‘Z-trip’? A Comprehensive Overview and a Case-series of Zolpidem Misuse

Abstract

Although believed safer compared to short-acting benzodiazepines (BZD), in the past few years a growing concern has developed relating to the abuse of Z-drugs, and specifically of zolpidem. Here we aim to review the evidence for the misuse of zolpidem and describe several related cases collected in Italy. A comprehensive overview is here carried by using several databases, and by combining the search strategy of free text terms and exploding a range of MESH headings relating to the topics of Zolpidem and Abuse and/or Misuse as follows:

Occurrence of involuntary movements after prolonged misuse of zolpidem: a case report

“…Using analysis of adverse drug reactions datasets supplied by the European Medicines Agency, zolpidem has been shown to induce craving and to be frequently involved in abuse and withdrawal problems (Victorri-Vigneau et al, 2007;Chattopadhyay et al, 2016;Schifano et al, 2019). Furthermore, a large number of surveys emphasize the association between zolpidem and the occurrence of psychomotor agitation and behavioral alterations involving bizarre behaviors and sleep-related complex behaviors (sleep-shopping, sleep-eating, sleep-driving, and sleep-conversations) with amnesia for the episode (Mendelson, 1994;Morgenthaler and Silber, 2002;Monti et al, 2017;Ho et al, 2020;Orsolini et al, 2021). Interestingly, in patients taking high doses of zolpidem (600-2000 mg/day), euphoria, high energy, sociability, talkativeness, and feelings of well-being have been described (Victorri-Vigneau et al, 2007;Sabe et al, 2019), along with psychotic symptoms such as delusions and hallucinations (Markowitz and Brewerton, 1996;Sabe et al, 2019).…”

“…From a pharmacological perspective, zolpidem is a non-benzodiazepine agonist of the gamma-aminobutyric acid receptor type A (GABA-A), selectively binding to the alfa1 subunit which is involved in sleep regulation (Orsolini et al , 2021). Although zolpidem is thought to be a safer drug compared to benzodiazepines, multiple cases of abuse and dependence have been reported since its introduction (Lin et al , 2017; Schifano et al , 2019; Sharma et al , 2019; Orsolini et al , 2021). In addition, a small number of cases have shown the occurrence of involuntary movements after prolonged zolpidem misuse.…”

“…Zolpidem was introduced in the 1980s for short-term treatment of insomnia and is Food and Drug Administration-approved for sleep induction. From a pharmacological perspective, zolpidem is a non-benzodiazepine agonist of the gamma-aminobutyric acid receptor type A (GABA-A), selectively binding to the alfa1 subunit which is involved in sleep regulation (Orsolini et al , 2021). Although zolpidem is thought to be a safer drug compared to benzodiazepines, multiple cases of abuse and dependence have been reported since its introduction (Lin et al , 2017; Schifano et al , 2019; Sharma et al , 2019; Orsolini et al , 2021).…”

An insight into zolpidem abuse and dependence

“…[1] W przeciwieństwie do doskonale już znanych benzodiazepin czy barbituranów, miały mieć niski potencjał nadużycia, uzależnienia I występowania działań niepożądanych, takich jak uczucie nadmiernego zmęczenia następnego dnia czy zespół odstawienny. [2] Zalecenie dotyczące stosowania zolpidemu obejmują przyjęcie minimalnej dawki tuż przed snem. W literaturze opisano natomiast wiele przypadków związanych z nadużywaniem tego leku klasy "Z" -szczególnie u osób starszych, osób z zaburzeniami nastroju, zaburzeniami lękowymi czy u osób z tendencjami do nadużywania substancji psychoaktywnych.…”

Development of two fully automated quick, easy, cheap, effective, rugged, and safe pretreatment methods for the extraction of psychotropic drugs from whole blood samples

“…In the first study for the automation of the QuEChERS extraction method, the target analytes were selected from psychotropic drugs. Minor tranquilizers, major tranquilizers, and antidepressants are representative basic drugs frequently prescribed in clinical treatments and often identified as causative drugs in suicide cases, toxicological cases, DUID (driving under the influence of drugs) cases, and sex-related crimes [25][26][27][28]. Considering the occurrence of poisoning cases and the current prescription drug situation, we carefully selected 14 psychotropic drugs, namely alprazolam, bromazepam, brotizolam, clonazepam, diazepam, etizolam, flunitrazepam, flurazepam, nimetazepam, nitrazepam, triazolam, carbamazepine, quetiapine, and zolpidem, as the analytes in this study.…”