Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE Trial.
BACKGROUND
Neurocognitive impairment in schizophrenia is severe and is an important predictor of functional outcome. The relative effect of the second-generation (atypical) antipsychotic drugs and older agents on neurocognition has not been comprehensively determined.


OBJECTIVE
To compare the neurocognitive effects of several second-generation antipsychotics and a first-generation antipsychotic, perphenazine.


METHODS
Randomized, double-blind study of patients with schizophrenia assigned to receive treatment with olanzapine, perphenazine, quetiapine fumarate, or risperidone for up to 18 months as reported previously by Lieberman et al. Ziprasidone hydrochloride was included after its approval by the Food and Drug Administration.


METHODS
Fifty-seven sites participated, including academic sites and treatment mental health facilities representative of the community.


METHODS
From a cohort of 1460 patients in the treatment study, 817 completed neurocognitive testing immediately prior to randomization and then after 2 months of treatment.


METHODS
The primary outcome was change in a neurocognitive composite score after 2 months of treatment. Secondary outcomes included neurocognitive composite score change at 6 months and 18 months after continued treatment and changes in neurocognitive domains.


RESULTS
At 2 months, treatment resulted in small neurocognitive improvements of z = 0.13 for olanzapine (P<.002), 0.25 for perphenazine (P<.001), 0.18 for quetiapine (P<.001), 0.26 for risperidone (P<.001), and 0.12 for ziprasidone (P<.06), with no significant differences between groups. Results at 6 months were similar. After 18 months of treatment, neurocognitive improvement was greater in the perphenazine group than in the olanzapine and risperidone groups. Neurocognitive improvement predicted longer time to treatment discontinuation, independently from symptom improvement, in patients treated with quetiapine or ziprasidone.


CONCLUSIONS
After 2 months of antipsychotic treatment, all groups had a small but significant improvement in neurocognition. There were no differences between any pair of agents, including the typical drug perphenazine. These results differ from the majority of previous studies, and the possible reasons are discussed.
Keefe
Richard S E
RS
Department of Psychiatry, John Umstead Hospital, Duke University Medical Center, Durham, NC 27710, USA. richard.keefe@duke.edu
Bilder
Robert M
RM
Davis
Sonia M
SM
Harvey
Philip D
PD
Palmer
Barton W
BW
Gold
James M
JM
Meltzer
Herbert Y
HY
Green
Michael F
MF
Capuano
George
G
Stroup
T Scott
TS
McEvoy
Joseph P
JP
Swartz
Marvin S
MS
Rosenheck
Robert A
RA
Perkins
Diana O
DO
Davis
Clarence E
CE
Hsiao
John K
JK
Lieberman
Jeffrey A
JA
D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use; D003072:Cognition Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D015331:Cohort Studies; D003987:Dibenzothiazepines / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests / Q000706:statistics & numerical data*; D000077152:Olanzapine; D010546:Perphenazine / Q000627:therapeutic use; D010879:Piperazines / Q000627:therapeutic use; D000069348:Quetiapine Fumarate; D018967:Risperidone / Q000627:therapeutic use; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D013844:Thiazoles / Q000627:therapeutic use; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D010879:Piperazines; D013844:Thiazoles; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; C092292:ziprasidone; D010546:Perphenazine; D018967:Risperidone; D000077152:Olanzapine