Alcoholic substitution therapy. What place for benzodiazepines?

Context. - Substitution therapy proposes to replace a substance on which the patient is dependent by another less harmful. Substitution substances are pharmacological analogues to addictive substances, used to facilitate the cessation or reduction of their use, and to reduce their deleterious consequences. Conventionally used for opioids or tobacco, there is to date no validated substitution treatment for alcohol addiction. The use rates of both alcohol and benzodiazepines are among the highest in France, and are frequently associated. France is a country in which alcohol is the second most frequent toxic used, and the most damaging determinant of health for mortality and morbidity after smoking. Meanwhile, alcohol and benzodiazepines are the two most common GABA(A) receptor agonists, with multiple similarities, despite some distinct chemical properties and actions. However, ethanol has a major toxicity for the body whereas benzodiazepines have a better safety profile, despite various risks and possible side effects. Benzodiazepines are the recommended treatment for alcohol withdrawal, but the guidelines are limited in time on the first two weeks, while only few studies have addressed the pros and cons of maintaining benzodiazepines beyond the detox period.Some arguments suggest that benzodiazepines could be a substitute for alcohol. Both are GABA(A) receptor agonists. In practice, it is frequent to observe crossed dependences, and, in particular, situations in which subjects with alcohol dependence change for benzodiazepine dependence. However, the medical practice of durably switching alcohol for benzodiazepines has been poorly explored. Objectives. - To review the pharmacological and clinical arguments for and against considering benzodiazepines as a potential substitution treatment for alcohol dependence. Methods. - A narrative review of international literature has been conducted using the following keyword algorithm: (substitution OR replacement OR maintenance) AND alcohol AND benzodiazepine*, without any limitation in time. Results. - Among a few hundred articles found on PubMed, only 3 were finally retained, with only 1 controlled study, no review of literature, supplemented by references found during the readings. The possibility of alcohol substitution by benzodiazepines is addressed, with a partial or approximate terminology reserve for qualifying this substitution. Diazepam appears as the molecule of choice. Such a substitution method, out of its usual field and in a design partly innovative in care, could decrease alcohol damages and perhaps consumption levels. Conclusions. - Given the impossibility of conducting the synthesis of a non-existent literature, only an exploratory approach is possible, no recommendation or indication of the use of benzodiazepine as an alcoholic substitution can be formulated, without development validation studies of a such hypothesis (including researches about safety, choice of molecule, ways of psychosocial support ... ). In order to rethink the place of benzodiazepines in alcohol treatment strategies, owing to their frequent consumption with alcohol, the possibility of an approached alcoholic substitution using these drugs should be considered further. The prolonged used of benzodiazepines after alcohol withdrawal could consist of a harm reduction approach which could help support a psychosocial recovery. Long half-life molecules could be safer and easier to use, and should warrant future clinical trials. (C) 2021 Elsevier Masson SAS. All rights reserved.

Automated summary

There is currently no validated substitution treatment for alcohol addiction, but benzodiazepines are considered as a potential substitute. However, research on this topic is extremely limited. Benzodiazepines may play a role in the treatment of alcohol dependence, but more research is needed for validation.