Zolpidem (Ambien®) versus Alprazolam (Xanax®)

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

Difference between Zolpidem and Alprazolam

Zolpidem and alprazolam work in similar ways but have different safety and side effects profiles.

Brand name/Year of initial approval Ambien®, 1992 Xanax®, 1981
Formulations Oral tablets, sublingual tablets, spray Oral tablets, disintegrating tablets, solution
Legal status Schedule IV
Controlled substance
Drug class Non-benzodiazepine sedative-hypnotic, short-acting Benzodiazepine, short-acting, high potency
FDA-approved Indications • Short-term treatment of insomnia • Anxiety disorders
• Panic disorders
Off-label uses
• Insomnia2
• Phobic disorders
• Anxiety symptoms associated with depression
Long-term use Not intended for long-term use on a daily basis.
Mechanism of action Zolpidem acts selectively at certain subtypes of GABA A (the alpha 1 isoform). Boosts chloride conductance through GABA-regulated channels. Shares effects of benzodiazepines. Alprazolam works via allosteric GABA (A) receptor stimulation. The drug
produces some antispasmodic and anticonvulsant effects.
Half-life 2.5-3 hours 11.2 hours
Oral bioavailability ~70% 100%
Metabolism, Elimination Hepatic metabolism, converted to inactive metabolites, which are excreted by the kidneys. Metabolized by liver (CYP3A4). Alprazolam and its metabolites are excreted primarily in the urine.
Contraindications • Hypersensitivity • Hypersensitivity to benzodiazepines
• Acute narrow angle glaucoma
• Simultaneous use with ketoconazole and itraconazole
Warnings & precautions • Sleep-driving and other complex behaviors
• Severe anaphylactic reactions
• Withdrawal reactions, including seizures
Elderly patients are more sensitive to the effects of the drug due to the decreased elimination and may experience oversedation, falls, and cognitive impairment.
• Drugs that inhibit cytochrome P450 3A metabolic pathway may have a profound effect on alprazolam clearance.
• CNS depression and impaired performance
Side effects Dizziness, drowsiness, confusion, headache, nausea, diarrhea, hallucinations, sleepwalking, amnesia.

Unlike benzodiazepines zolpidem produces minimal next-day hangover effects and
daytime drowsiness.
Drowsiness, light-headedness, daytime sedation, impaired coordination, cognitive impairment and confusion.
High amnestic potential.
• Rebound insomnia
• Somnambulistic behaviors
Abuse, dependence, and tolerance Relatively low risk of abuse, dependence, and tolerance comparative to benzodiazepines. High abuse and dependence potential.
Alprazolam withdrawal may be more severe that with other benzodiazepines3
Drug interactions Increased sedation when used concurrently with other CNS depressants, including alcohol. CNS depressants and alcohol can potentiate CNS depression.
Concurrent use of medications that inhibit cytochrome P450 3A (CYP3A) (e.g., ketaconazole, nefazodone, and ritonavir) can increase the blood levels of alprazolam.
Food No High-fat meal taken before Xanax XR tablets increases the bioavailability.
Pregnancy category C D
Onset of sedative effect Rapid onset Rapid onset
Effect on sleep architecture Have little effect on sleep architecture, (with only minor REM changes
Relative lack of effect on sleep stages. High doses suppress REM sleep.
Suppress slow-wave sleep and, possibly, rapid eye movement (REM) sleep.
Hypnotic efficacy Effective for difficulties with sleep initiation and sleep maintenance. Effective in inducing and maintaining sleep with short-term use 2
Rapid development of tolerance makes alprazolam of limited utility for chronic insomnia.


Currently there are no published head-to-head comparative clinical trials between zolpidem and alprazolam.

Alprazolam is a benzodiazepine anxiolytic/anti-anxiety medication, effective for anxiety attacks and panic. On the other hand, Zolpidem is a hypnotic and primarily used to promote sleep.

Zolpidem has more selective pharmacological profile.

Zolpidem is associated with higher incidence of fractures than alprazolam 4. Discontinuation after regular use of alprazolam can result in especially severe withdrawal symptoms.

Zolpidem may be preferred over alprazolam because of its rapid onset of action, short duration of hypnotic effect, and safety profile.

Further reading


  • 1. Michael. Patrick Adams, Leland N. Holland, Carol Urban. Pharmacology for nurses: a pathophysiologic approach, 4th Ed., Saunders. pp. 350-360
  • 2. Kales A, Bixler EO, Vela-Bueno A, Soldatos CR, Manfredi RL. Alprazolam: effects on sleep and withdrawal phenomena. J Clin Pharmacol. 1987 Jul;27(7):508-15. PubMed
  • 3. Juergens S. Alprazolam and diazepam: addiction potential. J Subst Abuse Treat. 1991;8(1-2):43-51. PubMed
  • 4. Finkle WD, Der JS, Greenland S, et al. Risk of fractures requiring hospitalization after an initial prescription for zolpidem, alprazolam, lorazepam, or diazepam in older adults. J Am Geriatr Soc. 2011 Oct;59(10):1883-90. PubMed

Published: November 22, 2016
Last updated: July 07, 2018


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