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Original Investigation
October 14, 2020

Adjunctive Psychotherapy for Bipolar Disorder: A Systematic Review and Component Network Meta-analysis

Author Affiliations
  • 1Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles
  • 2Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, United Kingdom
  • 3Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
  • 4Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine/School of Public Health, Kyoto, Japan
  • 5Department of Clinical Epidemiology, Kyoto University Graduate School of Medicine/School of Public Health, Kyoto, Japan
  • 6Brain and Mind Centre, The University of Sydney, Sydney, Australia
  • 7Institute of Neuroscience, Newcastle University, Newcastle, United Kingdom
  • 8Oxford Health National Health Service Foundation Trust, Warneford Hospital, Oxford, United Kingdom
JAMA Psychiatry. Published online October 14, 2020. doi:10.1001/jamapsychiatry.2020.2993
Key Points

Question  Which psychosocial interventions are associated with an improved course and medium-term outcomes of bipolar disorder?

Findings  In a systematic review and network meta-analysis of 39 randomized clinical trials of adjunctive psychotherapy, there was evidence that family, cognitive behavioral, and psychoeducational therapies were associated with reduced episode recurrence vs treatment as usual in individuals with bipolar disorder. Cognitive behavioral therapy was associated with greater stabilization of residual symptoms of depression compared with treatment as usual.

Meaning  This study suggests that outpatients with bipolar disorder receiving pharmacotherapy should also be offered psychosocial treatments that emphasize illness management strategies and enhance coping skills; delivering these components in family or group format may be especially advantageous.


Importance  Several psychotherapy protocols have been evaluated as adjuncts to pharmacotherapy for patients with bipolar disorder, but little is known about their comparative effectiveness.

Objective  To use systematic review and network meta-analysis to compare the association of using manualized psychotherapies and therapy components with reducing recurrences and stabilizing symptoms in patients with bipolar disorder.

Data Sources  Major bibliographic databases (MEDLINE, PsychInfo, and Cochrane Library of Systematic Reviews) and trial registries were searched from inception to June 1, 2019, for randomized clinical trials of psychotherapy for bipolar disorder.

Study Selection  Of 3255 abstracts, 39 randomized clinical trials were identified that compared pharmacotherapy plus manualized psychotherapy (cognitive behavioral therapy, family or conjoint therapy, interpersonal therapy, or psychoeducational therapy) with pharmacotherapy plus a control intervention (eg, supportive therapy or treatment as usual) for patients with bipolar disorder.

Data Extraction and Synthesis  Binary outcomes (recurrence and study retention) were compared across treatments using odds ratios (ORs). For depression or mania severity scores, data were pooled and compared across treatments using standardized mean differences (SMDs) (Hedges-adjusted g using weighted pooled SDs). In component network meta-analyses, the incremental effectiveness of 13 specific therapy components was examined.

Main Outcomes and Measures  The primary outcome was illness recurrence. Secondary outcomes were depressive and manic symptoms at 12 months and acceptability of treatment (study retention).

Results  A total of 39 randomized clinical trials with 3863 participants (2247 of 3693 [60.8%] with data on sex were female; mean [SD] age, 36.5 [8.2] years) were identified. Across 20 two-group trials that provided usable information, manualized treatments were associated with lower recurrence rates than control treatments (OR, 0.56; 95% CI, 0.43-0.74). Psychoeducation with guided practice of illness management skills in a family or group format was associated with reducing recurrences vs the same strategies in an individual format (OR, 0.12; 95% CI, 0.02-0.94). Cognitive behavioral therapy (SMD, −0.32; 95% CI, −0.64 to −0.01) and, with less certainty, family or conjoint therapy (SMD, −0.46; 95% CI, −1.01 to 0.08) and interpersonal therapy (SMD, –0.46; 95% CI, −1.07 to 0.15) were associated with stabilizing depressive symptoms compared with treatment as usual. Higher study retention was associated with family or conjoint therapy (OR, 0.46; 95% CI, 0.26-0.82) and brief psychoeducation (OR, 0.44; 95% CI, 0.23-0.85) compared with standard psychoeducation.

Conclusions and Relevance  This study suggests that outpatients with bipolar disorder may benefit from skills-based psychosocial interventions combined with pharmacotherapy. Conclusions are tempered by heterogeneity in populations, treatment duration, and follow-up.

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