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Association between hypnotics use and increased mortality: causation or confounding?

  • Pharmacoepidemiology and Prescription
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

Many research studies have found associations between benzodiazepines and/or z-hypnotics (BZZ) and increasing mortality, leading to a discussion about causation or confounding. This study suggests a factor that could produce this association through confounding.

Methods

The Norwegian population in 2010 supplied 8862 deaths ages 41–80 and 898,289 controls. Index dates were added to control records which corresponded to death dates. BZZ use was recorded for 2 years before death/index date.

Results

Persons exposed to BZZ were more likely (OR = 2.3) to die than those who were not. With proximity of death, increasingly larger proportions of the prospective deaths received prescriptions for BZZ, until in the last 2 months 40–45 % received BZZ. The frequency of BZZ use in controls increased with age as opposed to the death cohort where all ages showed similar rates of BZZ use. In the last few months before death, the youngest age group had an OR = 5.8 for BZZ use while the oldest age group an OR = 1.8, adjusted for age and sex. Opioid use showed a similar pattern of increasing use near death.

Conclusions

The increased use of BZZ with approaching death is consistent with increasing symptomatic treatment in terminal illness. Thus, the association of BZZ and mortality is more likely to be due to confounding than to causality. Further evidence from this and other research includes similar use patterns for other drugs such as opioids, the lack of specificity in cause of death and the size of the association regarding age and time to death.

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Acknowledgments

The authors would like to thank Drs. Svetlana Skurtveit, Christian Berg, and colleagues of the Norwegian Institute of Public Health, Oslo, Norway, for their support.

Conflict of interest

Neither author has any conflict of interest associated with any part of this study and article.

Author involvement

Both authors were involved at all stages of the research and writing of the article. While Dr. Neutel took the lead, Dr. Johansen was also involved in planning of the research methodology, the analysis of the data, and the editing of the paper.

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Authors and Affiliations

  1. School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, 451 Smyth Road (Room 3105) Roger-Guindon Building, Ottawa, K1H 8M5, Ontario, Canada

    C. Ineke Neutel & Helen L. Johansen

Authors
  1. C. Ineke Neutel
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  2. Helen L. Johansen
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Corresponding author

Correspondence to C. Ineke Neutel.

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Neutel, C.I., Johansen, H.L. Association between hypnotics use and increased mortality: causation or confounding?. Eur J Clin Pharmacol 71, 637–642 (2015). https://doi.org/10.1007/s00228-015-1841-z

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  • DOI: https://doi.org/10.1007/s00228-015-1841-z

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