Valproate prophylaxis in a prospective clinical trial of refractory bipolar disorder.

Abstract

The authors studied the efficacy of valproate plus lithium and of triple therapy with lithium, carbamazepine, and valproate in refractory bipolar illness. The subjects were 24 bipolar outpatients who had completed an intended 3-year crossover study comparing lithium, carbamazepine, and their combination. Patients entered a 1-year phase of valproate plus lithium because of inadequate response or major side effects, and patients with inadequate responses were offered an additional year of treatment with all three mood-stabilizing drugs. Six (33%) of the 18 evaluable patients had moderate to marked responses to valproate plus lithium; four of these six had not responded to any previous treatment condition. Three of seven patients responded to triple therapy, although only one response was marked. Some outpatients with bipolar disorder refractory to lithium and carbamazepine received clinically relevant prophylactic benefit from valproate when used with lithium or in triple therapy.