Anees Bahji1,2, Dylan Ermacora2, Callum Stephenson3, Emily R Hawken4,5, Gustavo Vazquez4,5. 1. Department of Psychiatry, 2129University of Calgary, Alberta, Canada. 2. Department of Public Health Sciences, 4257Queen's University, Kingston, Ontario, Canada. 3. School of Kinesiology and Health Studies, 4257Queen's University, Kingston, Ontario, Canada. 4. Department of Psychiatry, 4257Queen's University, Kingston, Ontario, Canada. 5. Providence Care Hospital, Kingston, Ontario, Canada.
Abstract
OBJECTIVE: We investigated the comparative efficacy and tolerability of augmentation strategies for bipolar depression. DATA SOURCES: We conducted a systematic review and network meta-analysis of 8 electronic databases for double-blind, randomized controlled trials of adjunctive pharmacotherapies for acute bipolar depression. DATA EXTRACTION AND SYNTHESIS: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and applied the Cochrane risk of bias tool for study quality appraisal. Two reviewers independently abstracted data. We resolved all discrepancies by consensus. MAIN OUTCOMES AND MEASURES: Primary outcomes were response and completion of treatment. We estimated summary rate ratios (RRs) and standardized mean differences (SMDs) relative to placebo controls using frequentist random-effects network meta-analysis. RESULTS: We identified 69 trials meeting eligibility criteria (8,007 participants, 42.8 years, 58.0% female). Adjunctive racemic intravenous ketamine, coenzyme Q10, pramipexole, fluoxetine, and lamotrigine were more effective than placebo. Summary RRs for response ranged between 1.51 (95% confidence interval [CI], 1.11 to 2.06) for fluoxetine and 12.49 (95% CI, 3.06 to 50.93) for racemic intravenous ketamine. For completion of treatment, risperidone appeared less tolerable than placebo (RR = 0.59; 95% CI, 0.38 to 0.94), while fluoxetine seemed more tolerable than placebo (RR = 1.13; 95% CI, 1.02 to 1.24). None of the investigated agents were associated with increased treatment-emergent mood switches. CONCLUSIONS AND RELEVANCE: The evidence for augmentation strategies in bipolar depression is limited to a handful of agents. Fluoxetine appeared to have the most consistent evidence base for both efficacy and tolerability. There remains a need for additional research exploring novel treatment strategies for bipolar depression, particularly head-to-head studies.
OBJECTIVE: We investigated the comparative efficacy and tolerability of augmentation strategies for bipolar depression. DATA SOURCES: We conducted a systematic review and network meta-analysis of 8 electronic databases for double-blind, randomized controlled trials of adjunctive pharmacotherapies for acute bipolar depression. DATA EXTRACTION AND SYNTHESIS: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and applied the Cochrane risk of bias tool for study quality appraisal. Two reviewers independently abstracted data. We resolved all discrepancies by consensus. MAIN OUTCOMES AND MEASURES: Primary outcomes were response and completion of treatment. We estimated summary rate ratios (RRs) and standardized mean differences (SMDs) relative to placebo controls using frequentist random-effects network meta-analysis. RESULTS: We identified 69 trials meeting eligibility criteria (8,007 participants, 42.8 years, 58.0% female). Adjunctive racemic intravenous ketamine, coenzyme Q10, pramipexole, fluoxetine, and lamotrigine were more effective than placebo. Summary RRs for response ranged between 1.51 (95% confidence interval [CI], 1.11 to 2.06) for fluoxetine and 12.49 (95% CI, 3.06 to 50.93) for racemic intravenous ketamine. For completion of treatment, risperidone appeared less tolerable than placebo (RR = 0.59; 95% CI, 0.38 to 0.94), while fluoxetine seemed more tolerable than placebo (RR = 1.13; 95% CI, 1.02 to 1.24). None of the investigated agents were associated with increased treatment-emergent mood switches. CONCLUSIONS AND RELEVANCE: The evidence for augmentation strategies in bipolar depression is limited to a handful of agents. Fluoxetine appeared to have the most consistent evidence base for both efficacy and tolerability. There remains a need for additional research exploring novel treatment strategies for bipolar depression, particularly head-to-head studies.
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