Cognitive effects of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: a randomized, open-label clinical trial (EUFEST).
OBJECTIVE
Cognitive impairment, manifested as mild to moderate deviations from psychometric norms, is present in many but not all schizophrenia patients. The purpose of the present study was to compare the effect of haloperidol with that of second-generation antipsychotic drugs on the cognitive performance of patients with schizophreniform disorder or first-episode schizophrenia.


METHODS
Subjects were 498 patients with schizophreniform disorder or first-episode schizophrenia who were randomly assigned to open-label haloperidol (1 to 4 mg/day [N=103]), amisulpride (200 to 800 mg/day [N=104]), olanzapine (5 to 20 mg/day [N=105]), quetiapine (200 to 750 mg/day [N=104]), or ziprasidone (40 to 160 mg/day [N=82]). The Rey Auditory Verbal Learning Test, Trail Making Test Part A and Part B, WAIS Digit Symbol Test, and Purdue Pegboard Test were administered at baseline and the 6-month follow-up evaluation.


RESULTS
Compared with scores at baseline, composite cognitive test scores improved for all five treatment groups at the 6-month follow-up evaluation. However, there were no overall differences among the treatment groups. In addition, there was a weak correlation between the degree of cognitive improvement and changes in Positive and Negative Syndrome Scale scores.


CONCLUSIONS
Treatment with antipsychotic medication is associated with moderate improvement in the cognitive test performance of patients who have schizophreniform disorder or who are in their first episode of schizophrenia. The magnitude of improvement does not differ between treatment with haloperidol and treatment with second-generation antipsychotics. Moreover, cognitive improvement is weakly related to symptom change.
Sheba Medical Center, Department of Psychiatry, Tel-Hashomer 52621, Ramat Gan, Israel. mdavidson6@gmail.com
Michael
M
Davidson
Silvana
S
Galderisi
Mark
M
Weiser
Nomi
N
Werbeloff
Wolfgang W
WW
Fleischhacker
Richard S
RS
Keefe
Han
H
Boter
Ireneus P M
IP
Keet
Dan
D
Prelipceanu
Janusz K
JK
Rybakowski
Jan
J
Libiger
Martina
M
Hummer
Sonia
S
Dollfus
Juan J
JJ
López-Ibor
Luchezar G
LG
Hranov
Wolfgang
W
Gaebel
Joseph
J
Peuskens
Nils
N
Lindefors
Anita
A
Riecher-Rössler
René S
RS
Kahn
D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D003072:Cognition Disorders / Q000139:chemically induced* / Q000175:diagnosis; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D011618:Psychotic Disorders / Q000175:diagnosis / Q000188:drug therapy*; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy; D012720:Severity of Illness Index; D055815:Young Adult
D014150:Antipsychotic Agents