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General Principle of Treatment of Sleep Dysfunction and Pharmacology of Drugs Used in Sleep Disorders

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Sleep Disorders Medicine

Abstract

The International Classification of Sleep Disorders has classified chronic insomnia in adult and elderly patients as primary or comorbid. Any strategy to the effective treatment of primary and comorbid insomnia combines both pharmacological and non-pharmacological measures. Several classes of medications are prescribed as hypnotics, including the benzodiazepine GABA-A receptor allosteric agonists (either benzodiazepinic or non-benzodiazepinic agents), the melatonin receptor agonist ramelteon, and low-dose doxepin which acts primarily as a histamine H1 receptor antagonist. Hypnotic drugs approved for the treatment of insomnia differ in pharmacokinetic properties including elimination half-life, time-to-peak plasma concentration, and the presence of active metabolites. As a result, they can improve sleep induction (triazolam, midazolam, zolpidem immediate-release, zaleplon, ramelteon) and/or sleep maintenance (temazepam, zolpidem extended-release, sublingual low-dose zolpidem, zopiclone, eszopiclone, low-dose doxepin) in patients with chronic primary insomnia or comorbid insomnia. Available evidence tends to indicate that in most cases, the incidence of adverse events resulting from the continued use of non-benzodiazepine hypnotic drugs is not significantly different from that of placebo.

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Abbreviations

AASM:

American Academy of Sleep Medicine

BZD:

Benzodiazepine

CNS:

Central nervous system

EEG:

Electroencephalogram

EMG:

Electromyogram

GABA:

Gamma-aminobutyric acid

GAD:

Generalized anxiety disorder

LPS:

Latency to persistent sleep

MCH:

Melanin-concentrating hormone

MDD:

Major depressive disorder

MOTN:

Middle of the night

NREMS:

Non-REM sleep

REMS:

REM sleep

SE:

Sleep efficiency

SOL:

Sleep onset latency

SWS:

Slow-wave sleep

TST:

Total sleep time

W:

Wakefulness

WASO:

Wake time after sleep onset

References

  1. Dement W, Kleitman N (1957) Cyclic variations in EEG during sleep and their relation to eye movements, body motility and dreaming. Electroencephalogr Clin Neurophysiol 9:673–690

    Article  CAS  PubMed  Google Scholar 

  2. Retschaffen A, Kales A (1968) A manual of standardized terminology techniques and scoring system for sleep stages in human subjects. National Institute of Health Publication No. 204. Washington DC Government Printing Office

    Google Scholar 

  3. Agnew HW, Webb WB, Williams RL (1967) Sleep patterns in late middle age males: an EEG study. Electroencephalogr Clin Neurophysiol 23:168–171

    Article  PubMed  Google Scholar 

  4. Iber C, Ancoli-Israel S, Chesson A, Quan SF (eds) (2007) The AASM manual for the scoring of sleep and associated events: rules, terminology, and technical specification, 1st edn. American Academy of Sleep Medicine, Westchester

    Google Scholar 

  5. International Classification of Sleep Disorders (2005) Diagnostic and coding manual, 2nd edn. American Academy of Sleep Medicine, Westchester, IL

    Google Scholar 

  6. Moser D, Anderer P, Gruber G, Parapatics S, Loretz E, Boeck M et al (2009) Sleep classification according to AASM and Rechtschaffen & Kales: effects on sleep scoring parameters. Sleep 32:139–149

    Article  PubMed  PubMed Central  Google Scholar 

  7. Jones BE (2003) Arousal systems. Front Biosci 8:s438–s451

    Article  CAS  PubMed  Google Scholar 

  8. Pace-Schott EF, Hobson JA (2002) The neurobiology of sleep: genetics, cellular physiology and subcortical networks. Nat Rev Neurosci 3:591–605

    Article  CAS  PubMed  Google Scholar 

  9. Brown RE, Basheer R, McKenna JT, Strecker RE, McCarley RW (2012) Control of sleep and wakefulness. Physiol Rev 92:1087–1187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. España RA, Scammell TE (2011) Sleep neurobiology from a clinical perspective. Sleep 34:845–858

    PubMed  PubMed Central  Google Scholar 

  11. Szymusiak R, Gvilia I, McGinty D (2007) Hypothalamic control of sleep. Sleep Med 8:291–301

    Article  PubMed  Google Scholar 

  12. Cespuglio R, Amrouni D, Meiller A, Buguet A, Gautier-Sauvigné S (2012) Nitric acid in the regulation of the sleep-wake states. Sleep Med Rev 16:265–279

    Article  PubMed  Google Scholar 

  13. Porkka-Heiskanen T, Kalinchuk AV (2011) Adenosine, energy metabolism and sleep homeostasis. Sleep Med Rev 15:123–135

    Article  PubMed  Google Scholar 

  14. Urade Y, Hayaishi O (2011) Prostaglandin D2 and sleep/wake regulation. Sleep Med Rev 15:411–418

    Article  PubMed  Google Scholar 

  15. Vincent SR (2010) Nitric oxide neurons and neurotransmission. Prog Neurobiol 90:246–255

    Article  CAS  PubMed  Google Scholar 

  16. Reinoso-Suárez F, de Andrés I, Rodrigo-Angulo ML, Garzón M (2001) Brain structures and mechanisms involved in the generation of REM sleep. Sleep Med Rev 5:63–77

    Google Scholar 

  17. Torterolo P, Lagos P, Monti JM (2011) Melanin-concentrating hormone: a new sleep factor? Front Neurol 2:1–12

    Article  Google Scholar 

  18. McCarley RW (2007) Neurobiology of REM and NREM sleep. Sleep Med 8:302–330

    Article  PubMed  Google Scholar 

  19. Monti JM, Torterolo P, Lagos P (2013) Melanin-concentrating hormone control of sleep-wake behavior. Sleep Med Rev 17:293–298

    Article  PubMed  Google Scholar 

  20. Srinivasan V, Smits M, Spence W, Lowe AD, Kayumov L, Pandi-Perumal SR et al (2006) Melatonin in mood disorders. World J Biol Psychiatry 7:138–151

    Article  PubMed  Google Scholar 

  21. Sateia MJ (2009) Update on sleep and psychiatric disorders. Chest 135:1370–1379

    Article  PubMed  Google Scholar 

  22. Sateia MJ, Pigeon WR (2004) Identification and management of insomnia. Med Clin North A 88:567–596

    Article  Google Scholar 

  23. Lichstein KL, Gellis LA, Stone KC, Nau SD (2006) Primary and secondary insomnia. In: Pandi-Perumal SR, Monti JM (eds) Clinical pharmacology of sleep. Birkhäuser Verlag, Basel, pp 1–9

    Google Scholar 

  24. Monti JM, Monti D (2000) Sleep disturbance in generalized anxiety disorder and its treatment. Sleep Med Rev 4:263–276

    Article  PubMed  Google Scholar 

  25. Monti JM, Pandi-Perumal SR, Langer SZ (2008) Zolpidem: its use in the treatment of sleep disorders. In: Pandi-Perumal SR, Verster JC, Monti JM, Langer SZ (eds) Sleep disorders—diagnosis and therapeutics. Informa Healthcare, London, pp 295–323

    Google Scholar 

  26. Monti JM, Pandi-Perumal SR (2007) Eszopiclone: its use in the treatment of insomnia. Neuropsychiatric Dis Treat 3:441–453

    CAS  Google Scholar 

  27. Hurst M, Noble S (1999) Zaleplon. CNS Drugs 11:387–392

    Article  CAS  Google Scholar 

  28. Fisher SP, Davidson K, Kulla A, Sugden D (2008) Acute sleep-promoting action of the melatonin agonist, ramelteon, in the rat. J Pineal Res 45:125–132

    Article  CAS  PubMed  Google Scholar 

  29. Miyamoto M, Nishikawa H, Doken Y, Hirai K, Uchikawa O, Ohkawa S (2004) The sleep-promoting action of ramelteon (TAK-375) in freely moving cats. Sleep 27:1319–1325

    Article  PubMed  Google Scholar 

  30. Yukuhiro N, Kimura H, Nishikawa H, Ohkawa S, Yoshikubo S, Miyamoto M (2004) Effects of ramelteon (TAK-375) on nocturnal sleep in freely moving monkeys. Brain Res 1027:59–66

    Article  CAS  PubMed  Google Scholar 

  31. France CP, Weltman RH, Koek W, Cruz CM, McMahon LR (2006) Acute and chronic effects of ramelteon in rhesus monkeys (Macaca mulatta): dependence liability studies. Behav Neurosci 120:535–541

    Article  CAS  PubMed  Google Scholar 

  32. Buysee DJ (2011) Insomnia: recent developments and future directions, 5th edn. Elsevier Saunders, St. Louis, pp 822–286 (Chapter 75, Principles and practice of sleep medicine)

    Google Scholar 

  33. Mets MA, van Deventer KR, Olivier B, Verster JC (2010) Critical appraisal of ramelteon in the treatment of insomnia. Nat Sci Sleep 2:257–266

    Article  PubMed  PubMed Central  Google Scholar 

  34. Zlotos DP (2005) Recent advances in melatonin receptor ligands. Arch Pharm (Weinheim). 338:229–247

    Article  CAS  PubMed  Google Scholar 

  35. Greeblatt DJ, Roth T (2012) Zolpidem for insomnia. Expert Opin Pharmacother 13:879–893

    Article  Google Scholar 

  36. Greenblatt DJ, Zammit GK (2012) Pharmacokinetic evaluation of eszopiclone: clinical and therapeutic implications. Expert Opin Drug Metabol Toxicol 8:1609–1618

    Article  CAS  Google Scholar 

  37. Drover DR (2004) Comparative pharmacokinetics and pharmacodynamics of short-acting hypnosedatives: zaleplon, zolpidem and zopiclone. Clin Pharmacokinet 43:227–238

    Article  CAS  PubMed  Google Scholar 

  38. Greenblatt DJ, Harmatz JS, Karim A (2007) Age and gender effects on the pharmacokinetics and pharmacodynamics of ramelteon, a hypnotic agent acting via melatonin receptors MT1 and MT2. J Clin Pharmacol 47:485–496

    Article  CAS  PubMed  Google Scholar 

  39. Miyamoto M (2009) Pharmacology of ramelteon, a selective MT1/MT2 receptor agonist: a novel therapeutic drug for sleep disorders. CNS Neurosci Ther 15:32–51

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Rudorfer MV, Potter WZ (1999) Metabolism of tricyclic antidepressants. Cell Mol Neurobiol 19:373–409

    Article  CAS  PubMed  Google Scholar 

  41. Kales A, Kales JD (1984) Evaluation and treatment of insomnia, 1st edn. Oxford Universtity Press, New York

    Google Scholar 

  42. Monti JM (1981) Sleep laboratory and clinical studies of the effects of triazolam, flunitrazepam and flurazepam in insomniac patients. Methods Find Exp Clin Pharmacol 3:303–326

    CAS  PubMed  Google Scholar 

  43. Mitler MM, Seidel WF, van den Hoed J, Greenblatt DJ, Dement WC (1984) Comparative hypnotic effects of flurazepam, triazolam, and placebo: a long-term simultaneous nighttime and daytime study. J Clin Psychopharmacol 4:2–13

    Article  CAS  PubMed  Google Scholar 

  44. Monti JM, Attali P, Monti D, Zipfel A, de la Giclais B, Morselli PL (1994) Zolpidem and rebound insomnia—a double-blind, controlled polysomnographic study in chronic insomniac patients. Pharmacopsychiatry 27:166–175

    Article  CAS  PubMed  Google Scholar 

  45. Greenblatt DJ (1991) Benzodiazepine hypnotics: sorting the pharmacokinetic facts. J Clin Psychiatry 52(Suppl):4–10

    PubMed  Google Scholar 

  46. Monti JM, Spence DW, Pandi-Perumal SR, Langer SZ, Hardeland R (2009) Pharmacotherapy of insomnia. Focus on zolpidem extended release. Clin Med Ther 1:123–140

    Google Scholar 

  47. Monti JM, Alvariño F, Monti D (2000) Conventional and power spectrum analysis of the effects of zolpidem on sleep EEG in patients with chronic primary insomnia. Sleep 23:1075–1084

    Article  CAS  PubMed  Google Scholar 

  48. Roth T, Hull SG, Lankford DA, Rosenberg R, Scharf MB, Intermezzo Study Group (2008). Low-dose sublingual zolpidem tartrate is associated with dose-related improvement in sleep onset and duration in insomnia characterized by middle-of-the- night (MOTN) awakenings. Sleep 31:1277–1284

    Google Scholar 

  49. Roth T, Krystal A, Steinberg FJ, Singh NN, Moline M (2013) Novel sublingual low-dose zolpidem tablet reduces latency to sleep onset following spontaneous middle-of-the-night awakening in insomnia in a randomized, double-blind, placebo-controlled, outpatient study. Sleep 36:189–196

    Article  PubMed  PubMed Central  Google Scholar 

  50. Cluydts R, Peeters K, de Bouyalsky I, Lavoisy J (1998) Comparison of continuous versus intermittent administration of zolpidem in chronic insomniacs: a double-blind, randomized pilot study. J Int Med Res 26:13–24

    Article  CAS  PubMed  Google Scholar 

  51. Perlis ML, McCall WV, Krystal AD, Walsh JK (2004) Long-term, non-nightly administration of zolpidem in the treatment of patients with primary insomnia. J Clin Psychiatry 65:1128–1137

    Article  CAS  PubMed  Google Scholar 

  52. Roth T, Soubrane C, Titeux L, Walsh JK, Zoladult Study Group (2006a) Efficacy and safety of zolpidem-MR: a double-blind, placebo-controlled study in adults with primary insomnia. Sleep Med 7:397–406

    Google Scholar 

  53. Erman M, Guiraud A, Joish VN, Lerner D (2008) Zolpidem extended-release 12.5 mg associated with improvements in work performance in a 6-month randomized, placebo-controlled trial. Sleep 31:1371–1378

    PubMed  PubMed Central  Google Scholar 

  54. Walsh JK, Soubrane C, Roth T (2008) Efficacy and safety of zolpidem extended release in elderly primary insomnia patients. Am J Geriatr Psychiatry 16:44–57

    Article  PubMed  Google Scholar 

  55. Joffe H, Partridge A, Giobbie-Hurder A, Li X, Habin K, Goss P et al (2010) Augmentation of venlafaxine and selective serotonin reuptake inhibitors with zolpidem improves sleep and quality of life in breast cancer patients with hot flashes: a randomized, double-blind, placebo-controlled trial. Menopause 17:908–916

    Article  PubMed  Google Scholar 

  56. Fava M, Asnis GM, Shrivastava R, Lydiard B, Bastani S, Sheehan DV et al (2011) Improved insomnia and sleep-related next-day functioning in patients with comorbid major depression and insomnia following concomitant zolpidem extended-release 12.5 mg and escitalopram treatment: a randomized controlled trial. J Clin Psychiatry 72:914–928

    Article  CAS  PubMed  Google Scholar 

  57. Lasch KE, Joish V, Zhu Y (2008) Improved sleep impact in patients with major depressive disorder treated with zolpidem extended-release in combination with escitalopram. Sleep 31:A325

    Google Scholar 

  58. Fava M, Asnis GM, Shrivastava R, Lydiard B, Bastani B, Sheehan D et al (2009) Zolpidem extended release improves sleep and next-day symptoms in comorbid insomnia and generalized anxiety disorder. J Clin Psychopharmacol 29:222–230

    Article  CAS  PubMed  Google Scholar 

  59. Roehrs TA, Randall S, Harris E, Maan R, Roth T (2011) Twelve months of nightly zolpidem does not lead to dose escalation: a prospective placebo-controlled study. Sleep 34:207–212

    Article  PubMed  PubMed Central  Google Scholar 

  60. Monti JM, Monti D (2006) Overview of currently available hypnotics. In: Pandi-Perumal SR, Monti JM (eds) Clinical pharmacology of sleep. Birkhäuser Verlag, Basel, pp 207–223

    Chapter  Google Scholar 

  61. Krystal AD, Erman M, Zammit GK, Soubrane C, Roth T, ZOLONG Study Group (2008) Long-term efficacy and safety of zolpidem extended-release 12.5 mg, administered 3 to 7 nights per week for 24 weeks, in patients with chronic primary insomnia: a 6-month, randomized, double-blind, placebo-controlled, parallel-group, multicenter study. Sleep 31:79–80

    Google Scholar 

  62. Dolder CR, Nelson MH (2008) Hypnosedative-induced complex behaviors: incidence, mechanisms and management. CNS Drugs 22:1021–1036

    Article  CAS  PubMed  Google Scholar 

  63. Musch B, Maillard F (1990) Zopiclone, the third generation hypnotic: a clinical overview. Int Clin Psychopharmacol 5(Suppl 2):147–158

    PubMed  Google Scholar 

  64. Noble S, Langtry HD, Lamb HM (1998) Zopiclone. An update of its pharmacology, clinical efficacy and tolerability in the treatment of insomnia. Drugs 55:277–302

    Article  CAS  PubMed  Google Scholar 

  65. Zammit GK, McNabb LJ, Caron J, Amato DA, Roth T (2004) Efficacy and safety of eszopiclone across 6-weeks of treatment for primary insomnia. Curr Med Res Opin 20:1979–1991

    Article  CAS  PubMed  Google Scholar 

  66. Krystal AD, Walsh JK, Laska E, Caron J, Amato DA, Wessel TC et al (2003) Sustained efficacy of eszopiclone over 6 months of nightly treatment: results of a randomized, double-blind, placebo-controlled study in adults with chronic insomnia. Sleep 26:793–799

    Article  PubMed  Google Scholar 

  67. Roth T, Walsh JK, Krystal A, Wessel T, Roehrs TA (2005) An evaluation of the efficacy and safety of eszopiclone over 12 months in patients with chronic primary insomnia. Sleep Med 6:487–495

    Article  PubMed  Google Scholar 

  68. Scharf M, Erman M, Rosenberg R, Seiden D, McCall WV, Amato D et al (2005) A 2-week efficacy and safety study of eszopiclone in elderly patients with primary insomnia. Sleep 28:720–727

    Article  PubMed  Google Scholar 

  69. McCall WV, Erman M, Krystal AD, Rosenberg R, Scharf M, Zammit GK et al (2006) A polysomnography study of eszopiclone in elderly patients with insomnia. Curr Med Res Opin 22:1633–1642

    Article  CAS  PubMed  Google Scholar 

  70. Oberndorfer S, Saletu-Zyhlarz G, Saletu B (2000) Effects of selective serotonin reuptake inhibitors on objective and subjective sleep quality. Neuropsychobiology 42:69–81

    Article  CAS  PubMed  Google Scholar 

  71. Fava M, McCall WV, Krystal A, Wessel T, Rubens R, Caron J et al (2006) Eszopiclone co-administered with fluoxetine in patients with insomnia coexisting with major depressive disorder. Biol Psychiatry 59:1052–1060

    Article  CAS  PubMed  Google Scholar 

  72. Pollack M, Kinrys G, Krystal A, McCall V, Roth T, Schaefer K et al (2008) Eszopiclone coadministered with escitalopram in patients with insomnia and comorbid generalized anxiety disorder. Arch Gen Psychiatry 65:551–562

    Article  CAS  PubMed  Google Scholar 

  73. Soares CN, Joffe H, Rubens R, Caron J, Roth T, Cohen L (2006) Eszopiclone in patients with insomnia during menopause and early postmenopause: a randomized controlled study. Obstet Gynecol 108:1402–1410

    Article  CAS  PubMed  Google Scholar 

  74. Walsh JK, Vogel GW, Scharf M, Erman M, William Erwin C, Schweitzer PK et al (2000) A five week, polysomnographic assessment of zaleplon 10 mg for the treatment of primary insomnia. Sleep Med 1:41–49

    Article  CAS  PubMed  Google Scholar 

  75. Elie R, Rüther E, Farr I, Emilien G, Salinas E (1999) Sleep latency is shortened during 4 weeks of treatment with zaleplon, a novel nonbenzodiazepine hypnotic. Zaleplon Clinical Study Group. J Clin Psychiatry 60:536–544

    Article  CAS  PubMed  Google Scholar 

  76. Fry J, Scharf M, Mangano R, Fujimori M (2000) Zaleplon improves sleep without producing rebound effects in outpatients with insomnia. Zaleplon Clinical Study Group. Int Clin Psychopharmacol 15:141–152

    Article  CAS  PubMed  Google Scholar 

  77. Ancoli-Israel S, Walsh JK, Mangano RM, Fujimori M (1999) Zaleplon, a novel nonbenzodiazepine hypnotic, effectively treats insomnia in elderly patients without causing rebound effects. J Clin Psychiatry 1:114–120

    Google Scholar 

  78. Hedner J, Yaeche R, Emilien G, Farr I, Salinas E (2000) Zaleplon shortens subjective sleep latency and improves subjective sleep quality in elderly patients with insomnia. The Zaleplon Clinical Investigator Study Group. Int J Geriatr Psychiatry 15:704–712

    Article  CAS  PubMed  Google Scholar 

  79. Scharf M (1999) A new option for insomnia. Heath News 5:4

    CAS  Google Scholar 

  80. Erman M, Seiden D, Zammit G, Sainati S, Zhang J (2006) An efficacy, safety, and dose-response study of ramelteon in patients with chronic primary insomnia. Sleep Med 7:17–24

    Article  PubMed  Google Scholar 

  81. Zammit G, Erman M, Wang-Weigand S, Sainati S, Zhang J, Roth T (2007) Evaluation of the efficacy and safety of ramelteon in subjects with chronic insomnia. J Clin Sleep Med 3:495–504

    PubMed  PubMed Central  Google Scholar 

  82. Mayer G, Wang-Weigand S, Roth-Schechter B, Lehmann R, Staner C, Partinen M (2009) Efficacy and safety of 6-month nightly ramelteon administration in adults with chronic primary insomnia. Sleep 32:351–360

    Article  PubMed  PubMed Central  Google Scholar 

  83. Roth T, Seiden D, Wang Weigand S, Zhang J (2007a) A 2-night, 3-period, crossover study of ramelteon’s efficacy and safety in older adults with chronic insomnia. Curr Med Res Opin 23:1005–1014

    Google Scholar 

  84. Roth T, Seiden D, Sainati S, Wang-Weigand S, Zhang J, Zee P (2006b) Effects of ramelteon on patient-reported sleep latency in older adults with chronic insomnia. Sleep Med 7:312–318

    Google Scholar 

  85. DeFronzo Dobkin R, Menza M, Bienfait KL, Allen LA, Marin H et al (2009) Ramelteon for the treatment of insomnia in menopausal women. Menopause Int 15:13–18

    Google Scholar 

  86. Gross PK, Nourse R, Wasser TE (2009) Ramelteon for insomnia symptoms in a community sample of adults with generalized anxiety disorder: an open lable study. J Clin Sleep Med 5:28–33

    PubMed  PubMed Central  Google Scholar 

  87. Gooneratne NS, Gehrman P, Gurubhagavatula I, Al-Shehabi E, Marie E, Schwab R (2010) Effectiveness of ramelteon for insomnia symptoms in older adults with obstructive sleep apnea: a randomized placebo-controlled pilot study. J Clin Sleep Med 6:572–580

    PubMed  PubMed Central  Google Scholar 

  88. Roth T, Rogowski R, Hull S, Schwartz H, Koshorek G, Corser B et al (2007b) Efficacy and safety of doxepin 1 mg, 3 mg, and 6 mg in adults with primary insomnia. Sleep 30:1555–1561

    Google Scholar 

  89. Krystal AD, Lankford A, Durrence HH, Ludington E, Jochelson P, Rogowski R et al (2011) Efficacy and safety of doxepin 3 mg and 6 mg in a 35-day sleep laboratory trial in adults with chronic primary insomnia. Sleep 34:1433–1442

    PubMed  PubMed Central  Google Scholar 

  90. Scharf M, Rogowski R, Hull S, Cohn M, Mayleben D, Feldman N et al (2008) Efficacy and safety of doxepin 1 mg, 3 mg, and 6 mg in elderly patients with primary insomnia: a randomized, double-blind, placebo-controlled crossover study. J Clin Psychiatry 69:1557–1564

    Article  CAS  PubMed  Google Scholar 

  91. Krystal AD, Durrence HH, Scharf M, Jochelson P, Rogowski R, Ludington E et al (2010) Efficacy and safety of doxepin 1 mg and 3 mg in a 12-week sleep laboratory and outpatient trial of elderly subjects with chronic primary insomnia. Sleep 33:1553–1561

    Article  PubMed  PubMed Central  Google Scholar 

  92. Lankford A, Rogowski R, Essink B, Ludington E, Heith Durrence H, Roth T (2012) Efficacy and safety of doxepin 6 mg in a four-week outpatient trial of elderly adults with chronic primary insomnia. Sleep Med 13:133–138

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacology and Therapeutics, School of Medicine Clinics Hospital, University of the Republic, Montevideo, Uruguay

    Jaime M. Monti

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  1. School of Graduate Medical Education, Seton Hall University, South Orange, New Jersey, USA

    Sudhansu Chokroverty

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Monti, J.M. (2017). General Principle of Treatment of Sleep Dysfunction and Pharmacology of Drugs Used in Sleep Disorders. In: Chokroverty, S. (eds) Sleep Disorders Medicine. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-6578-6_55

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