Zolpidem
Zolpidem is a licensed imidazopyridine hypnotic (Ambien), one of the most widely used Z-drugs for short-term insomnia. It selectively targets alpha-1 GABA-A subunits to induce sleep. It is well studied but notable for dependence and for complex sleep behaviours such as sleep-driving.
01 Overview
Zolpidem, best known by the brand Ambien, is prescribed worldwide for short-term treatment of insomnia and is effective at shortening the time to fall asleep. It is available in immediate-release, extended-release and sublingual formulations.
It acts at the GABA-A benzodiazepine site with relative selectivity for alpha-1 subunit-containing receptors, giving strong hypnotic effect with comparatively less muscle-relaxant activity. It is well characterised in humans but carries dependence potential and is strongly associated with complex sleep behaviours -- sleep-driving, sleep-walking and sleep-eating with amnesia -- which led regulators to lower recommended doses (particularly in women) and add boxed warnings.
02 Mechanism
Positive allosteric modulator at the GABA-A benzodiazepine site with preferential activity at alpha-1 subunit-containing receptors, promoting sleep.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Therapeutic (adult) | 5–10 mg/day | Oral | At bedtime; 5 mg for women and the elderly, 5-10 mg for men (immediate-release). |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Reduced sleep latencyFalls asleep faster, well demonstrated in trials. | Clinical | ||
| Sleep inductionReliable hypnotic effect with relatively little daytime carryover at low doses. | Clinical | ||
| SedationCNS depression; can persist with higher or extended-release doses. | Clinical |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Complex sleep behavioursSleep-driving, sleep-walking, sleep-eating and other activities while not fully awake, with amnesia; subject of an FDA boxed warning. | Severe | Rare but serious | Observational | |
| Dependence and rebound insomniaTolerance and dependence with continued use; rebound insomnia on stopping. | Moderate | Common with prolonged use | Clinical | |
| Next-day impairmentResidual drowsiness impairing driving, especially with extended-release and in women. | Moderate | Common | Clinical | |
| Additive respiratory depressionDangerous with opioids or alcohol. | Life-threatening | High risk in combination | Clinical |