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Sedative-hypnotic drugs

Last updated: July 27, 2021

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Sedative-hypnotics are a class of drugs that cause a dose-dependent depression of the CNS function, inducing sedation, sleep, and unconsciousness with increasing dose. Agents in this class of drugs include benzodiazepines and Z-drugs, barbiturates, and melatonin agonists. Most of the sedative-hypnotic drugs affect GABAergic transmission, increasing the inhibition of neuronal excitability, except for melatonin agonists, which act on hypothalamic melatonin receptors. Sedative-hypnotic drugs are used as anxiolytics, sedatives, muscle relaxants, anesthetics, and anticonvulsants. Common side effects result from excessive CNS depression and include confusion, drowsiness, somnolence, and respiratory depression. Long-term use of sedative-hypnotics is associated with a risk of dependence.

Overview of sedative-hypnotic drugs
Agents Indications Mechanism of action Adverse effects Contraindications Interactions
Benzodiazepines Short-acting (midazolam, triazolam, alprazolam , oxazepam )
  • Very high addictive potential
Intermediate-acting (temazepam, lormetazepam, lorazepam)
  • High to very high addictive potential
Long-acting (diazepam, clonazepam, chlordiazepoxide, tetrazepam)
  • High addictive potential
Benzodiazepine-like substances (Z-drugs; e.g., zolpidem, zaleplon, eszopiclon)
Barbiturates Ultra-short acting (i.e., 15 minutes–3 hours; e.g., thiopental)
Short-acting (i.e., 3–6 hours; e.g., pentobarbital)
Intermediate-acting (i.e., 6–12 hours; e.g., amobarbital)
Long-acting (i.e., 12–24 hour) Phenobarbital
Melatonin agonists (e.g., ramelteon)
  • Hypersensitivity [1]
Orexin antagonists (e.g., suvorexant)
  • Should not be taken together with CYP3A4 inhibiting drugs

Lorazepam, Oxazepam, and Temazepam are preferred in those who drink a LOT because they are not metabolized by the liver and therefore safe in alcoholic liver disease.

Remember ATOM for benzodiazepines with a short half-life: Alprazolam, Triazolam, Oxazepam, and Midazolam.

Mechanism of action

Benzo increases the frequenzo of Cl-channel opening.

Side effects

General adverse effects

  • Anterograde amnesia
  • Addictive potential
  • Drug tolerance
  • Drowsiness, sleepiness, or dizziness
  • Blunted affect
  • ↑ Appetite
  • Hangover effect
  • Paradoxical excitability [2]

Benzodiazepine overdose

Most cases of benzodiazepine overdose occur in patients who are on chronic benzodiazepine therapy. Flumazenil can precipitate withdrawal symptoms and seizures in patients with benzodiazepine dependence.

Benzodiazepine overdose is very rarely life-threatening unless associated with the co-ingestion of alcohol, opioids, barbiturates, first-generation antihistamines (e.g., diphenhydramine) or other respiratory or CNS depressants.

Benzodiazepine dependence [3]

Benzodiazepine dependence can develop even after just a few weeks of use. Therefore, benzodiazepines should only be prescribed when strongly indicated.

Contraindications for benzodiazepines [4]


  • Zolpidem (imidazopyridine): half-life up to 4.5 hours
  • Zaleplon (pyrazolopyrimidine): half-life ∼ 1 hour
  • Eszopiclone: half-life ∼ 6 hours


Mechanism of action


Z-drugs give you the Zzzz's (make you sleepy).

Side effects

  • Ataxia
  • Headaches
  • Confusion
  • Hangover effect (less common than in other sedative-hypnotic drugs)
    • Psychomotor depression
    • Amnesia
    • Sleepiness
    • Impaired cognitive functions
  • In the case of overdose
  • Development of drug tolerance and dependence
    • Significantly lower risk than with benzodiazepines, but should not be underestimated
    • After long-term use, the daily dose should be tapered gradually (there is a risk of developing withdrawal symptoms and memory impairment upon sudden cessation of therapy).


Agents and indications [5]

Overview of barbiturates and their indications
Duration of action Pharmacological agent


Ultra-short (15 minutes–3 hours)

Short (3–6 hours)
Intermediate (6–12 hours)
  • Amobarbital
  • Butalbital
Long (12–24 hours)
  • Primidone

Barbiturates are no longer used for sedation or long-term treatment of insomnia due to their low safety margin. They have been replaced by more effective drugs with fewer side effects (e.g., benzodiazepines).

Mechanism of action

Benzodiazepines increase the frequency of chloride channel opening, whereas barbiDURATes increase the DURATion of chloride channel opening.


Adverse effects

Accidental intraarterial injection of barbiturates

Barbiturate overdose

Barbiturate dependence


Ramelteon, tasimelteon, and agomelatine are melatonin receptor agonists.

Suvorex-ant is an orexin antagonist.

  1. ROZEREM (ramelteon) tablets.
  2. Mancuso CE et al.. Paradoxical Reactions to Benzodiazepines: Literature Review and Treatment Options. Pharmacotherapy. 2004; 24 (9): p.1177-1185. doi: 10.1592/phco.24.13.1177.38089 . | Open in Read by QxMD
  3. Soyka M. Treatment of benzodiazepine dependence. N Engl J Med. 2017; 376 (12): p.1147-1157. doi: 10.1056/nejmra1611832 . | Open in Read by QxMD
  4. Guina J, Merrill B. Benzodiazepines I: Upping the Care on Downers: The Evidence of Risks, Benefits and Alternatives. J Clin Med. 2018; 7 (2): p.17. doi: 10.3390/jcm7020017 . | Open in Read by QxMD
  5. Jacobson LH, Callander GE, Hoyer D. Suvorexant for the treatment of insomnia. Expert Review of Clinical Pharmacology. 2014; 7 (6): p.711-730. doi: 10.1586/17512433.2014.966813 . | Open in Read by QxMD
  6. Barbiturate (Oral Route, Parenteral Route, Rectal Route). Updated: January 1, 2017. Accessed: October 4, 2017.