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Meta-Analysis
. 2022 Jan:54:75-89.
doi: 10.1016/j.euroneuro.2021.08.264. Epub 2021 Sep 3.

Preventing new episodes of bipolar disorder in adults: Systematic review and meta-analysis of randomized controlled trials

Anastasiya Nestsiarovich  1 , Christopher E S Gaudiot  2 , Ross J Baldessarini  3 , Eduard Vieta  4 , Yiliang Zhu  5 , Mauricio Tohen  2
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Free article
Meta-Analysis

Preventing new episodes of bipolar disorder in adults: Systematic review and meta-analysis of randomized controlled trials

Anastasiya Nestsiarovich et al. Eur Neuropsychopharmacol. 2022 Jan.
Free article

Abstract

Uncertainty remains regarding the relative efficacy of maintenance pharmacotherapy for bipolar disorder (BD), and available data require updating. The present systematic review and meta-analysis aims to consolidate the evidence from the highest quality randomized controlled trials (RCTs) published up to July 2021, overcoming the limitations of earlier reviews. The PubMed and the Cochrane Central Register of Controlled Trials were searched for double-blind RCTs involving lithium, mood stabilizing anticonvulsants (MSAs), antipsychotics, antidepressants, and other treatments. Rates of new mood episodes with test vs. reference treatments (placebo or alternative active agent) were compared by random-effects meta-analysis. Polarity index was calculated for each treatment type. Eligible trials involved ≥6 months of maintenance follow up. Of 2,158 identified reports, 22 met study eligibility criteria, and involved 7,773 subjects stabilized for 1-12 weeks and followed-up for 24-104 weeks. Psychotropic monotherapy overall (including lithium, MSAs, and second generation antipsychotics (SGA) was more effective in preventing new BD episodes than placebo (odds ratio, OR=0.42; 95% confidence interval, CI 0.34-0.51, p<0.00001). Significantly lower risk of new BD episodes was observed with the following individual drugs: aripiprazole, asenapine, lithium, olanzapine, quetiapine, and risperidone long-acting (ORs varied 0.19-0.46). Adding aripiprazole, divalproex, quetiapine, or olanzapine/risperidone to lithium or an MSA was more effective compared with lithium or MSA monotherapy (OR=0.37; 95%CI 0.25-0.55, p<0.00001). Active treatment favored prevention of mania over depression. The key limitations were "responder-enriched" design in most trials and high outcomes heterogeneity. PROSPERO registration number is CRD42020162663.

Keywords: Bipolar disorder; Long-term; Maintenance; Meta-analysis; Review; Treatment.

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Conflict of interest statement

Declaration of Competing Interest Dr. Vieta has received grants and served as consultant, advisor, or speaker unrelated to this work from: AB-Biotics, Abbott, Allergan, Angelini, Dainippon-Sumitomo, Ferrer, Gedeon-Richter, Janssen, Lundbeck, Otsuka, Sage, Sanofi-Aventis, Sunovion, and Takeda pharmaceutical corporations. Dr. Tohen was supported by a grant from Atlas Foundation. He has also been a consultant, advisor, or speaker unrelated to this work from: Allergan, Alkermes, Abbott, AstraZeneca, BMS, Eli Lilly, Forest, Glaxo-SmithKline, Johnson & Johnson, Lundbeck, Merck, Minerva, Otsuka, Roche, Sunovion, Tecnofarma, and Teva pharmaceutical corporations, as well as Atlas Foundation, NIMH, and NARSAD. He was employed by Eli Lilly Corp. (1997–2008), as was his spouse (1998–2013). Dr. Baldessarini was supported by a grant from the Bruce J. Anderson Foundation and by the McLean Private Donors Psychiatric Research Fund. Dr. Zhu was supported by the National Institute of General Medical Sciences grants P20GM13042201, P20GM109089, and P20GM121196. Other authors (Dr. Nestsiarovich, Dr. Gaudiot) have no financial relationships with commercial entities that might appear to represent potential conflicts of interest with the work presented.

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