TY - JOUR
T1 - Divalproex ER combined with olanzapine or risperidone for treatment of acute exacerbations of schizophrenia
AU - Casey, Daniel E.
AU - Daniel, David G.
AU - Tamminga, Carol
AU - Kane, John M.
AU - Tran-Johnson, Tram
AU - Wozniak, Patricia
AU - Abi-Saab, Walid
AU - Baker, Jeff
AU - Redden, Laura
AU - Greco, Nicholas
AU - Saltarelli, Mario
N1 - Funding Information:
This study was supported by Abbott Laboratories, Abbott Park, IL. We thank Sharon Stec of Abbott Laboratories who served capably as clinical project manager for this study. We also thank the members of the Depakote ER Combination Treatment Study Group, as follows, for their enrollment of patients and participation in this study: Jose J Alvarez, MD, Comprehensive NeuroScience Inc., Melbourne, FL; Mohammed Bari, MD, Synergy Clinical Research, Chula Vista, CA; Louise M Beckett MD, IPS Research Company, Oklahoma City, OK; Jeffrey A Boren-stein, MD, Holliswood Hospital, Holliswood, NY; Guy E Brannon, MD, Brentwood Research Institute, Shreveport, LA; David W Brown, MD, Community Clinical Research Inc., Austin, TX; Jesse M Carr, MD California Clinical Trials Medical Group Inc., Glendale, CA; Lori L Davis, MD, Tuscaloosa VA Medical Center, Tuscaloosa, AL; David Feifel, MD, PhD, UCSD Medical Center, San Diego, CA; David H Flaherty, DO, Segal Institute for Clinical Research, North Miami, FL; Donald J Garcia, Jr, MD, Future Search Trials, Austin, TX; Lev Gertsik, MD, Cedars Sinai Medical Center, Los Angeles, CA; Steven Glass, MD, CNS Research Institute, PC, Clementon, NJ; Armen Goenjian, MD, Collaborative NeuroScience Network Inc., Garden Grove, CA; Clifford Goldman, MD, ClinSearch Inc., Kenilworth, NJ; Ram Gopalan, MD, Comprehensive Neuroscience of Northern Virginia, Falls Church, VA; Richard R Jaffe, MD, Belmont Center for Comprehensive Treatment, Philadelphia, PA; John Kasckow, MD, PhD, University of Cincinnati Medical Center, Cincinnati, OH; Richard D Knapp, DO, CORE Research Inc., Winter Park, FL; Mary Ann Knesevich, MD, University Hills Clinical Research, Irving, TX; Joseph Kwentus, MD, University of Mississippi Medical Center, Jackson, MS; Mark N Lerman, MD, Comprehensive NeuroScience Inc., Hoffman Estates, IL; Robert E Litman, MD, Centers for Behavioral Health, LLC, Rockville, MD; H Edward Logue, MD, Birmingham Psychiatry Pharmaceutical Studies Inc., Birmingham, AL; Joseph P McEvoy, MD, Duke University Medical Center, Butner, NC; Alexander L Miller, MD, University of Texas Health Science Center at San Antonio, San Antonio, TX; Michael G Plopper, MD, Sharp Mesa Vista Hospital, San Diego, CA; Raj Rajani, MD, Behavioral and Medical Research, LLC, Anaheim, CA; Robert A Riesenberg, MD, Atlanta Center for Medical Research, Atlanta, GA; Murray H Rosenthal, DO, Health-Quest Clinical Trials, San Diego, CA; David Sack, MD, Comprehensive NeuroScience Inc., Cerritos, CA; Scott D Segal, MD, Segal Institute for Clinical Research, North Miami, FL; Rajiv P Sharma, MD, The Psychiatric Institute University of Illinois at Chicago Medical Center, Chicago, IL; Anantha Shekhar, MD, PhD, Indiana University, Indianapolis, IN.
Funding Information:
Daniel Casey has received consultant fees from Abbott Laboratories, Bristol-Myers Squibb, Dainippon Sumitomo Pharmaceuticals, Janssen Pharmaceuticals, NuPathe Inc., Pfizer Inc., Solvay Pharmaceuticals and Wyeth Pharmaceuticals. He has been on Speakers Bureaus for Abbott Laboratories, Bristol-Meyers Squibb, Janssen Pharmaceuticals and Pfizer. Dr Casey receives financial support from Danicas Foundation. John Kane has served as a consultant for Abbott Laboratories, Astra-Zeneca, Bristol-Meyers Squibb, Janssen, Eli Lilly and Company, Pfizer Inc., Wyeth Pharmaceuticals and on Speakers Bureaus for Bristol-Meyers Squibb, Janssen, and Astra-Zeneca. Carol Tammin-ga has been a paid consultant for Acadia Pharmaceuticals, Intra-cellular Therapies, Orexigen, Alexza Pharmaceuticals, and Lunbeck Inc. She is on the Advisory Boards for Acadia Pharmaceutical and Intracellular Therapies. David Daniel is employed by United Biosource Corporation. Walid Abi-Saab and Patricia Wozniak are former employees of Abbott Laboratories. Laura Redden, Mario Saltarelli, Jeff Baker and Nicholas Greco are current employees of and owners of equity in Abbott Laboratories. Tram Tran-Johnson was an investigator in this study and reports no other financial conflicts.
PY - 2009/4
Y1 - 2009/4
N2 - 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.
AB - 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.
KW - Atypical antipsychotic
KW - Divalproex sodium ER
KW - Olanzapine
KW - Psychosis
KW - Risperidone
KW - Schizophrenia
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U2 - 10.1038/npp.2008.209
DO - 10.1038/npp.2008.209
M3 - Article
C2 - 19052541
AN - SCOPUS:62349135082
SN - 0893-133X
VL - 34
SP - 1330
EP - 1338
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
IS - 5
ER -