title: Divalproex ER combined with olanzapine or risperidone for treatment of acute exacerbations of schizophrenia.
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.
authors.affiliation: Oregon Health and Science University, Portland, OR 97239, USA. caseyd@ohsu.edu
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Casey
authors.forename: David G
authors.initials: DG
authors.lastname: Daniel
authors.forename: Carol
authors.initials: C
authors.lastname: Tamminga
authors.forename: John M
authors.initials: JM
authors.lastname: Kane
authors.forename: Tram
authors.initials: T
authors.lastname: Tran-Johnson
authors.forename: Patricia
authors.initials: P
authors.lastname: Wozniak
authors.forename: Walid
authors.initials: W
authors.lastname: Abi-Saab
authors.forename: Jeff
authors.initials: J
authors.lastname: Baker
authors.forename: Laura
authors.initials: L
authors.lastname: Redden
authors.forename: Nicholas
authors.initials: N
authors.lastname: Greco
authors.forename: Mario
authors.initials: M
authors.lastname: Saltarelli
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D011569:Psychiatric Status Rating Scales; D018967:Risperidone / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy*; D016896:Treatment Outcome; D014635:Valproic Acid / Q000097:blood / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D014635:Valproic Acid; D018967:Risperidone; D000077152:Olanzapine