Zolpidem (Ambien®) versus Temazepam (Restoril®)

Difference between Zolpidem and Temazepam

Zolpidem, a short half-life non-benzodiazepine, versus temazepam, a medium half-life benzodiazepine, comparison chart:

 
Zolpidem
Temazepam
Brand name/Year of initial approval Ambien®, 1992 Restoril®, 1981
Formulations Oral tablets, sublingual tablets, oral spray Oral capsules
Legal status Schedule IV
Controlled substance
Drug class Bon-benzodiazepine sedative-hypnotic, short-acting Benzodiazepine receptor agonist, intermediate acting
FDA-approved Indications • Short-term treatment of insomnia, generally for sleep-onset insomnia • Short-term treatment of insomnia (generally 7 to 10 days).
Mechanism of action • Zolpidem facilitates GABAergic neurotransmission through a positive allosteric modulation of GABA (A) receptors. • Non-selective modulation of GABA to increase GABA affinity for GABA receptor
Half-life 2.5-3 hours 8.8 hours (range from 3.5 to 18.4)
Oral bioavailability ~70% 96%
Metabolism, Elimination Hepatic metabolism, converted to inactive metabolites, which are excreted by the kidneys.

Elimination of the drug is slower in patients with chronic renal insufficiency.
No hepatic metabolism. Metabolized via conjugation.

80-90% of unchanged drug is excreated in the urine, 10% in the feces.
Contraindications • Hypersensitivity • Pregnancy
• Hypersensitivity
Warnings & precautions • Severe anaphylactic reactions • Severe anaphylactic reactions
• Use with caution in severely depressed patients or those with sings of latent depression
Abnormal behaviors May cause complex sleep-related behaviors such as sleep-eating or sleep-driving with no memory of the event.
Side effects • Dizziness, drowsiness, confusion, headache, nausea, diarrhea, hallucinations, sleepwalking, amnesia. • Hemodynamic side effects, orthostatic hypotension3
• Drowsiness, fatigue dizziness, daytime impairment, hangover
Rebound insomnia Zolpidem has no advantages over temazepam with respect to rebound insomnia2.
Driving ability after-midnight intake Both zolpidem and temazepam do not produce significant residual side effects on psychomotor performance 4.
Effects on physical performance capacity Single dose of either hypnotic does not negatively affect physical performance characteristics6.
Abuse, physical dependence, tolerance Zolpidem has lower risk for abuse, withdrawal, and tolerance compared to non-selective benzodiazepines
Drug interactions Increased sedation and depressive effects when taken with other CNS depressants.
Food interactions No
Pregnancy category C X
Can cause teratogenic effects on fetuses
Onset of sedative effect Rapid onset Delayed onset
Time to maximal drug effect 1 0.5-1.0 hours 2-3 hours
Advantages • Preferred hypnotic for people with problems falling asleep
• Sublingual zolpidem is a good choice for middle of the night wakening
• Less hangover effect
• Lower risk of tolerance and withdrawal
• Temazepam may be useful for concomitant anxiety.
• May be preferred hypnotic for insomniacs with liver disease.
• Due to longer half-life temazepam may be a better choice than zolpidem for insomniacs who awaken frequently (sleep maintenance insomnia)
Disadvantages   • More likely to cause hangover
• Slow gastrointestinal absorption compared to other sedative
• Temazepam has a slow onset of action and is not a ideal choice for sleep-onset insomnia

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Zolpidem is an imidazopyridine hypnotic that is biochemically distinct from classic benzodiazepines in that it may be selective for the BZ1 receptor subtype and shows a different pattern of distribution of binding sites1. Zolpidem lacks anxiolytic, muscle relaxant and anticonvulsant actions.

Transient insomnia
Results of double-blind study of efficacy of zolpidem versus temazepam in transient insomnia 5 Zolpidem Temazepam
Dose regimen 10 mg 15 min before lights out 15 mg 15 min before lights out
Hypnotic effects Reduced awakenings and wake after sleep onset  
Improved sleep efficiency and subjective sleep measures
Symbol copying test, morning sleepiness, morning concentration Not affected
Digit symbol substitution test Significantly reduced morning test performance  

Further reading

References

  • 1. Rush CR, Griffiths RR. Zolpidem, triazolam, and temazepam: behavioral and subject-rated effects in normal volunteers. J Clin Psychopharmacol. 1996 Apr;16(2):146-57. PubMed
  • 2. Voshaar RC1, van Balkom AJ, Zitman FG. Zolpidem is not superior to temazepam with respect to rebound insomnia: a controlled study. Eur Neuropsychopharmacol. 2004 Aug;14(4):301-6. PubMed
  • 3. Shi SJ, Garcia KM, Meck JV. Temazepam, but not zolpidem, causes orthostatic hypotension in astronauts after spaceflight. J Cardiovasc Pharmacol. 2003 Jan;41(1):31-9. PubMed
  • 4. Partinen M1, Hirvonen K, Hublin C, Halavaara M, Hiltunen H. Effects of after-midnight intake of zolpidem and temazepam on driving ability in women with non-organic insomnia. Sleep Med. 2003 Nov;4(6):553-61. PubMed
  • 5. Erman MK, Erwin CW, Gengo FM, et al. Comparative efficacy of zolpidem and temazepam in transient insomnia. Hum Psychopharmacol. 2001 Mar;16(2):169-176. PubMed
  • 6. Gremion G, Sutter-Weyrich C, Rostan A, Forster A. Physical performance and sedation: comparative study of the effects of a benzodiazepine (temazepam) and of a non-benzodiazepine hypnotic (zolpidem). Schweiz Z Sportmed. 1992 Sep;40(3):113-8. PubMed

Published: November 24, 2016
Last updated: November 28, 2016

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