Both lithium and valproate have been used to prevent relapses in bipolar disorder. In a recent unblinded randomized trial, 330 patients ≥ 16 years old were given combination therapy with lithium and valproate during an active run-in period lasting 4-8 weeks. Patients were then randomized to lithium, valproate, or combination therapy and followed for 24 months. The outcome measured was either a medication adjustment or hospitalization due to a new mood episode. This occurred in 54% of patients taking combination therapy (p = 0.0023 vs. valproate, NNT 7), 59% taking lithium (p = 0.0472 vs. valproate, NNT 10), and 69% taking valproate (level 2 [mid-level] evidence). While use of lithium (alone or with valproate) was statistically superior to valproate alone, this study did not find that combination therapy was significantly better than lithium alone. There were no significant differences among groups in serious adverse events (16 overall, including 6 deaths) (Lancet 2010 Jan 19 early online).

For more information, see the Bipolar disorder topic in DynaMed.