Translating Benzodiazepine Utilization Data into Meaningful Population Exposure: Integration of Two Metrics for Improved Reporting

Abstract

Drug utilization research on benzodiazepines remains important for measuring trends in consumption within and across borders over time for the sake of monitoring prescribing patterns and identifying potential population safety concerns. The defined daily dose (DDD) system by the World Health Organization (WHO) remains the internationally accepted standard for measuring drug consumption; however, beyond consumption, DDD-based results are difficult to interpret when individual agents are compared with one another or are pooled into a total class-based estimate. The diazepam milligram equivalent (DME) system provides approximate conversions between benzodiazepines and Z-drugs (i.e. zopiclone, zolpidem, zaleplon) based on their pharmacologic potency. Despite this, conversion of total dispensed benzodiazepine quantities into DME values retains diazepam milligrams as the total unit of measurement, which is also impractical for population-level interpretation. In this paper, we propose the use of an integrated DME-DDD metric to obviate the limitations encountered when the component metrics are used in isolation. Through a case example, we demonstrate significant change in results between the DDD and DME-DDD method. Unlike the DDD method, the integrated DME-DDD metric offers estimation of population pharmacologic exposure, and enables superior interpretation of drug utilization results, especially for drug class summary reporting.

Influence of covariates on heterogeneity in Hamilton Anxiety Scale ratings in placebo-controlled trials of benzodiazepines in generalized anxiety disorder: Systematic review and meta-analysis

“…However, the current classification systems are newer, and the HAM-A has been criticized as not being consistent with the current concept of Generalized Anxiety, though it correlates somewhat, and remains a standard outcome measure in psychopharmacological research. The use of the Ashton table to estimate diazepam equivalent doses, although common, has been questioned recently and alternative conversion standards suggested, though these have not had so extensive a use (Brandt et al, 2018).…”

“…However, the current classification systems are newer, and the HAM-A has been criticized as not being consistent with the current concept of Generalized Anxiety, though it correlates somewhat, and remains a standard outcome measure in psychopharmacological research. The use of the Ashton table to estimate diazepam equivalent doses, although common, has been questioned recently and alternative conversion standards suggested, though these have not had so extensive a use (Brandt et al, 2018). Most of the studies in the dataset were (if acknowledged or not) sponsored by various companies for the purpose of showing superiority to placebo or non-inferiority to alternative treatments according to the (then) standards required for licensing of new medications.…”

Is the Long-Term Use of Benzodiazepines Associated With Worse Cognition Performance in Highly Educated Older Adults?

“…Hypnotic drugs derived or connected with benzodiazepines (N05CF) were also included. Based on the self-report medication history obtained in the interviews and prescription record in the electronic medical record system, we converted the accumulated BZD dosage and average daily BZD dosage of each participant into diazepam equivalents (27). Based on the BZD use behavior provided in the participants medical information, the participants were divided into three BZD use groups: long-term BZD users (N = 47, BZD using time ≥180 day), and short-term BZD users (N = 46, BZD using time <180 day), and non-users (N = 47, never used BZD) (28).…”

Surveillance des substances contrôlées en établissements de santé : une contribution à la gestion de la crise des opioïdes au Canada

“…L'interprétation des études d'utilisation d'opioïdes par la population reposant sur les DDJ doit se faire avec précaution 22 . Ainsi, en complément des DDJ, on recommande l'analyse en équivalent en milligrammes de morphine orale, car la morphine est le médicament de référence pour le traitement de la douleur 18,[23][24][25] . Il en est de même pour les benzodiazépines, étant donné que les DDJ reflètent mal l'exposition clinique, car elles ne prennent pas en compte la puissance de ces molécules.…”

“…Il en est de même pour les benzodiazépines, étant donné que les DDJ reflètent mal l'exposition clinique, car elles ne prennent pas en compte la puissance de ces molécules. Ainsi, les investigateurs ont réalisé une analyse en équivalent en milligrammes de diazépam en complément des DDJ 25 . Cette unité permet une estimation de l'exposition pharmacologique de la population et une meilleure estimation de la puissance sédative 25 .…”