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Recurrence rates in stable bipolar disorder patients after drug discontinuation v. drug maintenance: a systematic review and meta-analysis

Published online by Cambridge University Press:  13 October 2020

Taro Kishi Open the ORCID record for Taro Kishi [Opens in a new window] ,
Yuki Matsuda ,
Kenji Sakuma ,
Makoto Okuya ,
Kazuo Mishima  and
Nakao Iwata
Taro Kishi*
Affiliation:
Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi470-1192, Japan
Yuki Matsuda
Affiliation:
Department of Psychiatry, Jikei University School of Medicine, Minato-ku, Tokyo, 105-8461, Japan
Kenji Sakuma
Affiliation:
Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi470-1192, Japan
Makoto Okuya
Affiliation:
Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi470-1192, Japan
Kazuo Mishima
Affiliation:
Department of Neuropsychiatry, Akita University Graduate School of Medicine, Akita, Japan
Nakao Iwata
Affiliation:
Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi470-1192, Japan
*
Author for correspondence: Taro Kishi, E-mail: [email protected]
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Abstract

Background

This random-effects model meta-analysis of double-blind, randomized placebo-controlled trials compared recurrence rates in bipolar disorder (BD) patients between antipsychotic/mood stabilizer discontinuation and maintenance groups.

Methods

We conducted systematic literature search of Embase, PubMed, and CENTRAL databases without language restriction from inception until 22 May 2020. Independent investigators assessed studies and extracted data. We calculated risk ratios (RRs) and numbers needed to benefit or harm (NNTB/NNTH). Primary outcome was the recurrence rate of any mood episode at 6 months. Secondary outcomes were recurrence rates of depressive episodes and manic/hypomanic/mixed episodes and all-cause discontinuation at 6 months. We also investigated these outcomes at 1, 3, 9, 12, 18, and 24 months.

Results

We identified 22 studies (n = 5462) receiving aripiprazole, asenapine, divalproex, long-acting injectable (LAI)-aripiprazole, LAI-risperidone, lamotrigine, lithium, olanzapine, paliperidone, or quetiapine. Mean study duration was 64.50 ± 69.35 weeks. The maintenance group demonstrated lower recurrence rates of any mood episode, depressive episodes, and manic/hypomanic/mixed episodes as well as reduced all-cause discontinuation at every observational point. The RRs (95% confidence interval, NNTB/NNTH) of recurrence rate at 6 months were 0.61 (0.54–0.70, 5) for any mood episode, 0.72 (0.60–0.87, 13) for depressive episodes, and 0.45 (0.36–0.57, 6) for manic/hypomanic/mixed episodes. The RR for all-cause discontinuation at 6 months was 0.71 (0.61–0.82, 6).

Conclusions

Maintaining drug treatment during clinically stable BD prevented recurrence for up to 24 months. Discontinuation of medications for ⩾1 month significantly increased recurrence risk. However, 47.3% of patients who discontinued drugs for 6 months did not experience recurrence.

Keywords

Antipsychoticsmood stabilizerrecurrence ratesystematic review and meta-analysisdouble-blind, randomized placebo-controlled trials
Type
Original Article
Information
Psychological Medicine , Volume 51 , Issue 15 , November 2021 , pp. 2721 - 2729
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Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

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Footnotes

The online version of this article has been updated since original publication. A notice detailing the changes has also been published at https://doi.org/10.1017/S0033291721001033

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