Euphoric effect induced by zolpidem: a case study of magnetoencephalography

Abstract

Initially, zolpidem, a non-benzodiazepine hypnotic agent, was considered to have fewer adverse reactions than traditional benzodiazepines. However, after zolpidem was approved for medical use, an increasing number of case reports have described abuse or dependence complications. We were especially interested in the cases of dependence that presented a paradoxical ‘euphoric’ effect of zolpidem. This article reports the case of a female zolpidem-dependent patient who presented with 6 years of daily use of 400–1400 mg of zolpidem. She reported subjective effects of euphoria, intense craving and the inability to stop drug ingestion. Her diagnoses were zolpidem dependence and a depressive episode induced by substance abuse. To explore the neural mechanisms of the euphoric effect caused by high-dose zolpidem, we performed repeated magnetoencephalography (MEG) recordings. Before undergoing detoxification, her MEG results indicated that cerebellar electrical signal activation increased when taking high zolpidem doses. However, the prefrontal and parietal lobes’ electrical signal activity showed a tendency to recover to a normal state as the withdrawal time progressed to completion. This case suggests that the cerebellum plays a role in the euphoria induced by high zolpidem doses and provides clues for further research.

Severe chronic abuse of zolpidem for over 10 years: a case report and review of similar cases

“…However, the most important complication of zolpidem is dependency and severe abuse followed by withdrawal symptoms. Previous studies mentioned inability to concentrate, lightheadedness, decreased sleep, sweating, marked irritability, palpitations, nausea, and dysphoria as abstinence symptoms ( 19 , 20 , 23 ). A report of a 20-year-old man with 1,200 mg/day abuse also demonstrated dysarthria due to excessive tension as a possible complication of zolpidem ( 24 ).…”

“…Another study gradually replaced tapering zolpidem with sertraline, pregabalin, and clonazepam in a case of 1,200 mg daily abuse ( 32 ). There have also been various detoxifying regimens; single pregabalin therapy, diazepam in addition to trazodone and propranolol, or bupropion and mirtazapine, which can be seen in Table 1 ( 20 , 26 , 27 ). To the best of our knowledge, as with benzodiazepines ( 33 ), there is no documented guideline to approach zolpidem abuse and patients are conditionally treated.…”

“…Withdrawal symptoms such as weakness of limbs, headaches, considerable irritability, inability to concentrate, tremors, sweating, palpitation, as well as seizures may occur during zolpidem overuse, calling into question the advantages of this medication ( 15 , 18 ). To date, there have been reports of extremely high daily doses of zolpidem overuse with doses up to 2,400 mg being among the highest ( 19 , 20 ). Herein, we report a 39-year-old woman presenting with 10 years of chronic zolpidem abuse: up to 6,000 mg/day as the first case with the highest level of consumption (>2,400 mg/day).…”

Navigating the complex landscape of benzodiazepine- and Z-drug diversity: insights from comprehensive FDA adverse event reporting system analysis and beyond

“…However, since their launch, the number of adverse event reports connected to the Z-drugs has been rising. They were shown to produce euphorogenic effects like prominently abused benzodiazepines such as lorazepam (Ativan), alprazolam (Xanax) and flunitrazepam (Rohypnol) (51). In addition, paradoxical reactions similar to those of BZDs have been described for Z-drugs as well (52).…”

O Uso De Zolpidem, Seus Efeitos Adversos E a Qualidade De Sono: Uma Análise Entre Os Estudantes De Medicina De Uma Instituição Do Oeste Do Paraná

“…Existem muitas causas de insônia, entre eles, os fatores psicológicos têm uma influência importante não só no processo e na duração da insônia, mas também no comportamento de procura de ajuda e nas escolhas de tratamento, incluindo aumentos ou reduções na dosagem de medicamentos (EDINOFF et al, 2021). Os fatores psicossociais mais frequentemente relatados que levam à insônia são eventos estressantes, enquanto as características cognitivas de altas expectativas de duração do sono e preocupação excessiva com a perda e distorção do sono podem afetar significativamente a automaticidade do sistema sono-vigília e o gerenciamento da dosagem de medicamentos (LYU et al, 2022).…”