The Tolerance and Dependence of Zolpidem, Not a ‘So Safe’ Drug?

Abstract

Zolpidem is a short-acting non-benzodiazepine hypnotics and has a short elimination half-life that was introduced in the 1980s. It has an favorable and safe profile compared to short-acting benzodiazepines (BZD), so it was expected that the disadvantages of BZD, such as sedation the next day and daytime sleepiness, as well as dependence and withdrawal symptoms, could be overcome. However, there is a growing body of case reports on zolpidem abuse and dependence, as well as withdrawal syndrome and epileptic seizures related to zolpidem discontinuation. Many subsequent studies have revealed that increasing concentrations of zolpidem result in loss of receptor selectivity, and binds to other subunits of the GABA-A receptor, similar to benzodiazepine. Nevertheless, zolpidem is one of the most commonly prescribed hypnotics in Korea, and related abuse and dependence cases are increasing. Thus, it is necessary to understand the developing mechanism of abuse and dependence related zolpidem, and be prepared with strategies to detoxify or intervene in any related condition.