Adjunctive divalproex and hostility among patients with schizophrenia receiving olanzapine or risperidone.
OBJECTIVE
This study compared the specific antihostility effects of atypical antipsychotic monotherapy (olanzapine or risperidone) with that of combination treatment with divalproex sodium among patients with schizophrenia experiencing an acute psychotic episode.


METHODS
A total of 249 inpatients with schizophrenia were randomly assigned to receive olanzapine plus placebo, olanzapine plus divalproex, risperidone plus placebo, or risperidone plus divalproex in a double-blind, 28-day multicenter trial. The target daily dose was 15 milligrams for olanzapine, 6 milligrams for risperidone, and up to 30 milligrams per kilogram (minimum, 15 milligrams per kilogram) for divalproex. The hostility item of the Positive and Negative Syndrome Scale (PANSS) was the principal outcome measure. Covariates included the PANSS items reflecting positive symptoms of schizophrenia (delusions, suspiciousness/persecution, grandiosity, unusual thought content, conceptual disorganization, and hallucinatory behavior).


RESULTS
Combination treatment with risperidone or olanzapine plus divalproex was associated with different scores on the hostility item of the PANSS compared with antipsychotic monotherapy. Combination therapy had a significantly greater antihostility effect at days 3 and 7 than monotherapy. This result was not seen beyond the first week of treatment, but there was a trend toward a difference in effect for the entire treatment period. The effect on hostility appears to be statistically independent of antipsychotic effect on other PANSS items reflecting delusional thinking, a formal thought disorder, or hallucinations.


CONCLUSIONS
Divalproex sodium may be useful as an adjunctive agent in specifically reducing hostility in the first week of treatment with risperidone or olanzapine among patients with schizophrenia experiencing an acute psychotic episode.
Citrome
Leslie
L
Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA. citrome@nki.rfmh.org
Casey
Daniel E
DE
Daniel
David G
DG
Wozniak
Patricia
P
Kochan
Lisa D
LD
Tracy
Katherine A
KA
D000374:Aggression / Q000187:drug effects*; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D006302:Health Services Research; D006801:Humans; D000077152:Olanzapine; D010919:Placebos; D018967:Risperidone / Q000008:administration & dosage / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy*; D014481:United States; D014635:Valproic Acid / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D014150:Antipsychotic Agents; D010919:Placebos; D001569:Benzodiazepines; D014635:Valproic Acid; D018967:Risperidone; D000077152:Olanzapine