REVIEW: Patient, treatment, and systems-level factors in bipolar disorder nonadherence: A summary of the literature.

This is a review of adherence determinants in bipolar disorder based on published prospective studies. Patient, treatment, and systems-level adherence determinants are summarized. The review concludes with recommendations on approaches that may minimize nonadherence. MEDLINE, PsychINFO, and the Cochrane Database were searched using key terms of adherence, compliance, or persistence, combined with terms of bipolar disorder, bipolar depression, or mania. Publications were filtered for randomized clinical trials (RCTs). Due to low yields of RCTs, we additionally included prospective nonrandomized clinical and epidemiologic studies, and prospective studies of severe mental illness that had a focus on adherence as an outcome and reported data separately for bipolar disorder. A targeted review of the broader bipolar literature provided background for concluding remarks. Twenty-two publications were identified describing RCTs with a specific population of bipolar disorder and a measure of adherence. Additional prospective nonrandomized studies were also identified. Studies identified three major categories of factors important to adherence: patient, treatment, and systems-associated factors. Patient factors include selected demographic features, symptom severity and phase of illness, presence of past suicide attempts, psychiatric comorbidity, illness and treatment duration, and relationship with providers. Treatment factors include type and intensity of pharmacotherapy and psychotherapy. Systems-level factors include differential levels of care access and costs. There is an overall lack of RCTs, and few prospective studies, on patient and systems-related determinants of adherence. Treatment-related determinants of adherence have the most evidence to date; however, would benefit from larger studies with diverse populations. Careful assessment of treatment adherence (including partial adherence) should be included in all prospective bipolar treatment studies, and studies should be conducted to prospectively evaluate interventions to minimize nonadherence.