Current Scheduling Status
Year(s) and type of review / ECDD meetings
Drug Class
Recommendation (from TRS)
Substance identification
Zolpidem is chemically N,N,6-trimethyl-2-p-tolylimidazo[1,2-a]pyridine-3-acetamide or N,N,6-trimethyl-2-(4-methylphenyl)imidazol[1,2-alpyridine-3-acetamide (CAS 82626-48-0). It is marketed under the trade names Ambien, Bikalm, Niotal, Stilnoct and Stilnox.
WHO review history
Zolpidem was pre-reviewed by the Committee at its twenty-ninth meeting in 1994 (10), at which time continued surveillance was recommended. The Committee pre-reviewed zolpidem again at its 31st meeting in 1998 (1), and recommended critical review in 2000, on the grounds that a greater number of reports on its abuse liability would be available by that date.
Similarity to known substances and effects on the CNS
Though chemically different from the benzodiazepines, zolpidem produces benzodiazepine-like effects, especially hypnotic effects. It acts as an agonist, binding with high and low affinity to BZ, and BZ, receptor subtypes, respectively.
Dependence potential
The results of laboratory studies in humans suggest that zolpidem and triazolam are generally similar in terms of producing reinforcing/
subjective effects. As with many of the benzodiazepines, there have been a number of case reports describing withdrawal symptoms after cessation of zolpidem administration. Although such symptoms do not necessarily lead to compulsory drug-taking (drug dependence) in humans, there are reports of clinically diagnosed cases of drug dependence resulting from prolonged use of zolpidem.
Actual abuse and or/evidence of likelihood of abuse
Epidemiological studies indicate that zolpidem is associated with a relatively low incidence of abuse. While there have been sporadic reports of cases of zolpidem abuse in the scientific literature, thesecases have typically involved patients with a history of drug abuse or chronic psychiatric disorders. Cases of zolpidem overdose requiring emergency treatment have been reported, but have rarely been fatal. Rates of actual abuse and dependence on zolpidem appear to be similar to those of other hypnotic benzodiazepines currently listed in Schedule IV. In terms of the numbers of cases of abuse, dependence
and withdrawal syndrome reported to the WHO Adverse Drug Reaction database, less than 10 benzodiazepines are ranked higher than zolpidem.
Therapeutic usefulness
Zolpidem is used for the treatment of insomnia in more than 80 countries.
Recommendation
Although zolpidem has a somewhat novel neuropharmacological profile relative to classic benzodiazepines, studies suggest that its abuse potential may be comparable to that of many benzodiazepines. Furthermore, rates of actual abuse and dependence on zolpidem, as well as the risk to public health of its abuse, appear to be similar to those of the hypnotic benzodiazepines currently placed in Schedule IV. The Committee therefore recommended that zolpidem be placed in Schedule IV of the 1971 Convention.
Zolpidem is chemically N,N,6-trimethyl-2-p-tolylimidazo[1,2-a]pyridine-3-acetamide or N,N,6-trimethyl-2-(4-methylphenyl)imidazol[1,2-alpyridine-3-acetamide (CAS 82626-48-0). It is marketed under the trade names Ambien, Bikalm, Niotal, Stilnoct and Stilnox.
WHO review history
Zolpidem was pre-reviewed by the Committee at its twenty-ninth meeting in 1994 (10), at which time continued surveillance was recommended. The Committee pre-reviewed zolpidem again at its 31st meeting in 1998 (1), and recommended critical review in 2000, on the grounds that a greater number of reports on its abuse liability would be available by that date.
Similarity to known substances and effects on the CNS
Though chemically different from the benzodiazepines, zolpidem produces benzodiazepine-like effects, especially hypnotic effects. It acts as an agonist, binding with high and low affinity to BZ, and BZ, receptor subtypes, respectively.
Dependence potential
The results of laboratory studies in humans suggest that zolpidem and triazolam are generally similar in terms of producing reinforcing/
subjective effects. As with many of the benzodiazepines, there have been a number of case reports describing withdrawal symptoms after cessation of zolpidem administration. Although such symptoms do not necessarily lead to compulsory drug-taking (drug dependence) in humans, there are reports of clinically diagnosed cases of drug dependence resulting from prolonged use of zolpidem.
Actual abuse and or/evidence of likelihood of abuse
Epidemiological studies indicate that zolpidem is associated with a relatively low incidence of abuse. While there have been sporadic reports of cases of zolpidem abuse in the scientific literature, thesecases have typically involved patients with a history of drug abuse or chronic psychiatric disorders. Cases of zolpidem overdose requiring emergency treatment have been reported, but have rarely been fatal. Rates of actual abuse and dependence on zolpidem appear to be similar to those of other hypnotic benzodiazepines currently listed in Schedule IV. In terms of the numbers of cases of abuse, dependence
and withdrawal syndrome reported to the WHO Adverse Drug Reaction database, less than 10 benzodiazepines are ranked higher than zolpidem.
Therapeutic usefulness
Zolpidem is used for the treatment of insomnia in more than 80 countries.
Recommendation
Although zolpidem has a somewhat novel neuropharmacological profile relative to classic benzodiazepines, studies suggest that its abuse potential may be comparable to that of many benzodiazepines. Furthermore, rates of actual abuse and dependence on zolpidem, as well as the risk to public health of its abuse, appear to be similar to those of the hypnotic benzodiazepines currently placed in Schedule IV. The Committee therefore recommended that zolpidem be placed in Schedule IV of the 1971 Convention.
ECDD Recommendation
Inclusion in Schedule IV of the 1971 Convention on Psychotropic Substances
Link to full TRS
who_trs_903.pdf1.33 MB