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Effectiveness of Antipsychotic Drugs in Patients with Chronic Schizophrenia
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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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“An example of an early precursor to the SMART is the Clinical Antipsychotics Trial of Intervention Effectiveness (CATIE) [54] in chronic schizophrenia.”
From Introduction to SMART designs for the development of adaptive interventions: with application to weight loss research (2014) · cites this paper as [54]
In the citing paper
“In schizophrenia, for example, recent studies have shown that since the introduction of second-generation antipsychotics, treatment efficacy has only marginally improved over traditional dopamine D-2 antagonists, which were introduced 50 years ago (Lieberman et al., 2005”
From Neuronal Dynamics and Neuropsychiatric Disorders: Toward a Translational Paradigm for Dysfunctional Large-Scale Networks (2012) · cites this paper as Lieberman et al., 2005
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“While effective in reducing the positive symptoms, the cognitive dysfunctions and negative symptoms, two major determinants for outcome and level of functioning, remained unchanged in the large majority of patients.”
From Neuronal Dynamics and Neuropsychiatric Disorders: Toward a Translational Paradigm for Dysfunctional Large-Scale Networks (2012) · cites this paper as Lieberman et al., 2005
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“Over the last 50 years, the pharmacological therapy of schizophrenia was based mainly on the dopamine hypothesis and made little progress (Lieberman et al., 2005”
From Neuronal Dynamics and Neuropsychiatric Disorders: Toward a Translational Paradigm for Dysfunctional Large-Scale Networks (2012) · cites this paper as Lieberman et al., 2005
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Metadata
- 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
- 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
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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