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A systematic review and meta-analysis of treatments for rapid cycling bipolar disorder

Research output: Contribution to journalReview articlepeer-review

Original languageEnglish
Pages (from-to)290-311
Number of pages22
JournalActa Psychiatrica Scandinavica
Issue number4
Early online date20 Jul 2022
Accepted/In press28 Jun 2022
E-pub ahead of print20 Jul 2022
PublishedOct 2022

Bibliographical note

Funding Information: In the last 3 years: Rebecca Strawbridge declares an honorarium from Lundbeck; Allan H. Young declares honoraria for speaking from Astra Zeneca, Lundbeck, Eli Lilly, Sunovion, honoraria for consulting from Allergan, Livanova and Lundbeck, Sunovion, Janssen, and research grant support from Janssen; Sameer Jauhar has received honoraria for educational talks given for Lundbeck, Sunovian and Janssen, on antipsychotics; Nefize Yalin has worked on studies conducted together with Janssen Cliag, Corcept Therapeutics and COMPASS Pathways. No other conflicts of interest are declared. Funding Information: This work is supported by the National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. Funding Information: We are grateful to the following individuals who communicated with the authors and where possible provided information about and/or data from their studies, including Prof Jay Amsterdam, Prof Gerhard Lenz, Prof Robert Post, Prof Mauricio Tohen and Tracy Dorsel on behalf of Eli Lilly. Publisher Copyright: © 2022 The Authors. Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.


King's Authors


Objectives: Rapid cycling is a common and disabling phenomenon in individuals with bipolar disorders. In the absence of a recent literature examination, this systematic review and meta-analysis aimed to synthesise the evidence of efficacy, acceptability and tolerability of treatments for individuals with rapid cycling bipolar disorder (RCBD). Method: A systematic search was conducted to identify randomised controlled trials assigning participants with RCBD to pharmacological and/or non-pharmacological interventions. Study inclusion and data extraction were undertaken by two reviewers independently. The primary outcome was continuous within-subject RCBD illness severity before and after treatment. Pre-post random effects meta-analyses were conducted for each outcome/intervention arm studied, generating a standardised effect size (hedge's g) and 95% confidence interval (CI). Results: A total of 34 articles describing 30 studies were included. A total of 16 separate pharmacological treatments were examined in contrast to 1 psychological therapy study. Only quetiapine and lamotrigine were assessed in >5 studies. By assessing 95% CI overlap of within-subject efficacy effects compared to placebo, the only interventions suggesting significant depression benefits (placebo g = 0.60) were olanzapine (with/without fluoxetine; g = 1.01), citalopram (g = 1.10) and venlafaxine (g = 2.48). For mania, benefits were indicated for quetiapine (g = 1.01), olanzapine (g = 1.19) and aripiprazole (g = 1.09), versus placebo (g = 0.33). Most of these effect sizes were from only one trial per treatment. Heterogeneity between studies was variable, and 20% were rated to have a high risk of bias. Conclusions: While many interventions appeared efficacious, there was a lack of robust evidence for most treatments. Given the limited and heterogeneous evidence base, the optimal treatment strategies for people with RCBD are yet to be established.

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