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A Randomized Controlled Trial

Robert Rosenheck, MD; Deborah Perlick, PhD; Stephen Bingham, PhD; Wen Liu-Mares, PhD; Joseph Collins, ScD; Stuart Warren, JD, PharmD; Douglas Leslie, PhD; Edward Allan, MD; E. Cabrina Campbell, MD; Stanley Caroff, MD; June Corwin, PhD; Lori Davis, MD; Richard Douyon, MD; Lawrence Dunn, MD; Denise Evans, MD; Ede Frecska, MD; John Grabowski, MD; David Graeber, MD; Lawrence Herz, MD; Kong Kwon, MD; William Lawson, MD; Felicitas Mena, MD; Javaid Sheikh, MD; David Smelson, PhD; Valerie Smith-Gamble, MD; for the Department of Veterans Affairs Cooperative Study Group on the Cost-Effectiveness of Olanzapine

JAMA. 2003;290:2693-2702.

Context  Although olanzapine has been widely adopted as a treatment of choice for schizophrenia, its long-term effectiveness and costs have not been evaluated in a controlled trial in comparison with a standard antipsychotic drug.

Objective  To evaluate the effectiveness and cost impact of olanzapine compared with haloperidol in the treatment of schizophrenia.

Design and Setting  Double-blind, randomized controlled trial with randomization conducted between June 1998 and June 2000 at 17 US Department of Veterans Affairs medical centers.

Participants  Three hundred nine patients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of schizophrenia or schizoaffective disorder, serious symptoms, and serious dysfunction for the previous 2 years. Fifty-nine percent fully completed and 36% partially completed follow-up assessments.

Interventions  Patients were randomly assigned to receive flexibly dosed olanzapine, 5 to 20 mg/d, with prophylactic benztropine, 1 to 4 mg/d (n = 159); or haloperidol, 5 to 20 mg/d (n = 150), for 12 months.

Main Outcome Measures  Standardized measures of symptoms, quality of life, neurocognitive status, and adverse effects of medication. Veterans Affairs administrative data and interviews concerning non-VA service use were used to estimate costs from the perspective of the VA health care system and society as a whole (ie, consumption of all resources on behalf of these patients).

Results  There were no significant differences between groups in study retention; positive, negative, or total symptoms of schizophrenia; quality of life; or extrapyramidal symptoms. Olanzapine was associated with reduced akathisia in the intention-to-treat analysis (P<.001) and with lower symptoms of tardive dyskinesia in a secondary analysis including only observations during blinded treatment with study drug. Small but significant advantages were also observed on measures of memory and motor function. Olanzapine was also associated with more frequent reports of weight gain and significantly greater VA costs, ranging from $3000 to $9000 annually. Differences in societal costs were somewhat smaller and were not significant.

Conclusion  Olanzapine does not demonstrate advantages compared with haloperidol (in combination with prophylactic benztropine) in compliance, symptoms, extrapyramidal symptoms, or overall quality of life, and its benefits in reducing akathisia and improving cognition must be balanced with the problems of weight gain and higher cost.

Author Affiliations: Department of Veterans Affairs Medical Center, West Haven, Conn (Drs Rosenheck, Perlick, Liu-Mares, and Leslie); Department of Psychiatry, Yale University School of Medicine, New Haven, Conn (Drs Rosenheck, Perlick, Liu-Mares, and Leslie); Department of Veterans Affairs Cooperative Studies Program Coordinating Center, Perry Point, Md (Drs Bingham and Collins); Department of Veterans Affairs Cooperative Studies Program Clinical Research Pharmacy Coordinating Center (Dr Warren) and Department of Veterans Affairs Medical Center (Dr Graeber), Albuquerque, NM; Department of Veterans Affairs Medical Center, Montrose, NY (Dr Allan); Department of Veterans Affairs Medical Center, Philadelphia, Pa (Drs Campbell and Caroff); Department of Veterans Affairs Medical Center, New York, NY (Dr Corwin); Department of Veterans Affairs Medical Center, Tuscaloosa, Ala (Dr Davis); Department of Veterans Affairs Medical Center, Miami, Fla (Dr Douyon); Department of Veterans Affairs Medical Center, Durham, NC (Dr Dunn); Department of Veterans Affairs Medical Center, Augusta, Ga (Dr Evans); Department of Veterans Affairs Medical Center, Bay Pines, Fla (Dr Frecska); Department of Veterans Affairs Medical Center, Detroit, Mich (Dr Grabowski); Department of Veterans Affairs Medical Center, Bedford, Mass (Dr Herz); Department of Veterans Affairs Medical Center, Brecksville, Ohio (Dr Kwon); Howard University Medical School, Washington, DC (Dr Lawson); Department of Veterans Affairs Medical Center, Tuskegee, Ala (Dr Mena); Department of Veterans Affairs Medical Center, Palo Alto, Calif (Dr Sheikh); Department of Veterans Affairs Medical Center, Lyons, NJ (Dr Smelson); and Department of Veterans Affairs Medical Center, Indianapolis, Ind (Dr Smith-Gamble).

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