to treat symptoms, particularly anxiety. We have had a number of patients with traumatic experiences and for them these medicines are being used to anaesthetise themselves."

The adult group tend to use benzodiazepines to treat anxiety and tend to be women, he says. They have a job, have a partner, friends and a social network, "but have a secret that they have been buying drugs online and not telling people. They are often quite ashamed about it, but they found they cannot cope without prescription medicines."

Benzodiazepines are currently prescribed on the NHS but are only supposed to be used in the short term. Research shows around four in every 10 people who take them every day for more than six weeks become addicted.

In the UK, alprazolam is not available on the NHS and can only be obtained on a private prescription. Tranquillisers are controlled under Class C of the Misuse of Drugs Act and possession without a prescription could lead to a prison sentence of up to 2 years and an unlimited fine.

Yasir Abbasi, a psychiatrist with Mersey Care NHS Trust, says: "In modern society we are so connected and always on the go. It can, on occasion, lead to individuals feeling more anxious compared to 30 years ago: constantly being connected and engaged in social interaction through smartphones which are constantly buzzing and sending us alerts. This can be part of the problem, which leads to people feeling more anxious."

He adds: "Self-medicating becomes the solution for some. In modern society we feel that there must be an answer in a pill for something we experience."

Abbasi gives the example of someone he saw recently, who was in their mid-40s. They had an accident years ago and began using painkillers. Three years down the line they still felt anxious and six months ago started taking benzodiazepines. Their GP eventually refused to prescribe them so they started buying the pills online. They ended up having an accidental overdose after increasing the dose themselves.

Abbasi says: "This is how it usually starts - people are prescribed [the pills] ... these are highly functioning individuals who become hooked on drugs."

They feel the fact they are buying these pills from online pharmacies legitimises what they are doing, he says. But buying drugs on the web is dangerous not only because of the legal implications but also because people cannot guarantee what they are actually getting. While websites may purport to sell pharmaceutical-grade substances, it is difficult to verify what is actually on offer. Some medicines can be bought legally on websites bearing a logo linking to the online register of regulated pharmacies.

Ellen (not her real name), 31, says she takes valium purchased online to cope with anxiety. "I tend to buy around 50 to 60 tablets and they will last me the year," she says.

Ellen has a busy job in communications and says she has to be on the ball: "I take valium when I feel like everything is getting on top of me or I need to get through a big presentation at work. Or if I need to sleep better ... I probably take a tablet a day for a few days once every two weeks maximum. It depends on the situation but there is no way I would be able to get these tablets on the NHS. Doctors would say my anxiety was not serious enough to warrant it."

She gets valium through a friend who buys it for her online, and says she hasn't built a tolerance because she uses the benzodiazepine infrequently throughout the year: "I would almost compare it to taking ... strong painkillers for a bad headache. It just takes away the physical experience of anxiety for a while. It calms me down so I can sleep better through the night."

The government has ordered an investigation into prescription drug misuse in the UK. Steve Brine, the public health minister, acted after it emerged that one in 11 (8.9%) patients treated by the NHS in England last year were given drugs that can induce dependency.

Abbasi welcomes government attention on the subject but says services must quickly adapt to the growing problem: "We have traditional services for addiction but the face of addiction is changing rapidly and we cannot just rely on traditional services. We need to invest to meet the challenges of 21st century."

Bowden-Jones hopes his clinic can open up a conversation about the scale of the problem and the type of issues people are facing. "If there is one common link between [all our patients] it is that they are underestimating the risks of medicines bought online and making an assumption that they are safer," he says.
Topics

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Rise in people seeking help over prescription pills bought online

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A pioneering clinic set up to help teenagers addicted to Xanax and other prescription drugs is being sought out by adults who use pills purchased illicitly on the internet. At the beginning of the year Dr Owen Bowden-Jones opened the Addiction to Online Medicine (Atom) service in London, a free, easy-to-access NHS clinic run by Central North West London NHS Foundation Trust that offers one-to-one meetings and group mindfulness sessions.