A randomized, placebo-controlled 12-month trial of divalproex and lithium in treatment of outpatients with bipolar I disorder

Background: Long-term outcomes are often poor in patients with bipolar diso rder despite treatment, more effective treatments are needed to reduce recu rrences and morbidity. This study compared the efficacy of dival-proex, lit hium, and placebo as prophylactic therapy. Methods: A randomized, double-blind, parallel-group multicenter study of tr eatment outcomes was conducted over a 52-week maintenance period. Patients who met the recovery criteria within 3 months of the onset of an index mani c episode (n = 372) were randomized to maintenance treatment with divalproe x, lithium, or placebo in a 2:1:1 ratio. Psychotropic medications were disc ontinued before randomization, except for open label divalproex or lithium, which were gradually tapered over the first 2 weeks of maintenance treatme nt. The primary outcome measure was time to recurrence of any mood episode. Secondary measures were time to a manic episode, time to a depressive epis ode, average change from baseline in Schedule fur Affective Disorders and S chizophrenia-Change Version subscale scores for depression and mania, and G lobal Assessment of Function scores. Results: The divalproex group did not differ significantly from the placebo group in time to any mood episode. Divalproex was superior to placebo in t erms of lower rates of discontinuation for either a recurrent mood episode or depressive episode. Divalproex was superior to lithium in longer duratio n of successful prophylaxis in the study and less deterioration in depressi ve symptoms and Global Assessment Scale scores. Conclusions: The treatments did not differ significantly on time to recurre nce of any mood episode during maintenance therapy. Patients treated with d ivalproex had better outcomes than those treated with placebo or lithium on several secondary outcome measures.