Maintenance treatment with quetiapine versus discontinuation after one year of treatment in patients with remitted first episode psychosis: randomised controlled trialBMJ 2010; 341 doi: https://doi.org/10.1136/bmj.c4024 (Published 19 August 2010) Cite this as: BMJ 2010;341:c4024
- Eric Y H Chen, professor1,
- Christy L M Hui, research fellow1,
- May M L Lam, clinical assistant professor1,
- Cindy P Y Chiu, clinical assistant professor1,
- C W Law, associate consultant2,
- Dicky W S Chung, consultant3,
- Steve Tso, associate consultant4,
- Edwin P F Pang, associate consultant3,
- K T Chan, medical officer4,
- Y C Wong, associate consultant3,
- Flora Y M Mo, associate consultant3,
- Kathy P M Chan, associate consultant5,
- T J Yao, associate professor6,
- S F Hung, consultant5,
- William G Honer, professor7
- 1Department of Psychiatry, University of Hong Kong, Hong Kong
- 2Department of Psychiatry, Queen Mary Hospital, Hong Kong
- 3Department of Psychiatry, Tai Po Hospital, Tai Po, Hong Kong
- 4Department of Psychiatry, Castle Peak Hospital, Tuen Mun, Hong Kong
- 5Department of Psychiatry, Kwai Chung Hospital, Kwai Chung, Hong Kong
- 6Clinical Trials Centre, University of Hong Kong, Queen Mary Hospital, Hong Kong
- 7University of British Columbia, Centre for Complex Disorders, BCMHARI, A3-127, Vancouver, BC, Canada
- Correspondence to: E Y H Chen
- Accepted 7 June 2010
Objective To study rates of relapse in remitted patients with first episode psychosis who either continued or discontinued antipsychotic drugs after at least one year of maintenance treatment.
Design 12 month randomised, double blind, placebo controlled trial.
Setting Early psychosis outpatient clinics in Hong Kong.
Participants 178 patients with first episode psychosis who had received at least one year of antipsychotic drug treatment between September 2003 and July 2006 and had no positive symptoms of psychosis.
Interventions Patients received either maintenance treatment with quetiapine (400 mg/day) or placebo and were followed up for the next 12 months or until a relapse occurred.
Main outcome measure Relapse assessed monthly and defined as re-emergence of psychotic symptoms (delusions, conceptual disorganisation, hallucinations, suspiciousness, and unusual thought content) according to predefined thresholds.
Results 178 patients were randomised (89 to quetiapine and 89 to placebo). The Kaplan-Meier estimate of the risk of relapse at 12 months was 41% (95% confidence interval 29% to 53%) for the quetiapine group and 79% (68% to 90%) for the placebo group (P<0.001). Although quetiapine was generally well tolerated, the rate of discontinuation due to adverse or serious adverse events was greater in the quetiapine group (18%; 16/89) than in the placebo group (8%; 7/89) (relative risk 2.29, 95% confidence interval 0.99 to 5.28; χ2=3.20, df=1; P=0.07).
Conclusion In a group of asymptomatic patients with first episode psychosis and at least one year of previous antipsychotic drug treatment, maintenance treatment with quetiapine compared with placebo resulted in a substantially lower rate of relapse during the following year.
Trial registration Clinical trials NCT00334035.
Contributions: EYHC, CLMH, MMLL, CWL, CPYC, SFH, and WGH conceived and designed the study. EYHC, CLMH, MMLL, CPYC, and DWSC obtained funding and supervised the study. EYHC, CLMH, MMLL, CPYC, CWL, DWSC, ST, EPFP, KTC, YCW, FYMM, KPMC, and SFH collected the data. CLMH, EYHC, WGH, and TJY analysed the data. All authors interpreted the data. EYHC, CLMH, and WGH drafted the manuscript. All authors had access to the data, critically revised the manuscript, and approved the final version. EYHC is the guarantor.
Funding: The study was supported by the Research Grants Council of Hong Kong (HKU 7655/05M) and an investigator initiated study award from AstraZeneca Pharmaceuticals. WGH was supported by the Michael Smith Foundation for Health Research and the British Columbia Mental Health and Addictions Services. AstraZeneca prepared the quetiapine and the placebo and packaged the study drugs according to the randomisation schedule. AstraZeneca played no role in the study design or conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, and approval of the manuscript. The only study data provided to AstraZeneca were reports of serious adverse events. The authors’ work was independent from the funders.
Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and all authors declare (1) Financial support for the submitted work from Research Grants Council of Hong Kong and AstraZeneca Pharmaceuticals. (2) EYHC has participated in paid advisory boards for Otsuka, has received educational grant support from Janssen-Cilag, and has received research funding from AstraZeneca, Janssen-Cilag, Pfizer, Eli Lilly, Sanofi-Aventis, and Otsuka; MMLL has done consultancy for Otsuka and Eli Lilly; DWSC has received research grants from Janssen-Cilag and Pfizer; WGH has participated in advisory boards for In-Silico Biosciences, Wyeth/Solvay, Janssen-Cilag, and AstraZeneca; has done consultancy for Novartis and AstraZeneca; and has received lecture fees from Janssen-Cilag, Pfizer, and AstraZeneca and educational grant support from Janssen-Cilag, Eli Lilly, and AstraZeneca; CLMH, CPYC, CWL, ST, EPFP, KTC, YCW, FYMM, KPMC, TJY, and SFH declare no relationships with commercial entities that might have an interest in the submitted work in the previous 3 years. All authors declare that they have (3) no spouses, partners, or children with financial relationships with commercial entities that may be relevant to the submitted work, and (4) no non-financial interests that may be relevant to the submitted work.
Ethical approval: The institutional review boards at each site gave ethical approval, and all participants provided written informed consent.
Data sharing: No additional data available.
- Accepted 7 June 2010
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