Zolpidem: Z-Drug Hypnotic for Short-Term Insomnia
Zolpidem (Stilnox, Ambien) is a non-benzodiazepine hypnotic (Z-drug) that binds selectively to the alpha-1 subunit of GABA-A receptors. Its selectivity for this subunit provides sedation/hypnosis with less anxiolytic and muscle-relaxant effect than benzodiazepines.
Approved only for short-term treatment of insomnia (2–4 weeks). Long-term use is associated with tolerance, dependence, rebound insomnia, and falls in elderly patients.
Mechanism of Action
Positive allosteric modulator of GABA-A receptors, preferentially binding alpha-1 subunit-containing receptors (mediating sedation). This selectivity is relative, not absolute, and at high doses broader GABA-A effects occur.
Indications & Use
Short-term treatment of insomnia (sleep onset and sleep maintenance difficulties). Maximum 4 weeks. Cognitive Behavioural Therapy for Insomnia (CBT-I) is the preferred long-term treatment.
Dosage
Standard: 10 mg immediately before bedtime. Elderly/hepatic impairment: 5 mg. Women: 5 mg recommended (slower metabolism than men). Do not take unless able to stay in bed for 7–8 hours. Extended-release formulation (CR) available for sleep maintenance.
Side Effects
Common: somnolence, headache, dizziness, anterograde amnesia. Important: complex sleep behaviours (sleep-walking, sleep-driving, sleep-eating) — often without recall. Next-day impairment (do not drive morning after 10 mg dose). Rebound insomnia on stopping.
Drug Interactions
CNS depressants (opioids, alcohol, benzodiazepines, antipsychotics): additive CNS depression — avoid combinations. CYP3A4 inhibitors (ketoconazole, clarithromycin): increase zolpidem exposure. CYP3A4 inducers: reduce efficacy.
Contraindications
Sleep apnoea syndrome, myasthenia gravis, severe hepatic impairment, respiratory failure. History of sleepwalking on any sedative. Pregnancy and breastfeeding. Avoid in elderly (falls, confusion, Beers Criteria).
Frequently Asked Questions
Can I drive the morning after taking zolpidem?
At 10 mg, next-day impairment is a real risk — particularly in women (slower clearance) and the elderly. The FDA recommends not driving the morning after a 10 mg dose. The 5 mg dose is safer for driving. If uncertain, do not drive.
Is zolpidem addictive?
Yes, dependence can develop, even at therapeutic doses. The risk increases with duration of use beyond 4 weeks. Do not stop abruptly after prolonged use — taper to avoid rebound insomnia and withdrawal.
What are complex sleep behaviours?
Zolpidem can cause sleepwalking, sleep-driving, sleep-eating, and other activities during partial sleep without conscious awareness. These are reported even at normal doses. If this occurs, stop zolpidem and consult your doctor.
References
- EMA Stilnox SPC 2023
- FDA Drug Safety Communication: Zolpidem 2019
- Qaseem A et al. Ann Intern Med 2016 (CBT-I)
Medical Disclaimer: This information is for educational purposes only and does not replace professional medical advice.