- Treatment for Bipolar Disorder [entered retrospectively]
- Objective. Assess the effect of drug and nondrug interventions for treating acute symptoms associated with bipolar disorder (BD) and preventing relapse.
Data sources. Ovid MEDLINE® and PsychInfo, the Cochrane Central Register of Controlled Trials, and Ovid Embase® bibliographic databases; hand searches of references of relevant systematic reviews through May, 2017.
Review methods. Eligible studies included randomized controlled trials and prospective cohorts with comparator arms enrolling adults with BD of any type with 3 weeks followup for acute mania, 3 months for depression, and 6 months for maintenance treatments. We excluded acute mania and depression studies with greater than 50 percent attrition.
Results. We synthesized evidence from 181 unique studies, 117 studies for 28 drugs, 64 studies for nondrug interventions. All drug findings with at least low-strength evidence were based on studies almost exclusively enrolling adults with BD-I. Asenapine, cariprazine, quetiapine, and olanzapine improved acute mania symptoms compared to placebo (low-strength evidence). However, improvements were of modest clinical significance, with values that were less than the minimally important difference, but still large enough that a reasonable proportion of participants likely received a benefit. Unpooled evidence indicated an overall beneficial effect of risperidone and ziprasidone on acute mania symptoms compared to placebo (low-strength evidence). Participants using antipsychotics, except quetiapine, reported more extrapyramidal symptoms compared to placebo, and those using olanzapine reported more clinically significant weight gain. Lithium improved acute mania in the short-term and prolonged time to relapse in the long-term compared to placebo (low-strength evidence). No difference was found between olanzapine and divalproex/valproate (low-strength evidence). For drugs not approved for BD, paliperidone also improved acute mania compared to placebo (low-strength evidence), while topiramate and allopurinol showed no benefit (low-strength evidence). Further, lithium improved acute mania better than topiramate, although withdrawals for adverse events were lower for topiramate. Only lithium reached a minimally important difference. All other drug comparisons to placebo or active controls for acute mania, depression, and maintenance had insufficient evidence. For psychosocial interventions, cognitive behavioral training (CBT) was no better for depression or mania symptoms than psychoeducation or other active psychosocial comparators (low-strength evidence). Systematic/collaborative care had no effect on relapse compared to inactive comparators (low-strength evidence). Evidence was insufficient for all other nondrug interventions.
Conclusions. We found no high- or moderate-strength evidence for any intervention to effectively treat any phase of any type of BD compared with placebo or an active comparator. Low-strength evidence showed improved mania symptoms for all FDA-approved antipsychotics, except aripiprazole, when compared with placebo for adults with BD-I. Low-strength evidence also showed benefit from lithium for acute mania in the short-term and resulted in longer periods of maintenance versus placebo in adults with BD-I. Participants using atypical antipsychotics, except quetiapine, reported more extrapyramidal symptoms compared with placebo, and those using olanzapine reported more clinically significant weight gain. Evidence was insufficient for most nondrug interventions. Low-strength evidence showed no benefit for CBT on mood symptoms compared with active controls or systematic/collaborative care compared with inactive controls on relapse. Information on harms was limited across all drug and nondrug studies. Future studies of BD treatments will require innovative ways to increase study completion rates.
- Authors of Report
- Methodology description
- Data entered retrospectively. Data available for download in attached Word Documents. Each file contains study demographics, risk of bias assessments, and study outcomes organized by intervention type (12 intervention types total).
- Funding Source