Effect of anxiolytic and hypnotic drug prescriptions on mortality hazards: retrospective cohort studyBMJ 2014; 348 doi: https://doi.org/10.1136/bmj.g1996 (Published 19 March 2014) Cite this as: BMJ 2014;348:g1996
- Scott Weich, professor of psychiatry1,
- Hannah Louise Pearce, prescribing and public health analyst2,
- Peter Croft, professor of primary care epidemiology3,
- Swaran Singh, professor of social and community psychiatry1,
- Ilana Crome, professor of addiction psychiatry4,
- James Bashford, lecturer in primary care research2,
- Martin Frisher, reader in health services research2
- 1Division of Mental Health and Wellbeing, Warwick Medical School, University of Warwick, Coventry, West Midlands CV4 7AL, UK
- 2School of Pharmacy, Keele University, Keele, Staffordshire, UK
- 3Institute of Primary Care and Health Sciences, Keele University, Keele, Staffordshire, UK
- 4Academic Psychiatry Unit, St George’s Hospital, South Staffordshire and Shropshire Healthcare NHS Foundation Trust, Stafford, Staffordshire, UK
- Correspondence to: S Weich
- Accepted 18 February 2014
Objective To test the hypothesis that people taking anxiolytic and hypnotic drugs are at increased risk of premature mortality, using primary care prescription records and after adjusting for a wide range of potential confounders.
Design Retrospective cohort study.
Setting 273 UK primary care practices contributing data to the General Practice Research Database.
Participants 34 727 patients aged 16 years and older first prescribed anxiolytic or hypnotic drugs, or both, between 1998 and 2001, and 69 418 patients with no prescriptions for such drugs (controls) matched by age, sex, and practice. Patients were followed-up for a mean of 7.6 years (range 0.1-13.4 years).
Main outcome All cause mortality ascertained from practice records.
Results Physical and psychiatric comorbidities and prescribing of non-study drugs were significantly more prevalent among those prescribed study drugs than among controls. The age adjusted hazard ratio for mortality during the whole follow-up period for use of any study drug in the first year after recruitment was 3.46 (95% confidence interval 3.34 to 3.59) and 3.32 (3.19 to 3.45) after adjusting for other potential confounders. Dose-response associations were found for all three classes of study drugs (benzodiazepines, Z drugs (zaleplon, zolpidem, and zopiclone), and other drugs). After excluding deaths in the first year, there were approximately four excess deaths linked to drug use per 100 people followed for an average of 7.6 years after their first prescription.
Conclusions In this large cohort of patients attending UK primary care, anxiolytic and hypnotic drugs were associated with significantly increased risk of mortality over a seven year period, after adjusting for a range of potential confounders. As with all observational findings, however, these results are prone to bias arising from unmeasured and residual confounding.
This study is based on data from the Full Feature General Practice Research Database obtained under licence from the UK Medicines and Healthcare Products Regulatory Agency (MHRA). However, the interpretation and conclusions contained in this study are those of the authors alone. Access to the General Practice Research Database was funded through the Medical Research Council’s licence agreement with MHRA. We thank Tarita Murray-Thomas at the MHRA for producing the dataset, and all contributing general practitioners and their patients. PC is a senior investigator for the National Institute for Health Research.
Contributors: SW, MF, SS, and IC had the original idea for this study. SW and MF were responsible for study hypotheses, design, data specification, analysis, and drafting of the manuscript. MF and HP undertook the analyses, and results were interpreted by all authors. PC advised on data analysis and interpretation of the study findings. MF had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. All authors contributed to the drafting of the manuscript. SW is the guarantor.
Funding: This study received no specific funding. This project was awarded a licence as part of a scheme operated by the UK Medical Research Council and Medicines and Healthcare products Regulatory Agency to provide data access on up to 100 000 patients. Data were based on records from 273 primary care practices in England, Scotland, Wales, and Northern Ireland. The providers of this license did not have any involvement in the conduct of the research and were not consulted in the drafting of the manuscript.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: This project was approved by the Warwick Medical School Biomedical Research Ethics Committee (reference 192-03-2012).
Data sharing: No additional data available. The study data remain the property of the Clinical Practice Research Datalink (formerly General Practice Research Database) and was provided to the authors under license.
Transparency: SW (the manuscript’s guarantor) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.
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