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Effectiveness Of Interventions To Improve Medication Adherence In Bipolar Disorder

Key Messages

The World Health Organization (WHO) has reported that 50% of patients from developed countries with chronic disease do not use their medications as recommended.
In bipolar disorder (BD) non-adherence to medication has been associated with a range of poor clinical outcomes including higher rates of hospital admission, higher rates of suicide, and recurrence of acute episodes, particularly mania.
Rates of relapse in BD have been reported to be as high as 40% in the first year, 60% in the second year, …

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Background & Purpose

The following is a summary of Crowe M. et al. Effectiveness of interventions to improve medication adherence in bipolar disorder. Australian & New Zealand Journal of Psychiatry 46(4) 317–326.

  • In BD non-adherence to medication has been associated with a range of poor clinical outcomes that included higher rates of hospital admissions, suicide, and recurrent of acute episodes, particularly mania. Numerous interventions have been studied in an attempt to improve mediation adherence in long-term conditions; however, it was found that less than half the interventions tested were associated with statistically increased medication adherence. The objective of this review was to identify which interventions enhanced medication adherence in BD, from the published literature of controlled trials between 2003 and 2011.
    • This review outlined the criteria of the trials that were included.
    • This review reports the rates of adherence in the trials included.
    • This review reported the clinical outcomes in the trials included.
    • This review outlined the characteristics of studies with positive outcomes.
    • This review outlined the definition and measurement of adherence.

Review Of Included Controlled Clinical Trial Characteristics

  • Intervention – 12-week, group-based psychoeducation for patient and significant other.
    • Outcome – Medication adherence significantly better in intervention group. Decreased relapse rates, longer time to relapse and decreased manic symptoms.
  • Intervention – Facilitation intervention for psychiatric advance directives. Two-hour, semi- structured, manualized interview and guided discussion of choices for planning mental health care during future period of incapacity.
    • Outcome – Receiving at least one requested medication at the 12-month follow-up predicted greater adherence at 12 months. Shared decision-making could have significant impact on adherence.
  • Intervention – Seven sessions of individual psychoeducation or seven sessions psychoeducation plus 13 sessions cognitive behavior therapy (CBT). Psychoeducation based on a partial CBT model.
    • Outcome – No differences in medication adherence at 1 year. Those who received CBT plus psychoeducation experienced 50% fewer days of depressed mood over 1 year.
  • Intervention – 6-week, manualized group Life Goals Program with optional monthly group sessions.
    • Outcome – No statistical difference in adherence between the two groups. Statistically significant differences between groups at 12 months but fewer than half completed intervention.
  • Intervention – 12-week, group Medication Adherence Skills Training for patients >50 years of age.
    • Outcome – Percentage of patients reporting non-adherence declined by 15%.
  • Intervention – Twenty session cognitive therapy modified by addition of emotive techniques.
    • Outcome – At post-treatment 40.7% TAU and 60.0% intervention reported adequate compliance. At 12-month follow-up 66.7% TAU and 60% intervention reported adequate compliance. Few patients complied with blood tests for serum concentration levels. Differences in medication adherence not significant but intervention group trended to longer time to depressive relapse and improved dysfunctional attitudes.
  • Intervention – Manualized 21 session group psychoeducation.
    • Outcome – Mean serum levels for intervention relatively stable and always higher than mean baseline. Mean levels for TAU greater variability and were highest at baseline. Differences between serum levels was small.
  • Intervention – Individual manualized cognitive therapy, 12-18 sessions plus two maintenance.
    • Outcome – The cognitive therapy group was significantly more compliant with medication at 24 months and 30 months. Control medication only intervention. Significant correlation between self and key worker reports of compliance.
  • Intervention – Manualized Interpersonal and Social Rhythm Therapy (IPSRT).
    • Outcome – No difference in mood stabilizer serum levels following acute phase treatment. A two-phase trial that found participants who received IPSRT in the acute phase experienced longer time to new affective episode and more likely to remain well in 2-year maintenance phase.
  • Intervention – Manualized 9-month family-focused therapy.
    • Outcome – Patients receiving family-focused therapy had higher mean drug adherence scores. Analyses revealed no effect of drug adherence on depression scores at follow-up but those more adherent had lower mania scores. It was suggested that medication adherence mediated the effects of psychosocial interventions on mania symptoms but not depressive symptoms. Intervention group had longer relapse-free intervals during 2 years than control.
  • Intervention – Manualized 9-month family focused psychoeducational therapy or individualized supportive therapy.
    • Outcome – No significant differences between groups on medication compliance over 24-month period. The intervention reduced risk of relapse and rehospitalization. The differences in relapse and rehospitalization particularly significant at 12-month follow- up.


  • While only a few of the interventions reviewed improved adherence, most were associated with improved clinical outcomes.
    • This raised the question about the relationship of adherence to clinical to outcome. Further research needs to explore this relationship in more detail.
  • The studies demonstrating a positive outcome used psychoeducation, cognitive therapy, and family -focused therapy.

Clinical Implications

  • Rates of relapse in BD (even when taking prophylaxis) have been reported to be as high as 40% in the first year, 60% in the second year and 73% over 5 years or more.
  • Even though most studies in this analysis found that the described interventions did not improve adherence, they did improve clinical outcomes. This may be related to the context of adherence management, problems associated with calculating average adherence to multiple medications, and reliance on single measures of adherence. Consequently, it is suggested assessing adherence for each medication separately and combining adherence measurements. A Cochrane review of interventions to improve mediation adherence in long-term conditions found that the common component to successful interventions was more frequent interaction with patients with attention to adherence.


This summation has been developed independently of the authors. The authors reported no conflicts of interest.