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.

Addiction of High Dose of Benzodiazepine: Verona Detox Approach With Flumazenil

“…This seems to have generated a vicious circle that has lasted for almost thirty years: a limited number of centers, albeit with numerous and well-documented cases and trials, but not sufficiently distributed to include the method in the guidelines, despite the truly impressive spread of prolonged BZD use, not infrequently with extra-therapeutic doses. A further demonstration of how much the use of high doses of BZD remains poorly studied and poorly defined is the difficulty of still finding an agreement on the definition of high dose ( 29 ).…”

The Relationship of Early Sleep Improvement With Response to Pharmacotherapy in Unipolar Psychotic Depression

“…Multivariate associations between EII and the outcome measures, ie, response on depression, remission of depression and remission of psychotic symptoms, were analyzed by conducting logistic regression models. Regression analyses were adjusted for gender, age, medication types, co-use of benzodiazepines (mean lorazepam equivalent [mg/d]) during conduct of the study, 34 pretreatment insomnia and pretreatment depression severity (HAM-D-17 score). Interaction effects between EII and medication types were analyzed after adding interaction terms, computed as the products of EII and venlafaxine, imipramine and venlafaxine plus quetiapine respectively, to the regression models.…”

“…Quetiapine was initiated at 100 mg/d (first 2 days), followed by 200 mg/d (days 3–5), 400 mg/d (days 6–9), and 600 mg/d (rest of the study). Before initiation of study medication patients were free of psychotropic medication for at least 4 days except for benzodiazepines, which were allowed to an equivalent of maximum 3 mg lorazepam per day during conduct of the study 34 . Severity of depressive symptoms was scored weekly using the HAM-D-17 35 .…”

“…Before initiation of study medication patients were free of psychotropic medication for at least 4 days except for benzodiazepines, which were allowed to an equivalent of maximum 3 mg lorazepam per day during conduct of the study. 34 Severity of depressive symptoms was scored weekly using the HAM-D-17. 35 Psychotic symptoms were assessed weekly on the basis of clinical impression and were scored dichotomously (present or absent).…”

Benzodiazepines in complex biological matrices: Recent updates on pretreatment and detection methods

“…The use of BDZs by adults in the United States and the number of deaths caused by illegal use of BDZs were higher than previously reported, and misuse accounted for about 20% of total usage [ 17 ]. Clinical cases and data demonstrate the prevalence of BDZs use and the threat to life caused by substance abuse exacerbated by unclear regulatory limits [ 18 ]. BDZs exist in complex matrix environments with tiny content, which requires sample preparations to pre-concentrate the target substance and avoid inferences from others.…”