Benzodiazepine high-doses: The need for an accurate definition

Abstract

Objectives: A clear definition of what we understand of high-dose misuse or of a 'markedly increased dose' (as stated by the DSM-5) is important and past definitions may be inadequate. The aim of this review is to describe the different definitions used and to test these definitions for their accuracy.

Methods: A narrative PubMed literature review was conducted based on articles published between 1 January 1990 and 31 December 2020 describing benzodiazepines (in MeSH Terms or MeSH Major Topic) and high-dose (or high-dosage). Specific definitions were applied to a population sample to show how definitions affect high-dose benzodiazepine prevalence.

Results: Multiples of an equivalent-diazepam dose or of the World Health Organization 'defined daily dosage' were used more frequently than the overstep of the recommended maximum therapeutic dosage as a cut-off point.

Conclusion: High-dose use is rare but the prevalence in the general population varies among studies, mainly due to different definitions, making both clinical and epidemiological comparisons between studies difficult. Defining a high-dose user as a person who takes at least a higher dose than the maximum usual therapeutic dose over a defined period of time therefore appears to be clinically more consistent.

Keywords: anxiolytics; benzodiazepine; high-dose use; hypnotics; long-term use.