Randomized, placebo-controlled pilot study of divalproex sodium in the treatment of acute exacerbations of chronic schizophrenia

Experimental and clinical data suggest that GABA-ergic drugs such as valpro ate may have a potential role in the treatment of schizophrenia. The author s designed a 21-day prospective, double-blind, randomized, placebo-controll ed pilot study of divalproex sodium as add-on treatment to haloperidol in 1 2 hospitalized patients with acute exacerbations of chronic schizophrenia, All patients received haloperidol 10 mg/day for 3 days and 15 mg/day for th e remaining 18 days, In addition, five patients were randomly assigned to r eceive divalproex augmentation and seven to receive placebo. The divalproex dose was adjusted to a target serum concentration of 75 mu g/mL for 2 week s; placebo replaced divalproex during the third and last weeks to determine any carryover effect. Psychiatric rating scales were administered at basel ine and on days 7, 14, and 21. Although the placebo group improved with hal operidol treatment, the divalproex group demonstrated greater improvement. On day 21, the divalproex group had greater improvement from baseline on th e Clinical Global Impression Scale (p less than or equal to 0.04), Brief Ps ychiatric Rating Scale (p less than or equal to 0.13), and Schedule for Ass essment of Negative Symptoms scores (p less than or equal to 0.007). After divalproex withdrawal on day 15, a carryover effect was observed during wee k 3. The authors concluded that the addition of divalproex sodium to standa rd antipsychotic drugs may prove effective in relieving the symptoms of acu te schizophrenia, Future studies may benefit from the design of this pilot study. However, it is premature to apply this augmentation strategy in the clinical setting just yet because of the small sample size and the likely h eterogeneity of the disorder.