Zolpidem

ATC code

N05CF02

Therapeutic class

Non-benzodiazepine hypnotic (Z-drug) · Selective GABA-A receptor agonist (α1 subunit)

Forms

oral tablet

Brand names

Ambien (US) · Zolpidem (US) · Zolpidem Cinfa (ES) · Zolpidem Cristers (FR) · Stilnox (FR)

Overall confidence

high

Regulatory sources consulted

openfda-label-021153ce-fe27-4ed1-8d88-b4157b0ed734
aemps-cima-ft-65400
ansm-bdpm-rcp-69329603
PubMed PMID:35843245 ↗
PubMed PMID:37048577 ↗
PubMed PMID:37549414 ↗
PubMed PMID:39522949 ↗
PubMed PMID:34121443 ↗
Flockhart Table
Professional Clinical Knowledge
OpenFDA · N05CF02
RxNorm rxcui 39993 ↗

Approved indications

Short-term treatment of insomnia characterized by difficulties with sleep initiation.
Management of catatonia, as a challenge agent, monotherapy, or augmentation. · off-label

Contraindications

Absolute

History of complex sleep behaviors after taking zolpidem.
Known hypersensitivity to zolpidem.
Severe respiratory insufficiency.
Sleep apnea syndrome.
Severe hepatic impairment.
Myasthenia gravis.

Clinical warnings

Boxed warning · Complex Sleep Behaviors: Sleep-walking, sleep-driving, and engaging in other activities while not fully awake may occur. Some of these events may result in serious injuries, including death. Discontinue immediately if a patient experiences a complex sleep behavior. — FDA
Major warning · CNS-Depressant Effects and Next-Day Impairment: Risk of psychomotor impairment, including driving ability, the next day. Risk increases with higher doses (10 mg), shorter sleep duration (<7-8h), and co-administration with other CNS depressants or alcohol. — FDA
Dependence and Withdrawal Symptoms: Prolonged use can lead to physical and psychological dependence. Abrupt discontinuation may cause withdrawal symptoms. Gradual dose reduction is recommended. — EMA SPC

Drug interactions

HighOpioidsN02A
Mechanism: Additive depressant effect on the central nervous system.
Recommendation: Concomitant use increases the risk of sedation, respiratory depression, coma, and death. Limit dosage and duration of both drugs and monitor closely.
FDA label
HighAlcoholV03AB16
Mechanism: Increased sedative effect and psychomotor impairment.
Recommendation: Avoid alcohol consumption during zolpidem treatment.
FDA labelEMA SPC
ModerateRifampinJ04AB02
Mechanism: Potent induction of CYP3A4, which accelerates zolpidem metabolism and significantly reduces its exposure and efficacy.
Recommendation: Concomitant use may decrease the effect of zolpidem. Consider an alternative hypnotic.
EMA SPC
ModerateKetoconazoleJ02AB02
Mechanism: Potent inhibition of CYP3A4, which decreases zolpidem metabolism and increases its exposure and sedative effects.
Recommendation: Concomitant use may increase the effect of zolpidem. Consider a zolpidem dose reduction and monitor for sedation.
FDA label

Adverse events

Common (≥1%)

somnolence · dizziness · headache · diarrhea · drugged feeling · anterograde amnesia

Rare but serious

complex sleep behaviors (e.g., sleep-driving) · anaphylaxis · angioedema · respiratory depression · dependence and abuse · worsening of depression or suicidal ideation

Pregnancy and lactation

Pregnancy: Use during the third trimester may cause respiratory depression and sedation in the neonate. Lactation: Excreted in breast milk. The manufacturer recommends pumping and discarding breast milk during treatment and for 23 hours after the last dose.

Recent literature (PubMed)

Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and network meta-analysis.
De Crescenzo F, et al. · Lancet · 2022 · Relevance 5/5
Metaanálisis en red de 154 ECA que compara 30 fármacos para el insomnio. Zolpidem demostró ser más eficaz que el placebo para el tratamiento agudo, con una certeza de evidencia de moderada a alta. Sin embargo, también se asoció con una menor tolerabilidad y mayor riesgo de eventos adversos en comparación con otros agentes como los DORA.
Alliance for Sleep Clinical Practice Guideline on Switching or Deprescribing Hypnotic Medications for Insomnia.
Watson NF, et al. · J Clin Med · 2023 · Relevance 5/5
Guía de práctica clínica que proporciona recomendaciones basadas en la evidencia para la deprescripción o el cambio de hipnóticos. Para zolpidem, especialmente en dosis supraterapéuticas, se recomienda una reducción gradual (tapering) para minimizar los síntomas de abstinencia y el insomnio de rebote.
Insomnia Management: A Review and Update.
Shaha DP · J Fam Pract · 2023 · Relevance 4/5
Revisión sobre el manejo del insomnio en atención primaria. Clasifica al zolpidem como un agonista del receptor de benzodiazepinas (BZRA) aprobado por la FDA y lo sitúa en el contexto de otras opciones farmacológicas, incluidos los nuevos antagonistas del receptor de orexina dual (DORA).
Zolpidem for the Management of Catatonia: A Systematic Review.
Gunther M, et al. · J Acad Consult Liaison Psychiatry · 2025 · Relevance 4/5
Revisión sistemática que examina el uso off-label de zolpidem para la catatonia. Analizando 35 casos, se encontró una tasa de respuesta positiva del 80%, sugiriendo que zolpidem es un agente farmacológico prometedor para la catatonia, ya sea como prueba diagnóstica, monoterapia o terapia de aumento.
Comparative efficacy of lemborexant and other insomnia treatments: a network meta-analysis.
McElroy H, et al. · J Manag Care Spec Pharm · 2021 · Relevance 4/5
Metaanálisis en red que compara lemborexant con otros tratamientos para el insomnio, incluido zolpidem. Los resultados mostraron que, aunque zolpidem es eficaz, otros agentes como lemborexant y eszopiclona pueden tener perfiles de eficacia superiores en ciertas mediciones objetivas y subjetivas del sueño.