In Bipolar Disorder, Lithium Alone or with Valproate Is More Effective Than Valproate Alone

Lithium carbonate and valproate sodium are each recommended as monotherapy for preventing relapses in patients with bipolar disorder and are sometimes used in combination. However, combination therapy and monotherapy have never been compared rigorously.

In this international trial, investigators enrolled 459 adults with bipolar I disorder who were in remission. For 4 to 8 weeks, patients received both drugs; lithium was titrated to a therapeutic level, and valproate was titrated to the highest tolerated dose. The 330 patients who adhered to and tolerated this run-in therapy then were randomized to receive either lithium or valproate monotherapy or to continue combination therapy for as long as 24 months. Treatment assignment was unblinded.

Th…