zolpidem

General Information

Zolpidem is a non-benzodiazepine hypnotic (“Z-drug”) approved for insomnia and often used when rapid sleep onset is the primary target symptom.

Immediate-release formulations mainly target sleep-onset insomnia, while extended-release products may help sleep maintenance but can increase next-day impairment; match formulation to the sleep complaint rather than escalating dose.

Key safety issues are complex sleep behaviors (boxed warning), next-day impairment, and additive sedation with alcohol or other CNS depressants—risks that are amplified in older adults and in serious mental illness with polypharmacy.

The zolpidem compare view, zolpidem evidence feed, and zolpidem print page can support aligning sleep goals with safety planning.

Treat zolpidem as a time-limited adjunct alongside CBT-I and sleep hygiene; avoid chronic, open-ended refills. Use short prescriptions, define a stop plan, and discontinue if complex sleep behaviors or unsafe next-day impairment emerge.

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Positive allosteric modulator of GABA-A receptors producing hypnotic effects.

Classified as a “Z-drug”; hypnotic/sedative effects are dose dependent and interact strongly with other CNS depressants.

• GABA-A receptor facilitation (non-benzodiazepine hypnotic class).

Metabolism and Pharmacokinetics

• Rapid absorption; food delays onset and reduces peak exposure (label).
• Mean elimination half-life ~2.5 hours (range ~1.4–4.5 hours) in healthy adults (label).
• Converted to inactive metabolites eliminated primarily by renal excretion; CYP3A4 interactions can be clinically relevant.
• Exposure increases in older adults and hepatic impairment, increasing next-day impairment and fall risk; use the lowest effective dose and reassess safety after initiation or dose changes.

Dosing and Administration

• Take immediately before bedtime, only when able to remain in bed for a full night.
• Food (especially high-fat meals) can delay onset; when rapid sleep onset is the goal, avoid taking with or immediately after a heavy meal.
• Use the lowest effective dose; avoid dose escalation when insomnia is driven by untreated mood symptoms, substances, pain, or sleep apnea.
• Avoid dosing after alcohol or other sedatives; reassess frequently and avoid open-ended refills.
• Avoid “middle of the night” redosing; if awakenings persist, reassess the diagnosis and consider alternatives rather than increasing hypnotic burden.

Monitoring & Labs

• Assess next-day impairment (driving, work, falls) after initiation and dose changes; lower the dose or stop if safety is compromised.
• Screen for complex sleep behaviors and discontinue immediately if they occur.
• Reassess for untreated sleep apnea, substance use, and mood episodes when insomnia persists rather than escalating hypnotics.
• If continued beyond a brief course, plan taper attempts and reinforce CBT-I to reduce rebound insomnia.

Sources: FDA/DailyMed label; AASM insomnia guideline; evidence reviews.

Adverse Effects

Interactions

• Avoid alcohol and other CNS depressants (opioids, benzodiazepines, sedating antipsychotics).
• CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, ritonavir) can increase exposure; inducers (e.g., rifampin, St. John’s wort) can reduce efficacy—reassess sedation and response when interacting drugs change.
• Avoid combining with other sedative-hypnotics when possible; if combinations are unavoidable, start lower and increase follow-up frequency to reduce falls and driving risk.

Other Useful Information

• Favor CBT-I and sleep hygiene first; use zolpidem for short, clearly bounded courses with stop plans.
• Avoid in untreated sleep apnea or when nighttime wandering is a safety concern.
• If insomnia is chronic, treat underlying drivers rather than escalating hypnotic doses.
• Use short prescriptions with planned follow-up; discontinue if complex sleep behaviors, next-day impairment, or unsafe nighttime behaviors occur.

References

1. Ambien (zolpidem tartrate) prescribing information — DailyMed (2025)
2. Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline — Journal of Clinical Sleep Medicine (2017)
3. Efficacy and Acceptability of Pharmacological Interventions for Insomnia in Patients With Severe Mental Illness — Acta Psychiatrica Scandinavica (2025)
4. Residual effects of medications for sleep disorders on driving performance — European Neuropsychopharmacology (2024)