Valproate v. lithium in the treatment of bipolar disorder in clinical practice: observational nationwide register-based cohort study.

BACKGROUND: Valproate is one of the most used mood stabilisers for bipolar disorder, although the evidence for the effectiveness of valproate is sparse. AIMS: To compare the effect of valproate v. lithium for treatment of bipolar disorder in clinical practice. METHOD: An observational cohort study with linkage of nationwide registers of all people with a diagnosis of bipolar disorder in psychiatric hospital settings who were prescribed valproate or lithium in Denmark during a period from 1995 to 2006. RESULTS: A total of 4268 participants were included among whom 719 received valproate and 3549 received lithium subsequent to the diagnosis of bipolar disorder. The rate of switch/add on to the opposite drug (lithium or valproate), antidepressants, antipsychotics or anticonvulsants (other than valproate) was increased for valproate compared with lithium (hazard ratio (HR) = 1.86, 95% CI 1.59-2.16). The rate of psychiatric hospital admissions was increased for valproate v. lithium (HR = 1.33, 95% CI 1.18-1.48) and regardless of the type of episode leading to a hospital admission (depressive or manic/mixed). Similarly, for participants with a depressive index episode (HR = 1.87, 95% CI 1.40-2.48), a manic index episode (HR = 1.24, 95% CI 1.01-1.51) and a mixed index episode (HR = 1.44, 95% CI 1.04-2.01), the overall rate of hospital admissions was significantly increased for valproate compared with lithium. CONCLUSIONS: In daily clinical practice, treatment with lithium seems in general to be superior to treatment with valproate.