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Sleep Disorders Medication

  • Author: Roy H Lubit, MD, PhD; Chief Editor: Iqbal Ahmed, MBBS, FRCPsych(UK)  more...
 
Updated: Jan 28, 2015
 

Medication Summary

Many agents are useful in treating insomnia. Short-term drug therapy is preferred to restore a normal sleep pattern. Generally, hypnotic drugs are approved for 2 weeks or less of continuous use. In chronic insomnia, longer courses may be indicated, which require long-term monitoring to ensure ongoing appropriate use of the medication.

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Benzodiazepines

Class Summary

Benzodiazepine receptor agonists are the mainstay in treatment of insomnia. Flurazepam, temazepam, quazepam, estazolam, and triazolam are the benzodiazepines that are approved by the US Food and Drug Administration (FDA) as hypnotics. These drugs bind to a special benzodiazepine site on the gamma-aminobutyric acid (GABA) receptor complex, enhancing the activity of this neurotransmitter. All have variable half-lives and different metabolites that affect their onset and duration of action.

This class of drugs suppresses rapid eye movement (REM) sleep and reduces stages 3 and 4 sleep while increasing stage 2 sleep. The drug described here, temazepam, is only 1 example of this class of medications.

Temazepam (Restoril)

 

Temazepam's intermediate rate of absorption and duration of action make it useful for treating initial and middle insomnia. Because temazepam has no active metabolite, cognitive impairment and grogginess the following day are reduced. Temazepam enhances the inhibitory effects of the GABA neurotransmitter on neuronal excitability that results by increased neuronal permeability to chloride ions. The shift in chloride ions results in hyperpolarization and stabilization of the neuronal membrane.

Triazolam (Halcion)

 

Triazolam is frequently chosen as a short-term adjunct to behavioral therapy. This short-acting agent is effective in helping patients fall asleep. It is not effective in persons with sleep maintenance problems. Triazolam enhances the inhibitory effects of the GABA neurotransmitter on neuronal excitability that results by increased neuronal permeability to chloride ions. The shift in chloride ions results in hyperpolarization and stabilization of the neuronal membrane.

Estazolam

 

Estazolam is an intermediate-acting agent with a slow onset of action and a long duration. It is a good agent for sleep-maintenance insomnia. It enhances the inhibitory effects of the GABA neurotransmitter on neuronal excitability that results by increased neuronal permeability to chloride ions. The shift in chloride ions results in hyperpolarization and stabilization of the neuronal membrane.

Quazepam (Doral)

 

Quazepam is used for sleep-maintenance insomnia. It enhances the inhibitory effects of the GABA neurotransmitter on neuronal excitability that results by increased neuronal permeability to chloride ions. The shift in chloride ions results in hyperpolarization and stabilization of the neuronal membrane.

Flurazepam

 

Flurazepam is frequently chosen as a short-term treatment of insomnia. It enhances the inhibitory effects of the GABA neurotransmitter on neuronal excitability that results by increased neuronal permeability to chloride ions. The shift in chloride ions results in hyperpolarization and stabilization of the neuronal membrane.

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Nonbenzodiazepine Hypnotics

Class Summary

These agents are used for the treatment of acute and short-term insomnia.

Zolpidem (Ambien, Edluar, Zolpimist, Intermezzo)

 

Zolpidem binds at a benzodiazepine receptor subtype (omega I). This receptor is found more in the central nervous system (CNS) than in the peripheral nervous system, which helps to account for the drug's hypnotic effect without significant muscle-relaxant properties. Unlike benzodiazepines, zolpidem does not suppress normal sleep architecture.

Zolpidem is rapidly absorbed, with a fast onset of action (20-30 min), and thus is a good drug for sleep induction. It decreases sleep latency and increases sleep duration.

Zaleplon (Sonata)

 

Zaleplon is not structurally related to benzodiazepines, barbiturates, or other drugs with known hypnotic properties. It interacts with the GABA-benzodiazepine receptor complex, causing sedation. It should be taken immediately before bedtime.

Zaleplon decreases the time to sleep onset. Its shorter onset of action means that peak serum concentrations are achieved within 1 hour of administration. This may account for the lower incidence of daytime grogginess and the reduced withdrawal rebound insomnia.

Eszopiclone (Lunesta)

 

Eszopiclone is a nonbenzodiazepine hypnotic pyrrolopyrazine derivative of the cyclopyrrolone class. Its precise mechanism of action is unknown, but it is believed to interact with GABA receptors at binding domains close to or allosterically coupled to benzodiazepine receptors. It is indicated for treatment of insomnia by decreasing sleep latency and improving sleep maintenance. It has a short half-life (6 h).

The starting dose is 1 mg immediately before bedtime, with at least 7-8 h remaining before the planned time of awakening. The dose may be increased if clinically warranted to 2-3 mg HS in nonelderly adults, and 2 mg in elderly or debilitated patients.

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Melatonin Receptor Agonists

Class Summary

Melatonin receptor agonists (tasimelteon, ramelteon) have been approved by the FDA. Tasimelteon is indicated for non–24-hour sleep-wake disorder. Ramelteon is indicated for insomnia characterized by difficulty with sleep onset.

Tasimelteon (Hetlioz)

 

Tasimelteon is a melatonin receptor agonist with high affinity for MT1 and MT2 receptors in the suprachiasmatic nucleus of the brain. MT1 and MT2 are thought to synchronize the body's melatonin and cortisol circadian rhythms with the day-night cycle in patients with non–24-hour disorder. It is indicated for non–24-hour sleep-wake disorder in the totally blind.

Ramelteon (Rozerem)

 

Ramelteon is a melatonin receptor agonist with high selectivity for human melatonin MT1 and MT2 receptors. MT1 and MT2 are thought to promote sleep and to be involved in maintenance of circadian rhythm and normal sleep-wake cycles. Ramelteon is indicated for insomnia characterized by difficulty with sleep onset.

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Antidepressants, Other

Class Summary

Although no antidepressants have been specifically approved for use in the treatment of sleep disorders, the cyclic antidepressant trazodone is routinely used for this purpose.

Trazodone (Olepro)

 

Trazodone's mechanism of action is not fully understood but is believed to involve selective inhibition of serotonin uptake by brain synaptosomes and potentiation of behavioral changes induced by the serotonin precursor 5-HT. The major adverse effect of trazodone is sedation.

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Orexin Receptor Antagonists

Class Summary

Orexin promotes wakefulness. Antagonism of the orexin receptor suppresses this action by orexin.

Suvorexant

 

Suvorexant is an orexin receptor antagonist. The orexin neuropeptide signaling system is a central promoter of wakefulness. Blocking the binding of wake-promoting neuropeptides orexin A and orexin B to receptors OX1R and OX2R by suvorexant is thought to suppress wake drive. It is indicated for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance.

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Contributor Information and Disclosures
Author

Roy H Lubit, MD, PhD Private Practice

Roy H Lubit, MD, PhD is a member of the following medical societies: American Academy of Child and Adolescent Psychiatry

Disclosure: Nothing to disclose.

Coauthor(s)

Curley L Bonds, II, MD Professor and Chair, Department of Psychiatry and Human Behavior, Charles Drew University of Medicine and Science; Health Sciences Clinical Professor, Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, David Geffen School of Medicine

Curley L Bonds, II, MD is a member of the following medical societies: Academy of Psychosomatic Medicine, American Medical Association, National Medical Association, American Psychiatric Association

Disclosure: Nothing to disclose.

Michael A Lucia, MD, FAASM Owner/CEO, Pulmonary, Allergy and Sleep Medicine, Sierra Pulmonary and Sleep Consultants, LLC

Michael A Lucia, MD, FAASM is a member of the following medical societies: Nevada State Medical Association, American Academy of Sleep Medicine, American Association of Cardiovascular and Pulmonary Rehabilitation

Disclosure: Nothing to disclose.

Chief Editor

Iqbal Ahmed, MBBS, FRCPsych(UK) Faculty, Department of Psychiatry, Tripler Army Medical Center; Clinical Professor of Psychiatry, Uniformed Services University of the Health Sciences; Clinical Professor of Psychiatry, Clinical Professor of Geriatric Medicine, University of Hawaii, John A Burns School of Medicine

Iqbal Ahmed, MBBS, FRCPsych(UK) is a member of the following medical societies: Academy of Psychosomatic Medicine, American Neuropsychiatric Association, American Society of Clinical Psychopharmacology, Royal College of Psychiatrists, American Association for Geriatric Psychiatry, American Psychiatric Association

Disclosure: Nothing to disclose.

Acknowledgements

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Reference Salary Employment

References
  1. Zammit GK, Weiner J, Damato N, et al. Quality of life in people with insomnia. Sleep. 1999 May 1. 22 Suppl 2:S379-85. [Medline].

  2. Chen Q, Hayman LL, Shmerling RH, Bean JF, Leveille SG. Characteristics of Chronic Pain Associated with Sleep Difficulty in Older Adults: The Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly (MOBILIZE) Boston Study. J Am Geriatr Soc. 2011 Aug. 59(8):1385-92. [Medline].

  3. Yaffe K, Laffan AM, Harrison SL, et al. Sleep-disordered breathing, hypoxia, and risk of mild cognitive impairment and dementia in older women. JAMA. 2011 Aug 10. 306(6):613-9. [Medline].

  4. Rajaratnam SM, Barger LK, Lockley SW, et al. Sleep disorders, health, and safety in police officers. JAMA. 2011 Dec 21. 306(23):2567-78. [Medline].

  5. Morin CM, Vallières A, Guay B, Ivers H, Savard J, Mérette C, et al. Cognitive behavioral therapy, singly and combined with medication, for persistent insomnia: a randomized controlled trial. JAMA. 2009 May 20. 301(19):2005-15. [Medline].

  6. Elie R, Ruther E, Farr I, Salinas E. Sleep latency is shortened during 4 weeks of treatment with zaleplon, a novel nonbenzodiazepine hypnotic. Zaleplon Clinical Study Group. J Clin Psychiatry. 1999 Aug. 60(8):536-44. [Medline].

  7. Lockley S, Dressman M, Xiao C, Fisher D, Torres R, Lavedan C, et al. Tasimelteon treatment entrains the circadian clock and demonstrates a clinically meaningful benefit blind individuals with non-24-hour circadian rhythms. Presented at ENDO 2013: the Endocrinology Society 95th Annual Meeting. San Francisco. (SUN-134).

  8. Lockley S, Dressman M, Xiao C, Licamele L, Polymeropoulos M. RESET study demonstrates that tasimelteon maintains entrainment of melatonin and cortisol in totally blind individuals with non-24-hour circadian rhythms. Presented at ENDO 2013: the Endocrinology Society 95th Annual Meeting. San Francisco. (SUN-137).

  9. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed, Text Revision (DSM-IV-TR). Washington, DC: American Psychiatric Association; 2000.

  10. Anders TF, Eiben LA. Pediatric sleep disorders: a review of the past 10 years. J Am Acad Child Adolesc Psychiatry. 1997 Jan. 36(1):9-20. [Medline].

  11. Benca RM, Ancoli-Israel S, Moldofsky H. Special considerations in insomnia diagnosis and management: depressed, elderly, and chronic pain populations. J Clin Psychiatry. 2004. 65 Suppl 8:26-35. [Medline].

  12. Bryant PA, Trinder J, Curtis N. Sick and tired: Does sleep have a vital role in the immune system?. Nat Rev Immunol. 2004 Jun. 4(6):457-67. [Medline].

  13. Chen W, Kushida CA. Nasal obstruction in sleep-disordered breathing. Otolaryngol Clin North Am. 2003 Jun. 36(3):437-60. [Medline].

  14. Ford DE, Kamerow DB. Epidemiologic study of sleep disturbances and psychiatric disorders. An opportunity for prevention?. JAMA. 1989 Sep 15. 262(11):1479-84. [Medline].

  15. Gillin JC, Byerley WF. Drug therapy: The diagnosis and management of insomnia. N Engl J Med. 1990 Jan 25. 322(4):239-48. [Medline].

  16. Hauri PJ, Hayes B, Sateia M, et al. Effectiveness of a sleep disorders center: a 9-month follow-up. Am J Psychiatry. 1982 May. 139(5):663-6. [Medline].

  17. Kaplan HI, Sadock BJ, Grebb JA. Normal sleep and sleep disorders. Kaplan and Sadock's Synopsis of Psychiatry. 7th ed. Baltimore, Md: Williams & Wilkins; 1994. 699-716.

  18. Lamberg L. Promoting adequate sleep finds a place on the public health agenda. JAMA. 2004 May 26. 291(20):2415-7. [Medline].

  19. Lamberg L. Sleep-disordered breathing may spur behavioral, learning problems in children. JAMA. 2007 June. 27;297(24):2681-3. [Medline].

  20. Loewy DH, Black JE. Effective management of transient and chronic insomnia. CNS News. McMahon Publishing Group: New York, NY; 2000. 19-22. [Full Text].

  21. No authors listed. Beauty sleep for the heart. Harv Heart Lett. 2004 May. 14(9):7. [Medline].

  22. Richert AC, Baran AS. A review of common sleep disorders. CNS Spectr. 2003 Feb. 8(2):102-9. [Medline].

  23. Schuen JN, Millard SL. Evaluation and treatment of sleep disorders in adolescents. Adolesc Med. 2000 Oct. 11(3):605-16. [Medline].

  24. Schwab RJ. Disturbances of sleep in the intensive care unit. Crit Care Clin. 1994 Oct. 10(4):681-94. [Medline].

  25. Veasey SC. Sedating, not treating sleep apnea: hit & run in primary care. J Clin Sleep Med. 2005 Oct 15. 1(4):372-3. [Medline].

  26. Zorner D, Geisler P. [Diagnostic Spectrum and Filtration Function of Outpatient Sleep Clinics]. Psychiatr Prax. 2003 May. 30(Suppl 2):173-175. [Medline].

  27. Belsomra (survorexant) prescribing information. [package insert]. Whitehouse Station, NJ 08889: August, 2014. Available at [Full Text].

 
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