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Most treatment guidelines for bipolar disorder list lithium and valproate as first-line mood stabilizers, although lithium prescriptions have declined recently. In a randomized, open-label, multisite, international, 2-year trial, researchers compared the effectiveness of lithium, valproate, and their combination in preventing relapse.
First, 459 nonacutely ill patients with bipolar I disorder (74% without history of mood-stabilizer maintenance) received the combination at minimally effective doses (typically, for 4–8 weeks). The 330 participants who tolerated combination treatment were then randomized to continue the combination or to receive either monotherapy (the other drug was gradually withdrawn). Treatment groups were balanced for mult…