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

Adel A. Wassef, Sharon G. Dott, Ann Harris, Alston Brown, Michael O'Boyle, Walter Meyer, Robert M. Rose

Research output: Contribution to journalArticle

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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 μg/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 ≤ 0.04), Brief Psychiatric Rating Scale (p ≤ 0.13), and Schedule for Assessment of Negative Symptoms scores (p ≤ 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.

Original languageEnglish (US)
Pages (from-to)357-361
Number of pages5
JournalJournal of Clinical Psychopharmacology
Volume20
Issue number3
DOIs
StatePublished - Jun 2000

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Valproic Acid
Schizophrenia
Placebos
Haloperidol
Therapeutics
Brief Psychiatric Rating Scale
Symptom Assessment
Sample Size
gamma-Aminobutyric Acid
Antipsychotic Agents
Psychiatry
Appointments and Schedules
Serum

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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Randomized, placebo-controlled pilot study of divalproex sodium in the treatment of acute exacerbations of chronic schizophrenia. / Wassef, Adel A.; Dott, Sharon G.; Harris, Ann; Brown, Alston; O'Boyle, Michael; Meyer, Walter; Rose, Robert M.

In: Journal of Clinical Psychopharmacology, Vol. 20, No. 3, 06.2000, p. 357-361.

Research output: Contribution to journalArticle

Wassef, Adel A. ; Dott, Sharon G. ; Harris, Ann ; Brown, Alston ; O'Boyle, Michael ; Meyer, Walter ; Rose, Robert M. / Randomized, placebo-controlled pilot study of divalproex sodium in the treatment of acute exacerbations of chronic schizophrenia. In: Journal of Clinical Psychopharmacology. 2000 ; Vol. 20, No. 3. pp. 357-361.
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