Divalproex ER combined with olanzapine or risperidone for treatment of acute exacerbations of schizophrenia

Daniel E. Casey, David G. Daniel, Carol Tamminga, John M. Kane, Tram Tran-Johnson, Patricia Wozniak, Walid Abi-Saab, Jeff Baker, Laura Redden, Nicholas Greco, Mario Saltarelli

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

The objective of this study was to evaluate the efficacy and safety of divalproex sodium extended release (divalproex ER) vs placebo in combination with olanzapine or risperidone for the treatment of acute exacerbations of schizophrenia. In this 12-week, randomized, double-blind, parallel-group, multi-center trial, a total of 402 patients were randomized and treated; 103 received olanzapine/placebo, 99 received olanzapine/divalproex ER, 101 received risperidone/placebo, and 99 received risperidone/divalproex ER. Divalproex ER was initiated on day 1 at 20 mg/kg per day q AM and was titrated to clinical effect on days 3, 7, and 10, not to exceed a maximum dosage of 35 mg/kg per day. Olanzapine and risperidone were initiated at 5 and 2 mg/day q PM, respectively, increased to 10 and 4 mg/day on day 3, and increased to fixed target doses of 15 and 6 mg/day on day 6. No significant treatment difference was demonstrated between the combination therapy and antipsychotic monotherapy groups on the primary efficacy variable of the mean change from baseline to day 14 last observation carried forward on the Positive and Negative Syndrome Scale (PANSS) total score, although antipsychotic monotherapy did demonstrate superiority to combination therapy on the PANSS Negative subscale at several time points. Combination therapy also failed to show an advantage over antipsychotic monotherapy at day 84 on the PANSS total score. Most adverse events observed in the study were mild to moderate in severity, and the overall number of adverse events did not differ significantly between the combination therapy groups and their corresponding antipsychotic monotherapy group.

Original languageEnglish (US)
Pages (from-to)1330-1338
Number of pages9
JournalNeuropsychopharmacology
Volume34
Issue number5
DOIs
StatePublished - Apr 1 2009

Keywords

  • Atypical antipsychotic
  • Divalproex sodium ER
  • Olanzapine
  • Psychosis
  • Risperidone
  • Schizophrenia

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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    Casey, D. E., Daniel, D. G., Tamminga, C., Kane, J. M., Tran-Johnson, T., Wozniak, P., Abi-Saab, W., Baker, J., Redden, L., Greco, N., & Saltarelli, M. (2009). Divalproex ER combined with olanzapine or risperidone for treatment of acute exacerbations of schizophrenia. Neuropsychopharmacology, 34(5), 1330-1338. https://doi.org/10.1038/npp.2008.209