title: Randomized, placebo-controlled pilot study of divalproex sodium in the treatment of acute exacerbations of chronic schizophrenia.
abstract: Experimental and clinical data suggest that GABA-ergic drugs such as valproate may have a potential role in the treatment of schizophrenia. The authors designed a 21-day prospective, double-blind, randomized, placebo-controlled pilot study of divalproex sodium as add-on treatment to haloperidol in 12 hospitalized patients with acute exacerbations of chronic schizophrenia. All patients received haloperidol 10 mg/day for 3 days and 15 mg/day for the remaining 18 days. In addition, five patients were randomly assigned to receive divalproex augmentation and seven to receive placebo. The divalproex dose was adjusted to a target serum concentration of 75 microg/mL for 2 weeks; placebo replaced divalproex during the third and last weeks to determine any carryover effect. Psychiatric rating scales were administered at baseline and on days 7, 14, and 21. Although the placebo group improved with haloperidol treatment, the divalproex group demonstrated greater improvement. On day 21, the divalproex group had greater improvement from baseline on the Clinical Global Impression Scale (p < or = 0.04), Brief Psychiatric Rating Scale (p < or = 0.13), and Schedule for Assessment of Negative Symptoms scores (p < or = 0.007). After divalproex withdrawal on day 15, a carryover effect was observed during week 3. The authors concluded that the addition of divalproex sodium to standard antipsychotic drugs may prove effective in relieving the symptoms of acute 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 heterogeneity of the disorder.
authors.affiliation: University of Texas Health Sciences Center at Houston-Harris County Psychiatric Center, 77021, USA.
authors.forename: A A
authors.initials: AA
authors.lastname: Wassef
authors.forename: S G
authors.initials: SG
authors.lastname: Dott
authors.forename: A
authors.initials: A
authors.lastname: Harris
authors.forename: A
authors.initials: A
authors.lastname: Brown
authors.forename: M
authors.initials: M
authors.lastname: O'Boyle
authors.forename: W J
authors.initials: WJ
authors.lastname: Meyer
authors.forename: R M
authors.initials: RM
authors.lastname: Rose
mesh_terms: D000208:Acute Disease; D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D002908:Chronic Disease; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D018755:GABA Agonists / Q000627:therapeutic use*; D006220:Haloperidol / Q000627:therapeutic use; D006801:Humans; D008297:Male; D010865:Pilot Projects; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D014635:Valproic Acid / Q000627:therapeutic use*
chemical_list: D014150:Antipsychotic Agents; D018755:GABA Agonists; D014635:Valproic Acid; D006220:Haloperidol