• We onducted a placeplacebo-controlled, double-blind valproate, iginally developed as an antiepileptic, patients with acute manic episodes who had previously failed to respond to or to tolerate lithium carbonate. Treatment duration was 7 to 21 days, with no other psychotropic medications permittedcept lorazepammg/d during the first 10 days of treatment. Serum valproateations were measured three times weekly; an unblindedator then adjusted dosage to produce serum concentrations between 50 and 100 mValproated superior to placebo in alleviating manic symptoms. The 17 patients randomized to active drug demonstrated a median 54% decrease in scores on the Young Mania Rating Scale as compared with a median 5.0%rease among the 19patients receiving placebo. On the 100-point Global Assessment Scale of overall psychiatric functioning, patients receiving vim-te proved by a median of 20 points as compared with a zero-point change with placebo. Significant differences also emerged on the Brief Psychiatric Rating Scale and in the number of supplemental doses of lorazepam by the patients in each group. Substantial antimanicappeared within 1 to 4 days of achieving therapeutic serum valproateations. Adverse effects were infrequent, with no adverse effect appearing significantly more frequently with valproateh placebo. We conclude that valproatets a useful new drug for the treatment of manic patients.