Cited by 5,892Schizophrenia research and treatmentMental Health and PsychiatryBipolar Disorder and Treatment

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Effectiveness of Antipsychotic Drugs in Patients with Chronic Schizophrenia

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Lieberman, Jeffrey A., Stroup, T. Scott, McEvoy, Joseph P., Swartz, Marvin S., Rosenheck, Robert A., Perkins, Diana O., Keefe, Richard S.E., Davis, Sonia M., Davis, Clarence E., Lebowitz, Barry D., Severe, Joanne, Hsiao, John K.·2005·New England Journal of Medicine

DOI 10.1056/nejmoa051688

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Abstract

BACKGROUND: The relative effectiveness of second-generation (atypical) antipsychotic drugs as compared with that of older agents has been incompletely addressed, though newer agents are currently used far more commonly. We compared a first-generation antipsychotic, perphenazine, with several newer drugs in a double-blind study. METHODS: A total of 1493 patients with schizophrenia were recruited at 57 U.S. sites and randomly assigned to receive olanzapine (7.5 to 30 mg per day), perphenazine (8 to 32 mg per day), quetiapine (200 to 800 mg per day), or risperidone (1.5 to 6.0 mg per day) for up to 18 months. Ziprasidone (40 to 160 mg per day) was included after its approval by the Food and Drug Administration. The primary aim was to delineate differences in the overall effectiveness of these five treatments. RESULTS: Overall, 74 percent of patients discontinued the study medication before 18 months (1061 of the 1432 patients who received at least one dose): 64 percent of those assigned to olanzapine, 75 percent of those assigned to perphenazine, 82 percent of those assigned to quetiapine, 74 percent of those assigned to risperidone, and 79 percent of those assigned to ziprasidone. The time to the discontinuation of treatment for any cause was significantly longer in the olanzapine group than in the quetiapine (P<0.001) or risperidone (P=0.002) group, but not in the perphenazine (P=0.021) or ziprasidone (P=0.028) group. The times to discontinuation because of intolerable side effects were similar among the groups, but the rates differed (P=0.04); olanzapine was associated with more discontinuation for weight gain or metabolic effects, and perphenazine was associated with more discontinuation for extrapyramidal effects. CONCLUSIONS: The majority of patients in each group discontinued their assigned treatment owing to inefficacy or intolerable side effects or for other reasons. Olanzapine was the most effective in terms of the rates of discontinuation, and the efficacy of the conventional antipsychotic agent perphenazine appeared similar to that of quetiapine, risperidone, and ziprasidone. Olanzapine was associated with greater weight gain and increases in measures of glucose and lipid metabolism.

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Authors: Lieberman, J. A., Stroup, T. S., McEvoy, J. P., Swartz, M. S., Rosenheck, R. A., Perkins, D. O., Keefe, R. S. E., Davis, S. M., Davis, C. E., Lebowitz, B. D., Severe, J., & Hsiao, J. K.
Affiliations: New York State Psychiatric Institute (US)
Duke University (US)
Yale University (US)
University of North Carolina at Chapel Hill (US)
National Institutes of Health (US)
ORCID: Lieberman, Jeffrey A.
Stroup, T. Scott
McEvoy, Joseph P.
Swartz, Marvin S.
Rosenheck, Robert A.
Perkins, Diana O.
Keefe, Richard S.E.
Lebowitz, Barry D.
Hsiao, John K.
Venue: New England Journal of Medicine
Publisher: Massachusetts Medical Society
Published: 2005-09-22
Volume: 353
Issue: 12
Pages: 1209-1223
ISSN: 0028-4793 (ISSN-L)
1533-4406
DOI: 10.1056/nejmoa051688
OpenAlex: W2159155203
Cited by: 5,892
References: 32
Citations by year: 2026: 95 · 2025: 89 · 2024: 135 · 2023: 129 · 2022: 191 · 2021: 166 · 2020: 338 · 2019: 207 · 2018: 211 · 2017: 220 · 2016: 231 · 2015: 277 · 2014: 325 · 2013: 361 · 2012: 379
FWCI: 258.86
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: New England Journal of Medicine (publishedVersion)
PubMed (publishedVersion)
Funders: Bristol-Myers Squibb
Eli Lilly and Company
Pfizer
AstraZeneca
GlaxoSmithKline
Case Western Reserve University
Foundation of Hope for Research and Treatment of Mental Illness
Otsuka Pharmaceutical
National Institutes of Health (n01mh90001-21-0-0)
University of North Carolina at Chapel Hill
National Institute of Mental Health (N01 MH90001, MH90001)
Janssen Pharmaceuticals
School of Medicine, University of North Carolina at Chapel Hill
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Social Sciences › Arts and Humanities › Philosophy › Mental Health and Psychiatry
Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
Keywords: schizophrenia, antipsychotic drugs, atypical antipsychotics, typical antipsychotics, perphenazine, olanzapine, quetiapine, risperidone, ziprasidone, treatment discontinuation, treatment efficacy, adverse effects, weight gain, metabolic effects, extrapyramidal symptoms, chronic schizophrenia, double-blind comparison, long-term treatment
MeSH terms: Quetiapine Fumarate, Olanzapine, Adult, Benzodiazepines, Chronic Disease, Dibenzothiazepines, Double-Blind Method, Female, Humans, Lipids, Male, Patient Compliance, Perphenazine, Piperazines, Schizophrenia, Thiazoles, Antipsychotic Agents, Weight Gain, Proportional Hazards Models, Treatment Outcome, Risperidone

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