Cognitive improvement after treatment with second-generation antipsychotic medications in first-episode schizophrenia: is it a practice effect?
BACKGROUND
Cognitive impairment in schizophrenia is frequent, involves multiple domains, and is enduring. Numerous recent clinical trials have suggested that second-generation antipsychotic medications significantly enhance cognition in schizophrenia. However, none of these studies included healthy controls undergoing repeated testing to assess the possibility that improvements might reflect simple practice effects.


OBJECTIVE
To report the results on cognition of a randomized comparison of 2 widely prescribed second-generation antipsychotic medications, olanzapine and risperidone, in patients with first-episode schizophrenia and a healthy control group.


METHODS
Randomized clinical trial.


METHODS
Hospital-based research units. Patients A total of 104 participants with first-episode schizophrenia and 84 healthy controls.


METHODS
Cognitive assessment of all study participants occurred at baseline, 6 weeks later, and 16 weeks later. Neurocognitive tests included measures of working memory and attention, speed, motor function, episodic memory, and executive function.


RESULTS
No differential drug effects were observed. Of 16 cognitive measures, 9 demonstrated improvement over time and only 2 demonstrated greater rates of change than those observed in the healthy control group undergoing repeated assessment. The composite effect size for cognitive change was 0.33 in the healthy control group (attributed to practice) and 0.36 in the patients with first-episode schizophrenia. Improvements in cognition in the first-episode schizophrenia group could not be accounted for by medication dose, demographic variables, or intellectual level.


CONCLUSIONS
The cognitive improvements observed in the trial were consistent in magnitude with practice effects observed in healthy controls, suggesting that some of the improvements in cognition in the first-episode schizophrenia group may have been due to practice effects (ie, exposure, familiarity, and/or procedural learning). Our results also indicated that differential medication effects on cognition were small. We believe that these findings have important implications for drug discovery and the design of registration trials that attempt to demonstrate cognitive enhancement.
Goldberg
Terry E
TE
Zucker Hillside Hospital, 7559 263rd Street, Glen Oaks, NY 11004, USA. tgoldber@nshs.edu
Goldman
Robert S
RS
Burdick
Katherine E
KE
Malhotra
Anil K
AK
Lencz
Todd
T
Patel
Raman C
RC
Woerner
Margaret G
MG
Schooler
Nina R
NR
Kane
John M
JM
Robinson
Delbert G
DG
D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000494:pharmacology / Q000627:therapeutic use; D003071:Cognition / Q000187:drug effects; D003072:Cognition Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D035061:Control Groups; D005260:Female; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D000077152:Olanzapine; D011214:Practice, Psychological; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D012107:Research Design / Q000592:standards; D018967:Risperidone / Q000494:pharmacology / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D018967:Risperidone; D000077152:Olanzapine