Abuse, dependence, and epileptic seizures after zolpidem withdrawal: Review and case report

The imidazopyridine zolpidem is a short-acting hypnotic chemically distinct from benzodiazepines (BZs). According to its peculiar neuropharmacologic activity (selectivity for the omega 1-BZ receptors), zolpidem is expected to be a pure hypnotic, without the other effects of BZs. In particular, it has been stressed that zolpidem is well tolerated in adults and in the elderly, and that tolerance, abuse, dependence, rebound insomnia, and other withdrawal effects do not develop in relation to zolpidem administration. However, despite these assumptions, zolpidem abuse, dependence, and withdrawal effects have been recently discussed and reviewed herein. In addition, the case of a 43-year-old woman who had an epileptic attack after abrupt interruption of an abused, high dose of zolpidem (600 mg/d), is reported and discussed. At the clinical level, it is stressed that the subjective effects of zolpidem are comparable to those of other BZs, and that abuse, dependence, and withdrawal seizures cannot be avoided simply shifting the regimen of a BZ abuser to zolpidem. At the pharmacologic level, it is important to note that zolpidem's clinical effects cannot be explained on the basis of the old distinction between omega 1 and 2 receptors because this distinction is no longer valid; the new classification of GABA(A) receptor subtypes is reported and zolpidem activity at this level is discussed herein.