Use of naloxone in the treatment of benzodiazepine poisoning

We read with interest the recent article by Solhi et al., ¹ studying the use of naloxone in benzodiazepine poisoning treatment and the comments by Jang et al. ² It is an interesting topic and we would like to express our thoughts on these comments and concerns based on the literature review.

Jang et al. had a concern: ‘Since naloxone is a known antidote for opioid toxicity, it is very important to exclude their presence to validate the data obtained’. ² This is a good point to make this article better. However, this might not affect the final conclusion in this study based on the results.

First, a number of studies show that the prevalence of current benzodiazepine use in methadone-maintenance treatment populations varies between 24.9% and 50.6%. ^3,4 However, prevalence data suggest that most benzodiazepine users do not take illegal drugs. ^{4 –6} In the study by Solhi et al., after a naloxone injection, 80%–100% of the patients, varying by type of benzodiazepine, significantly improved the main signs and symptoms such as lethargy, weakness, and ataxia, while there was no improvement in the control groups. It is unlikely that 80%–100% of the patients in this study were using illegal drug or synthetic opioids. In another word, there must be few, if not all, patients without any illegal drug or synthetic opioid use, whose symptoms and clinical signs were improved by naloxone, but not by control treatments.

Second, animal studies provide direct evidence that naloxone antagonizes gamma-aminobutyric acid (GABA)/benzodiazepine receptor functions. Electrophysiological data show that GABA-induced inhibition of neuronal firing in the brain of rat can be antagonized by naloxone. ⁷ Furthermore, in experimental animals, naloxone antagonizes various benzodiazepine-induced behaviors, for example, hyperdipsia, hyperphagia, anticonflict effects, and anxiolytic-like effects. ^{8 –11} These data suggest the direct interaction of naloxone with GABA/benzodiazepine receptor functions.

In summary, this study provides useful information on the treatment of benzodiazepine poisoning by naloxone. The nature of the mechanism involved, which needs further study, might involve its interaction with GABA receptors.