Mood stabilizers in the prevention of recurrent affective disorders: a meta-analysis

Acta Psychiatr Scand. 1999 Dec;100(6):406-17. doi: 10.1111/j.1600-0447.1999.tb10890.x.


Objective: To determine by meta-analysis the efficacy of mood stabilizers in preventing recurrence of bipolar or unipolar mood disorders and to consider the evidence for a lithium withdrawal-induced relapse syndrome.

Method: Controlled studies of lithium, valproate and carbamazepine in preventing future episodes of affective disorders were classified according to methodological rigour, and meta-analyses were performed overall and on each type.

Results: A total of 19 blinded, randomized, controlled trials of prophylaxis in 865 patients found lithium highly effective (74% recurrence on placebo vs. 29% on lithium). In the mirror-image studies, whose substantial lithium vs. prior treatment difference cannot be explained by withdrawal relapse, lithium reduced relapse by 50% (bipolar) and 58%(unipolar).

Conclusion: Maintenance lithium produces a highly significant reduction in relapses. The mirror-image studies had not been systematically analysed previously, and they support the effectiveness of lithium. We also failed to find sufficient evidence to prove that the lithium-withdrawal relapse phenomenon exists.

Publication types

  • Meta-Analysis

MeSH terms

  • Antimanic Agents / adverse effects
  • Antimanic Agents / pharmacology
  • Antimanic Agents / therapeutic use*
  • Carbamazepine / pharmacology
  • Carbamazepine / therapeutic use*
  • Humans
  • Lithium Carbonate / adverse effects
  • Lithium Carbonate / pharmacology
  • Lithium Carbonate / therapeutic use*
  • Mood Disorders / drug therapy*
  • Mood Disorders / prevention & control
  • Prognosis
  • Recurrence
  • Substance Withdrawal Syndrome
  • Treatment Outcome
  • Valproic Acid / pharmacology
  • Valproic Acid / therapeutic use*


  • Antimanic Agents
  • Lithium Carbonate
  • Carbamazepine
  • Valproic Acid