NDLI: Antipsychotic Drug Effects on Brain Morphology in First-Episode Psychosis

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Antipsychotic Drug Effects on Brain Morphology in First-Episode Psychosis

Content Provider	JAMA Network
Author	Lieberman, Jeffrey A. Tollefson, Gary D. Charles, Cecil Zipursky, Robert Sharma, Tonmoy Kahn, Rene S. Keefe, Richard S. E. Green, Alan I. Gur, Raquel E. McEvoy, Joseph Perkins, Diana Hamer, Robert M. Gu, Hongbin Tohen, Mauricio
Copyright Year	2005
Abstract	Background: Pathomorphologic brain changes occurring as early as first-episode schizophrenia have been extensively described. Longitudinal studies have demonstrated that these changes may be progressive and associated with clinical outcome. This raises the possibility that antipsychotics might alter such pathomorphologic progression in early-stage schizophrenia. Objective: To test a priori hypotheses that olanzapine-treated patients have less change over time in whole brain gray matter volumes and lateral ventricle volumes than haloperidol-treated patientsandthat gray matter and lateral ventricle volume changes are associated with changes in psychopathology and neurocognition. Design: Longitudinal, randomized, controlled, multisite, double-blind study. Patients treated and followed up for up to 104 weeks. Neurocognitive and magnetic resonance imaging ( MRI) assessments performed at weeks 0 (baseline), 12, 24, 52, and 104. Mixed-models analyses with time-dependent covariates evaluated treatment effects on MRI end points and explored relationships between MRI, psychopathologic, and neurocognitive outcomes. Setting: Fourteen academic medical centers ( United States, 11; Canada, 1; Netherlands, 1; England, 1). Participants: Patients with first-episode psychosis ( DSM- IV) and healthy volunteers. Interventions: Random allocation to a conventional antipsychotic, haloperidol (2-20 mg/d), or an atypical antipsychotic, olanzapine (5-20 mg/d). Main Outcome Measures: Brain volume changes assessed by MRI. Results: Of 263 randomized patients, 161 had baseline and at least 1 postbaseline MRI evaluation. Haloperidol-treated patients exhibited significant decreases in gray matter volume, whereas olanzapine-treated patients did not. A matched sample of healthy volunteers (n = 58) examined contemporaneously showed no change in gray matter volume. Conclusions: Patients with first-episode psychosis exhibited a significant between-treatment difference in MRI volume changes. Haloperidol was associated with significant reductions in gray matter volume, whereas olanzapine was not. Post hoc analyses suggested that treatment effects on brain volume and psychopathology of schizophrenia may be associated. The differential treatment effects on brain morphology could be due to haloperidol-associated toxicity or greater therapeutic effects of olanzapine.
Ending Page	370
Starting Page	361
Page Count	10
File Format	PDF HTM / HTML
ISSN	0003990X
DOI	10.1001/archpsyc.62.4.361
Issue Number	4
Journal	Archives of General Psychiatry
Volume Number	62
Language	English
Publisher	American Medical Association
Publisher Date	2005-04-01
Access Restriction	Open
Subject Keyword	magnetic resonance imaging haloperidol antipsychotic agents psychotic disorders schizophrenia brain olanzapine atypical antipsychotic first-generation antipsychotics brain volume lateral ventricle netherlands toxic effect gray matter surrogate endpoints psychopathology treatment outcome
Content Type	Text
Resource Type	Article
Subject	1200/1201 Psychiatry and Mental Health

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