High-dose zolpidem dependence - Psychostimulant effects? A case report and literature review

Abstract

Zolpidem, an imidazoline nonbenzodiazepine sedative drug, is used widely. Initial reports showed minimal abuse potential. However, multiple reports have appeared of dose escalation and abuse. Subjective effects of high-dose zolpidem are not known. In light of accumulating evidence of abuse potential, we hereby report a case of high-dose dependence and a review of relevant literature. A 33-year-old male presented with 5 years of daily use of 600–1700 mg of zolpidem tartrate. He reported subjective effects of euphoria, intense craving, and inability to stop use. Loss of receptor specificity, pharmacokinetic factors, and different receptor distributions can explain paradoxical stimulatory effects of high-dose zolpidem. Further studies are required to characterize subjective effects of high-dose zolpidem.

Dependence, withdrawal and rebound of CNS drugs: an update and regulatory considerations for new drugs development

“…Dependence following the use of zolpidem has been known since the 1990s as occurring mainly in people abusing it. There are also a considerable number of zolpidem dependence case reports in the scientific literature ( Aragona, 2000 ; Tripodianakis et al , 2003 ; Cubala and Landowski, 2007 ; Victorri-Vigneau et al , 2007 ; Victorri-Vigneau et al , 2014 ; Chattopadhyay et al , 2016 ).…”

Zolpidem Use and Suicide Death in South Korea: A Population‐Based Case–Control Study

“…Insomnia (ICD-10: G47, F51), the main cause for taking zolpidem, was also considered a confounding factor. We used the Charlson comorbidity index (CCI), a weight index of 19 chronic comorbid diseases (e.g., cancer, diabetes, myocardial infarction, moderate or severe renal disease, hemiplegia, liver disease, chronic pulmonary disease), according to previous diagnoses, during a period of 1 year before the index date (Charlson, Pompei, Ales, & MacKenzie, 1987;Quan et al, 2005).…”

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

“…In recent years, zolpidem abuse and addiction have been progressively documented in several case reports and case series, particularly among female patients with psychiatric comorbidities such as panic disorder, drug or alcohol use disorders, and pain syndromes (Rush, 1998;Hajak et al, 2003;Lin et al, 2017;Cheng et al, 2019;Jang et al, 2019;Lugoboni et al, 2019;Sabe et al, 2019;Sharma et al, 2019). 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).…”

“…In recent years, zolpidem abuse and addiction have been progressively documented in several case reports and case series, particularly among female patients with psychiatric comorbidities such as panic disorder, drug or alcohol use disorders, and pain syndromes (Rush, 1998; Hajak et al , 2003; Lin et al , 2017; Cheng et al , 2019; Jang et al , 2019; Lugoboni et al , 2019; Sabe et al , 2019; Sharma et al , 2019). 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).…”