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

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

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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Adult
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use*
  • Bipolar Disorder / drug therapy*
  • Depression / epidemiology
  • Depression / etiology
  • Double-Blind Method
  • Female
  • Humans
  • Lamotrigine / adverse effects
  • Lamotrigine / therapeutic use*
  • Lithium / adverse effects
  • Lithium / therapeutic use*
  • Male
  • Middle Aged
  • Randomized Controlled Trials as Topic
  • Recurrence

Substances

  • Antipsychotic Agents
  • Lithium
  • Lamotrigine