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Efficacy and Tolerability of Olanzapine, Quetiapine, and Risperidone in the Treatment of Early Psychosis: A Randomized, Double-Blind 52-Week Comparison
Abstract
OBJECTIVE: This 52-week randomized, double-blind, flexible-dose, multicenter study evaluated the overall effectiveness (as measured by treatment discontinuation rates) of olanzapine, quetiapine, and risperidone in patients early in the course of psychotic illness. METHOD: Patients were randomly assigned to treatment with olanzapine (2.5-20 mg/day), quetiapine (100-800 mg/day), or risperidone (0.5-4 mg/day) administered in twice-daily doses. Statistical analyses tested for noninferiority in all-cause treatment discontinuation rates up to 52 weeks (primary outcome measure) based on a prespecified noninferiority margin of 20%. RESULTS: A total of 400 patients were randomly assigned to treatment with olanzapine (N=133), quetiapine (N=134), or risperidone (N=133). The mean modal prescribed daily doses were 11.7 mg for olanzapine, 506 mg for quetiapine, and 2.4 mg for risperidone. At week 52, all-cause treatment discontinuation rates were 68.4%, 70.9%, and 71.4% for olanzapine, quetiapine, and risperidone, respectively. Reductions in total score on the Positive and Negative Syndrome Scale (PANSS) were similar for the three treatment groups, but reductions in PANSS positive subscale scores were greater in the olanzapine group (at 12 weeks and at 52 weeks or withdrawal from study) and the risperidone group (at 12 weeks). The most common elicited adverse events for olanzapine were drowsiness (53%), weight gain (51%), and insomnia (38%); for quetiapine, drowsiness (58%), increased sleep hours (42%), and weight gain (40%); and for risperidone, drowsiness (50%), menstrual irregularities in women (47%), and weight gain (41%). CONCLUSIONS: Olanzapine, quetiapine, and risperidone demonstrated comparable effectiveness in early-psychosis patients, as indicated by similar rates of all-cause treatment discontinuation.
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“In general, a majority of completed and ongoing trials follow the MATRICS guidelines17 for studying an adjunctive/cotreatment agent in a randomized, placebo-controlled trial consisting of clinically stable participants with schizophrenia.17,51–53”
From Clinical trials of potential cognitive-enhancing drugs in schizophrenia: what have we learned so far? (2013) · cites this paper as [53]
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Metadata
- Authors
- McEvoy, J. P., Lieberman, J. A., Perkins, D. O., Hamer, R. M., Gu, H., Lazarus, A., Sweitzer, D., Olexy, C., Weiden, P., & Strakowski, S. D.
- Affiliations
- Duke Medical Center (US)
- Venue
- American Journal of Psychiatry
- Published
- 2007-07
- Volume
- 164
- Issue
- 7
- Pages
- 1050-1060
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- OpenAlex
- W2156730504
- Cited by
- 377
- References
- 32
- Citations by year
- 2026: 9 · 2025: 3 · 2024: 7 · 2023: 9 · 2022: 19 · 2021: 17 · 2020: 8 · 2019: 13 · 2018: 16 · 2017: 19 · 2016: 19 · 2015: 16 · 2014: 19 · 2013: 27 · 2012: 33
- FWCI
- 22.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Keywords
- early psychosis, olanzapine, quetiapine, risperidone, antipsychotic efficacy, treatment discontinuation, non-inferiority, adverse events, weight gain, sleepiness, PANSS, atypical antipsychotics, long-term antipsychotic treatment, tolerability, menstrual irregularity, insomnia, sleep duration, bipolar disorder
- MeSH terms
- Quetiapine Fumarate, Olanzapine, Adolescent, Adult, Benzodiazepines, Dibenzothiazepines, Double-Blind Method, Drug Administration Schedule, Female, Humans, Male, Patient Dropouts, Psychiatric Status Rating Scales, Psychotic Disorders, Schizophrenia, Sleep Wake Disorders, Sleep Stages, Antipsychotic Agents, Weight Gain, Treatment Outcome, Risperidone
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