Zolpidem stimulant effect: Induced mania case report and systematic review of cases

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

“…Motivations may include strategy to cope with everyday activities, to overcome daily social, professional and family problems, anxiolytic effect and mood enhancement and psychostimulant potentiation. Sabe et al [23] suggested that zolpidem dependence may develop for reaching a "sedative or hypnotic effect", "antidepressant-like effect, anxiolytic effect, or pleasant effect" and "being able to cope with everyday problems"; or, finally, for the "stimulation, euphoric or manic effect". Since zolpidem effect lasted no more than one hour, the subject usually repeats the intake in the daytime in order to maintain a basic euphoric effect [29].…”

“…amnestic episodes [53]; an anxiolytic effect, euphoria, exaltation, hyperactivity and stimulation; hence, zolpidem may be used to achieve these paradoxical effects and not for sedation [29]. Moreover, the stimulating and euphoric effect could be likely be explained by a dopaminergic activity of zolpidem as well [58,76] which may explain the occurrence of psychotic symptoms, psychomotor agitation and hallucinations in some clinical cases [23,40,[77][78][79][80]. In fact, the "amphetamine/cocaine-like" zolpidem effect may be explained by its activity in increasing dopamine release through switching-off the firing of GABA neurons that tonically inhibit dopamine cell firing [81].…”

“…Considered the frequency of zolpidem abuse and dependence similar to that of BZDs, zolpidem was transferred to Schedule IV of the 1971 Convention (i.e., for drugs inducing dependence such as BZDs) in 2001 [12,15]. In fact, despite the minimal abuse potential showed by initial reports, zolpidem abuse and dependence have been increasingly recorded in multiple case reports and case series [14,16,17], especially at very high doses, amongst subjects with a history of drug and/or alcohol addiction, and through idiosyncratic intake modalities [2,[17][18][19][20][21][22][23][24][25]. A second subset of individuals abusing or depending on Z-drugs include female patients with psychiatric comorbidities and/or pain syndromes, who were originally started with these molecules for insomnia but who developed tolerance and withdrawal phenomena [17,18,22,24,[26][27][28].…”

“…High-dose (600−2,000 mg daily) zolpidem use was associated with psychostimulant effects, such as feelings of well-being, euphoria ("high"), energy, alertness, sociability, talkativeness [23,29,36]. Moreover, other unexpected effects, such as sleepwalking, sleep-driving, sleep-related eating disorders or engaging in other activities while not fully awake, were reported [36][37][38][39].…”

“…These findings induced the Food and Drug Administration (FDA), in a recent Drug Safety Communication [37], to require a stronger warning related to those complex sleep behaviours occurring after Z-drugs intake, by adding a contraindication in prescribing these drugs in patients who have already experienced an episode of complex sleep behaviours due to resulting serious injuries and fatalities. Furthermore, delusions and psychotic experiences were also reported following high-dose use of zolpidem [23,40]. Finally, intense craving, inability to stop use and withdrawal were associated with long-term high dose zolpidem consumption [29,36].…”