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Br J Psychiatry. 2011 Jul;199(1):57-63. doi: 10.1192/bjp.bp.110.084822. Epub 2011 May 18.

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

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Psychiatric Center Copenhagen, University Hospital of Copenhagen, Rigshospitalet, Copenhagen, Denmark.



Valproate is one of the most used mood stabilisers for bipolar disorder, although the evidence for the effectiveness of valproate is sparse.


To compare the effect of valproate v. lithium for treatment of bipolar disorder in clinical practice.


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.


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.


In daily clinical practice, treatment with lithium seems in general to be superior to treatment with valproate.

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