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Jennifer B. Levin

Anna Krivenko

Molly Howland

Rebecca Schlachet

Martha Sajatovic

Abstract

Poor medication adherence is a pervasive problem that causes disability and suffering as well as extensive financial costs among individuals with bipolar disorder (BD). Barriers to adherence are numerous and cross multiple levels, including factors related to bipolar pathology and those unique to an individual's circumstances. External factors, including treatment setting, healthcare system, and broader health policies, can also affect medication adherence in people with BD. Fortunately, advances in research have suggested avenues for improving adherence. A comprehensive review of adherence-enhancement interventions for the years 2005-2015 is included. Specific bipolar adherence-enhancement approaches that target knowledge gaps, cognitive patterns, specific barriers, and motivation may be helpful, as may approaches that capitalize on technology or novel drug-delivery systems. However, much work remains to optimally facilitate long-term medication adherence in people with BD. For adherence-enhancement approaches to be widely adapted, they need to be easily accessible, affordable, and practical.

Keywords

Bipolar Disorder Medication Adherence Prospective Memory Poor Adherence Brief Psychiatric Rate Scale

These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

1. Velligan DI, Weiden PJ, Sajatovic M, Scott J, Carpenter D, Ross R, et al. The expert consensus guideline series: adherence problems in patients with serious and persistent mental illness. J Clin Psychiatry. 2009;70(Suppl 4):1-46 (quiz 7-8).

2. Levin JB, Krivenko A, Bukach A, Tatsuoka C, Cassidy KA, Sajatovic M. A reexamination of non-psychiatric medication adherence in individuals with bipolar disorder and medical comorbidities. J Nerv Ment Dis (Epub 10 June 2016).

© Springer International Publishing Switzerland 2016

Authors and Affiliations

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Medication Adherence in Patients with Bipolar Disorder: A Comprehensive Review

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Jennifer B. Levin Anna Krivenko Molly Howland Rebecca Schlachet Martha Sajatovic Poor medication adherence is a pervasive problem that causes disability and suffering as well as extensive financial costs among individuals with bipolar disorder (BD). Barriers to adherence are numerous and cross multiple levels, including factors related to bipolar pathology and those unique to an individual's circumstances.

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This shows how a doctor could misdiagnose a patient with bipolar disorder with something different, questions asked.

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Bipolar Disorder: Misdiagnosed with Depression

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This video shows the symptoms, different types of bipolar disorder, the high points of a person's life with the disorder, and low points. It also shows examples of what may cause their mood to change so oddly.  It shows the progression of their mood changes in an average persons life, a person with depression, and the 2 types of bipolar disorder. Shows the unknown causes but what could contribute to the disorder like genetics and more. Tells how some treatments have side effects

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Bipolar disorder (depression & mania) - causes, symptoms, treatment & pathology

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This image provides things that people with the disorder may be experiencing and people and doctors are not aware of it.

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This shows how a doctor is not paying attention and is too busy on their phone to care for their patient. That situation can lead to many different problems and possibly misdiagnosis. The patient may not be getting treated seriously because that doctor may think it is a different disease.

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This can show people that dealing with bipolar disorder is not hard but but not easy at the same time.

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This describe that bipolar disorder and depression kind of tie in together

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This image describes how much a mood can change with the disorder.... one minute the person could be feeling really happy and energized. Then the next minute they can feel the life getting sucked out of them and depressed and lonely.

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This is where to find how to help and handle people with bipolar disorder

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What You Can Do to Support a Friend or Family Member
Having a loved one with bipolar disorder can put a strain on your relationship and disrupt all aspects of family life. But your patience, love and support can make a real difference in their treatment and recovery. You can help by learning all you can about the illness, offering hope and encouragement, keeping track of their symptoms, and being a partner in your loved one's treatment. But caring for a person with bipolar disorder will take a toll if you neglect your own needs, so it's important to find a balance between supporting your loved one and taking care of yourself.
How can you help someone with bipolar disorder?

Dealing with the ups and downs of bipolar disorder can be difficult-and not just for the person with the illness. The moods and behaviors of a person with bipolar disorder affect everyone around-especially family members and close friends. During a manic episode, you may have to cope with reckless antics, outrageous demands, explosive outbursts, and irresponsible decisions. And once the whirlwind of mania has passed, it often falls on you to deal with the consequences. During episodes of depression, you may have to pick up the slack for a loved one who doesn't have the energy to meet responsibilities at home or work.

The good news is that most people with bipolar disorder can stabilize their moods with proper treatment, medication, and support-and you can play a significant role in your loved one's recovery. Often, just having someone to talk to can make all the difference to their outlook and motivation.

Other ways to help someone with bipolar disorder

You can also support your loved one by:

Learning about bipolar disorder. Learn everything you can about the symptoms and treatment options. The more you know about bipolar disorder, the better equipped you'll be to help your loved one and keep things in perspective.

Encouraging the person to get help. The sooner bipolar disorder is treated, the better the prognosis, so urge your loved one to seek professional help right away. Don't wait to see if they will get better without treatment.

Being understanding. Let your friend or family member know that you're there if they need a sympathetic ear, encouragement, or assistance with treatment. People with bipolar disorder are often reluctant to seek help because they don't want to feel like a burden to others, so remind the person that you care and that you'll do whatever you can to help.

Showing patience. Getting better takes time, even when a person is committed to treatment. Don't expect a quick recovery or a permanent cure. Be patient with the pace of recovery and prepare for setbacks and challenges. Managing bipolar disorder is a lifelong process.

The importance of support in bipolar disorder recovery

People with bipolar disorder do better when they have support from family members and friends. They tend to recover more quickly, experience fewer manic and depressive episodes, and have milder symptoms.

Bipolar disorder and the family

Living with a person who has bipolar disorder can cause stress and tension in the home. On top of the challenge of dealing with your loved one's symptoms and their consequences, family members often struggle with feelings of guilt, fear, anger, and helplessness. Ultimately, the strain can cause serious relationship problems. But there are better ways to cope.

The first step to successfully dealing with bipolar disorder is for families to learn to accept the illness and its difficulties. When you're feeling frustrated or guilty, remember that bipolar disorder isn't anyone's fault. Accepting bipolar disorder involves acknowledging that things may never again be "normal." Treatment can make a huge difference for your loved one, but it may not take care of all symptoms or impairments. To avoid disappointment and resentments, it's important to have realistic expectations. Expecting too much of your family member is a recipe for failure. On the other hand, expecting too little can also hinder recovery, so try to find a balance between encouraging independence and providing support.

Tips for coping with bipolar disorder in the family

Accept your loved one's limits - Your loved one with bipolar disorder can't control their moods. They can't just snap out of a depression or get a hold of themselves during a manic episode. Neither depression nor mania can be overcome through self-control, willpower, or reasoning. So telling your loved one to "Stop acting crazy" or to "Look on the bright side" won't help.

Accept your own limits - You can't rescue your loved one with bipolar disorder, nor can you force them to take responsibility for getting better. You can offer support, but ultimately, recovery is in the hands of the person with the illness.

Reduce stress - Stress makes bipolar disorder worse, so try to find ways to reduce stress in your loved one's life. Ask how you can help and volunteer to take over some of the person's responsibilities if needed. Establishing and enforcing a daily routine-with regular times for getting up, having meals, and going to bed-can also reduce family stress.

Communicate openly - Open and honest communication is essential to coping with bipolar disorder in the family. Share your concerns in a loving way, ask your loved one how they're feeling, and make an effort to truly listen-even if you disagree with your loved one or don't relate to what's being said.

Supporting a person with bipolar disorder

What you can say that helps:

You are not alone in this. I'm here for you.

I understand you have a real illness and that's what causes these thoughts and feelings.

You may not believe it now, but the way you're feeling will change.

I may not be able to understand exactly how you feel, but I care about you and want to help.

You are important to me. Your life is important to me.

Adapted from: The Depression and Bipolar Support Alliance

Convincing a person with bipolar disorder to see a doctor

Aside from offering emotional support, the best way to help your loved one with bipolar disorder is by encouraging and supporting treatment. Often, that can be more of a challenge than it sounds. Since people with bipolar disorder tend to lack insight into their condition, it's not always easy to get them to a doctor. When your loved one is manic, they feel great and don't realize there's a problem. When your loved one is depressed, they may recognize something's wrong, but often lack the energy to seek help.

If your loved one won't acknowledge the possibility of bipolar disorder, don't argue about it. The idea may be frightening to them, so be sensitive. Suggest a routine medical checkup instead, or a doctor's visit for a specific symptom, such as insomnia, irritability, or fatigue (you can privately call ahead to tell the doctor of your concerns about bipolar disorder).

Things you can say that might help:

Bipolar disorder is a real illness, like diabetes. It requires medical treatment.

You're not to blame for bipolar disorder. You didn't cause it. It's not your fault.

You can feel better. There are many treatments that can help.

When bipolar disorder isn't treated, it usually gets worse.

Supporting a loved one during bipolar disorder treatment

Once your friend or family member agrees to see a doctor, you can help by being a partner in treatment. Your support can make a big difference in their treatment success, so offer to be involved in any way your loved one wants or needs.

Things you can do to support a loved one's bipolar disorder treatment:

Find qualified doctors and therapists

Set up appointments and go along

Offer your insights to the doctor

Monitor your loved one's moods

Learn about their medications

Track treatment progress

Watch for signs of relapse

Alert the doctor to problems

Encourage your loved one to take bipolar disorder medication

Medication is the cornerstone of treatment for bipolar disorder, and most people need it to regulate their moods and avoid relapse. Despite the need for medication, many people with bipolar disorder stop taking it. Some quit because they're feeling better, others because of side effects, and yet others because they enjoy the symptoms of mania. People who don't think they have a problem are particularly likely to stop taking medication.

You can help your loved one with bipolar disorder stay on track by emphasizing the importance of medication and making sure they take all prescriptions as directed. Also encourage your loved one to speak to their doctor about any bothersome side effects. Side effects can be very unpleasant if the dose of the medication is too low or too high, but a change in medication or dosage may solve the problem. Remind your loved one that abruptly stopping medication is dangerous.

Watch for warning signs of bipolar disorder relapse

Even if your loved one with bipolar disorder is committed to treatment, there may be times when their symptoms get worse. Take action right away if you notice any troubling symptoms or mood changes. Point out the emerging bipolar symptoms to your loved one and alert the doctor. With swift intervention, you may be able to prevent an episode of mania or depression from developing fully.

Mania warning signs and symptoms:

Speaking rapidly

Increase in activity level

Irritability or aggression

Depression warning signs and symptoms:

Fatigue and lethargy

Sleeping more

Trouble concentrating

Loss of interest in activities

Withdrawing from others

Change in appetite

Coping with mania and depression: Tips for family and friends

If it's not possible to prevent your loved one relapsing, there are things you can do to cope during a manic or depressive episode.

Don't take bipolar symptoms personally. When in the midst of a bipolar episode, people often say or do things that are hurtful or embarrassing. When manic, your loved one may be reckless, cruel, critical, and aggressive. When depressed, they may be rejecting, irritable, hostile, and moody. It's hard not to take such behaviors personally, but try to remember that they're symptoms of your loved one's mental illness, not the result of selfishness or immaturity.

Be prepared for destructive behaviors. When manic or depressed, people with bipolar disorder may behave in destructive or irresponsible ways. Planning ahead for how to handle such behavior can help. When your loved one is well, negotiate a treatment contract that gives you advance approval for protecting them when symptoms flare up. Agree on specific steps you'll take, such as removing credit cards or car keys, going together to the doctor, or taking charge of household finances.

Know what to do in a crisis. It's important to plan ahead for times of crisis so you can act quickly and effectively when it occurs. Having a crisis plan can help. Make sure to include a list of emergency contact information for doctors, therapists, and other friends or family members who will help. Also include the address and phone number of the hospital where you'll take your loved one if necessary.

Call 911 (or your country's emergency services number) in an emergency. If your loved one with bipolar disorder is suicidal or violent, don't try to handle the situation alone. If you're worried that your loved one may hurt you, get to safety and then call the police. If your loved one is suicidal, don't leave them alone. Call for an ambulance and stay with your loved one until it arrives.

Supporting someone who is manic

Spend time with the person. People who are manic often feel isolated from other people. Spending even short periods of time with them helps. If your loved one has a lot of energy, walk together. This allows your loved one to keep on the move but still share your company.

Answer questions honestly. However, do not argue or debate with your loved one during a manic episode. Avoid intense conversation.

Don't take any comments personally. During periods of high energy, your loved one may say and do things that they wouldn't usually say or do, including focusing on negative aspects of others. If needed, stay away from the person and avoid arguments.

Prepare easy-to-eat foods and drinks. It's difficult for your loved one to sit down to a meal during periods of high energy, so try offering them peanut butter and jelly sandwiches, apples, cheese crackers, and juices, for example.

Avoid subjecting your loved one to a lot of activity and stimulation. It's better to keep surroundings as quiet as possible.

Allow your loved one to sleep whenever possible. During periods of high energy, sleeping is difficult but short naps taken throughout the day can help. Sometimes your loved one may feel rested after only 2 to 3 hours of sleep.

Source: The Palo Alto Medical Foundation

Taking care of yourself when a loved one has bipolar disorder

It's easy to neglect your own needs when you're supporting someone with a mental illness. But if you don't take care of yourself, you run the risk of burnout -and that won't help you or your loved one with bipolar disorder. When you take care of yourself both emotionally and physically, you'll be able to better cope with the stress of caring for someone with bipolar disorder and have the energy you need to support your loved one's recovery.

Focus on your own life. Supporting your loved one may involve some life adjustments, but make sure you don't lose sight of your own goals and priorities. Don't give up friendships, plans, or activities that bring you joy.

Seek support. Dealing with a loved one's mental illness can be painful and isolating. Make sure you're getting the emotional support you need to cope. Talk to someone you trust about what you're going through. It can also help to get your own therapy or join a support group.

Set boundaries. Be realistic about the amount of care you're able to provide without feeling overwhelmed and resentful. Set limits on what you're willing and able to do, and stick to them. Letting bipolar disorder take over your life isn't healthy for you or your loved one.

Manage stress. Stress takes a toll on the body and mind, so find ways to keep it in check. Make sure you're eating right and getting enough sleep and exercise. You can also keep stress under control by practicing relaxation techniques such as meditation.

Ask for help. If your friend or family member needs more assistance than you can give, ask for help from others. Turn to other relatives or close friends, or contact a bipolar disorder support organization.

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Helping Someone with Bipolar Disorder What You Can Do to Support a Friend or Family Member Having a loved one with bipolar disorder can put a strain on your relationship and disrupt all aspects of family life. But your patience, love and support

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En Espanol:

Clinical Trials:

What is Bipolar Disorder?

Bipolar disorder is a mental health disorder characterized by extreme highs and lows in mood and energy. While everyone experiences ups and downs, the severe shifts that happen in bipolar disorder can have a serious impact on a person's life. More than 3.3 million American adults (1.7%) suffer from bipolar disorder in a given year. [1]

Contrary to how it is sometimes used in conversation, a diagnosis of bipolar disorder does not mean a person is highly emotional but rather refers to someone who experiences extended periods of mood and energy that are excessively high and or/irritable to sad and hopeless, with periods of normal mood in between.

It typically begins in adolescence or early adulthood and continues throughout life. It is often not recognized as an illness and people who have it may suffer needlessly for years.

Bipolar disorder can be extremely distressing and disruptive for those who have this disease, their spouses, family members, friends, and employers. Although there is no known cure, bipolar disorder is treatable, and recovery is possible. Individuals with bipolar disorder can and do have successful relationships and meaningful jobs. The combination of medication, therapy, healthy lifestyle, and support helps the vast majority of people return to productive, fulfilling lives.
"Bipolar disorder is treatable, and recovery is possible."
What Causes Bipolar Disorder?

Although a specific genetic link to bipolar disorder has not been pin pointed, research shows that bipolar disorder tends to run in families.

People may inherit a tendency to develop the illness, which can then be triggered by environmental factors such as distressing life events.

Brain development, structure and chemicals called neurotransmitters, which act as messengers between nerve cells, are also thought to play a role in the development of bipolar disorder.[2]

What are the Symptoms of Bipolar Disorder?

Bipolar disorder is often difficult to recognize and diagnose. It causes a person to have a high level of energy, unrealistically expansive thoughts or ideas, and impulsive or reckless behavior. These symptoms may feel good to a person, which may lead to denial that there is a problem.

Another reason bipolar disorder is difficult to diagnose is that its symptoms may appear to be part of another illness or attributed to other problems such as substance abuse, poor school performance, or trouble in the workplace.

Symptoms of bipolar disorder fall into two categories: mania and depression.

Mania
The symptoms of mania, which can last up to three months if untreated include:

Depression
An episode of depression can come before or after a manic, hypomanic, or normal period of mood. Symptoms include:

Excessive energy, activity, restlessness, racing thoughts and rapid talking (also called "pressured speech").

Extreme "high" or euphoric feelings-a person may feel "on top of the world" and even bad news or tragic events, can't change this.

Being easily irritated or distracted.

Decreased need for sleep-an individual may go days with little or no sleep without feeling tired.

Unrealistic beliefs in one's ability and powers-a person may experience feelings of exaggerated self-confidence or unwarranted optimism. This can lead to over ambitious work plans and the belief that nothing can stop him or her from accomplishing any task.

Uncharacteristically poor judgment-a person may make poor decisions which may lead to unrealistic involvement in activities, meetings and deadlines, reckless driving, spending sprees, and/or foolish business ventures.

Unusual sex drive or abuse of drugs (particularly cocaine, alcohol or sleeping medications).

Provocative, intrusive, or aggressive behavior-a person may become enraged or paranoid if his or her grand ideas are stopped, or extreme social plans are refused.

Signs of psychosis (learn more about psychosis here)

Persistent sad, anxious or empty mood.

Changes in sleep such as, getting too much or too little, or waking in the middle-of-the-night or unusually early in the morning

Reduced appetite and weight loss, or increased appetite accompanied by weight gain.

Irritability or restlessness

Difficulty concentrating, remembering or making decisions. These may often impact a person's ability to fulfill work, school or other life obligations.

Fatigue or loss of energy.

Persistent physical symptoms that don't respond to treatment, such as chronic pain or digestive issues (like upset stomach or diarrhea).

Feeling guilty, hopeless or worthless.

Thoughts of death or suicide, including suicide attempts.

If you or someone you know is in crisis, call 1-800-273-TALK (8255), visit your local emergency room or call 911.

What is the Difference Between Mania and Hypomania? [3]

Mania is when a person has:

at least 3 of the symptoms listed above for mania that last for at least one week, and

serious impairment in work or school functioning or in usual social activities or relationships with others, or

symptoms severe enough to require hospitalization to prevent a person from hurting their self or others, or

psychotic features.

Hypomania is when a person has:

at least 3 of the symptoms listed above for mania that last at least 4 days, and

a change in their ability to function that is not typical of that person when they aren't showing symptoms,

changes in mood and ability to function that are noticeable by others,

symptoms that are not severe enough to cause serious impairment in social or work/school functioning, or to necessitate hospitalization, and

no psychotic features.

In summary, hypomania is a less severe and more brief form of mania.

Diagnoses and Other Terms Associated with Bipolar Disorder

Bipolar I Disorder: Bipolar I Disorder is given when a person has at least one episode of mania. While a person with Bipolar I might only experience manic episodes, it often includes episodes of depression and hypomania. Hypomania includes the same symptoms of mania but can be shorter in duration and less severe. They do not include symptoms of psychosis or require hospitalization.

Bipolar II Disorder: Bipolar II Disorder includes at least one major depressive episode and at least one hypomanic episode. Individuals with bipolar II also tend to have longer periods of depression than people with bipolar I.

Cyclothymic Disorder: Sometimes called cyclothymia, this disorder includes episodes of hypomania and depressive symptoms that occur on a fairly regular basis. While changes in mood are not as extreme as those associated with Bipolar I and Bipolar II Disorders, it can still cause serious problems in a person's life and may later progress to symptoms of mania, hypomania, and depression.

Rapid Cycling: Rapid cycling is a term used when an individual experiences four or more episodes of hypomania, mania, or depression within a 12-month time period.

Mixed Episode: A mixed episode occurs when a person is experiencing symptoms of both depression and mania or hypomania at the same time. Individuals with bipolar disorders are at an increased risk for suicide, and this risk is thought to be especially high during mixed episodes.

What are the Treatments for Bipolar Disorders?

A combination of medication, therapy, lifestyle changes, and support from family, friends and peers help individuals with bipolar disorder to stabilize their mood and to live the lives they want. Finding the treatment plan that works best for a person is critical for recovery.

Medication: Common medications used in treating bipolar disorder are lithium, anticonvulsants, and mood stabilizers. Other medications used include antipsychotics, benzodiazepines, and beta-blockers. As with all medications, medications used to treat bipolar disorder can have mild to serious side effects so it is important to talk with your doctors about how you are feeling.
Learn more about medications.

Therapy: Both group and individual therapy can be helpful in bipolar disorder. Common types of therapy used are Cognitive Behavioral Therapy (CBT), Dialectical Behavior Therapy (DBT), and family-focused therapies.
Learn more about therapy.

Lifestyle changes: Healthy lifestyles changes can be an important part of overall recovery. This includes: sticking to a regular sleep schedule; reducing consumption of alcohol, caffeine, and similar substances; and exercising regularly. Some may use meditation, mind-body practices, and spirituality as resources as well.
Learn more about living a healthy lifestyle.

Support: Support and self-help groups are invaluable resources for learning coping skills, feeling accepted, and avoiding social isolation. In addition to in-person support groups and drop-in centers, there are many online communities where individuals can also find support. Additional support can be provided through employment, housing, and psychosocial rehabilitation programs.
Learn more about recovery and support.

Friends and family can also join support groups to better understand how to offer encouragement and support their loved ones.
Learn more about what you can do to support someone close to you.

From our Partners:

Read stories from people living with Bipolar Disorder on The Mighty.

Other Resources:

National Suicide Prevention Lifeline
1-800-273-TALK (8255)
http://www.suicidepreventionlifeline.org
Ryan Licht Sang Bipolar Foundation
www.ryanlichtsangbipolarfoundation.org
Juvenile Bipolar Research Foundation
914-468-1297
www.jbrf.org
Sources
National Foundation for Depressive Illness
1-800-239-1265
www.depression.org

Depression and Bipolar Support Alliance (DBSA)
1-800-826-3632
www.dbsalliance.org

[1] Kessler, R. C., Petukhova, M., Sampson, N. A., Zaslavsky, A. M., & Wittchen, H.U. (2012). Twelve-month and lifetime prevalence and lifetime morbid risk of anxiety and mood disorders in the United States. International Journal of Methods in Psychiatric Research, 21(3), 169-184. http://doi.org/10.1002/mpr.1359

[2] http://www.nimh.nih.gov/health/topics/bipolar-disorder/index.shtml

[3] http://www.bipolarworld.net/Bipolar%20Disorder/Diagnosis/dsmv.htm (Adapted from DSM V)

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Bipolar Disorder: What You Need to Know Bipolar Disorder and African Americans Bipolar Disorder in Children Infographic: Life with Bipolar Mood Disorders "What is Bipolar Disorder?" A Guide to Hope and Recovery for African Americans Staying Well When You Have a Mental Illness PDF

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Even though doctors may not give patients enough care for bipolar disorder it could be cause by believing it is another illness they did not diagnose the patient with the disorder and got it confuse with a different  mental disorder

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Across the web you'll find increasing attention being given to the identification of bipolar mood symptoms and patterns. Solid educational information is important for those who are concerned that they may have bipolar disorder.

Even the best diagnosticians find that arriving at the diagnosis is a difficult endeavor. We're not yet at a point where we have easily obtainable biologically based tests that result in a definitive diagnosis. Similarly, we're far from being able to predict the disorder based upon genetic testing.

We're still faced with the reality of a mental health clinician sitting with a patient and relying upon clinical interview to come up with a clear picture to identify or rule out the presence of bipolar disorder. Sometimes even with extensive inquiry and careful consideration of the data obtained, clinicians still miss the bipolar diagnosis. It happens even with the most seasoned mental health professionals. I'd be dishonest if I said it's never happened to me. Longitudinal studies have shown us that the average time from initial onset of symptoms to an accurate bipolar diagnosis is ten to twelve years!

The reality is bipolar disorder is usually difficult to diagnose based on just an initial diagnostic interview with an individual. The diagnosis has to do with very broad patterns that exist over time. When meeting with a patient for the first time, all I'm really able to see is his or her behavior and mood state in the present, which excludes about 90% of the additional information that's required to ascertain the diagnosis. The acquisition of that 90% relies upon the clinician's ability to ask the right questions and the patient's ability to provide comprehensive and accurate answers. Even then, careful attention is needed before the bipolar picture can coalesce with validity.

Bipolar symptoms present in many different forms and patterns. Each individual brings his or her own unique stamp to the clinical picture. We see variance in symptom acuity, symptom duration and symptom manifestations. While symptoms such as elevated energy, decreased need for sleep and accelerated thinking are common to most bipolar elevated mood states, one individual's hypomania/mania may be evident through euphoria and grandiosity while the mood elevation of another may entail irritability and outbursts of anger. Still a third may manifest his or her symptoms primarily through hyper- sexuality and impulsive spending. Further compounding the diagnostic challenge is the fact that the disorder often coexists with other psychiatric diagnoses such that we get a layering or commingling of symptoms from different diagnoses. The mental health professional is then faced with sorting out what symptoms belong to what diagnoses and how the different sets of symptoms may possibly potentiate each other.

I find that the three diagnoses which are most often confused with bipolar disorder or potentially coexist and therefore interfere with the diagnosis are: 1) unipolar depression, 2) attention deficit-hyperactivity disorder and 3) the group of personality disorders. In this latter realm, the individuals we most often see coming in for treatment are those diagnosed with borderline and/or narcissistic personality characteristics. There are certainly other personality disorders that can come into this mix but we find that individuals with borderline/narcissistic features tend more often to seek psychotherapy. Additionally, some of the symptoms within these two personality types can easily be mistaken as belonging to the bipolar continuum (see previous Bipolar You blog: The Relationship between Narcissism and Bipolar Disorder).

So the question for the remaining discussion is: What are some of the guidelines that help us distinguish between straight depression, attention deficit-hyperactivity disorder, personality disorders and bipolar disorders?

Let's start with the most common: unipolar depression. More often than not, bipolar disorder begins with episodes of depression. In fact, we may see adolescents go through a few years of intermittent depressive episodes during high school before they manifest the kind of mood elevation which tips the scale towards a bipolar diagnosis.

There may also be some symptoms within the overall depressive profile that can tip us off to the underlying bipolar disorder. I'm referring to things such as periods of feeling energized while also being irritable, angry and very pessimistic about life. With these people, their depressive symptoms have not flattened them out. It's more like the intense negative feelings are accompanied by a degree of agitation. These individuals may also find that their agitation interferes with their ability to get a good night's sleep. But, these small clues, in and of themselves do not rise to the level of a bipolar diagnosis. They are just features that should garner our attention and possibly alert us that there is more present than easily meets the eye.

The next essential element is to obtain information about the broader family history of psychiatric diagnoses, and particularly bipolar disorder. If someone comes in presenting primarily with depressive symptoms but he/she has a parent, a sibling, a grandparent or even an aunt or uncle with bipolar disorder, then one has to approach the initial unipolar presentation of depression as if it may part of a broader bipolar disorder. I think of this as "bipolar brewing" where someone has the genetic predisposition but they've not yet manifested the full range of bipolar symptoms. In these instances the individual wouldn't be diagnosed with the disorder simply because of his/her genetics, but the treatment approach would likely be different than if there was no mood disorder evidence in the family background.

The other diagnostic piece that needs to be asked of almost any patient who comes into treatment is: "What is your mood and behavior like when you're feeling really good?" To take that even further, the individual should be asked, "Does your mood ever become more intense or more elevated than what you normally experience when you're in a generally good mood." You'd be surprised how often that simple line of questioning is omitted. After all, when someone comes in seeking help and everything he or she is talking about looks like, sounds like and feels like depression, it's easy to conclude that the individual should be treated for depression and possibly even be prescribed an antidepressant.

Here's the rub: Antidepressants, when prescribed to someone who is genetically predisposed towards bipolarity, may indeed precipitate hypomanic or manic symptoms, thus bringing about the bipolar diagnosis. We can't ever know with certainty whether that individual would have manifested bipolar symptoms if antidepressants were not prescribed. Had the right questions been asked up-front, the same individual may have been prescribed a mood stabilizer prior to the utilization of an antidepressant and his or her progression into hypomania or mania may have been averted.

The second complicated diagnostic issue involves attention deficit-hyperactivity disorder. This is a neurologic disorder which manifests through symptoms of attention and hyperactivity. With regard to attention we see behavior such as: poor attention to detail, frequent inattention or losing focus, difficulty following through with instructions relating to tasks, chores or homework, difficulty with organizing tasks and activities, frequently losing or misplacing things and consistent forgetfulness. In relation to hyperactivity we see: difficulties sitting still, tendencies to move around or be excessively active in situations where this is inappropriate, difficulty engaging in quiet leisure activities, excessive degree of physical activity - often acting "as if driven by a motor," and excessive talking. There is a further variation on hyperactivity including impulsivity. This can entail: tendencies to blurt out answers to questions before they have been completely asked, difficulties awaiting one's turn and tendencies to interrupt or intrude on others. Impulsivity can also entail rapidly making choices that do not reflect good judgment. Most of the preceding symptom descriptions reflect ADHD criteria from DSM-IV TR (American Psychiatric Association).

What's complicated about the above symptom list is that many of the same ones can be present during a hypomanic or manic episode. An individual's physical energy can be so elevated that he or she can easily appear to be hyperactive. There is also such cognitive acceleration and mood intensity that an individual's memory, attention to detail, capacity to remain focused and ability to appropriately inhibit action are all impaired. So how do we distinguish these sets of symptoms that can look so similar to each other?

The first part of the answer involves an important caveat: the distinction does not readily apply to those who are diagnosed with childhood bipolar disorder as such can exert its influence just as early as does ADHD. The salient differences are that feelings of grandiosity, intense elation and/or intense anger, racing cognition and lessened need for sleep are more salient in childhood bipolar than they are in attention deficit-hyperactivity disorder. This doesn't mean there won't be any of these themes in the attention deficit-hyperactivity realm but the preceding symptom cluster will likely have a stronger presence in childhood bipolar disorder as opposed to attention deficit disorder.

Now let's return to distinctions between attention deficit-hyperactivity disorder and bipolar disorder in adults. It's actually rather simple. The adult with bipolar disorder who did not have childhood bipolar disorder will have experienced a point of symptom onset sometime after mid to late adolescence. The implication here is that if I'm inquiring about symptom onset and the individual being assessed reports that none of his or her symptoms were present prior to some point in adolescence or early adulthood, then it's not likely that symptoms being discussed are reflective of ADHD.

A second key distinction is that many of the attention deficit-like symptoms that are typically present during elevated mood phases are absent during midrange mood and to a lesser extent, depressed mood, though sometimes depression does interfere with attention, concentration and memory so we can see what may appear as an overlap of ADHD and bipolar symptoms during depressed mood. The one obvious period of time when the attention-deficit-like symptoms are absent for the bipolar individual is during mid-range mood. This isn't the case for someone with attention deficit-hyperactivity disorder because their symptoms are part of their baseline functioning. They don't experience periods of time when their ADHD symptoms are absent. That's not to say there isn't some variability of symptom intensity, but the attention deficit individual won't have periods where attentional, focusing, organizational and impulse inhibitory functioning are perfectly normal. Keeping the above distinctions in mind, the tuned in diagnostician can usually tease out the differences between ADHD and bipolar disorder.

The differentiation of personality disorder symptoms from bipolar disorder entails two key variables, one of which is similar to the ADHD distinction. That is, if an individual struggles with personality disorder symptoms, their struggles will typically be ongoing. Similar to ADHD, there may be some variability in symptom acuity, but the individual typically won't have times where he or she is not under the influence of the psychological processes underlying the personality disorder. Individuals with personality disorders don't get to have a vacation from their personality dynamics. Conversely, the bipolar individual whose symptoms (impulsivity, hypersexuality, anger/irritability, tendencies towards idealization or devaluation, feelings of grandiosity, etc.) may look like they belong to a personality disorder diagnosis will present with enough of a difference within mid-range mood that most of the same symptoms will be absent.

The second critical distinction between the personality disorders and bipolar disorder is that all personality disorder issues manifest in relation to interpersonal relationships. The struggles which may activate strong personality disordered symptoms are almost always within the interpersonal realm. While there is some overlap here with bipolar disorder in the sense that interpersonal stresses may activate a shift in mood phase, bipolar individuals will also tell you that there are times when the onset of their symptoms, whether elevated or depressed, will seem to come out of nowhere. There is no obvious trigger or precipitant for their mood destabilization. The only reliable explanation is that there's been an endogenous shift in their brain activity and their neurochemistry.

The above discussion is by no means exhaustive regarding differential diagnostic distinctions between bipolar disorder and other psychiatric disorders that share similar symptoms. But it should give you a good sense of the kinds of issues the clinician will be looking at when trying to sort through whether one has bipolar disorder, another diagnosis or coexisting diagnoses.

I recommend that you be cautious if a mental health professional arrives at the bipolar diagnosis after only a short period of time with you or with a family member. The narrow exception here would entail someone with a strong genetic bipolar background who presents with hallmark bipolar symptoms in the absence of any other issues that may stimulate questions about comorbidity. But even here, in the name of thoroughness, diagnosticians should nonetheless be cautious about reaching conclusions prematurely.

Once a mental health professional has arrived at a valid bipolar diagnosis I feel most comfortable when the diagnosis is presented as a strong possibility along with a clear explanation of the basis upon which the conclusion has been reached. The patient should also be cautioned that the diagnosis will only be conclusively ascertained over a more extended period of time and that both patient and clinician will be looking at this together as treatment proceeds.

One last thing to keep in mind: If the diagnostic conclusion of your mental health professional doesn't ring true for you, if you do not get a thorough and detailed explanation as to why the bipolar diagnosis is likely, it is absolutely appropriate to pursue a second opinion.

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Russ Federman, Ph.D., ABPP is in private practice in Charlottesville, VA ( www.RussFederman.com). He is co-author of Facing Bipolar: The Young Adult's Guide to Dealing with Bipolar Disorder (New Harbinger Publications). www.BipolarYoungAdult.com

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Across the web you'll find increasing attention being given to the identification of bipolar mood symptoms and patterns. Solid educational information is important for those who are concerned that they may have bipolar disorder. Even the best diagnosticians find that arriving at the diagnosis is a difficult endeavor.

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Behav Modif. Author manuscript; available in PMC 2013 Jun 24.

Published in final edited form as:

Abstract

Treatment adherence is a frequent problem in bipolar disorder, with research showing that upwards of 60% of bipolar patients are at least partially nonadherent to medications. Treatment nonadherence is consistently predictive of a number of negative outcomes in bipolar samples, and the discontinuation of mood stabilizers places these patients at high risk for relapse. Several types of adjunctive treatment (family, psychoeducational, cognitive-behavioral) have been investigated for improving symptoms and functioning in bipolar patients with some success. To date, less attention has been paid to developing treatments specifically to promote treatment adherence to and engagement with pharmacological as well as behavioral treatments in patients with bipolar disorder. First, we review the effects of adjunctive interventions specifically on treatment adherence outcomes in 14 published clinical trials. Based on this empirical knowledgebase, we present a preliminary description of the treatment strategies that appear most promising for improving adherence. We also provide research recommendations for developing more effective interventions for the purpose of improving bipolar treatment adherence. Special treatment considerations, including the potential impact of comorbid substance abuse and bipolar depression, are discussed.

Keywords: bipolar disorder, adherence, psychosocial treatments, mood stabilizers, clinical trials, bipolar depression, substance use disorders

Bipolar disorder is typically a chronic and severe mental illness present in 1-2% of the general population ( Kessler et al., 1994; Regier et al., 1988). If diagnoses of bipolar II disorder are included in estimates, the prevalence increases to 3.9% ( Kessler, Chiu, Demler, Merikangas, & Walters, 2005). Bipolar disorder is reported to be the 6 th leading cause of disability worldwide in those ages 15-44 ( Murray & Lopez, 1996), and recent estimates suggest that medication and treatment costs for bipolar patients exceed $17,000 per individual annually ( Stender, Bryant-Comstock, & Phillips, 2002). The societal and personal burdens of bipolar disorder are due in part to its typically impairing course of illness. Over 70% of bipolar patients experience at least one recurrence within 4 years of the index episode ( Gitlin, Swendsen, Heller, & Hammen, 1995). Judd et al. (2002) studied the symptomatic course in bipolar I patients for an average of 13 years, and reported that individuals spent 32% of the time with clinically significant depression symptoms, 9% with manic symptoms, and 6% with mixed symptoms. Unfortunately, these high rates of relapse, symptomatic illness, and impairment are frequently reported even in bipolar samples receiving maintenance pharmacotherapy ( Gitlin et al., 1995; Harrow, Goldberg, Grossman, & Meltzer, 1990; Miller, Uebelacker, Keitner, Ryan, & Solomon, 2004).

A World Health Organization ( WHO, 2003) report defined treatment adherence broadly as: "The extent to which a person's behavior-taking medication, following a diet, and/or executing lifestyle changes, corresponds with agreed recommendations from a healthcare provider" (p. 3). On average, treatment nonadherence rates of 25% have been reported across a variety of general medical conditions ( DiMatteo, 2004). However, individuals being treated for psychiatric disorders tend to exhibit even higher rates ( Cramer & Rosenheck, 1998). Although efficacious treatments are available for bipolar patients, research shows that upwards of 60% of these patients are at least partially treatment nonadherent to medication ( Lingam & Scott, 2002), and that nonadherence predicts negative short- and long-term outcomes in those with the disorder ( Keck et al., 1998). Therefore, there is an urgent need to identify cost-effective and efficacious adjunctive interventions that can improve treatment adherence in bipolar patients. In this paper, we examine the effects of current psychosocial interventions for improving treatment adherence in bipolar patients, and attempt to distill the strategies that appear most promising for further study. Based on this review, we provide recommendations for developing and testing novel interventions designed specifically to promote bipolar treatment adherence.

THE SCOPE OF THE BIPOLAR NONADHERNCE PROBLEM

Treatment nonadherence is predictive of a number of negative outcomes in bipolar patients ( Keck et al., 1998; Scott & Pope, 2002b; Strakowski et al., 1998). In fact, some argue that nonadherence is responsible for the disorder's "efficacy-effectiveness gap," or the finding that 66% of bipolar patients respond to lithium in clinical trials, but only about 33% show similar improvements in clinical practice ( Schou, 1997; Scott, 2002). A comprehensive review of the effects of nonadherence and factors predictive of this problem are beyond the scope of the current paper. Interested readers are referred to recent comprehensive reviews in this area ( Colom, Vieta, Tacchi, Sanchez-Moreno, & Scott, 2005; Lingam & Scott, 2002). A brief overview is presented below.

Although estimates vary considerably across studies, recent reviews of the literature have reported that bipolar medication nonadherence rates typically range between 20% to 60%, with an average of 40% ( Berk, Berk, & Castle, 2004; Colom, Vieta, Tacchi et al., 2005; Lingam & Scott, 2002). For example, using a definition of missing 30% or more of medication doses, Scott and Pope (2002a) reported that 32% of patients prescribed mood stabilizers reported being nonadherent within the past month, and that 50% were nonadherent during the previous 2 years. Several factors appear to predict nonadherence in bipolar patients, including a history of nonadherence, longer duration of treatment, increased complexity of medication regimen, decreased insight into illness, more negative beliefs about medications, poorer patient-doctor alliance, as well as the presence of psychotic features, personality disorders, and comorbid substance abuse ( Berk et al., 2004; Colom, Vieta, Tacchi et al., 2005; Lingam & Scott, 2002; Miklowitz, 1992; Sajatovic, Bauer, Kilbourne, Vertrees, & Williford, 2006; Scott & Pope, 2002a)

Regardless of the specific method used to define nonadherence in past studies, findings consistently suggest that bipolar nonadherence is predictive of negative outcomes such as relapse, hospitalization, functional impairment, and suicidality ( Gonzalez-Pinto et al., 2006; Keck et al., 1998; Strakowski et al., 1998). For example, Scott and Pope (2002b) prospectively followed 98 patients prescribed mood stabilizers and reported significantly more patients with subtherapeutic (81%) compared to therapeutic (9%) blood levels of mood stabilizers required hospitalization. In recent years, there has been much effort devoted to developing efficacious pharmacological and, more recently, behavioral treatments for patients with bipolar disorder. However, the high rates of nonadherence commonly found in this population pose significant challenges to the implementation of currently available, state-of-the-art interventions.

DEFINING BIPOLAR TREATMENT ADHERENCE

Definitions of Adherence

Treatment adherence can be difficult to study because the concept often is defined differently across populations, and even differently among studies within the same population. Similar to the wide range of nonadherence rates often reported among bipolar samples (20-60%), estimates have been equally variable among studies of patients with unipolar depression (10-60%) ( Lingam & Scott, 2002) and schizophrenia (4-72%) ( Lacro, Dunn, Dolder, Leckband, & Jeste, 2002). Factors affecting the frequently discrepant nonadherence rates reported in past research include the population or subpopulation under investigation, type of treatment, specific characteristics of the sample, length of the assessment period, method of measurement, and criteria for designating "nonadherence," to name just a few. Therefore, estimates of nonadherence should be interpreted cautiously because rates tend to vary considerably as a function of the particular definition of nonadherence preferred by different researchers, as well as the measurement strategies employed to examine the problem in each study. These sometimes idiosyncratic definitions of adherence can lead to divergent conclusions about the impact of the problem and how it should be addressed in treatment.

In an attempt to improve the understanding of bipolar nonadherence, Colom, Vieta, Tacchi, et al. (2005) listed several different ways of categorizing nonadherence behaviors: 1) full nonadherence, or complete noncompliance with all provider instructions; 2) selective nonadherence, or compliance with some but not all instructions (e.g., taking only one of two prescribed medications); 3) intermittent adherence, or noncompliance, but only during certain periods (e.g., not taking medications when abusing alcohol or drugs); 4) late adherence or nonadherence, or initial noncompliance followed by later adherence (e.g., increased adherence over time due to improved insight into illness or specific intervention efforts), or vice versa; 5) abuse, or taking more medication than prescribed (e.g., attempts by patients to increase a medication's effectiveness by taking more of it); and 7) behavioral nonadherence, or adherence to the nonmedication aspects of treatments. The last concept, behavioral nonadherence, includes a broader array of behaviors than simply taking medications as prescribed, and encompasses important treatment issues, such as attendance at scheduled appointments and the implementation of recommended lifestyle changes (e.g., diet/exercise plans or behavioral strategies designed to improve mood and regulate activity levels).

Behavioral nonadherence is particularly relevant to the current discussion as it has received surprisingly little attention in past research on bipolar disorder. This may be the case because behavioral nonadherence tends to be more complicated and difficult to measure compared with medication adherence, and also because psychosocial treatments for bipolar disorder have only recently begun to receive widespread clinical acceptance and serious attention from researchers. Although the evidence to date is limited, as few studies have examined behavioral nonadherence specifically in bipolar patients, the available evidence suggests that the problem is similar to that of medication nonadherence. For example, studies of severely mentally ill samples that have included bipolar patients have frequently reported high rates of community treatment attrition and failure to attend referral appointments ( Nuttbrock, Ng-Mak, Rahav, & Rivera, 1997; Primm et al., 2000; Rosenheck, Frisman, & Gallup, 1995). Recently, Gaudiano and Miller (2006) identified predictors of treatment attendance in bipolar I patients enrolled in a larger clinical trial. Results showed that both patients' initial expectancies for improvement and the quality of the patient-doctor alliance significantly predicted time remaining in treatment up to 28 months following hospitalization. Moreover, a longer time remaining in active treatment was associated with less time spent symptomatically ill over follow-up.

Measures of Adherence

As the previous discussion illustrates, the process of defining treatment adherence begins at the conceptual level. However, equally important to defining adherence is the measurement strategy used for assessing the problem. Typically, measures of adherence are divided into two broad categories: objective and subjective ( Hearnshaw & Lindenmeyer, 2006). Commonly used objective measures relevant to bipolar patients include serum levels of mood stabilizers, pharmacy records of prescription fills, pill counts, and missed appointments ( Lingam & Scott, 2002; Sajatovic, Davies, & Hrouda, 2004). Subjective methods include patient self-report, and measures designed for this purpose have been developed for bipolar patients specifically, such as the Lithium Attitudes Questionnaire ( Harvey, 1991). Corroborative reports from significant others and treatment providers are frequently used to help verify patient reports. Although some may find the use of self-report strategies for assessing bipolar treatment adherence to be questionable, researchers have reported high levels of agreement (91%) between self-report and more objective adherence data (e.g., serum drug levels) ( Lam et al., 2003). Furthermore, objective data from blood lithium levels can be less accurate than patient self-report in some cases, especially when patient report can be corroborated by informants ( Colom et al., 2000). Unfortunately, the measurement of specific behavioral adherence variables in bipolar patients has been largely ignored in the literature.

Based on a recent review of the literature on treatment adherence among bipolar patients, Sajatovic et al. (2004) recommend a multi-modal assessment of bipolar treatment adherence that includes a variety of different strategies. Some researchers have developed methods for combining methods in an attempt to improve and verify data on adherence. For example, Colom et al. (2000) assessed adherence based on patient interview, family member interview, and plasma drug levels. "Good compliance" was demonstrated when all three criteria suggested medication adherence. Other studies have used "blind," independent psychiatrists to categorize patients according to their level of adherence based on available adherence information ( Miklowitz et al., 2000). Although these composite measures are likely to provide a more complete picture of adherence behaviors, they also are more likely to vary across different studies, making inter-study comparisons of adherence rates sometimes difficult to interpret.

REVIEW OF THE EFFECTS OF PSYCHOSOCIAL INTERVENTIONS ON BIPOLAR TREATMENT ADHERENCE

Selection of Studies for Review

Our aim was to review outcomes related to treatment adherence in published studies of psychosocial interventions for bipolar disorder. Therefore, we conducted a literature search of all published randomized controlled trials in this area. Relevant studies were identified from MEDLINE, PsychINFO, and the National Institutes of Health Computer Retrieval of Information on Scientific Projects (CRISP) databases, as well as the reference lists of review articles. Studies were included in the current review if they met the following criteria: a) random assignment to conditions, b) inclusion of a psychosocial treatment in at least one treatment arm, and c) report of at least one medication-related adherence outcome (e.g., blood levels of mood stabilizers). A total of 36 studies were identified and evaluated for possible review. Of this initial pool, 14 clinical trials met our review criteria and are summarized below. The most frequent reasons (non-mutually exclusive) for exclusion were: a) failure to use random assignment ( n = 7), b) failure to report adherence outcomes ( n = 9), and/or c) description of follow-up results from trials already included in our sample ( n = 6). Each article was reviewed to collect information on study methodology (e.g., design, treatment conditions, sample characteristics), as well as outcomes related to treatment adherence. As recommended by Colom, Vieta, Tacchi, et al. (2005), we attempted to examine behavioral indices of adherence in addition to medication-related measures when available, including attrition and session attendance rates. However, study findings related to measures of symptoms and functioning are not described in detail here in the interests of space. Interested readers are referred to recent review articles that provide detailed descriptions of the primary findings from these trials ( Bauer, 2001; Craighead & Miklowitz, 2000; Miklowitz, 2006; Otto, Reilly-Harrington, & Sachs, 2003; Rouget & Aubry, 2007; Vieta et al., 2005).

Although most psychosocial interventions tested in the selected studies contained strategies for improving bipolar treatment adherence, few of these trials were designed to assess treatment adherence programs specifically. Only two of the selected studies tested an intervention primarily designed to improve bipolar treatment adherence ( Cochran, 1984; Peet & Harvey, 1991). In the remaining cases, treatment adherence was reported either as a secondary outcome or in order to determine if treatment differences on primary outcomes were, in fact, explained by nonadherence. Furthermore, methods used for assessing adherence in these studies were quite variable; although measures of adherence to mood stabilizers were consistently reported in the selected trials. Given the aforementioned caveats, findings from these trials can not provide definitive conclusions about the efficacy of psychosocial interventions for improving bipolar treatment adherence. However, we believe that reviewing the findings from these trials can be helpful for designing future psychosocial interventions to improve bipolar adherence specifically. For each category of intervention reviewed, we first summarize effects related to medication adherence, followed by a discussion of behavioral adherence outcomes.

Summary of Study Results Related to Adherence

Cognitive-Behavioral Interventions

See for a summary of reviewed studies. Of the 14 trials identified for this review, 6 focused on the efficacy of adjunctive cognitive-behavioral therapies (CBT) for bipolar disorder ( Ball et al., 2006; Cochran, 1984; Lam et al., 2000; Lam et al., 2003; Schmitz et al., 2002; Scott et al., 2006). Findings from 4 of these studies suggested that the addition of a cognitive-behavioral intervention might enhance treatment adherence ( Cochran, 1984; Lam et al., 2000; Lam et al., 2003; Schmitz et al., 2002); although only one trial specifically targeted adherence as a primary treatment outcome ( Cochran, 1984).

Table 1

Medication adherence

Cochran (1984) evaluated standard care alone versus standard care plus a 6 week CBT-based compliance intervention, and utilized a multi-modal assessment of adherence which included self, informant, and physician report, as well as serum lithium levels, chart review, and an independently rated 3-point "compliance index." Across the 6-month post-treatment follow-up, patients in the experimental condition were significantly less likely to be rated as having "major noncompliance" problems on the compliance index, were significantly less likely to terminate the use of lithium against medical advice, and were significantly less likely to be hospitalized. Moreover, patients in the experimental condition were significantly more likely to be rated as "adherent" as per physician report and compliance index rating at post-treatment and at the 6-month follow-up. However, these effects were not evident at 3-month follow-up, and there were no differences between groups at any time point on self-reported adherence, informant ratings, or serum lithium levels. These mixed findings may have been related to limitations of the study, which included a small sample size and physician ratings that were not blind to experimental treatment condition. This limitation is particularly noteworthy, as physician ratings did not significantly correlate with self-report and informant ratings.

Through their treatment development work focused on cognitive therapy (CT) for relapse prevention in bipolar disorder, Lam and colleagues (2000; 2003) have also demonstrated some support for the notion that adjunctive cognitive-behavioral interventions may enhance treatment adherence. In an initial small-scale pilot trial evaluating CT versus treatment as usual (TAU), Lam et al. (2000) failed to find post-treatment differences in adherence as measured by the self-report Medication Compliance Questionnaire (MCQ), but reported significantly better adherence in the experimental condition at 6 months post-treatment. In a larger trial of this work ( Lam, Hayward, Watkins, Wright, & Sham, 2005; Lam et al., 2003), in which 103 patients were randomized to receive 6 months of either "minimal psychiatric care" alone or with the addition of CT for relapse prevention, the patients in the experimental condition reported significantly greater compliance on the MCQ at immediate post-treatment. These results extended to 18 and 24 months post-treatment, although they were not replicated at the 12 month post-treatment assessment. As roughly half of the sample failed to comply with scheduled blood draws, serum mood stabilizer concentrations were only reported at immediate post-treatment, at which time there was a statistical trend such that patients enrolled in the experimental condition were more likely to have "adequate" serum levels than patients enrolled in the control condition.

In the only study reviewed targeting patients with bipolar disorder and comorbid substance use disorders, Schmitz et al. (2002) randomly assigned 46 individuals to either 12 weeks of low-intensity medication monitoring alone or in combination with CBT. The CBT condition showed somewhat better medication adherence on a composite measure derived from patient self-report and blood levels of mood stabilizers.

Despite the findings reported above, additional randomized trials have failed to demonstrate a link between cognitive-behavioral interventions and enhanced medication adherence. For example, in the largest trial of CBT for bipolar disorder to date ( Scott et al., 2006), in which 253 patients with severe and recurrent bipolar disorder were randomized to either CBT or TAU, there was no group difference in adherence to any psychotropic medication. However, the authors did not report how medication adherence was assessed in this study. Similarly, although Ball et al. (2006) hypothesized that patients enrolled in a CT intervention for relapse prevention would demonstrate greater medication adherence when compared to patients enrolled in TAU, there was no group difference in self-reported adherence at post-treatment or at 12 month follow-up. Given poor compliance with blood tests for serum mood stabilizer concentrations in this study sample, serum level data were not compared across groups.

Behavioral adherence

Results from CBT interventions were more inconsistent when behavioral indices of adherence were examined. In the Cochran (1984) study, mean number of CBT sessions attended was not reported, nor was the attrition rate for the control group. In addition, close to 30% of the patients enrolled in the trial did not designate an informant for participation. From a behavioral perspective, patients enrolled in the studies by Lam and colleagues (2000; 2003) were relatively adherent to the experimental intervention. That is, in both the pilot and larger-scale trials, patients were offered 12 to 20 sessions of CT and attended a mean of 16 and 14 sessions, respectively. Attrition rates did not differ between the experimental and control conditions. Although treatment retention was low in both groups, Schmitz et al. (2002) reported that more patients completed CBT (60%) than medication monitoring alone (33%). Also, the CBT group attended significantly more medication monitoring sessions. In the Scott et al. (2006) study, it is important to note that approximately 40% of patients enrolled in the CBT condition did not receive "all planned components of the package" (pp. 315-316). Further, although patients were offered up to 20 sessions of CT for relapse prevention in the Ball et al. (2006) study, the mean number of CT sessions attended was not reported.

Psychoeducation

Taken together, results from trials evaluating the efficacy of psychoeducational approaches for bipolar disorder have been similarly mixed. Of the 5 studies identified for this review, 3 studies provided some evidence that adjunctive psychoeducation (PE) might enhance treatment adherence ( Clarkin, Carpenter, Hull, Wilner, & Glick, 1998; Colom et al., 2003; Harvey & Peet, 1991), and 2 did not show such benefits ( Perry, Tarrier, Morriss, McCarthy, & Limb, 1999; van Gent & Zwart, 1991).

Medication adherence

Following a 6-week education program designed to enhance lithium knowledge and attitudes, patients were significantly less likely to report missed medication doses than patients enrolled in a waitlist control ( Harvey & Peet, 1991; Peet & Harvey, 1991). However, there was no group difference in serum lithium levels at post-treatment. When data were combined for the two treatment groups, increased lithium knowledge was significantly associated with patient-reported tablet compliance and with serum lithium levels. In addition, Clarkin et al. (1998) evaluated differences in adherence among married patients randomized to receive either medication management alone or medication management plus a 25-session PE intervention with their spouses. Using a likert-type rating scale, self-reported medication adherence was found to be relatively good in both patient groups. Yet patients in the experimental intervention were significantly more medication adherent at post-treatment.

Colom and colleagues (2003; 2005) recently reported results of a group PE to prevent recurrence in remitted patients with bipolar disorder. In this trial, patients were randomized to receive either group PE or nonstructured group therapy. In comparison to controls, patients who had completed the PE group were significantly more likely to have adequate serum lithium levels at post-treatment, 18 months, and 24 months. Yet it is important to note that these findings may have been driven by differential attrition, as patients in the experimental condition were more than two times more likely to withdraw from treatment, and analyses were not conducted on an intent-to-treat basis. Thus, greater adherence to lithium among patients who completed the experimental condition may have been an artifact of their adherence to treatment, more generally. Also of note, there were no group differences in serum lithium levels at the 12-month assessment, nor were there group differences in serum concentrations of other mood stabilizing medications (e.g., valproate, carbamazepine) at any time point. Although adherence was also assessed via interview with the patient and with a significant other, data from these interviews were not reported.

We identified 2 randomized trials of PE that failed to demonstrate a differential treatment effect on medication adherence. In particular, Perry, Tarrier, Morriss, McCarthy, & Limb (1999) randomized patients to receive 6 months of routine care or routine care plus PE aimed at relapse prevention, and found no group difference in serum concentrations of mood stabilizers at post-treatment or at one-year follow-up. van Gent and Zwart (1991) evaluated a 5-week PE for partners of patients with bipolar disorder in comparison to an assessment-only condition, and reported no group difference in adherence, measured categorically based on change in lithium serum levels between blood draws, at post-treatment or at 6-month follow-up.

Behavioral adherence

Although the outcomes reported in the Harvey and Peet (1991) study were generally positive with regard to PE and medication adherence, less is known about adherence to the interventions themselves. For example, the authors failed to report mean number of PE sessions attended; although there was no differential attrition between groups. In the Clarkin et al. (1998) study, the control condition had seven times as many drop outs as PE prior to completion. Session attendance was relatively high in both groups as reported by Colom et al. (2003), with patients attending an average of 19 PE and 18 control group sessions out of a total of 21. Overall, however, patients in the PE condition were twice as likely to withdraw from the study. As the attrition rate for the control condition was not reported in the Perry et al. (1999) study, differential treatment effects could not be assessed. However, it is noteworthy that slightly over 20% of patients in the experimental condition had withdrawn from treatment. Of those that remained, adherence to the intervention was relatively good, with patients in the experimental condition attending an average of 9 out of a maximum 12 sessions that were offered. Finally, van Gent & Zwart (1991) did not report data on behavioral adherence.

Family-Focused Therapy

Although fewer in number, trials of Family Focused Therapy (FFT, Miklowitz & Goldstein, 1997) have had a large impact on clinical recommendations regarding the treatment for bipolar disorder. Of these, we identified 2 randomized FFT trials for the purposes of this review. Although there are additional trials evaluating these treatments ( Miklowitz et al., 2004; Miklowitz et al., 2007), including an integrated family and individual therapy (IFIT, Miklowitz, Richards et al., 2003) protocol that includes elements of FFT and Interpersonal and Social Rhythm Therapy (IPSRT, Frank, 2005), such studies did not systematically report medication adherence outcomes.

Medication adherence

In their outcome trial of 9 months of FFT versus crisis management (CM), Miklowitz and colleagues (2003; 2000) reported no difference between groups at post-treatment on a medication compliance index that incorporated patient report, physician report, and laboratory blood monitoring data. At one-year post-treatment, however, patients who had completed FFT were significantly more likely to be rated as adherent on the compliance index. In a separate trial evaluating 9 months of FFT versus individual therapy for bipolar disorder, Rea et al. (2003) reported no difference in psychiatrist-rated medication adherence at mid-treatment, post-treatment, or at one-year follow-up.

Behavioral adherence

Although the average patient was reasonably medication adherent in the study by Miklowitz et al. (2000), attrition was relatively high in both treatment groups, especially within the CM condition (39%). In addition, session attendance across the 9 months of treatment was not reported. However, there was no difference in the frequency of psychiatry visits at any time point. In Rea et al. (2003), the attrition rate for each group was virtually identical, with approximately 20% of patients in each condition withdrawing from treatment. Mean number of FFT sessions attended was not reported.

Interpersonal and Social Rhythm Therapy

Similar to FFT, randomized controlled trials of IPSRT ( Frank, 2005) have been fewer in number. To date, IPSRT has been evaluated in 2 large trials, although adherence outcomes were not reported in the more recent of the two ( Miklowitz et al., 2007). In their investigation of IPSRT versus intensive clinical management (ICM), Frank et al. (2005) reported no difference in mood-stabilizer serum levels following acute phase treatment. However, in this study, length of acute phase treatment was dependent upon when patients met criteria for clinical stabilization, and some patients failed to achieve stabilization. Similar to findings by Rea et al. (2003), Frank et al. reported an attrition rate that was identical for the IPSRT and ICM conditions, with approximately 21% of patients in each group withdrawing from treatment.

POTENTIALLY PROMISING STRATEGIES FOR IMPROVING BIPOLAR ADHERENCE

Given the mixed evidence described above, it is important to note that any definitive conclusions regarding the utility of psychosocial interventions for increasing medication and behavioral adherence in bipolar disorder would be premature. Nevertheless, a review of the relevant literature suggests that there are a number of potentially promising strategies that would benefit from increased empirical and clinical attention. Indeed, 4 out of the 6 CBT trials and 3 out of the 5 PE trials reviewed above indicated some benefit of adjunctive psychotherapy. Although data from FFT and IPSRT trials were generally less favorable, it is important to note that the trials evaluating these treatments utilized active controls, whereas the majority of the remaining trials relied upon treatment as usual as the comparator.

Notably, there was substantial heterogeneity across studies in terms of how medication adherence was addressed within the respective treatments. Studies that fared particularly well benefited from directly targeting knowledge and attitudes about medication using either cognitive-behavioral ( Cochran, 1984) or didactic ( Peet & Harvey, 1991) approaches. Further supporting this approach, Peet and Harvey (1991) found that increased knowledge of and improved attitudes toward lithium were both significantly associated with adherence outcomes over time. Similarly, Scott and Tacchi (2002) conducted a small open trial ( n = 10) using a tailored version of CBT that produced significant improvements in attitudes toward lithium, which predicted medication adherence. An integrated psychoeducational component emphasizing the role of medication adherence in preventing episode relapse and recurrence was also shown to be promising in some ( Colom et al., 2003; Lam et al., 2000; Lam et al., 2003), but not all studies ( Scott et al., 2006). In contrast, treatments that addressed medication adherence in a more nonspecific manner appeared to be less effective in generating positive adherence outcomes ( Ball et al., 2006; Perry et al., 1999).

In addition to considering how investigators chose to target adherence within each intervention, it may also be useful to consider potential dose-response relationships within treatments. Indeed, although medication adherence was presumably addressed on an as-needed basis for the duration of treatment, interventions varied considerably in the proportion of time specifically dedicated to this topic. For example, treatments that fared particularly well focused exclusively on medication adherence ( Cochran, 1984; Peet & Harvey, 1991) or otherwise devoted several sessions to a discussion of pharmacotherapy ( Colom et al., 2003). One additional benefit of such targeted interventions is that they may be more cost-effective. For example, Cochran (1984) and Peet and Harvey (1991) reported positive adherence outcomes after only 6 weeks of treatment focused solely on medication adherence. Similarly, positive results for treatment adherence have been obtained in studies using relatively low-intensity, yet targeted, interventions in other populations (e.g., the BRENDA model, see Starosta, Leeman, & Volpicelli, 2006). In contrast, longer duration interventions that only devoted a small fraction of time to medication adherence generated poorer adherence outcomes ( Perry et al., 1999; Scott et al., 2006).

Although the evidence is mixed, the inclusion of a family member or significant other in psychotherapy for bipolar disorder deserves continued empirical attention in the adherence literature. Indeed, some ( Clarkin et al., 1998; Miklowitz, George et al., 2003) but not all ( Rea et al., 2003; van Gent & Zwart, 1991) studies suggest that family interventions may enhance medication adherence. Among the studies that have reported null effects, it is important to note that van Gent and Zwart (1991) did not include patients in their intervention, and lack of an immediate post-treatment effect for FFT may have been related to the use of an active treatment control in these trials ( Miklowitz et al., 2000; Rea et al., 2003). For example, Miklowitz et al. (2000) reported relatively high rates of medication adherence in both FFT and crisis management (CM), each of which included active family member participation. Further, there is some preliminary evidence that the effects of FFT on medication adherence may be more enduring, as there was a significant, albeit small, effect of improved adherence in FFT versus CM at approximately 1 year post-treatment ( Miklowitz, George et al., 2003).

Finally, there was little clear evidence that the interventions reviewed above improved behavioral adherence specifically. Only a few studies showed significantly different attrition rates, although the lack of significance in several studies may have been due to relatively small sample sizes. The study by Schmitz et al. (2002) indicated that bipolar patients with a comorbid substance use problem, for which treatment drop out is a particular concern, were retained in treatment at about twice the rate in the CBT condition compared to the medication monitoring alone condition. However, the study by Colom et al. (2003) reported significantly more drop out in the PE condition compared to the control condition, which may suggest problems with treatment acceptability. In the broader literature, there is reason to believe that the inclusion of a family member or significant other may be particularly useful in enhancing behavioral treatment adherence (e.g., by encouraging session attendance) ( Fals-Stewart & O'Farrell, 2003; Uebelacker, Weishaar, & Miller, in press). In the Clarkin et al. (1998) study, patients receiving the marital intervention had better treatment retention. Nevertheless, studies of FFT failed to show differences in treatment retention ( Miklowitz et al., 2000; Rea et al., 2003). It is clear from our review that much more work is needed developing strategies to retain bipolar patients in treatment, as well as ways of measuring importance behavioral adherence variables.

RESEARCH ISSUES RELATED TO DEVELOPING AND TESTING NOVEL BIPOLAR ADHERENCE PROGRAMS

There are a number of challenges faced when conducting randomized controlled trials of bipolar disorder in general, and these difficulties are amplified when the aim is to test the efficacy of a bipolar treatment adherence program. Below, we discuss methodological issues raised during our review of the extant literature and potential ways of addressing them.

Sample Characteristics

One of the difficulties with conducting bipolar treatment studies is dealing with patient heterogeneity. Review of the sample characteristics in the studies presented in highlights the diverse characteristics of bipolar patients included in past trials. When developing a novel bipolar adherence program, important decisions need to be made regarding a variety of possible inclusion/exclusion criteria, including diagnostic subtypes (bipolar I vs II), episode status at study entry (in episode vs in remission), type of mood episode (manic, depressed, or mixed), treatment setting (hospital vs outpatient), and potential comorbidities (psychiatric and general medical). Although it is generally considered preferable to reduce heterogeneity as much as possible when conducting efficacy trials, issues of internal and external validity need to be appropriately balanced in bipolar treatment studies, both to accurately represent the diverse characteristics of these patients and to ensure that any new treatment will be transportable to routine practice settings.

There are a number of potential differences between patients diagnosed with bipolar I versus II disorder, as well as differences in their respective treatment. Studies of bipolar I patients in particular are urgently needed, as these patients tend to have higher nonadherence rates. In addition, patients currently in episode receiving acute treatment in a hospital setting are at elevated risk for nonadherence and relapse after discharge, making them prime candidates for adherence interventions. However, bipolar outpatients in remission at study entry may actually prove more amenable to adherence interventions, and thus it may be easier to detect changes in their status over time. For example, studies by Colom et al. (2003; Colom, Vieta, Sanchez-Moreno et al., 2005) and Lam et al. (2005; 2003) found positive effects on adherence measures in samples of initially remitted patients; whereas Miklowitz et al. (2000; Miklowitz, George et al., 2003) found advantages for their intervention only over longer-term follow-up in a sample that was in a mood episode at study entry. Further, adherence interventions may need to contain distinctive elements for addressing mania versus depression, as the preferred treatments for different phases of bipolar illness vary. Therefore, the decision to recruit patients with a particular type of mood episode should largely be dictated by the content and aims of the particular intervention being tested. Finally, given the high comorbidity rates (e.g., anxiety disorders, Gaudiano & Miller, 2005) found in bipolar patients that make it the rule rather than the exception, the use of overly restrictive exclusion criteria would be unlikely to produce an adherence program that is generalizable to the majority of patients.

Choice of Comparison Conditions

Another key issue that emerged from our review of past studies was the diversity of comparison conditions used to assess psychosocial treatment efficacy in bipolar patients. Most psychosocial interventions for bipolar disorder have been adjunctive in nature and compared to some form of "treatment as usual," which was usually pharmacotherapy alone. All patients in a bipolar adherence intervention trial, regardless of whether or not they are assigned to the experimental intervention, also would be receiving a primary treatment that most likely includes pharmacotherapy. Depending upon the aims of the proposed bipolar adherence program, patients also may be required to receive some form of behavioral treatment or therapy when appropriate, especially if they are experiencing depressive symptoms. Therefore, treatment as usual, as long as it is properly specified and defined, may also prove a useful backdrop for testing novel bipolar adherence programs. Alternatively, if the adherence intervention is specifically designed to target a particular type of treatment (e.g., lithium compliance or a particular behavioral therapy), then it may be necessary to provide the primary treatment as part of the study. Doing so would help to better isolate the effects of the adherence intervention on this specific aspect of a patient's more comprehensive treatment regimen.

It is important to note that a study design containing only primary treatments would not provide sufficient evidence that any increases in adherence observed during the study could be attributed to the adjunctive adherence intervention itself. It is possible that increases in adherence merely would be an artifact of the additional professional contact received by patients in the adherence intervention, if the comparison group received no additional intervention. Therefore, patients assigned to the adherence intervention should preferably be compared against a group of patients receiving some additional components that could help to compensate for the non-unique aspects of the adherence intervention. For example, providing increased assessment and periodic contact with a healthcare professional who refrains from discussing adherence to the control patients in a study may prove useful for substantiating the specific efficacy of a novel adherence program. It is important to note that of the two previous trials reviewed that specifically tested adherence programs ( Cochran, 1984; Peet & Harvey, 1991), both were employed as adjuncts to pharmacotherapy, but did not control for the extra treatment provided. Thus, more sophisticated designs will need to be employed in future research on this topic.

Measurement Issues

As discussed, defining and measuring treatment adherence can be complicated, and this is especially the case with bipolar patients given the diversity of treatments they may be receiving. Our review of previous bipolar trials demonstrated that beneficial effects could be found using self-report, clinician-rated, and objective indices of adherence. In addition, newer technologies, such as "ecological momentary assessment" via personal digital assessment devices ( Stone & Shiffman, 2002) or microelectronic devices for recording pill bottles ( Choo et al., 1999), may help to increase the accuracy of assessment strategies and to provide more detailed information about potential contextual factors that may influence adherence behaviors. However, it is important to note that in almost every trial that we examined, the primary focus was on medication adherence specifically. For the purposes of our review, we also attempted to examine the potential effects on behavioral adherence by using proxy measures, such as attrition and treatment attendance rates. However, this information has been inconsistently reported in the literature. It will be necessary for future studies of bipolar adherence programs to include more specific measures of behavioral adherence, such as the newly-developed, clinician-rated measure called the Psychosocial Treatment Compliance Scale ( Tsang, Fung, & Corrigan, 2006).

We were able to identify only one example of a bipolar psychosocial treatment study that specifically included the assessment of behavioral adherence. Bauer et al. (1998) reported findings from an open trial of the Life Goals Program, which is a group-based psychosocial intervention for bipolar patients focused on education and goal achievement. The study included behavioral adherence measures relevant to the psychosocial intervention: 1) session attendance rate; 2) overall duration of enrollment; 3) level of session participation; 4) completion of therapy assignments; and 5) achievement of functional goals. By measuring these variables, the researchers were able to demonstrate that their intervention was well tolerated by patients and produced good behavioral adherence to the treatment.

Finally, an issue that is particularly relevant to psychosocial trials for bipolar disorder is the complex relationship among adherence behaviors, symptomatic improvement, and other clinical variables. One would hypothesize that an adherence intervention should be able to demonstrate that earlier improvement in adherence behaviors is predictive of later symptomatic improvement, at least to a certain degree. However, the relationship between symptomatic improvement and adherence is likely interactional and reciprocal, such that improvement in symptoms affects adherence behaviors, and vice versa. Thus, more sophisticated statistical techniques may be necessary to examine the specific effects of an adherence intervention. An example of how some researchers have attempted to address this issue can be found in the seminal treatment trial of FFT. Miklowitz et al. (2000) conducted a series of analyses demonstrating that, when psychosocial treatment and medication adherence were evaluated together as predictors of symptom ratings over time, psychosocial treatment accounted for unique variance in depression symptom ratings whereas medication adherence did not, and adherence accounted for unique variance in mania symptomatology whereas psychosocial treatment did not.

SPECIAL CONSIDERATIONS FOR BIPOLAR ADHERENCE PROGRAMS

It has been observed that the efficacy of currently available treatments for bipolar patients tends to decrease considerably when these same treatments are delivered in the community ( Schou, 1997; Scott, 2002). One reason for this problem may lie in the fact that some important aspects of bipolar illness are not being adequately addressed in the existing treatment literature. Below, we provide examples of two important aspects of bipolar illness that require careful consideration when developing and testing psychosocial interventions, which are especially relevant to the topic of adherence: comorbid substance use disorders and bipolar depression.

Comorbid Substance Use Disorders

Most of the studies that we reviewed specifically excluded patients with comorbid drug or alcohol use disorders. However, the co-occurrence of these disorders is substantial. Epidemiological research suggests that up to 60% of individuals diagnosed with bipolar disorder have a lifetime history of a substance use disorder (SUD) ( Regier et al., 1990). Comorbid SUDs have been shown to be related to a variety of negative factors in bipolar patients, including earlier age of illness onset, higher frequency of mood episodes, greater symptom severity and impairment, shorter time to relapse, and higher rates of suicide attempts (for a review, see Salloum & Thase, 2000). Furthermore, the most important predictor of nonadherence in bipolar patients is the presence of a comorbid SUD ( Lingam & Scott, 2002; Strakowski et al., 1998).

Although a frequent clinical concern in bipolar patients, we are aware of only three published studies of psychosocial treatments for bipolar substance abusers specifically. The pilot study of CBT for bipolar patients with SUDS by Schmitz et al. (2002) is reviewed above. In addition, Weiss et al. (2000) recruited 45 bipolar patients with SUDs in sequential blocks to receive group CBT (12-20 sessions) or outpatient pharmacotherapy and other community treatments. After 6 months, those receiving CBT showed significantly greater improvements in addiction severity, manic symptoms, and percentage of months abstinent. No group differences in self-reported medication compliance were found, although overall adherence in the sample was good. Most recently, Weiss et al. (2007) published findings from a larger randomized trial ( n = 62) in which bipolar patients with comorbid SUDs received integrated group CBT or group drug counseling. The CBT group demonstrated better substance abuse outcomes during treatment and at follow-up. In addition, group attendance was significantly higher in the CBT condition (70% vs. 54%). Unfortunately, medication adherence rates were not reported in the study. Even though SUDs are highly comorbid with bipolar disorder and predictive a number of negative outcomes, especially nonadherence to treatments, it is important to note that none of the aforementioned studies tested interventions primarily designed to improve adherence. Thus, there is an urgent need to develop treatments specifically for bipolar patients dealing with drug and alcohol problems that targets nonadherence behaviors.

Furthermore, the issue of drug and alcohol use also appears relevant to primary clinical trials of bipolar disorder, even though most researchers exclude patients with a current SUD. Given the high lifetime prevalence of these disorders, many bipolar patients in these studies are likely to have a past SUD. Recently, we examined the potential effect of a past SUD diagnosis on the future course of bipolar disorder in patients taking part in a clinical trial of pharmacotherapy and family therapy ( Gaudiano, Uebelacker, & Miller, in press). Patients were recruited during an acute episode and their mood symptoms and substance abuse were assessed longitudinally for up to 28 months. Somewhat surprisingly, 48% of the sample met criteria for a past SUD based on structured clinical interview. Those with a remitted (≥ 1 year) SUD showed a poorer acute treatment response, a longer time to remission of their acute mood episode, and a greater percentage of time with subthreshold but clinically significant depression and manic symptoms over follow-up compared to those without a SUD history. Subsequent substance abuse assessed during follow-up could not fully account for the poorer course of illness. These findings demonstrate that it is important to screen for and assess substance abuse in patients participating in clinical trials, as lifetime history of a SUD may act as a moderator of treatment outcome. Furthermore, careful attention may need to be given to addressing drug and alcohol use in psychosocial interventions for bipolar patients, even if substance abuse is not the present clinical focus.

Bipolar Depression

Noticeably absent from the literature on psychosocial interventions and treatment adherence in bipolar disorder is a focus on the depressive phase of the illness. Indeed, within the trials reviewed above, depressed patients represented only a small proportion of the samples studied. Yet the issue of treatment adherence may be particularly relevant to bipolar depression, as it currently dominates the long-term clinical course of the disorder ( Judd et al., 2002; Miller et al., 2004), is associated with significant functional impairment ( Calabrese, Hirschfeld, Frye, & Reed, 2004), and confers substantial risk for suicide ( Tondo, Isacsson, & Baldessarini, 2003). Thus, if left untreated, bipolar depression is likely to be associated with significant morbidity and mortality.

Although this pernicious symptom course may be largely accounted for by the more limited armamentarium of effective treatments for bipolar depression ( Thase, 2005), it is unclear to what extent it may also be accounted for by nonadherence to treatment. Indeed, there is reason to believe that certain depressotypic features adversely impact adherence behaviors, potentially contributing to the vicious cycle of depression that has emerged in bipolar disorder. For example, negative cognitions, especially those related to hopelessness about the future or helplessness about being able to reduce one's own symptoms, might interfere with adherence to both behavioral and pharmacological interventions ( Basco, Merlock, & McDonald, 2004). Moreover, concentration difficulties may make it difficult for patients to manage their medications ( Osterberg & Blaschke, 2005). Further impacting risk for treatment nonadherence, rates of alcohol dependence may be higher in bipolar depression in comparison to mania ( Baethge et al., 2005). Finally, although there has been little empirical investigation of this notion, there has been a longstanding clinical belief that, when faced with the intense despair of depression, certain patients may abstain from treatment with a mood stabilizing agent with the hope that elevated or euphoric mood might return.

Emerging data suggest that adjunctive behavioral interventions may be particularly important for the treatment of bipolar depression ( Miklowitz et al., 2007). Consequently, enhancement of adherence to behavioral treatments represents a critical target for bipolar depression. As discussed earlier, one promising strategy for promoting adherence to behavioral interventions is to actively encourage the participation of family members, who may provide support around session attendance or engage in the intervention themselves ( Clarkin et al., 1998; Miklowitz et al., 2000; Rea et al., 2003). Not only is increased adherence to behavioral treatment likely to result in positive symptomatic outcomes for those who present with bipolar depression, but such interventions may be useful in targeting depression-related obstacles to medication adherence, as reviewed above. Although there is less evidence supporting a direct link between medication nonadherence and depressive symptomatology ( Miklowitz et al., 2000), increased medication adherence is nevertheless critical during this period given that it promotes continued mania prophylaxis. Furthermore, to the extent that certain medications, such as lithium, have been demonstrated to significantly reduce suicide risk ( Goodwin et al., 2003), a focus on both behavioral and pharmacological adherence continues to be warranted.

CONCLUSIONS

There exists an urgent need to develop and test novel treatment adherence programs for bipolar patients. Our review of the current psychosocial treatment literature suggests several promising approaches that have the potential for improving bipolar adherence, including cognitive-behavioral, psychoeducational, and family-based interventions. These strategies appear worthy of further clinical refinement and continued testing. However, the evidence for the efficacy of existing treatment adherence strategies is modest, and the study of behavioral (in contrast to medication) adherence in bipolar patients is only in its early stages. Thus, there is a particular need for future research efforts to focus on the development of novel, evidence-based programs that specifically target a variety of treatment-related adherence behaviors, and are based on interventions that currently show the most promise. Such programs may become the linchpins that will help bridge the current gap between the efficacy and effectiveness of the treatments for bipolar disorder.

Acknowledgments

This work was supported in part by grants from the National Institute of Mental Health (MH076937) and National Alliance for Research on Schizophrenia and Depression (2007 Young Investigator) awarded to Dr. Gaudiano.

Biographies

Brandon A. Gaudiano, Ph.D. is Assistant Professor of Psychiatry & Human Behavior (Research) at Brown Medical School and Research Psychologist at Butler Hospital's Psychosocial Research Program. Dr. Gaudiano's research interests include the study of severe mood disorders and the development of novel psychosocial interventions. Currently, he has an NIMH grant to develop a behavioral treatment for patients with psychotic major depression, and a NARSAD grant to develop a treatment adherence program for bipolar patients.

Lauren M. Weinstock, Ph.D. is a Postdoctoral Fellow in the Department of Psychiatry & Human Behavior at Brown Medical School and Butler Hospital's Psychosocial Research Program. Dr. Weinstock's research interests include the study and treatment of unipolar and bipolar mood disorders. Her fellowship is supported by an NIMH grant to develop a behavioral treatment for atypical depression.

Ivan W. Miller, Ph.D. is Professor of Psychiatry & Human Behavior at Brown Medical School and the Director of Butler Hospital's Psychosocial Research Program. His research interests include the study of mood disorders, the development of family-based interventions, and the use of psychosocial treatments in combination with medications. Dr. Miller's current NIH-funded projects include treatment development for suicidal patients and Iraq War veterans.

Footnotes

¹Differing opinions exist regarding the preferred term to use when describing the degree to which patients follow treatment provider recommendations ( Hearnshaw & Lindenmeyer, 2006). Although originally referred to as "compliance" in the literature, this term has fallen out of favor with researchers because it inaccurately implies a one-sided relationship in which the patient is expected to follow the physician's treatment prescriptions without question. Terms such as "adherence" and "concordance" have become increasingly popular in the literature since the 1980s, and are thought to better reflect the two-way relationship between the provider and the patient that takes into account important factors such as the working alliance and patients' treatment preferences ( Gaudiano & Miller, 2006). For the sake of the current discussion, we generally prefer the term "adherence" as it is most commonly used in the literature today, and tends to focus on specific treatment-related behaviors that stem from the provider-patient relationship.

References

Basco MR, Merlock M, McDonald N. Treatment compliance. In: Johnson SL, Leahy RL, editors. Psychosocial Treatment of Bipolar Disorder. New York: Guilford; 2004. pp. 245-264.

Frank E. Treating bipolar disorder: A clinician's guide to Interpersonal and Social Rhythm Therapy. New York: Guilford; 2005.

Gaudiano BA, Uebelacker LA, Miller IW. Impact of remitted substance use disorders on the future course of bipolar I disorder: Findings from a clinical trial. Psychiatry Research in press. [PMC free article] [PubMed]

Lam DH, Bright J, Jones S, Hayward P, Schuck N, Chisholm D, Sham P. Cognitive therapy for bipolar illness: a pilot study of relapse prevention. Cognitive Therapy and Research. 2000;24:503-520.

Miklowitz DJ, Goldstein MJ. Bipolar disorder: A family-focused treatment approach. New York: Guilford; 1997.

Murray C, Lopez A. The global burden of disease. World Health Organization. Cambridge, MA: Harvard University; 1996. [PMC free article] [PubMed]

Schmitz JM, Averill P, Sayre S, McCleary P, Moeller FG, Swann A. Cognitive-behavioral treatment of bipolar disorder and substance abuse: a preliminary randomized study. Addictive Disorders and Their Treatment. 2002;1:17-24.

Uebelacker L, Weishaar M, Miller I. Family and relationship problems. In: Whisman M, editor. Cognitive therapy for complex and comorbid depression. New York: Guilford; in press.

WHO. Adherence to long-term therapies: evidence for action. Geneva: WHO; 2003.

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Improving Treatment Adherence in Bipolar Disorder: A Review of Current Psychosocial Treatment Efficacy and Recommendations for Future Treatment Development

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Behav Modif. Author manuscript; available in PMC 2013 Jun 24. Published in final edited form as: Treatment adherence is a frequent problem in bipolar disorder, with research showing that upwards of 60% of bipolar patients are at least partially nonadherent to medications.

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Background Information about bipolar disorder 

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Background Information about bipolar disorder 

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This is where you can find all you need and want to know about the disorder.

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National Institute of Mental Health (NIMH)

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Overview

Bipolar disorder (formerly called manic-depressive illness or manic depression) is a mental disorder that causes unusual shifts in mood, energy, activity levels, concentration, and the ability to carry out day-to-day tasks.

There are three types of bipolar disorder. All three types involve clear changes in mood, energy, and activity levels. These moods range from periods of extremely "up," elated, irritable, or energized behavior (known as manic episodes) to very "down," sad, indifferent, or hopeless periods (known as depressive episodes). Less severe manic periods are known as hypomanic episodes.

Bipolar I Disorder- defined by manic episodes that last at least 7 days, or by manic symptoms that are so severe that the person needs immediate hospital care. Usually, depressive episodes occur as well, typically lasting at least 2 weeks. Episodes of depression with mixed features (having depressive symptoms and manic symptoms at the same time) are also possible.

Bipolar II Disorder- defined by a pattern of depressive episodes and hypomanic episodes, but not the full-blown manic episodes that are typical of Bipolar I Disorder.

Cyclothymic Disorder (also called Cyclothymia)- defined by periods of hypomanic symptoms as well as periods of depressive symptoms lasting for at least 2 years (1 year in children and adolescents). However, the symptoms do not meet the diagnostic requirements for a hypomanic episode and a depressive episode.

Sometimes a person might experience symptoms of bipolar disorder that do not match the three categories listed above, which is referred to as "other specified and unspecified bipolar and related disorders."

Bipolar disorder is typically diagnosed during late adolescence (teen years) or early adulthood. Occasionally, bipolar symptoms can appear in children. Bipolar disorder can also first appear during a woman's pregnancy or following childbirth. Although the symptoms may vary over time, bipolar disorder usually requires lifelong treatment. Following a prescribed treatment plan can help people manage their symptoms and improve their quality of life.

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Bipolar disorder (formerly called manic-depressive illness or manic depression) is a mental disorder that causes unusual shifts in mood, energy, activity levels, concentration, and the ability to carry out day-to-day tasks. There are three types of bipolar disorder. All three types involve clear changes in mood, energy, and activity levels.