Early onset of treatment efficacy is especially important for severe mania syndromes. Lithium has usually a delayed onset of response, which is disadvantageous for inpatient treatment of severe mania. Valproate is effective in treating acute mania and has sedative properties. It has, however, a response rate of approximately only two thirds. Therefore, the initial combination of valproate and lithium was evaluated in a prospective case series of 12 patients, and a retrospective analysis was carried out for 5 patients in comparison with a pretreatment period when lithium therapy was applied without valproate. Outcome criterion for analysis was the latency of response and remission, as well as the amount of neuroleptics used for additional sedation. Patients had a mania syndrome-severity score comparable with the mean mania score of the bipolar manic patients treated in the same unit. All patients under the combination treatment responded. The response occurred within a shorter time compared with the lithium pretreatment episode, which is statistically marginally significant, and the use of neuroleptic medication could be markedly reduced from 18,601.6 mg chlorpromazine equivalents to 3,927.6 mg (p < 0.025). The initial valproate-lithium combination therapy seems to be a safe and effective way to treat severe mania syndromes in the clinic.

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