Drugs affecting sleep and wakefulness: a review


  • Avishek Amar Department of Pharmacology, JIPMER, Pondicherry, India




Circadian rhythm, Insomnia, Orexinergic system, Sleep, Wakefulness


It was in the second half of the twentieth century that Sleep Medicine was recognized as an immensely respected field of clinical research. As a result, past few decades have seen this field making some giant strides towards a better understanding of the neurochemical mechanisms that regulate the state of sleep and wakefulness. This involves a complex interplay of neuronal systems, neurotransmitters and some special nuclei located in the brain. Major wakefulness promoting nuclei being the orexinergic neurons in the lateral hypothalamic region and the tuberomammillary nucleus (TMN) while the sleep-promoting nucleus being ventrolateral preoptic nucleus (VLPO). Sleep-related complaints are one of the common complaints encountered by the physicians and the psychiatrists. As, long-standing sleep disturbances can have far-reaching implications on an individual’s physical, mental and social wellbeing, the importance of drugs affecting sleep and wakefulness could not be stressed upon anymore. Broadly, the sleep disorders are classified as insomnia, hypersomnia, and parasomnia and the presently available drugs work either by acting on the sleep-promoting GABAergic system like benzodiazepines, barbiturates etc. or by interacting with wakefulness promoting system like histaminergic system, 5- hydroxtryptaminergic system, orexinergic system etc. There are drugs which interact with other mechanisms which modulate arousal, like melatonin receptor agonists which promote sleep and adenosine receptor antagonists which promote wakefulness. This review article tries to have an overview of the available drugs for use in pathological states of sleep and wakefulness with a special emphasis on the commonly prescribed drugs and the recently approved one’s.


Stahl SM. Stahl’s essential psychopharmacology: neuroscientific basis and practical application. 4th Ed. New York, Cambridge University Press; 2013:444-471.

Killgore WDS, Killgore DB, Day LM, Li C, Kamimori GH, Balkin TJ. The effects of 53 hours of sleep deprivation on moral judgement. Sleep 2007;30(3):345-52.

Centers for Disease Control and Prevention. Unhealthy sleep-related behaviours: 12 states, 2009. Morbid Mortal Wkly Rep. 2009;60(08):233-8.

Kumar VM. Sleep and sleep disorders. Indian J of Chest Dis and Allied Scienc. 2008;50(1):129-36.

Sateia MJ. International classification of sleep disorders-: highlights and modifications. Chest Journal. 2014;146(5):1387-94.

Watson CJ, Baghdoyan HA, Lydic R. Neuropharmacology of Sleep and Wakefulness. Sleep medicine clinics. 2010;5(4):513-28.

Barrett KE, Barman SM, Boitano S, Brooks HL. Ganong’s review of medical physiology. 25th ed. New Delhi. Lange; 2016:504-535.

Lie JD, Tu KN, Shen DD, Wong BM. Pharmacological Treatment of Insomnia. Pharmacy and Therapeutics. 2015;40:759.

Lee-Iannotti JK, Parish JM. Suvorexant: a promising, novel treatment for insomnia. Neuropsychiatric disease and treatment. 2016;12:491-5.

Schutte-Rodin S, Broch L, Buysse D, Dorsey C, Sateia M. Clinical guideline for the evaluation and management of chronic insomnia in adults. J Clin Sleep Med. 2008;4(5):487-504.

Neubauer DN. New and emerging pharmacotherapeutic approaches for insomnia. International Review of Psychiatry. 2014;26(2):214-24.

Longo LP, Johnson B. Addiction: part I. Benzodiazepines- side effects, abuse risk, and alternatives. Am Fam Physician. 2000;61(7):2121-8.

Richey MS, Krystal DA. Pharmacological advances in the treatment of insomnia. Current Pharmaceutical Design. 2011;17:1471-5.

Greenblatt DJ, Legangneux E, Harmatz JS. Dynamics and kinetics of a modified-release formulation of zolpidem: comparison with immediate-release standard zolpidem and placebo. J Clin Pharmacol. 2006;46(12):1469-80.

Roehrs T, Merlotti L, Zorick F, Roth T. Sedative, memory, and performance effects of hypnotics. Psychopharmacology (Berl). 1994;116:130-4.

Zammit GK, Corser B, Doghramji K, Fry JM, James S, Krystal A, et al. Sleep and residual sedation after administration of zaleplon, zolpidem, and placebo during experimental middle-of-the-night awakening. J Clin Sleep Med. 2006;2(4):417-23.

Roth T, Walsh JK, Krystal A. An evaluation of the efficacy and safety of eszopiclone over 12 months in patients with chronic primary insomnia. Sleep Med. 2005;6(6):487-95.

Zammit GK, McNabb LJ, Caron J, Amato DA, Roth T. Efficacy and safety of eszopiclone across 6-weeks of treatment for primary insomnia. Curr Med Res Opin. 2004;20(12):1979-91.

Szabadi E. Drugs for sleep disorders: mechanisms and therapeutic prospects. Brit J of Cli Pharmac. 2006;61(6):761-6.

Simpson D, Curran MP. Ramelteon: a review of its use in insomnia. Drugs. 2008;68(13):1901-19.

Emet M, Ozcan H, Ozel L, Yayla M, Halici Z, Hacimuftuoglu A. A Review of Melatonin, Its Receptors and Drugs. The Eurasian Journal of Medicine. 2016;48(2):135-41.

Lee-Iannotti JK, Parish JM. Suvorexant: a promising, novel treatment for insomnia. Neuropsychiatric disease and treatment. 2016;12:491-5.

Herring WJ, Snyder E, Budd K, Hutzelmann J, Snavely D, Liu K, et al. Orexin receptor antagonism for treatment of insomnia A randomized clinical trial of suvorexant. Neurology. 2012;79(23):2265-74.

Sun H, Kennedy WP, Wilbraham D, Lewis N, Calder N, Li X, et al. Effects of suvorexant, an orexin receptor antagonist, on sleep parameters as measured by polysomnography in healthy men. Sleep. 2013;36(2):259-67.

Michelson D, Snyder E, Pardis E. Safety and efficacy of suvorexant during 1-year treatment of insomnia with subsequent abrupt treatment discontinuation: a phase 3 randomised, double blind, placebo-controlled trial. Lancet Neurol. 2014;13:461-71.

Stahl SM. Mechanism of action of trazodone: a multifunctional drug. CNS Spectr. 2009;14(10):536-46.

Thorpy MJ. Update on therapy for narcolepsy. Current treatment options in neurology. 2015;17(5):1-12.

Barateau L, Lopez R, Dauvilliers Y. Treatment Options for Narcolepsy. CNS drugs. 2016;30(5):369-79.

Syed YY. Pitolisant: first global approval. Drugs 2016;76(13):1313-8.




How to Cite

Amar, A. (2018). Drugs affecting sleep and wakefulness: a review. International Journal of Basic & Clinical Pharmacology, 7(6), 1057–1064. https://doi.org/10.18203/2319-2003.ijbcp20182088



Review Articles