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Mortality Risk Associated with Haloperidol Use Compared with Other Antipsychotics: An 11-Year Population-Based Propensity-Score-Matched Cohort Study

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Abstract

Background

Haloperidol remains a frequently prescribed first-generation antipsychotic. However, haloperidol-associated mortality risk by all causes, cardiovascular disease (CVD), and pneumonia compared with other antipsychotics is unknown.

Objective

This study investigated the mortality risk associated with long-term haloperidol treatment versus that with other antipsychotics.

Methods

We identified incident antipsychotic users from 2004 to 2014 in the Clinical Data Analysis and Reporting System (CDARS), a population-based clinical database managed by the Hong Kong Hospital Authority. We included patients who were aged ≥ 18 and received antipsychotics for any indication apart from terminal illnesses or management of acute behavioural disturbance. Patients on haloperidol and other antipsychotic agents (risperidone, quetiapine, olanzapine, chlorpromazine, aripiprazole, sulpiride, amisulpride, or trifluoperazine) were matched by propensity score. Hazard ratios (HRs) for all-cause mortality and death due to CVD and pneumonia were estimated with 95% confidence intervals (CIs) using a Cox proportional hazards model.

Results

In total, 136,593 users of antipsychotics were included. During a mean follow-up of 3.2 years, the incidence of all-cause mortality ranged from 186.8/1000 person-years for haloperidol to 10.4/1000 person-years for trifluoperazine. The risk of all-cause mortality was lower with non-haloperidol antipsychotics than with haloperidol, with HRs ranging from 0.68 (95% CI 0.64–0.72 [chlorpromazine]) to 0.43 (95% CI 0.36–0.53 [trifluoperazine]). Risperidone, quetiapine, sulpiride, chlorpromazine, aripiprazole, and trifluoperazine were associated with a significantly lower risk of pneumonia-related mortality. A significantly lower risk of CVD mortality was observed for risperidone, sulpiride, chlorpromazine, and quetiapine.

Conclusion

Haloperidol was associated with increased overall mortality when compared with other antipsychotics in long-term follow-up. Treatment with haloperidol should be carefully considered, especially in older patients and patients at risk of CVD or pneumonia, since the risk of death appears to be lower with non-haloperidol agents.

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Acknowledgements

The authors thank the Accident and Emergency Department and the Department of Pharmacy, Queen Elizabeth Hospital (Dr. Stephen Yeung Chi Yeung, Dr. Gordon Wong, Dr. Wilson Leung, Mr. Howard Yip Ho Wah, Mr. Wong Chi Yip, Mr. Johnson Tse, Dr. Karen Chan Kin Ling), and Dr. LP Leung (Emergency Medicine Unit, The University of Hong Kong) for their contribution to the study design. We thank Ms. Lisa Lam for editing and proof-reading.

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Authors and Affiliations

  1. Department of Pharmacology and Pharmacy, Centre for Safe Medication Practice and Research, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Office 02-08, 2/F Laboratory Block, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China

    Kim S. J. Lao, Ian C. K. Wong, Joseph E. Blais & Esther W. Chan

  2. Global Medical Affairs, Merck Research Laboratories, MSD, Shanghai, China

    Kim S. J. Lao

  3. Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK

    Angel Y. S. Wong

  4. Research Department of Practice and Policy, UCL School of Pharmacy, London, UK

    Ian C. K. Wong & Frank M. C. Besag

  5. East London NHS Foundation Trust, Bedfordshire, UK

    Frank M. C. Besag

  6. Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK

    Frank M. C. Besag

  7. Department of Psychiatry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China

    W. C. Chang, Edwin H. M. Lee & Eric Y. H. Chen

  8. State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong SAR, China

    W. C. Chang & Eric Y. H. Chen

Authors
  1. Kim S. J. Lao
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  2. Angel Y. S. Wong
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  7. Eric Y. H. Chen
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  9. Esther W. Chan
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Corresponding author

Correspondence to Esther W. Chan.

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Funding

This study was supported by the General Research Fund, Research Grants Council, Hong Kong (project reference 17111615) and partially funded by the Early Career Scheme, Research Grants Council, Hong Kong (project reference 789813). The funders had no role in the design, analysis, interpretation, or publication of this study.

Conflict of interest

All authors declare that no other support has been received from any organization for the submitted work; no other financial relationships exist with any organizations that might have an interest in the submitted work in the previous 3 years; no other relationships exist or activities have been undertaken that could appear to have influenced the submitted study. KSJL was formerly employed by the University of Hong Kong, where most of the work was completed, and is currently employed by MRL, MSD China at submission. Outside the submitted work, AYSW has received Institutional Strategic Support Fund 3 Pump Priming Grant, and is currently supported by British Heart Foundation Immediate Postdoctoral Basic Science Research Fellowship. EWC has received research funding from the Wellcome Trust, UK; the National Natural Science Fund of China, China; The Hong Kong Research Grants Council, The Research Fund Secretariat of the Food and Health Bureau, the Narcotics Division of the Security Bureau of HKSAR, Hong Kong; Bristol-Myers Squibb, Pfizer, Bayer, and Janssen, a division of Johnson & Johnson, and Takeda for work unrelated to this study. ICKW has received grants from the Research Grants Council (RGC, Hong Kong), the Innovative Medicines Initiative (IMI), Shire, Janssen-Cilag, Eli-Lily, Pfizer, Bayer, and the European Union FP7 program outside the submitted work; is a member of the National Institute for Health and Care Excellence (NICE) ADHD guideline group and the British Association for Psychopharmacology ADHD guideline group; and an advisor to Shire. EYHC has completed work for Otsuka, Janssen, and DSK Biopharma. FMCB, WCC, EHML, and JEB have no conflicts of interest that are directly relevant to the content of this article.

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Lao, K.S.J., Wong, A.Y.S., Wong, I.C.K. et al. Mortality Risk Associated with Haloperidol Use Compared with Other Antipsychotics: An 11-Year Population-Based Propensity-Score-Matched Cohort Study. CNS Drugs 34, 197–206 (2020). https://doi.org/10.1007/s40263-019-00693-5

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  • DOI: https://doi.org/10.1007/s40263-019-00693-5

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