Top

CNS Drugs

Published in:

01-08-2010 | Adis Drug Profile

Low-Dose Doxepin

In the Treatment of Insomnia

Authors: Juliane Weber, M. Asif A. Siddiqui, Antona J. Wagstaff, Paul L. McCormack

Published in: CNS Drugs | Issue 8/2010

Abstract

Doxepin binds with high specificity and affinity to the histamine H₁ receptor compared with other receptors. Therefore, at low doses, doxepin selectively antagonises H₁ receptors, which is believed to promote the initiation and maintenance of sleep.

In three large, well designed, phase III trials in adult or elderly patients with chronic primary insomnia, oral, low-dose doxepin 3 or 6 mg once daily improved wake time after sleep onset, total sleep time and sleep efficiency to a significantly greater extent than placebo.

Significant between-group differences in polysomnographic sleep recordings that favoured low-dose doxepin were evident after a single administration of the drug. Other efficacy measures, including patient-reported sleep quality, also favoured low-dose doxepin over placebo.

Symptom control was maintained for up to 12 weeks of low-dose doxepin administration and there was no evidence of physical dependence or worsening insomnia after doxepin withdrawal.

Oral, low-dose doxepin 6 mg was also significantly more effective than placebo in a large, well designed trial modelling transient insomnia in healthy adults, according to polysomnographic recordings (e.g. in latency to persistent sleep).

Oral, low-dose doxepin was generally well tolerated in clinical trials.

Diagnostic and statistical manual of mental disorders. Fourth edition, Text Revision. Washington, DC: American Psychiatric Association, 2000

Krystal AD. Treating the health, quality of life, and functional impairments in insomnia. J Clin Sleep Med 2007 Feb 15; 3(1): 63–72PubMed

Doghramji K. The epidemiology and diagnosis of insomnia. Am J Manag Care 2006 May; 12: S214–20PubMed

Becker PM. Pharmacologic and nonpharmacologic treatments of insomnia. Neurol Clin 2005 Nov; 23(4): 1149–63PubMedCrossRef

Passarella S, Duong MT. Diagnosis and treatment of insomnia. Am J Health Syst Pharm 2008; 65(10): 927–34PubMedCrossRef

Tariq SH, Pulisetty S. Pharmacotherapy for insomnia. Clin Geriatr Med 2008; 24(1): 93–105PubMedCrossRef

Somaxon Pharmaceuticals Inc. Somaxon presents pharmacological data on doxepin at the 21st European College of Neuropsychopharmacology Congress [media release]. 2008 Sep3

Mansbach R. In vitro pharmacological profile of doxepin, a sleep-promoting histamine H1 antagonist [abstract no. P.2.d.023]. Eur Neuropsychopharmacol 2008; 18 Suppl. 4: S 357. Plus poster presented at the 21st Congress of the European College of Neuropsychopharmacology; 2008 Aug 30–Sep 3; Barcelona

Somaxon Pharmaceuticals Inc. Silenor® (doxepin) tablets for oral administration: US prescribing information [online]. Available from URL: http://www.silenor.com/pdf/Full_Package_Insert.Silenor.pdf [Accessed 2010 Jun 8]

10.

Stahl SM. Selective histamine H1 antagonism: novel hypnotic and pharmacologic actions challenge classical notions of antihistamines. CNS Spectr 2008 Dec; 13(12): 1027–38PubMed

11.

Singh H, Becker PM. Novel therapeutic usage of low-dose doxepin hydrochloride. Expert Opin Investig Drugs 2007 Aug; 16(8): 1295–305PubMedCrossRef

12.

Rodenbeck A, Cohrs S, Jordan W, et al. The sleep-improving effects of doxepin are paralleled by a normalized plasma cortisol secretion in primary insomnia: a placebo-controlled, double-blind, randomized, cross-over study followed by an open treatment over 3 weeks. Psycho-pharmacology (Berl) 2003 Dec; 170(4): 423–8CrossRef

13.

Hajak G, Rodenbeck A, Adler L, et al. Nocturnal melatonin secretion and sleep after doxepin administration in chronic primary insomnia. Pharmacopsychiatry 1996 Sep; 29(5): 187–92PubMedCrossRef

14.

Lankford A, Hull S, Scharf MB, et al. Efficacy and safety of doxepin 3 and 6 mg in adults with primary insomnia [abstract no. NR593 plus poster]. 160th Annual Meeting of the American Psychiatric Association; 2007 May 19–24; San Diego (CA), 253-4

15.

Lankford A, Hull S, Scharf M, et al. Efficacy and safety of doxepin 3 and 6 mg in adults with primary insomnia [abstract no. 0750]. Sleep 2007; 30 Suppl. : A 256. Plus oral presentation from the 21st Annual Meeting of the Associated Professional Sleep Societies; 2007 Jun 9–14; Minneapolis (MN)

16.

Krystal A, Lankford A, Jochelson P, et al. Efficacy of doxepin 3 and 6 mg on early morning awakenings in adults with primary insomnia [abstract no. NR6-084 plus poster]. 161st Annual Meeting of the American Psychiatric Association; 2008 May 3–8; Washington, DC

17.

Jochelson P, Gotfried M, Hull S, et al. Efficacy and safety of doxepin 1 and 3 mg in a 3-month trial of elderly adults with chronic primary insomnia [abstract no. NR6-090]. 161st Annual Meeting of the American Psychiatric Association; 2008 May 3–8; Washington, DC, 316

18.

Roth T, Gotfried M, Hull S, et al. Long-term efficacy and safety of doxepin 1 and 3 mg in elderly subjects with chronic primary insomnia [abstract plus poster]. 161st Annual Meeting of the American Psychiatric Association; 2008 May 3–8; Washington, DC

19.

Roth T, Durrence H, Gotfried M, et al. Efficacy and safety of doxepin 1 and 3 mg in a 3-month trial of elderly adults with chronic primary insomnia [abstract no. 0701]. Sleep 2008; 31 Suppl. : A 230. Plus oral presentation from the 22nd Annual Meeting of the Associated Professional Sleep Societies; 2008 Jun 7–12; Baltimore (MD)

20.

Segal S, Lankford A, Borders J, et al. Efficacy and safety of doxepin 6 mg in a 4-week outpatient trial of elderly adults with primary insomnia [abstract no. NR6-091]. 161st Annual Meeting of the American Psychiatric Association; 2008 May 3–8; Washington, DC, 316-7

21.

World Intellectual Property Organization. (WO/2008/011150) Methods of improving the pharmacokinetics of doxepin [online]. Available from URL: http://www.wipo.int/pctdb/en/wo.jsp?WO=2008011150S&IA=US2007016464&DISPLAY=DESC [Accessed 2008 Sep 3]

22.

Virtanen R, Scheinin M, Iisalo E. Single dose pharmacokinetics of doxepin in healthy volunteers. Acta Pharmacol Toxicol 1980 Nov; 47(5): 371–6CrossRef

23.

Lankford A, Krystal A, Durrence H, et al. Doxepin 3 and 6 mg in a 35-day trial of adults with primary insomnia: effects following discontinuation [abstract no. 0783]. Sleep 2008; 31 Suppl. : A256–7. Plus poster presented at the 22nd Annual Meeting of the Associated Professional Sleep Societies; 2008 Jun 7–12; Baltimore (MD)

24.

Roth T, Rogowski R, Hull S, et al. Efficacy and safety of doxepin 1 mg, 3 mg, and 6 mg in adults with primary insomnia. Sleep 2007 Nov 1; 30(11): 1555–61PubMed

25.

Scharf M, Rogowski R, Hull S, et al. 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 2008 Oct; 69(10): 1557–64PubMedCrossRef

26.

Schwartz H, Hull S, Seiden D, et al. Efficacy and safety of doxepin 6 mg in a model of transient insomnia [abstract no. NR594 plus poster]. 160th Annual Meeting of the American Psychiatric Association; 2007 May 19–24; San Diego (CA), 254

Title: Low-Dose Doxepin
In the Treatment of Insomnia
Authors: Juliane Weber
M. Asif A. Siddiqui
Antona J. Wagstaff
Paul L. McCormack
Publication date: 01-08-2010
Publisher: Springer International Publishing
Published in: CNS Drugs / Issue 8/2010
Print ISSN: 1172-7047
Electronic ISSN: 1179-1934
DOI: https://doi.org/10.2165/11200810-000000000-00000

At a glance: The STEP trials

Springer Medicine

Low-Dose Doxepin

In the Treatment of Insomnia

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 8/2010

Potential Psychiatric Applications of Metabotropic Glutamate Receptor Agonists and Antagonists

Awakenings and Awareness Recovery in Disorders of Consciousness

Cost Effectiveness of Pharmacotherapy for the Prevention of Migraine

Nervous System Effects of Antituberculosis Therapy

The Relationship between Benzodiazepine Use and Traffic Accidents