Spectrum of effectiveness of valproate in neuropsychiatry.

Valproate is principally effective in manic aspects of bipolar disorder. Tolerability has been somewhat more favorable for valproate than comparators, with the frequent adverse effects being gastrointestinal disturbances and weight gain. Total cholesterol and low-density lipoproteins are reduced by valproate. Valproate is effective and well tolerated when combined with lithium or antipsychotic drugs. Valproate is efficacious in mixed and euphoric mania. In studies of maintenance versus placebo and active comparators, patients initially treated with divalproex for mania had more robust long-term benefits than in the full sample analyses. In maintenance treatment, patients whose valproate serum levels were between 75 and 99 microg/ml had longer time to discontinuation for any reason or a new mood episode than did patients receiving placebo. The profile of utility in bipolar disorders is principally for core features of manic symptomatology (e.g., impulsivity, hyperactivity and irritability), with little evidence of benefit for anxiety or psychosis. Valproate appears useful in other disorders that have behavioral dimensions inclusive of the domains that valproate benefits in bipolar disorders, such as schizophrenia.