Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial
Open accessAbstract
Background Second-generation antipsychotic drugs were introduced over a decade ago for the treatment of schizophrenia; however, their purported clinical effectiveness compared with first-generation antipsychotic drugs is still debated. We aimed to compare the effectiveness of second-generation antipsychotic drugs with that of a low dose of haloperidol, in first-episode schizophrenia. Methods We did an open randomised controlled trial of haloperidol versus second-generation antipsychotic drugs in 50 sites, in 14 countries. Eligible patients were aged 18-40 years, and met diagnostic criteria for schizophrenia, schizophreniform disorder, or schizoaffective disorder. 498 patients were randomly assigned by a web-based online system to haloperidol (1-4 mg per day; n=103), amisulpride (200-800 mg per day; n=104), olanzapine (5-20 mg per day; n=105), quetiapine (200-750 mg per day; n=104), or ziprasidone (40-160 mg per day; n=82); follow-up was at 1 year. The primary outcome measure was all-cause treatment discontinuation. Patients and their treating physicians were not blinded to the assigned treatment. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN68736636. Findings The number of patients who discontinued treatment for any cause within 12 months was 63 (Kaplan-Meier estimate 72%) for haloperidol, 32 (40%) for amisulpride, 30 (33%) for olanzapine, 51 (53%) for quetiapine, and 31 (45%) for ziprasido…
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A large randomized clinical trial of first-episode patients treated with different antipsychotic drugs found that all antipsychotic drugs were associated with a greater than 7% increase in weight during the trial; proportion of patients affected ranged from 37% (ziprasidone) to 86% (olanzapine).
“A large randomized clinical trial of first-episode patients treated with different antipsychotic drugs (Kahn et al. 2008) found that all antipsychotic drugs were associated with a greater than 7% increase in weight during the trial; proportion of patients affected ranged from 37% (ziprasidone) to 86% (olanzapine).”
From Excess early mortality in schizophrenia. (2014) · cites this paper as Kahn et al. 2008
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- Authors
- Kahn, R. S., Fleischhacker, W. W., Boter, H., Davidson, M., Vergouwe, Y., Keet, I. P., Gheorghe, M. D., Rybakowski, J. K., Galderisi, S., Libiger, J., Hummer, M., Dollfus, S., López-Ibor, J. J., Hranov, L. G., Gaebel, W., Peuskens, J., Lindefors, N., Riecher-Rössler, A., & Grobbee, D. E.
- Affiliations
- University Medical Center Utrecht (NL)
- Innsbruck Medical University (AT)
- Sheba Medical Center (IL)
- Poznan University of Medical Sciences (PL)
- Charles University (CZ)
- Centre Hospitalier Universitaire de Caen Normandie (FR)
- Hospital Clínico San Carlos (ES)
- KU Leuven (BE)
- Karolinska Institutet (SE)
- Corresponding author
- Kahn, René S
- ORCID
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2008-03
- Volume
- 371
- Issue
- 9618
- Pages
- 1085-1097
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- OpenAlex
- W2159039084
- Cited by
- 1,088
- References
- 3
- Citations by year
- 2026: 18 · 2025: 17 · 2024: 29 · 2023: 38 · 2022: 31 · 2021: 38 · 2020: 45 · 2019: 47 · 2018: 52 · 2017: 54 · 2016: 62 · 2015: 75 · 2014: 66 · 2013: 78 · 2012: 107
- FWCI
- 75.62
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- edoc (University of Basel) (acceptedVersion)
- Archivio Istituzionale della Ricerca - Università degli Studi della Campania "Luigi Vanvitelli" (submittedVersion)
- edoc (University of Basel)
- Funders
- Bristol-Myers Squibb
- Sanofi
- 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
- first-episode schizophrenia, schizophreniform disorder, atypical antipsychotics, haloperidol, amisulpride, olanzapine, quetiapine, ziprasidone, treatment discontinuation, schizoaffective disorder, intention-to-treat analysis, antipsychotic switching
- MeSH terms
- Quetiapine Fumarate, Olanzapine, Amisulpride, Adolescent, Adult, Benzodiazepines, Dibenzothiazepines, Female, Haloperidol, Humans, Male, Patient Compliance, Piperazines, Schizophrenia, Sulpiride, Thiazoles, Antipsychotic Agents, Linear Models, Proportional Hazards Models, Treatment Outcome
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