Severe Chronic Abuse of Zolpidem in Refractory Insomnia

Abstract

Zolpidem is an imidazopyridine nonbenzodiazepine hypnotic drug with a high affinity to the α1 subunit of the gamma amino butyric acid A receptor It is the first pharmacological option in the short-term management of sleep-onset insomnia. Initially considered a safer drug compared to benzodiazepines because of lower liability for abuse and dependence, recently, an increasing body of reports has questioned zolpidem's proneness to misuse. In this report, we describe a case of serious zolpidem abuse requiring pharmacological washout during hospitalization because of previous withdrawal seizures in a patient with chronic sleep-onset and maintenance insomnia.

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

“…Three subjects were affected with a mood disorder (e.g., Dysthymic Disorder or MDD) accompanied with a secondary insomnia, which is comparable with clinical cases previously described [45,46,50,53,71,88,[90][91][92][95][96][97][98]. Two cases reported previous traumatic experiences (physical and/or sexual and/or psychological abuse) which may partially explain zolpidem abuse as a tool to relieve and cope with stress-related disorders, as previously reported in literature [52,89]. A case involved a woman with a BZD dependence whilst in four cases here described, the subjects were affected with a Personality Disorder (mainly belonging to the 'Cluster B', i.e., Narcissistic [n = 2], Borderline [n = 1] and Antisocial [n = 1]), of which two with a current or previous SUD (e.g., a cocaine use disorder, n = 1) or AUD (n = 1), as previously described [22,45,48,60,62,63,71,97].…”

“…The elderly people seemed to firstly take zolpidem as sleep aid and then progressively increase doses as they experience anxiolytic effects, at supratherapeutic doses. In fact, the increasing risk of zolpidem overdose amongst the elderly, who usually manifest depressive symptoms accompanied with anxiety, may be easily explained by anxiolytic zolpidem effect at higher doses [38,[45][46][47][48][49][50][51][52]. Conversely, female subjects who usually abuse zolpidem, are those suffering from iatrogenic insomnia or secondary to a minor psychiatric disorder (i.e., mild depression, dysthymia, or anxiety) (see Table 1) [53][54][55][56][57].…”

“…Similarly, pregabalin potently binds to the 2-delta regulatory subunit of voltage Ca ＋＋ channels, thus inhibiting activity-dependent Ca ＋＋ influx in presynaptic neurons, which results in a reduced release of excitatory neurotransmitters [87]. This activity may explain its efficacy in treating zolpidem dependence [52,88]. Overall, long-acting BZDs have been suggested as the ideal substitute for zolpidem (e.g., clonazepam, diazepam, chlordiazepoxide) by using a cross-titration strategy with an adequate and equivalent diazepam dosage [39,45,46,52,53,67,72,[89][90][91].…”

An Insight into Z-Drug Abuse and Dependence: An Examination of Reports to the European Medicines Agency Database of Suspected Adverse Drug Reactions

“…Together with the World Health Organization’s Drug Monitoring Program, the EV database is considered a worldwide reference standard (Schifano and Chiappini, 2018). Most literature papers, so far, were based on small case series/single case studies (Aranko et al, 1991; Sikdar and Ruben, 1996; Rooney and O’Conner, 1998; Wong et al, 2005; Flynn and Cox, 2006; Chiaro et al, 2018). Conversely, current findings referred to overall much larger (e.g., 33 240 ADRs; corresponding to some 6246 unique cases) numbers of patients presenting with Z-drug misuse issues.…”

Zolpidem: Efficacy and Side Effects for Insomnia

“…Rebound insomnia and withdrawal symptoms have been linked to zolpidem use after stopping the medication suddenly, even if the patient took the therapeutic dose, with an even higher risk in those with concurrent drug or alcohol dependence. 43,44 Misuse-, abuse-, dependence-, and withdrawal-related ADRs have been shown to make up 11.35% (95% CI 11.21-11.49%) of total ADRs seen with zolpidem.…”