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Venlafaxine is an SNRI (serotonin-norepinephrine reuptake inhibitor) that works by preventing the reuptake of serotonin (5-HT), and norepinephrine (NE) levels in the synaptic cleft of the brain, the medication increases the availability of these neurotransmitters.

The medication achieves the action by binding to serotonin and norepinephrine transporters at the receptor level, inhibiting, preventing reabsorption or reuptake of the neurotransmitters into the presynaptic neuron (Cui et al., 2024).

Venlafaxine also increases dopamine neurotransmission in the frontal cortex through inactivation by norepinephrine reuptake in this part of the brain.

It results in better mood control, decreased anxiety levels, and improvement in emotional well-being.

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Venlafaxine is approved by the FDA for major depressive disorder (MDD), generalized anxiety disorder (GAD), social anxiety disorder, and panic disorder.

Common off-label uses include post-traumatic stress disorder (Fanelli et al., 2021).

The medication has been prescribed to treat Marcos's depression and anxiety symptoms, which are likely aggravated by his work-related stress.

Therapeutic benefits of the dual-action antidepressant include improving mood, interest, sleep, and motivation and reducing anxiety.

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Depression is often associated with low levels of serotonin and norepinephrine.

The antidepressant effect of venlafaxine is achieved through its augmenting impact on the serotonergic neurotransmission associated with mood and sleep functions.

Increasing noradrenergic neurotransmission boosts norepinephrine levels, improving energy, focus, and motivation (Stahl, 2021).

The dual neurotransmitter action makes venlafaxine effective for depressive and anxiety symptoms.

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Side effects of Venlafaxine include:

Nausea or dry mouth

Feeling tired or dizzy

Blurry vision or vision changes

Headache

Increased heart rate

Trouble sleeping

Increased sweating

*These symptoms are mild and should go away within a few days to weeks.

More severe side effects include:

Cardiac - high blood pressure

Mental Health - mania, trouble sleeping, worsen anxiety and depression

Increased suicide risk

Serotonin syndrome

Increased risk of bleeding when taken with over-the-counter Anti-inflammatory drugs

Discontinuation Syndrome

Lung Disease - interstitial lung disease

Additional risks and side effects are associated with Smoking and Alcohol use and Drug-Drug Interactions (See Table 1 for interaction summary).

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Combined Interaction Overview

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Both smoking and consuming alcohol can worsen the side effects of Venlafaxine.

Alcohol can increase sedation and worsen CNS side effects like drowsiness, confusion, or dizziness. It can also interfere with SNRIs, such as Venlafaxine effectiveness, and liver metabolism, increasing toxicity risk.

Cigarette smoke contains compounds that activate liver enzymes, that break down a drug. Smoking can alter the metabolism of Venlafaxine by speeding up its break down, making it less effective at the prescribed dose. Additionally, Venlafaxine can cause inflammation of the lungs, called interstitial lung disease. Smoking can increase the risk of lung disease and reduce respiratory function and rate. Overall, smoking increases the strain on the heart, nervous system, and respiratory function, which is especially concerning given a cardiac history and use of other CNS-active drugs.

Together, both smoking and alcohol should be avoided to reduce the worsening of side effects and to ensure the benefits of Venlafaxine, including zopiclone and bisoprolol. Avoiding smoking and alcohol will also ensure functional safety, cardiac balance, reduced risk of lung infection and respiratory strain.

See Table 1 for an outline of drug-drug interaction and added negative effects of both alcohol consumption and smoking.

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Both zopiclone and venlafaxine combine to have a central nervous system (CNS) depressant effect. Combined use increases the risk of sedation, confusion, impaired judgement, and falls; this risk is worsened with alcohol consumption.

Venlafaxine can cause drowsiness, dizziness, and impaired coordination, especially when starting the medication.

Zopiclone is a sedative-hypnotic, used to help with sleep, and it enhances GABA activity, further suppressing CNS function.

Close monitoring is required for sleep quality (excessive daytime sleepiness) and energy levels.

Do not drive, use heavy machinery, or do anything that requires you to be alert until you know you can function normally.

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Venlafaxine can increase blood pressure and heart rate, and at higher doses, it may prolong the QT interval, increasing the risk of arrhythmias. For this reason, a history of cardiac dysrhythmia requires essential heart monitoring for blood pressure and heart rate. More specifically:

Venlafaxine may increase blood pressure and heart rate, especially at higher doses.

Bisoprolol, a beta-blocker, works to lower heart rate and blood pressure.

This combination requires monitoring of blood pressure, heart rate, and any signs of palpitations or chest pain due to medication dosage and usage, alcohol use, and male gender.

Be consistent to the daily dose and monitor any abrupt changes to the heart.

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Venlafaxine can increase the risk of suicidal thoughts or feelings especially in the first few weeks of treatment or when the dose is changed. This risk may be higher in people under 18; however, it can affect adults too. The risk also increases in individuals with a history of depression, anxiety, or PTSD.

Close monitoring is needed for mood changes, abrupt mental health symptoms, and suicidal thoughts and ideation.

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Gastrointestinal side effects and associated risks: 

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Gastrointestinal side effects and associated risks: 

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Common GI issues:

Nausea

Dry mouth

Loss of appetite

Constipation

Vomiting

These symptoms can discourage adherence if not managed.

Venlafaxine can slow bowel motility, especially when combined with other CNS depressants like zopiclone or a low-fiber diet.

Substances like, alcohol can dehydrate the body, disrupt gut flora, and disrupt electrolytes balance (low sodium levels). Combined with Venlafaxine-induced sweating, dry mouth, or nausea, this can raise the risk of dehydration, blood pressure changes, kidney stain, and drug clearance.

Ensure adequate fluid intake.

Take Venlafaxine with food.

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Serotonin Syndrome results from too much serotonin build up in the body. This can occur with Venlafaxine, either on its own or when combined with other medications or substances that affect serotonin (like certain antidepressants, cold medications, herbs, or recreational drugs).

Although rare, this condition can be serious and life-threatening.

Get immediate help if you experience the following symptoms:

Sweating, fever, or flushing

Confusion

Feeling agitated or restless

Seeing or hearing unusual things

Dizziness

Fast or racing heartbeat

Nausea, vomiting, or diarrhea

Muscle twitching, stiffness, or tremor

Seizures

To reduce risk of increase serotonin levels, avoid the following herbs:

Ginkgo

St John's Wort

Continue to inform your health care provider of any supplements.

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Stopping Venlafaxine can cause withdrawal symptoms such as:

dizziness

nausea

irritability

shaking

confusion

tiredness

restlessness

nausea

vomiting

diarrhea

Given a history of stress, anxiety, and PTSD, sudden withdrawal could worsen one's mental condition and symptoms.

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In summary, get immediate help if you notice:

Chest pain or have a fast heart rate

Experience severe headaches or confusion

Have worsening mood or thoughts of self-harm (thoughts and ideation of suicide)

Seizures

Do not drive, use heavy machinery, or do anything that requires you to be alert.

Do not take over-the-counter anti-inflammatory drugs, such as aspirin, Advil, Motrin, ibuprofen. Taking these drugs with Venlafaxine raises the risk of bleeding. Tell your doctor right away if you notice any abnormal bleeding or bruising.

Do Not Stop the Medication Suddenly:

Even when you feel better.

ALWAYS talk to your doctor before stopping Venlafaxine. Missing doses or stopping can cause discontinuation syndrome and worsen anxiety or depression. Take it at the same time every day for the best results.

Report Any Heart-Related or Mood Changes Immediately:

Tell your doctor if you feel chest pain, fast heart rate, or light-headedness. With a heart history, early reporting is essential for safety.

Avoid Alcohol and Limit Sedating Medications:

Combining Venlafaxine, alcohol, and zopiclone may intensify side effects like severe drowsiness, increased fall risk, and worsened depression and confusion. Avoid alcohol to reduce the risk of CNS depression or falls.

Stay Hydrated and Eat Well:

Take Venlafaxine with food.

Drink plenty of water daily—aim for at least 1 to 2 liters. Watch for signs of dehydration, such as dry mouth, dizziness, or dark urine.

Eat Fiber-Rich Foods, such as whole grains, fruits, vegetables, and legumes, to help reduce constipation. A gentle fiber supplement may also be needed.

Watch for appetite changes and track any significant shifts in appetite or weight. Let your healthcare provider know if you eat much less or more than usual.

Tips for Success

Set a daily reminder to take your dose, drink water, eat well, and avoid alcohol and smoking.

Speak to (or get in touch) a health care provider and mental health or addiction counsellor, including Substance Use Support Services, to reduce alcohol consumption and smoking. Access online support forums and Mental Health Counselling Programs or speak to your healthcare provider for mental health support.

Keep a mood journal to track changes and share with your healthcare provider.

Stay in touch with your support system—you are not alone.

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Fanelli, D., Weller, G., & Liu, H. (2021). New serotonin-norepinephrine reuptake inhibitors and their anesthetic and analgesic considerations. Neurology International, 13(4), 497–509. https://doi.org/10.3390/neurolint13040049

Mayo Clinic. (2024). Venlafaxine (Oral Route) Description and Brand Names - Mayo Clinic. Www.mayoclinic.org. https://www.mayoclinic.org/drugs-supplements/venlafaxine-oral-route/description/drg-20067379

Puckey, M. (2018). Bisoprolol. Drugs.com. https://www.drugs.com/bisoprolol.html

Stahl, S. M. (2021). Stahl's essential psychopharmacology: Prescriber's Guide (7th ed.). Cambridge University Press. https://doi.org/10.1017/9781108921275

The American Association of Psychiatric Pharmacists, & National Alliance on Mental Illness. (2016, January). Venlafaxine (Effexor) | NAMI. Www.nami.org; National Alliance on Mental Illness. https://www.nami.org/about-mental-illness/treatments/mental-health-medications/types-of-medication/venlafaxine-effexor/

Thornton, P. (2023, April 4). Zopiclone: Uses, Dosage, Side Effects, Warnings. Drugs.com. https://www.drugs.com/zopiclone.html