Effect of divalproex combined with olanzapine or risperidone in patients with an acute exacerbation ofschizophrenia

Daniel E. Casey, David G. Daniel, Adel A. Wassef, Katherine A. Tracy, Patricia Wozniak, Kenneth W. Sommerville

Research output: Contribution to journalArticlepeer-review

207 Scopus citations


This double-blind, randomized, multicenter study investigated the use of divalproex with an antipsychotic agent in patients hospitalized for acute exacerbation of schizophrenia. Patients (n = 249) who met DSM-IV criteria for schizophrenia were randomly assigned toreceive olanzapine monotherapy, risperidonemonotherapy, divalproex plus olanzapine, or divalproex plus risperidone for 28 days.Divalproex was initiated at 15 mg/kg/day and titrated over 12 days to a maximum dosage of 30 mg/kg/day. Olanzapine and risperidone, were, respectively, initiated at 5 and 2 mg/day and were titrated over the first 6 days to respective target fixed daily dosages of 15 and6mg/day. Improvements from baseline were observed at allevaluation points throughout the 28-day treatment period in the twocombination therapy and the two antipsychotic monotherapy groups, with statistically significant treatment differences favoringcombination therapy as soon as day 3 for Positive and Negative Syndrome Scale (PANSS) totalscore, derived Brief Psychiatric RatingScale (BPRSd) totalscore, as wellas PANSS and BPRSd subscales. These findings were confirmed inpost hocrepeated-measures analysesof variance in which treatment differences favoring combination therapy were observed for PANSS total (p = 0.020) and PANSS positivescale scores (p = 0.002). Both combination therapy and antipsychotic monotherapy were welltolerated. Treatment with divalproex incombination with an atypicalantipsychotic agent resulted in earlier improvements in a range of psychotic symptoms among acutelyhospitalized patients with schizophrenia. Further evaluation is warranted to confirm these findings.

Original languageEnglish (US)
Pages (from-to)182-192
Number of pages11
Issue number1
StatePublished - Jan 2003
Externally publishedYes


  • Divalproex
  • Olanzapine
  • Psychosis
  • Risperidone
  • Schizophrenia

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health


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