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Three Part Question

In [adult patients with benzodiazepine overdose], what [clinical features] are associated with [significant morbidity and mortality]?

Clinical Scenario

A 23 year old male is brought in to your emergency department after ingesting a handful of pills in an attempt to kill himself. His friends bring in an empty bottle of the only medication he took, the benzodiazepines he takes for intermittent anxiety. You wonder what symptoms he exhibits puts him at a high risk for complications from his ingestion.

Search Strategy

Medline 1946-09/12 using OVID interface, Cochrane Library (2012), PubMed clinical queries
[benzodiazepines/poisoning OR benzodiazepines/toxicity]. Limit to English language, humans

Search Outcome

110 papers were identified; case-series that presented crude data were excluded. Six clinical trials were found that were relevant to the clinical question. All six trials were summarized in a single systematic review published in 2009.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Charlson F. Degenhardt L. McLaren J. Hall W. Lynskey M. 2009 Australia	Patient groups included the general population, drug misusers and the elderly (>65 years of age). Definitions of benzodiazepine use varied from daily use to weekly use.	Systematic review of six prospective cohort studies.	Increased mortality or adverse outcomes in heavy or dependent users.	Some evidence of increased mortality in these populations.	The studies did not look at illicit benzodiazepine use in the general population. Specific causes of death not identified in certifications of death. Number, type, and frequency of benzodiazepine use is not well delineated in any of the studies, and polysubstance ingestions are confounders. The methods used to select studies, assess validity, and extract data were not described and so it is not known whether efforts were made to reduce reviewer error or bias.

Comment(s)

This paper reviews prospective cohort studies regarding benzodiazepine use as related to morbidity/mortality. The studies do not provide sufficient data for conclusive evidence of increased morbidity/mortality for people using benzodiazepines in a medical versus extra-medical manner. The authors’ conclusions appeared to reflect the limited and diverse evidence, but the lack of reporting and limitations of the review methods along with uncertainty about the inclusion criteria, mean that they should be interpreted with caution.

Editor Comment

KMJ

Clinical Bottom Line

Further studies will be needed to better risk stratify factors that increase morbidity and mortality in benzodiazepine users.

References

1. Charlson F. Degenhardt L. McLaren J. Hall W. Lynskey M. A systematic review of research examining benzodiazepine-related mortality Pharmacoepidemiol Drug Saf 2009; 18(2):93-103.