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Low-Dose Doxepin

In the Treatment of Insomnia

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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.

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Acknowledgements and Disclosures

The manuscript was reviewed by: M.W. Johnson, Behavioral Pharmacology Research Unit, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; H. Singh, Sleep Medicine, Tri-Valley Sleep Center, San Ramon, California, USA.

The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

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  1. Adis, a Wolters Kluwer Business, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, North Shore 0754, Auckland, New Zealand

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

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  1. Juliane Weber
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  2. M. Asif A. Siddiqui
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  3. Antona J. Wagstaff
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  4. Paul L. McCormack
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Correspondence to Paul L. McCormack.

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Weber, J., Siddiqui, M.A.A., Wagstaff, A.J. et al. Low-Dose Doxepin. CNS Drugs 24, 713–720 (2010). https://doi.org/10.2165/11200810-000000000-00000

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