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Meta-Analysis
. 2019 Sep;39(3):241-246.
doi: 10.1002/npr2.12056. Epub 2019 Apr 26.

Efficacy and safety of lithium and lamotrigine for the maintenance treatment of clinically stable patients with bipolar disorder: A systematic review and meta-analysis of double-blind, randomized, placebo-controlled trials with an enrichment design

Kazuto Oya  1 , Kenji Sakuma  1 , Satoru Esumi  2 , Yasuhiko Hashimoto  3 , Masakazu Hatano  1   4 , Yuki Matsuda  5 , Yuki Matsui  6 , Nobumi Miyake  7 , Ikuo Nomura  1 , Makoto Okuya  1 , Nakao Iwata  1 , Masaki Kato  8 , Ryota Hashimoto  9 , Kazuo Mishima  10 , Norio Watanabe  11 , Taro Kishi  1
Affiliations
Meta-Analysis

Efficacy and safety of lithium and lamotrigine for the maintenance treatment of clinically stable patients with bipolar disorder: A systematic review and meta-analysis of double-blind, randomized, placebo-controlled trials with an enrichment design

Kazuto Oya et al. Neuropsychopharmacol Rep. 2019 Sep.

Abstract

Aim: Whether patients with adult bipolar disorder (BD) who have been clinically stabilized with lithium or lamotrigine should continue this medication is not established fully. This systematic review and meta-analysis evaluated the efficacy and safety of lithium and lamotrigine for maintenance treatment in clinically stable patients with adult BD.

Methods: This meta-analysis included only double-blind, randomized, placebo-controlled trials with an enrichment design that selected patients who responded acutely to lithium or lamotrigine. Reports prior to November 15, 2018, were retrieved from the PubMed/Cochrane Library/Embase. The primary outcome was the relapse rate due to any mood episode at the study endpoint. Other outcomes were relapse rates due to a manic/hypomanic/mixed episode or depression at the study endpoint, discontinuation rate, death, and death by suicide. Risk ratios (RRs) (95% confidence intervals) were calculated. When the random-effects model showed significant differences between groups, the number-needed-to-treat (NNT) was estimated.

Results: The search retrieved two studies regarding lithium (N = 218) and four evaluating lamotrigine (N = 706). Both drugs were superior to placebo for reducing the relapse rate due to any mood episode [lithium: RR = 0.52 (0.41-0.66), P < 0.00001, I2 = 0%, NNT = 2.3 (1.6-4.2); lamotrigine: RR = 0.81 (0.70-0.93), P = 0.004, I2 = 0%, NNT = 8.3 (5.0-25.0)] and all-cause discontinuation. There were no significant differences in other outcomes between lithium or lamotrigine and the placebo groups.

Conclusion: Both drugs showed benefit for preventing relapse in clinically stable patients with adult BD. However, the number of studies and patients in this analysis was small.

Keywords: bipolar disorder; lamotrigine; lithium; meta-analysis; systematic review.

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Conflict of interest statement

The authors have declared that there are no conflicts of interest in relation to the subject of this study. We have had the following interests within the past 3 years. Dr. Oya has received speaker's honoraria from Chugai, Dainippon Sumitomo, Eisai, Eli Lilly, Janssen, Kissei, Meiji, MSD, Otsuka, and Tanabe‐Mitsubishi and has received research grants from Fujita Health University School of Medicine. Dr. Sakuma has received speaker's honoraria from Meiji, Otsuka, and Torii. Dr. Esumi has no conflict of interest relationship with any company. Dr. Hashimoto has no conflict of interest relationship with any company. Mr. Hatano has received speaker's honoraria from Otsuka. Dr. Matsuda has received speaker's honoraria from Dainippon Sumitomo, Eisai, Eli Lilly, GlaxoSmithKline, Otsuka, Pfizer, and Tanabe‐Mitsubishi and has received a grant‐in‐aid for Young Scientists (B). Dr. Matsui has received speaker's honoraria from Dainippon Sumitomo, Janssen, and Meiji. Dr. Miyake has received speaker's honoraria from Dainippon Sumitomo, Eisai, Meiji, Otsuka, and Tanabe‐Mitsubishi. Dr. Nomura has received speaker's honoraria from Meiji, MSD, Janssen, Otsuka, and Torii. Dr. Okuya has received speaker's honoraria from Meiji and Torii. Dr. Iwata has received speaker's honoraria from Astellas, Dainippon Sumitomo, Eli Lilly, GlaxoSmithKline, Janssen, Meiji, Novartis, Otsuka, Pfizer, Shionogi, and Yoshitomi and research grants from GlaxoSmithKline and Otsuka. Dr. Kato has received grant funding from Japan Society for the Promotion of Science, SENSHIN Medical Research Foundation and Japan Research Foundation for Clinical Pharmacology, and speaker's honoraria from Dainippon Sumitomo, Eli Lilly, GlaxoSmithKline, Janssen, Meiji, MSD, Ono, Otsuka, Pfizer, Shionogi, Takeda, and Tanabe‐Mitsubishi. Dr. Hashimoto has received speaker's honoraria from Dainippon Sumitomo, Mnochida, Novartis, Takeda, Meiji Seika, Shionogi, Eli Lilly, and Astellas Dr. Mishima has received research support from the Japanese Ministry of Health, Labor and Welfare, the Japanese Ministry of Education, Science, and Technology, and the National Center of Neurology and Psychiatry Intramural Research Grant for Neurological and Psychiatric Disorders and speaker's honoraria from Eisai, Takeda, Astellas, and Janssen along with research grants from Eisai, Nobelpharma, and Takeda. Dr. Watanabe has received research funds from the Japanese Ministry of Health Labor and Welfare, and the Japanese Ministry of Education, Science, and Technology and also received royalties from Sogensha and Akatsuki. Dr. Kishi has received speaker's honoraria from Daiichi Sankyo, Dainippon Sumitomo, Eisai, Eli Lilly, Janssen, Otsuka, Meiji, MSD, Tanabe‐Mitsubishi, and Yoshitomi and has received a Health Labor Sciences Research Grant and a Fujita Health University School of Medicine research grant.

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