Treatment of benzodiazepine dependence

Abstract

Introduction and Aims: The consumption of benzodiazepines, including Z‐drugs, can undermine recovery from addictions and other high prevalence psychiatric conditions. They are negatively associated with functional and economic performance, and contribute to all‐cause mortality including escalation of preventable suicide risk. Dependence, abuse and diversion of benzodiazepines are iatrogenic risks which have been acknowledged in the literature for decades. Attempts to detoxify often fail due to a paucity of efficacious treatments, leading to a cycle of perceived futility and therapeutic nihilism. The aim of this presentation is to summarise the current and future treatments for benzodiazepine dependence.

Design and Methods: The author presents current algorithms and consensus statements on this topic, countervailed by early findings for a world first clinical trial of slow subcutaneous flumazenil infusion using a double‐blind placebo‐controlled crossover methodology.

Results: Although results are currently incomplete and not yet independently verified, primary and secondary outcome measures are approaching 100%, without significant adverse outcomes.

Discussion: Flumazenil treatment was generally supported by patients and nursing staff. The positive outcomes garnered so far belie some of this study's limitations, but may contribute to a new paradigm in treating benzodiazepine dependence. The proposed mechanism of action and clinical applicability is discussed. Some serendipitous findings also include a signal for reduction in opioid and tobacco use, steatohepatitis, vestibular disorder, perimenopausal symptoms, pre‐menstrual dysphoria and circadian desynchrony. These positive results need to be interpreted with some caution.

Conclusions: Flumazenil used in low doses as a neutral allosteric modulator may be a safe, effective and non‐invasive treatment for benzodiazepine dependence which may work by re‐setting the GABA‐A set point, and could be made available to a broader range of clinicians following appropriate training.

Disclosure of Interest Statement: The author declares no conflict of interests related to this manuscript. TM has received honoraria, fees and/or provision of professional development resources from Servier, Indivior, Otsuka/Lundbeck, Australian and New Zealand Mental Health Association and HealtheCare.