Strategies for Increasing Treatment Adherence in Bipolar Disorder

Michael E. Thase, MD

Departments of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia Veterans Affairs Medical Center, and the University of Pittsburgh Medical Center, Philadelphia and Pittsburgh

Although bipolar disorder cannot be cured, effective medications are available that can shorten the duration of illness episodes and reduce the rates of relapse. However, treatment nonadherence is high among patients with bipolar disorder. Discontinuing medication—especially abruptly—increases patients’ risk of relapse and decreases their time in remission, making treatment adherence a pivotal goal in the management of bipolar disorder.1,2

Predictors of Treatment Nonadherence

Patient-related factors. Patient-related predictors of nonadherence include young age, male gender, and single status.1,3 Patients’ attitudes toward bipolar disorder (eg, not believing it is a chronic illness, not accepting the diagnosis), as well as their beliefs regarding medication (such as fear of becoming dependent or of experiencing negative side effects), can also affect treatment adherence. Patients may feel stigmatized by taking psychotropic medications—in fact, nearly a third of patients reported that individuals in their family or support system advised them not to take medication.4 Axis II comorbidities (particularly personality disorders) and substance use disorders are strongly associated with noncompliance in bipolar disorder.3

Illness-related factors. A history of manic episodes has been associated with poor treatment adherence, possibly because patients with more manic features may have poorer insight into their illness than those with depressive features.1 Other illness-related​ predictors of nonadherence include an early onset of illness, a recent bipolar diagnosis, fewer episodes, and being in the first year of lithium treatment.1,3

Medication-related factors. Nonadherence to medication may be prompted by the occurrence of intolerable adverse effects (particularly weight gain and drowsiness), the perception that too many medications were prescribed, and concerns about taking drugs over the long-term.4 Multiple agents or a complicated regimen can contribute to forgetting to take pills, while lack of access to medications—including cost and transportation problems—can also affect a patient’s ability to adhere to treatment.

Strategies to Increase Adherence

AV 1. Addressing Treatment Nonadherence in Bipolar Disorder (02:06)

As many as 52% of patients with bipolar disorder may be nonadherent to their medications.5 The most common means of assessing medication adherence are self-report and physician rating; however, both patients and physicians tend to underestimate nonadherence.6 Several strategies are available to help physicians more accurately estimate and then improve adherence among their patients (AV 1).

Build an alliance. A strong therapeutic alliance between physicians and patients can improve treatment adherence, and an integral part of that relationship should be effective communication. Physicians should convey the severity and chronicity of bipolar disorder and the importance of treatment adherence in attaining and maintaining remission. Like anyone who needs long-term treatment, most people with bipolar disorder will have periods of nonadherence, but they need to understand that abrupt discontinuation of their medication will hasten a depressive or manic relapse. In turn, physicians need to understand their patients’ concerns regarding treatment. Physicians and patients endorse significantly different reasons for why patients discontinue medications for bipolar disorder, indicating a need for more effective communication and patient education (P = .005, AV 2).7


AV 2. Primary Reasons for Stopping Medication Endorsed by Clinicians and Their Patients (00:36)

Data from Pope and Scott7

Monitor adherence. Physicians should ask patients at each visit about adherence in a nonjudgmental way, perhaps by noting the difficulty in taking medications over the long-term and asking patients how often that has caused them to miss a dose.8 If there have been periods of nonadherence, physicians should ask what prompted the nonadherence, what the patients were hoping for, and what changes they noticed during or after stopping treatment, and use this conversation as an opportunity to teach patients about the importance of long-term treatment.

Adherence can also be monitored through the use of patient questionnaires, discussions with family members, pill counts, and electronic medication monitors; for certain medications, blood level monitoring is possible.8 Tracking prescription refill rates is also effective; for example, a patient refilling a 30-day supply of medication every 6 weeks is missing approximately a third of the doses.

Simplify medication routines. When patients have been stable for at least 6 months, physicians should collaborate with them to try to simplify pharmacotherapy regimens and then carefully taper any medications that can be discontinued. One option may be initiating psychosocial interventions such as family-focused therapy, interpersonal and social rhythm therapy, or cognitive-behavioral therapy, all of which have been shown to improve outcomes in bipolar depression, in place of a medication.9 Replacing a medication with psychotherapy reduces the risk of adverse effects and/or a treatment-emergent affective switch, which may be caused by an antidepressant, and patients often prefer psychotherapy taking another medication. Group psychoeducation for patients and their caregivers has also been shown to improve outcomes.10,11 Psychoeducation may reduce caregivers’ burden and improve their attitude toward medication adherence, making them part of the therapeutic alliance.

Address tolerability issues. Physicians should monitor for and proactively address adverse effects. Side effects that may cause patients to discontinue medications include acne, hair loss, upset stomach, tremor, sedation, sexual dysfunction, and weight gain. For additional information on adverse events of bipolar medications, see "Bipolar Disorder Maintenance Treatment: Monitoring Effectiveness and Safety."

Treat comorbidities and interepisode symptoms. Patients should be treated for comorbid disorders, including substance use disorders, and interepisode symptoms, such as sleep disturbances, that can adversely affect neurocognitive and psychosocial functioning and, therefore, adherence.


AV 3. Strategies to Enhance Medication Adherence (00:40)

The main treatment for bipolar disorder is pharmacotherapy, but nonadherence is common. Factors contributing to nonadherence vary and may be patient-, medication-, or illness-related. However, forming a strong alliance with patients can help physicians monitor for adherence problems and implement interventions as necessary. Patients’ attitudes toward their illness and their medications can affect adherence, so physicians should provide education to help patients accept their diagnosis and the severity and chronicity of their illness. Simplifying patients’ medication regimens, monitoring for and proactively treating intolerable side effects, and treating comorbidities can help patients maintain treatment adherence and achieve optimal outcomes (AV 3).

Drug Names

Lithium (Lithobid and others)

For Clinical Use


  • Monitor your patients with bipolar disorder for medication nonadherence
  • Educate patients and caregivers about the severity and chronicity of bipolar disorder and about the necessity for medication adherence
  • Simplify medication regimens when possible and address adverse effects
  • Treat comorbidities and interepisode symptoms that can adversely affect functioning and adherence


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