[Zolpidem: the risk of tolerance and dependence according to case reports, systematic studies and recent...

Our group as well as about 20 other publications report cases of dependence from zolpidem. Furthermore, there is epidemiological and polysomnographic evidence that there is a risk for tolerance and dependence for zolpidem although lower than in the case of benzodiazepines. Recent molecularbiological findings offer interesting data in this respect. Whereas in the recommended dose range zolpidem almost exclusively binds to the alpha(1) subunit of the GABA(A) receptor associated with sleep promotion, in higher doses it also binds the alpha(2), alpha(3) and alpha(5) subunits typically targeted by benzodiazepines and associated with anxiolytic effects. Moreover, because age, gender and alcohol were shown to significantly affect expression of these subunits in individual brain regions, dosage and duration of treatment with zolpidem as well as age, gender and additional consumption of alcohol, a history of abuse and dependence might play a role in the development of tolerance and dependence in individual patients.