TY - JOUR
T1 - Efficacy and safety of lithium and lamotrigine for the maintenance treatment of clinically stable patients with bipolar disorder
T2 - A systematic review and meta-analysis of double-blind, randomized, placebo-controlled trials with an enrichment design
AU - Oya, Kazuto
AU - Sakuma, Kenji
AU - Esumi, Satoru
AU - Hashimoto, Yasuhiko
AU - Hatano, Masakazu
AU - Matsuda, Yuki
AU - Matsui, Yuki
AU - Miyake, Nobumi
AU - Nomura, Ikuo
AU - Okuya, Makoto
AU - Iwata, Nakao
AU - Kato, Masaki
AU - Hashimoto, Ryota
AU - Mishima, Kazuo
AU - Watanabe, Norio
AU - Kishi, Taro
N1 - Funding Information:
Funding information The present study was supported by the Health and Labor Sciences Research Grants (H29-Seishin-Ippan-001). The current study was conducted as part of a ?Study on the actual status of psychotropic drug prescription in Japan and clinical practice guideline for proper use and cessation of psychotropic drugs.? We greatly appreciate Drs. Ken Inada (Tokyo Women's Medical University, School of Medicine), Takeshi Inoue (Tokyo Medical University), Toshihiko Matsumoto (National Center of Neurology and Psychiatry), Takashi Okada (Nagoya University Graduate School of Medicine), Tsukasa Sasaki (University of Tokyo), Yoshio Yamanouchi (National Center of Neurology and Psychiatry), and Takashi Yoshio (Toho University) for their helpful advice on this article. We also thank Mr. Miyanohara (Fujita Health University School of Medicine) for his technical support.
PY - 2019/9/1
Y1 - 2019/9/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85071784836&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85071784836&partnerID=8YFLogxK
U2 - 10.1002/npr2.12056
DO - 10.1002/npr2.12056
M3 - Article
C2 - 31026388
AN - SCOPUS:85071784836
VL - 39
SP - 241
EP - 246
JO - Neuropsychopharmacology Reports
JF - Neuropsychopharmacology Reports
SN - 1340-2544
IS - 3
ER -