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, Kenji Sakuma, Satoru Esumi, Yasuhiko Hashimoto, Masakazu Hatano, Yuki Matsuda, Yuki Matsui, Nobumi Miyake, Ikuo Nomura, Makoto Okuya, Nakao Iwata, Masaki Kato, Ryota Hashimoto, Kazuo Mishima, Norio Watanabe, Taro Kishi

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)241-246
Number of pages6
JournalNeuropsychopharmacology reports
Volume39
Issue number3
DOIs
Publication statusPublished - 01-09-2019

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Bipolar Disorder
Lithium
Meta-Analysis
Randomized Controlled Trials
Placebos
Safety
Numbers Needed To Treat
Recurrence
Odds Ratio
Therapeutics
PubMed
Pharmaceutical Preparations
Suicide
Libraries
lamotrigine
Confidence Intervals
Depression
Mortality

All Science Journal Classification (ASJC) codes

  • Clinical Psychology
  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

Oya, Kazuto ; Sakuma, Kenji ; Esumi, Satoru ; Hashimoto, Yasuhiko ; Hatano, Masakazu ; Matsuda, Yuki ; Matsui, Yuki ; Miyake, Nobumi ; Nomura, Ikuo ; Okuya, Makoto ; Iwata, Nakao ; Kato, Masaki ; Hashimoto, Ryota ; Mishima, Kazuo ; Watanabe, Norio ; Kishi, Taro. / 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. In: Neuropsychopharmacology reports. 2019 ; Vol. 39, No. 3. pp. 241-246.
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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.",
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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. / Oya, Kazuto; Sakuma, Kenji; Esumi, Satoru; Hashimoto, Yasuhiko; Hatano, Masakazu; Matsuda, Yuki; Matsui, Yuki; Miyake, Nobumi; Nomura, Ikuo; Okuya, Makoto; Iwata, Nakao; Kato, Masaki; Hashimoto, Ryota; Mishima, Kazuo; Watanabe, Norio; Kishi, Taro.

In: Neuropsychopharmacology reports, Vol. 39, No. 3, 01.09.2019, p. 241-246.

Research output: Contribution to journalArticle

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

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.

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