Physostigmine as a treatment for gamma-hydroxybutyrate toxicity: a review

Gamma-hydroxybutyrate is a potent sedative-hypnotic agent and a popular drug of abuse. In the United States, gamma-hydroxybutyrate is a Schedule I controlled substance (sodium oxybate) with orphan drug status for the treatment of narcolepsy within approved clinical studies. Physostigmine is a carbamate inhibitor of acetylcholinesterase that is reported to attenuate the sedative effects of a number of drugs, including gamma-hydroxybutyrate. We reviewed the literature that pertains to the use of physostigmine to treat gamma-hydroxybutyrate-induced sedation.

A structured literature search was performed to identify articles in which physostigmine and gamma-hydroxybutyrate were mentioned. Keywords were used to identify relevant articles in the Medline database, and the reference sections of articles identified by this method were hand-checked to identify additional articles. Those articles that presented original evidence pertaining to the use of physostigmine to treat gamma-hydroxybutyrate-induced sedation were included in this review; those that did not were rejected.

The literature search identified 22 articles, six of which did not pertain to the subject matter. Of the 16 articles which remained, 12 were rejected because they offered opinions without presenting original evidence. Of the four articles that presented original evidence, there were no in vitro studies and no animal studies. There were two small case series in which physostigmine was given to treat acute gamma-hydroxybutyrate toxicity in an emergency department setting, and two larger series in which physostigmine was given to attenuate the sedation induced by gamma-hydroxybutyrate in a more structured anesthesia setting. Although these references report that physostigmine attenuates gamma-hydroxybutyrate-induced sedation, there are methodological flaws and confounding factors that limit the scope of the conclusions that can be drawn from them.

There is currently insufficient scientific evidence to support the routine use of physostigmine in the treatment of gamma-hydroxybutyrate toxicity. Further studies are needed to determine the role, if any, for physostigmine in this setting.