Impact of second-generation antipsychotics and perphenazine on depressive symptoms in a randomized trial of treatment for chronic schizophrenia.
BACKGROUND
According to the American Psychiatric Association Clinical Practice Guidelines for schizophrenia, second-generation antipsychotics may be specifically indicated for the treatment of depression in schizophrenia. We examined the impact of these medications on symptoms of depression using the data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE), conducted between January 2001 and December 2004.


METHODS
Patients with DSM-IV-defined schizophrenia (N = 1,460) were assigned to treatment with a first-generation antipsychotic (perphenazine) or one of 4 second-generation drugs (olanzapine, quetiapine, risperidone, or ziprasidone) and followed for up to 18 months (phase 1). Patients with tardive dyskinesia were excluded from the randomization that included perphenazine. Depression was assessed with the Calgary Depression Scale for Schizophrenia (CDSS). Mixed models were used to evaluate group differences during treatment with the initially assigned drug. An interaction analysis evaluated differences in drug response by whether patients had a baseline score on the CDSS of ≥ 6, indicative of a current major depressive episode (MDE).


RESULTS
There were no significant differences between treatment groups on phase 1 analysis, although there was a significant improvement in depression across all treatments. A significant interaction was found between treatment and experiencing an MDE at baseline (P = .05), and further paired comparisons suggested that quetiapine was superior to risperidone among patients who were in an MDE at baseline (P = .0056).


CONCLUSIONS
We found no differences between any second-generation antipsychotic and the first-generation antipsychotic perphenazine and no support for the clinical practice recommendation, but we did detect a signal indicating a small potential difference favoring quetiapine over risperidone only in patients with an MDE at baseline.
Addington
Donald E
DE
Department of Psychiatry, Foothills Hospital, 1403 29th St NW, Calgary, Alberta, Canada. addingto@ucalgary.ca
Mohamed
Somaia
S
Rosenheck
Robert A
RA
Davis
Sonia M
SM
Stroup
Thomas Scott
TS
McEvoy
Joseph P
JP
Swartz
Marvin S
MS
Lieberman
Jeffrey A
JA
D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000191:economics* / Q000627:therapeutic use*; D002908:Chronic Disease; D015897:Comorbidity; D003863:Depression / Q000188:drug therapy* / Q000191:economics / Q000453:epidemiology; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000191:economics / Q000453:epidemiology; D004311:Double-Blind Method; D016527:Drug Costs / Q000706:statistics & numerical data; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010546:Perphenazine / Q000191:economics* / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy* / Q000191:economics / Q000453:epidemiology; D012565:Schizophrenic Psychology; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D010546:Perphenazine