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

Abstract

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.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Miklowitz reported receiving research support from the National Institute of Mental Health, the Danny Alberts Foundation, the Attias Family Foundation, the Carl and Roberta Deutsch Foundation, the Kayne Family Foundation, AIM for Mental Health, and the Max Gray Fund; receiving book royalties from Guilford Press and John Wiley and Sons; and serving as principal investigator on 4 of the included trials in this meta-analysis. Dr Furukawa reported receiving personal fees from Mitsubishi-Tanabe, MSD, and Shionogi; and receiving a grant from Mitsubishi-Tanabe, outside the submitted work; having a patent (2018-177688) pending; and being Diplomate of the Academy of Cognitive Therapy. Dr Scott reported being a distinguished founding fellow of the International Academy of CBT; receiving grant funding from the UK Medical Research Council and the UK National Institutes for Health Research for Patient Benefit programme; and serving as principal investigator on 2 of the included trials in this analysis. Dr Cipriani reported receiving research and consultancy fees from INCiPiT (Italian Network for Paediatric Trials), CARIPLO Foundation, and Angelini Pharma. No other disclosures were reported.

Figures

Figure 1.. PRISMA Flow Diagram

Figure 2.. Geometry of Networks for Treatment-Level Comparisons

Network structure for the 4 outcomes examined in this article. Nodes denote treatments, and lines denote trials performing the corresponding treatment comparison. The size of a node is proportional to the number of studies that included the corresponding treatment. The thickness of the lines corresponds to the number of studies performing each comparison (also indicated by the number on each line). CBT indicates cognitive behavioral therapy; IPSRT, interpersonal and social rhythm therapy; and TAU, treatment as usual.