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General practice / Family practice
Original research
Association between prescription of hypnotics/anxiolytics and mortality in multimorbid and non-multimorbid patients: a longitudinal cohort study in primary care
  1. Kristjan Linnet1,
  2. Johann Agust Sigurdsson1,2,
  3. Margret Olafia Tomasdottir3,
  4. Emil Larus Sigurdsson1,3,
  5. Larus Steinthor Gudmundsson4
  1. 1 Development Centre for Primary Healthcare in Iceland, Primary Health Care of the Capital Area, Reykjavik, Iceland
  2. 2 General Practice Research Unit, Department of Public Health and Nursing, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
  3. 3 Department of Family Medicine, Faculty of Medicine, University of Iceland School of Health Sciences, Reykjavik, Iceland
  4. 4 Faculty of Pharmaceutical Sciences, School of Health Sciences, University of Iceland, Reykjavik, Iceland
  1. Correspondence to Kristjan Linnet; kristjan.linnet{at}heilsugaeslan.is

Abstract

Objectives To assess the risk of mortality in primary care patients, multimorbid (≥2 chronic conditions) or not, prescribed hypnotics/anxiolytics.

Design A longitudinal cohort study

Setting Primary healthcare in the Reykjavik area.

Participants 114 084 individuals (aged 10–79 years, average 38.5, SD 18.4) contacting general practitioners during 2009–2012 (mortality follow-up to 31 December 2016). Of those, the reference group comprised 58 560 persons who were neither multimorbid nor had redeemed prescriptions for hypnotics/anxiolytics. Participants (16 108) redeeming prescriptions for hypnotics/anxiolytics on a regular basis for 3 consecutive years were considered as consistent, long-term users. They were subdivided into low-dose (1–300 defined daily doses (DDD)/3 years), medium-dose (301–1095 DDDs/3 years) and high-dose users (>1095 DDDs/3 years). All six groups taking these drugs were compared with the reference group.

Main outcome measures All-cause mortality.

Results HRs were calculated with the no multimorbidity—no drug group as a reference, using Cox proportional hazards regression model adjusting for age, sex and the number of chronic conditions (n=111 767), patients with cancer excluded. During follow-up, 516 358 person-years in total, 1926 persons died. Mean follow-up was 1685 days (4.6 years), range 1–1826 days (5.0 years). For all multimorbid patients who took no drugs the HR was 1.14 (95% CI 1.00 to 1.30) compared with those without multimorbidity. HRs in the non-multimorbid participants varied from 1.49 to 3.35 (95% CI ranging from 1.03 to 4.11) with increasing doses of hypnotics/anxiolytics, and correspondingly from 1.55 to 3.52 (1.18 to 4.29) in multimorbid patients.

Conclusions Mortality increased in a dose-dependent manner among both multimorbid and non-multimorbid patients taking hypnotics/anxiolytics. This increase was clearly associated with prescribing of these drugs. Their use should be limited to the recommended period of 2–4 up to 6 weeks; long-term use may incur increased risk and should be re-examined.

  • mortality
  • hypnotics
  • anxiolytics
  • multimorbidity
  • primary care

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/bmjopen-2019-033545

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    Footnotes

    • Contributors KL, LSG and JAS initiated and designed the study. KL, LSG, JAS, MOT and ELS performed further development. KL and LSG drafted the manuscript with input from JAS which was critically reviewed by all authors. LSG performed the statistical analysis. KL, LSG, JAS, MOT and ELS read and approved the final version of the manuscript.

    • Funding This research was supported by the Research Fund of the Icelandic College of Family Physicians and the Fund of Scientific Research of the Pharmaceutical Society of Iceland.

    • Competing interests None declared.

    • Patient consent for publication Not required.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement The data is retrieved from a medical records database in the Primary Healthcare of the Capital Area (PHCA), the Icelandic Medicine Register (IMR) and the National Cause of Death Registry of the Directorate of Health. The encrypted data is kept at the Directorate of Health and can made available on a reasonable request if permitted by the above-mentioned health authorities.