Zolpidem (Ambien®)

Zolpidem in Brief
  • Generic name: Zolpidem tartrate
  • Brand names: Ambien®, Ambien CR®, Edluar®, Zolpimist®, Intermezzo®
  • Therapeutic class: Sedative-hypnotic drug
  • Pharmacologic class: Imidazopyridine; Non-benzodiazepine GABA receptor agonist
  • FDA Approved: December 16, 1992
  • Pregnancy Category: C
  • Originally discovered: France France

Based on "Sleep Disorders Medicine"
written by Dr. Sudhansu Chokroverty, MD

FDA approved uses

  • Short-term insomnia management

Off-label uses & Therapeutic perspectives

  • Restless leg syndrome 2
  • Catatonia 4
  • Parkinson's disease - may improve motor symptoms in patients with Parkinson's disease6


Zolpidem "pros" and "cons"

zolpidem for insomnia


  • Quick onset of sleep-inducing effect.
  • Good choice for sleep-onset insomnia. Sublingual zolpidem is more effective than an equivalent dose of oral zolpidem in terms of sleep inducing properties8.
  • Extended release formulation has a longer half-life and is suitable for both sleep onset and sleep maintenance insomnia.
  • Long-term efficacy. Zolpidem extended-release (taken 3 to 7 nights per week) provides sustained improvements in sleep onset and maintenance with beneficial effects on next-day concentration and morning sleepiness for up to 6 months9.
  • Unlike the benzodiazepines, zolpidem has little effect on the stages of sleep 10.
  • Minimal residual day time sedation or fading of hypnotic action. Does not appear to have significant effects on next-day psychomotor performance. However, morning sedation or prolongation of reaction-time can occur if zolpidem is taken late at night.
  • No or little rebound insomnia 5.
  • Low risk of tolerance and physical dependence; low abuse potential. May cause less dependence than some other sedative hypnotics, especially in those without a history of substance abuse.
  • Safety in overdose - even large doses do not markedly depress respiration.
  • Zolpidem may have a lower incidence of delirium compared with traditional benzodiazepines.
  • Favorable toxicological profile.
  • Improves sleep and decreases central apnea/hypopnea events in patients with idiopathic central sleep apnea 13.


  • Controlled substance Schedule IV.
  • Night-time eating: zolpidem may cause sleep-related eating disorder 3 (episodes of eating or drinking after arousal from night sleep, unaware in the most cases, with adverse consequences).
  • Plasma levels of zolpidem immediate release often decline too quickly for effective sleep maintenance.
  • May produce tolerance, physical dependence, and withdrawal.
  • Zolpidem causes side effects on body balance and is associated with falls 12.
  • Most common side effects are daytime sedation, confusion, dizziness, nausea, vomiting, amnesia.
  • Impaired liver or kidney function can increase serum drug levels.
  • Rebound insomnia may occur when zolpidem is discontinued.
  • Abnormal sleep behaviors (somnambulism)15 - sleep walking, sleep driving 7 with no memory, or other activities that may be performed during sleep.
  • Long-term use of zolpidem increases the risk of head injury or fracture 14.
  • Long-term treatment is associated with the increased risk of Parkinson's disease16.
  • Heavy users of zolpidem are at 7-fold increased odds of acute pancreatitis17.

Mode of action

The hypnotic effect of Zolpidem is due to modulation of GABA (gamma-aminobutyric acid), an important inhibitory neurotransmitter. Although zolpidem is a nonbenzodiazepine and differs structurally from the benzodiazepines, the drug acts in a similar way.

Zolpidem binds to the alpha-receptor subunits (as do benzodiazepines) and facilitates the opening of chloride channels in response to GABA. However, unlike benzodiazepines, which activate all alpha receptor subtypes nonselectively, zolpidem binds preferentially to the alpha1 subtype which is thought to explain its reduced muscle relaxant and antiepileptic effects.

Onset of hypnotic effect: rapid onset, within 7-27 min; the drug should be taken immediately before going to bed.

Duration of hypnotic effect: 6 to 8 hours.

Time to clear out of the system

The plasma half- life is approximately 2.5-3 hours.


History of discovery

In early 1980s scientists at French company Laboratoires d’Etudes et de Recherches Synthélabo (now Sanofi-Aventis) considered to develop a hypnotic agent having a pharmacological and clinical profile with potential benefits over the benzodiazepines, including a rapid onset of hypnotic effect, short duration of action, and the absence of active metabolites. Scientists synthesized a group of imidazopyridines that possessed hypnotic activity in laboratory animals. Among these chemicals zolpidem was found to combine the above beneficial properties. A short time later, research was shown that zolpidem reduced the number of awakenings and total wake time without significantly modifying slow wave sleep and REMs.

The drug was first introduced to the market as a treatment for insomnia in France in 1988. Ambien® was introduced to the market in the United States in 1992.

Further reading


  • 1. U.S. FDA Ambien® Prescribing Information
  • 2. Bezerra ML, Martínez JV. Zolpidem in restless legs syndrome. Eur Neurol. 2002;48(3):180-1.
  • 3. Najjar M. Zolpidem and Amnestic Sleep Related Eating Disorder. J Clin Sleep Med. 2007 Oct 15; 3(6): 637–638. PubMed
  • 4. Peglow S, Prem V, McDaniel W. Treatment of catatonia with zolpidem. J Neuropsychiatry Clin Neurosci. 2013 Summer;25(3):E13. PubMed
  • 5. Swainston Harrison T, Keating GM. Zolpidem: a review of its use in the management of insomnia. CNS Drugs. 2005;19(1):65-89. PubMed
  • 6. Daniele A, Panza F, Greco A, Logroscino G, Seripa D. Can a Positive Allosteric Modulation of GABAergic Receptors Improve Motor Symptoms in Patients with Parkinson's Disease? The Potential Role of Zolpidem in the Treatment of Parkinson's Disease. Parkinsons Dis. 2016;2016:2531812. PubMed
  • 7. Poceta JS. Zolpidem ingestion, automatisms, and sleep driving: a clinical and legal case series. J Clin Sleep Med. 2011 Dec 15;7(6):632-8. PubMed
  • 8. Staner C, Joly F, Jacquot N, Vlasova ID, Nehlin M, Lundqvist T, Edenius C, Staner L. Sublingual zolpidem in early onset of sleep compared to oral zolpidem: polysomnographic study in patients with primary insomnia. Curr Med Res Opin. 2010 Jun;26(6):1423-31. PubMed
  • 9. Krystal AD, Erman M, Zammit GK, Soubrane C, Roth T; ZOLONG Study Group. Long-term efficacy and safety of zolpidem extended-release 12.5 mg, administered 3 to 7 nights per week for 24 weeks, in patients with chronic primary insomnia: a 6-month, randomized, double-blind, placebo-controlled, parallel-group, multicenter study. Sleep. 2008 Jan;31(1):79-90. PubMed
  • 10. Monti JM. Effect of zolpidem on sleep in insomniac patients. Eur J Clin Pharmacol. 1989;36(5):461-6. PubMed
  • 11. Verster JC, Volkerts ER, Olivier B, Johnson W, Liddicoat L. Zolpidem and traffic safety - the importance of treatment compliance. Curr Drug Saf. 2007 Sep;2(3):220-6. PubMed
  • 12. Kolla BP, Lovely JK, Mansukhani MP, Morgenthaler TI. Zolpidem is independently associated with increased risk of inpatient falls. J Hosp Med. 2013 Jan;8(1):1-6. PubMed
  • 13. Quadri S, Drake C, Hudgel DW. Improvement of idiopathic central sleep apnea with zolpidem. J Clin Sleep Med. 2009 Apr 15;5(2):122-9. PubMed
  • 14. Lai MM, Lin CC, Lin CC, Liu CS, Li TC, Kao CH. Long-term use of zolpidem increases the risk of major injury: a population-based cohort study. Mayo Clin Proc. 2014 May;89(5):589-94. PubMed
  • 15. Paulke A, Wunder C, Toennes SW. Sleep self-intoxication and sleep driving as rare zolpidem-induced complex behaviour. Int J Legal Med. 2015 Jan;129(1):85-8. PubMed
  • 16. Yang YW, Hsieh TF, Yu CH, Huang YS, Lee CC, Tsai TH. Zolpidem and the risk of Parkinson's disease: a nationwide population-based study. J Psychiatr Res. 2014 Nov;58:84-8. PubMed
  • 17. Lai SW, Lin CL, Liao KF. Increased relative risk of acute pancreatitis in zolpidem users. Psychopharmacology (Berl). 2015 Jun;232(12):2043-8. PubMed

Published: November 21, 2016
Last updated: January 03, 2018

Interesting facts
Ambien facts
  • Zolpidem tartrate is not a benzodiazepine itself, but binds to benzodiazepine receptors.
  • Do not take zolpidem if you unable to get 7-8 hours of sleep11.

More Facts
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