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

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.