Tolerance and withdrawal with zolpidem

Cavallaro, Roberto; Regazzetti, M. G.; Covelli, Giampiero; Smeraldi, Enrico

doi:10.1016/0140-6736(93)91522-n

Cited by 60 publications

(21 citation statements)

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“…Other medications included fentanyl and desipramine. Similar findings were described with two additional cases of seizures upon zolpidem withdrawal [94,95].…”

Section: Zolpidemsupporting

confidence: 84%

Risk of seizures associated with psychotropic medications: emphasis on new drugs and new findings

Lee¹,

Finley²,

Alldredge³

2003

Expert Opinion on Drug Safety

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Psychotropic medications in the classes of antidepressants, antipsychotics and mood stabilisers have been recognised in the literature and clinical settings as having high epileptogenic potential. Among these three classes, clozapine, tricyclic antidepressants (TCAs) and lithium are agents that clinicians have historically recognised as precipitants of drug-induced seizures. There are few reports that review the epileptogenic risk of newer psychotropic agents; in this qualitative review, the authors provide an update on the most recently published reports on seizures associated with antidepressants, antipsychotics, mood stabilisers, anxiolytics and sedative-hypnotics. In general, the epileptogenic risks of the newer psychotropic agents appear to be quite low as long as dosing strategies are consistent with recommended guidelines. Whilst newer psychotropic medications appear to be safe in patients with epilepsy, few studies have specifically addressed this population. In addition, the potential for drug interactions between antiepileptic drugs and psychotropics may be substantial with certain agents. For example, many psychotropes are both substrates and inhibitors of cytochrome P450 (CYP450) isoenzymes, whilst many antiepileptic drugs are both substrates and inducers of CYP450 activity. Every attempt should be made to minimise potential interactions when these agents are concomitantly administered.

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“…Other medications included fentanyl and desipramine. Similar findings were described with two additional cases of seizures upon zolpidem withdrawal [94,95].…”

Section: Zolpidemsupporting

confidence: 84%

Risk of seizures associated with psychotropic medications: emphasis on new drugs and new findings

Lee¹,

Finley²,

Alldredge³

2003

Expert Opinion on Drug Safety

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“…Zolpidem, an imidazopyridine, which binds selectively at w,-receptor subtype within GABAA receptor supramolecular complex, with a half-life of about 2 h, did not show rebound phenomena in controlled polysomnographic studies (Monti, 1989;Bessett er al., 1990;Kurtz et al, 1990;Scharf et al, 1991;Roehrs et al, 1992;Monti, 1994). Cases of tolerance and withdrawal phenomena with zolpidem have been anecdotally reported (Cavallaro et al, 1993).The clinical relevance of chronic use of hypnotics and the importance of rebound phenbmena for the risk of long term use is still an open issue and deserves further investigation in an experimental design closer to the present use of triazolam: in fact, most studies on this drug have been performed with high dosages (0-5 mg), which is higher than the currently recommended dosage (Maczaj, 1993). The purpose of this study was to evaluate and compare the occurrence of rebound insomnia following the abrupt withdrawal of zolpidem and triazolam given at the doses recommended by the manufacturers in insomniac patients (10 mg zolpidem and 0.25 mg triazolam).…”

Section: Introductionmentioning

confidence: 93%

Rebound insomnia after abrupt discontinuation of hypnotic treatment: double-blind randomized comparison of zolpidem versus triazolam

Silvestri¹,

Ferrillo²,

Murri³

et al. 1996

Hum. Psychopharmacol. Clin. Exp.

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Rebound insomnia is a transient intense worsening of sleep usually appearing within 3 days from the abrupt discontinuation of benzodiazepines (mainly short-acting), following long term use and abuse of these hypnotics. Zolpidem is an imidazopyridine, that binds selectively at mi-receptor subtypes within the GABAA receptor supramolecular complex. It has a rapid onset of action and short-elimination half-life; it reduces the latency of sleep and prolongs the duration of sleep in patients with insomnia, without any major effects on sleep stages and rebound effects upon discontinuation.The present multicentre trial (three Italian centres) was aimed at assessing the symptoms/signs of rebound insomnia after discontinuation of either zolpidem or triazolam. A double-blind, randomized, parallel group trial of 20-day duration was carried out in 22 patients suffering from either transient insomnia, or short-term (situational stress) insomnia, or patients who were poor sleepers. The trial consisted of three periods: a 3-day run-in period with placebo, a 14-day active treatment period (zolpidem 10 mg od or triazolam 0.25 mg od), a 3day withdrawal period with placebo.There were statistically significant [ p = 0.0064 for Total Sleep Time (TST) and p = 0.0051 for Sleep Efficiency (SE%)] differences between triazolam-and zolpidem-treated patients during the first withdrawal night versus baseline: TST decreased to 34.5 rnin after trkolam but increased to 43.8 min after zolpidem, and a similar evolution was shown on SETo (a decrease of 6.3 per cent after triazolam and an increase of 9.9 per cent after zolpidem). Also the Wake-time After Sleep Onset (WASO) showed a statistically significantly (p = 0.0083) different pattern, during the first withdrawal night, remaining decreased after zolpidem (37.5 min) but suddenly increasing after triazolam (1 7-3 rnin).Also the subjective time to fall asleep changed with a statistically significant difference (p = 0.042), being increased after triazolam (8.6 min) and decreased after zolpidem (20-8 min).The results of the study demonstrate the presence of clear rebound insomnia after triazolam discontinuation, whereas such a drawback is absent with zolpidem. This allows the abrupt discontinuation of zolpidem without any need for a tapering procedure and without any risk of pharmacological dependence.

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“…Although the initial clinical trials did not report clear evidence of abuse potential, there have been numerous case reports of chronic abuse and tolerance to zolpidem. 16,24,25 This suggests that zolpidem has a higher abuse potential than the physician may realize and can be a cause of withdrawal symptoms, as was seen in this case. 26…”

Section: Drug Tolerancementioning

confidence: 68%

Intractable Nausea Caused by Zolpidem Withdrawal: A Case Report

Baruch

Vernon²,

Hasbun³

2007

Journal of Addiction Medicine

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First launched in France in 1988, zolpidem (Ambien®) is a short-acting hypnotic agent. Early studies reported that that the development of physical dependence and tolerance to sedative-hypnotic drugs, such as the depressant and anticonvulsant effects evidenced with benzodiazepines, is not found with zolpidem. Direct to consumer advertising by the manufacturer continues to state that the risk for dependency is low; however, recent publications seem to contradict this. Additionally, adverse drug reactions affecting the central nervous system, gastrointestinal tract, and respiratory system have been reported. Other studies have examined the interactions of selective serotonin reuptake inhibitors and zolpidem as a possible cause of hallucinations. With continued physician marketing efforts touting the safety and efficacy of zolpidem, there is a high likelihood to overlook the risk of dependency and the symptoms related to zolpidem withdrawal. We report a case of a 41-year-old female who developed a dependency to zolpidem, who on her own decided to decrease her dosage, resulting in intractable nausea requiring hospitalization. Reported cases of zolpidem withdrawal have occurred with doses in excess of 160 mg per day, none of these have reported with intractable nausea as the sole symptom. In our reported case, although exceeding recommended dosage withdrawal phenomenon seemed to be severe after withdrawal from a comparatively low dose of zolpidem. Before zolpidem is prescribed, patient education should include warnings about the potential problems associated with dependency and abrupt discontinuation. Education about this common and likely underrecognized clinical phenomenon will help prevent future episodes and minimize the risk of misdiagnosis.

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Tolerance and withdrawal with zolpidem

Cited by 60 publications

References 0 publications

Risk of seizures associated with psychotropic medications: emphasis on new drugs and new findings

Risk of seizures associated with psychotropic medications: emphasis on new drugs and new findings

Rebound insomnia after abrupt discontinuation of hypnotic treatment: double-blind randomized comparison of zolpidem versus triazolam

Intractable Nausea Caused by Zolpidem Withdrawal: A Case Report

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