zolpidem dependence in a geriatric patient: a case report.

CASE REPORT

A 78-year-old man was admitted to the Third Psychiatric Department of AHEPA General Hospital, Thessaloniki, Greece, for detoxification of zolpidem. The patient had developed tolerance, abuse, and dependence on benzodiazepines that had been prescribed for him since the age of 53; his use had escalated to a minimum of 12 mg bromazepam daily.

DISCUSSION

Zolpidem was the first nonbenzodiazepine hypnotic that was widely used as first-line treatment for insomnia. Because it binds to benzodiazepine receptors, zolpidem may exhibit partial agonist properties that explain the lack of rebound insomnia, tolerance, dependence, and withdrawal symptoms of benzodiazepines.

ACKNOWLEDGMENTS

Conflict of Interest: The authors have received support from various pharmaceuticals companies to participate in medical congresses. No other conflict of interest exists.

Which cytochrome is involved in the metabolism of zolpidem?

Metabolism of zolpidem mediated by human cytochromes P450 (CYP); so that CYP3A4 has a dominant role and CYP2C9, 1A2, 2D6, and 2C19 have a contributory role in decreasing order of importance; but CYP 2A6, 2E1, or 2C8 have no role in zolpidem metabolism.[5,6]

What receptors are benzodiazepines bind to?

Benzodiazepines exert their effects through three subtypes of GABA-A receptors.[2,3,4,6,7,8,9,10,12] Binding to omega 1 (ω1) subtype has hypnotic and anxiolytic effects and binding to omega 2 (ω2) receptor has anxiolytic, myorelaxant, respiratory depression, psychomotor dysfunction effects, and anticonvulsant property. Omega 3 (ω3) subtype has different structure and function and are on glial cells and other cells.[7] Zolpidem as an imidazopyridine is not considered a classic benzodiazepine because of lack of diazepine cycle in chemical structure, but its clinical effect is through benzodiazepine receptors and its effect could be blocked by benzodiazepine antagonists such as flumazenil.[1,7–8]

Does Zolpidem have a residual effect?

Zolpidem has a sedation property without interfering with other benzodiazepine properties linked to other receptor subtypes. Zolpidem has no residual effects and this may be due to its rapid metabolism via CYP3A4 and CYP1A2 isoenzymes and a short elimination half-life.[1,2,3,6,8]

Is Zolpidem safe for elderly?

Several studies have reported efficacy and safety of zolpidem, its well-tolerance in adults and elderly during administration[2,3,4,6,11] and minimal risk of abuse or dependence.[2,3,4,6,10–11]

Is Zolpidem a hypnotic?

Zolpidem, a nonbenzodiazepine hypnotic, binds to the benzodiazepine binding site on the gamma-aminobutyric acid type A (GABA-A) receptors. Many studies have reported efficacy and safety of zolpidem in treatment of insomnia, low abuse, and dependence capability. However, many cases of zolpidem abuse and dependence were reported around the world. This case showed that zolpidem can exert abuse capability, euphoric mood, tolerance, and withdrawal syndrome.