Comparative efficacy and tolerability of pharmacological treatments for the treatment of acute bipolar depression: A systematic review and network meta-analysis

•We reviewed the peer-reviewed academic literature to synthesize evidence for the comparative efficacy and acceptability of treatments for bipolar depression.•50 randomized controlled trials were identified and data across studies were pooled by way of network meta-analysis.•Escitalopram, phenelzine...

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Bibliographic Details
Published in:Journal of affective disorders 2020-05, Vol.269, p.154-184
Main Authors: Bahji, Anees, Ermacora, Dylan, Stephenson, Callum, Hawken, Emily R., Vazquez, Gustavo
Format: Article
Language:English
Subjects:
Antipsychotic Agents - adverse effects
Bipolar disorder
Bipolar Disorder - drug therapy
Comparative effectiveness
Depression
Humans
Lurasidone Hydrochloride - therapeutic use
Meta-analysis
Network Meta-Analysis
Olanzapine - therapeutic use
Pharmacotherapies
Review
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Summary:•We reviewed the peer-reviewed academic literature to synthesize evidence for the comparative efficacy and acceptability of treatments for bipolar depression.•50 randomized controlled trials were identified and data across studies were pooled by way of network meta-analysis.•Escitalopram, phenelzine, moclobemide, carbamazepine, sertraline, lithium, paroxetine, aripiprazole, gabapentin and ziprasidone appear to be ineffective as compared to placebo in treatment of bipolar depression.•Divalproex, olanzapine/fluoxetine, olanzapine, quetiapine, cariprazine, and lamotrigine, appear to be effective as compared to placebo in treatment of bipolar depression according to the network meta-analysis.•Aripiprazole showed higher discontinuation rates versus placebo due to the appearance of any adverse event.•Quetiapine was better than placebo at reducing treatment-emergent affective switches. We investigated the comparative efficacy and tolerability of pharmacological treatment strategies for the treatment of acute bipolar depression. A systematic review and network meta-analysis was conducted by searching eight registries for published and unpublished, double-blind, randomized controlled trials of pharmacotherapies for the acute treatment of bipolar depression. PRISMA guidelines were used for abstracting data, while the Cochrane Risk of Bias Tool was used to assess data quality. Data extraction was done independently by two reviewers, with discrepancies resolved by consensus. Data were pooled using a random-effects model. Primary outcomes were efficacy (response and remission rate) and acceptability (completion of treatment and dropouts due to adverse events). Summary odds ratios (ORs) were estimated using pairwise and network meta-analysis with random effects. Identified citations (4,404) included 50 trials comprising 11,448 participants. Escitalopram, phenelzine, moclobemide, carbamazepine, sertraline, lithium, paroxetine, aripiprazole, gabapentin and ziprasidone appear to be ineffective as compared to placebo in treatment of bipolar depression. Divalproex, olanzapine/fluoxetine, olanzapine, quetiapine, cariprazine, and lamotrigine, appear to be effective as compared to placebo in treatment of bipolar depression according to the network meta-analysis. Aripiprazole showed higher discontinuation rates versus placebo due to the appearance of any adverse event. Quetiapine was better than placebo at reducing treatment-emergent affective switches. For Bipolar I Disorder, c
ISSN:0165-0327
1573-2517
DOI:10.1016/j.jad.2020.03.030