Doxepin in the treatment of primary insomnia: A placebo-controlled, double-blind, polysomnographic study

ArticleinThe Journal of Clinical Psychiatry 62(6):453-63 · July 2001with778 Reads
DOI: 10.4088/JCP.v62n0609 · Source: PubMed
Abstract
Over recent years, the use of antidepressants for the symptomatic treatment of insomnia has grown substantially, but controlled studies are still lacking. Our study is the first investigation to prove objective efficacy and tolerability of low doses of a sedating antidepressant in a randomized, double-blind, and placebo-controlled manner in patients with primary insomnia. Forty-seven drug-free patients meeting DSM-IV criteria for primary insomnia (mean +/- SD duration of complaints = 11.2+/-9.7 years) received either 25-50 mg of the tricyclic antidepressant doxepin or placebo for 4 weeks followed by 2 weeks of placebo withdrawal. Sleep was measured by polysomnography at baseline and the first night of application, at 4 weeks of treatment and the first to third night of withdrawal, and after 2 weeks of withdrawal. In the doxepin-treated patients who completed the study (N = 20, 47.6+/-11.3), medication significantly increased sleep efficiency after acute (night 1, p < or = .001) and subchronic (night 28, p < or = .05) intake compared with the patients who received placebo (N = 20, 47.4+/-16.8 years of age). Latency to sleep onset was not affected since the patients had normal baseline sleep latencies. Investigators found doxepin to cause significantly (p < or = .05) better global improvement at the first day of treatment. Patients rated sleep quality (p < or = .001) and working ability (p < or = .005) to be significantly improved by doxepin during the whole treatment period. Overall rebound in sleep parameters was not observed, but patients with severe rebound insomnia were significantly more frequent in the doxepin group (night 29, p < .01, night 30, p < or = .01; night 31, p < or = .05). No significant group differences in side effects were found, but 2 doxepin-treated patients dropped out of the study due to specific side effects (increased liver enzymes, leukopenia, and thrombopenia). The results support the effectiveness of low doses of doxepin to improve sleep and working ability in chronic primary insomniacs, although subjective effects were light to moderate, and in some patients, rebound insomnia and specific side effects have to be considered.
    • "This drug is used for the treatment of depression and/ or anxiety. It can also be used for chronic urticaria and in the management of pain [13, 14]. Tertiary amine TCAs, such as doxepin hydrochloride, are more potent inhibitors of serotonin reuptake than secondary amine TCAs. "
    [Show abstract] [Hide abstract] ABSTRACT: In the present paper, the physicochemical incompatibility of doxepin with dextrose was evaluated in solid-state mixtures. The compatibility was evaluated using different physicochemical methods such as differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy and mass spectrometry. Non-isothermally stressed physical mixtures were used to study the solid-state kinetic parameters. Different thermal models such as Friedman, Flynn–Wall–Ozawa and Kissinger–Akahira–Sunose were used for the characterization of the drug–excipient mixtures. Overall, the incompatibility of doxepin as a tertiary amine with dextrose as a reducing carbohydrate was successfully assessed. DSC-based kinetic analysis is a simple and fast method in evaluation of different drug–excipient mixtures incompatibility. Finally, it can be recommended to exclude dextrose from doxepin pharmaceutical formulations and also to apply the easy and versatile DSC method in kinetic study of drug–excipient incompatibility.
    Article · Sep 2015
    • "In the high dose range, doxepine has antihistamine , anticholinergic, anti-serotonergic and antiadrenergic effects, but in hypnotic doses (<10 mg), it has a relatively pure anti-histamine effect. Doxepin has been shown to have both sleep initiation and maintenance improvements in the nights following use in several randomized control trials in both middle and older aged adults, as assessed by PSG111112113114115. As of yet, doxepin has not been tested in menopausal related insomnia symptoms. "
    [Show abstract] [Hide abstract] ABSTRACT: Understanding sleep complaints among menopausal women is an emerging area of clinical and research interest. Several recent reviews have focused on mechanisms of menopausal insomnia and symptoms. In this review, we present a discussion on the most relevant and recent publications on the treatment of sleep disorders for menopausal women, with a focus on menopause-related insomnia, insomnia symptoms, and obstructive sleep apnea. We discuss both nonpharmacological and pharmacological treatments, including cognitive-behavioral therapy for insomnia (CBT-I), complementary and alternative medicine, hormone replacement therapy, sedative hypnotics, antidepressants, and continuous positive airway pressure. In addition, we briefly discuss methods and considerations of assessment of sleep disorders in menopausal women.
    Full-text · Article · Feb 2015
    • "Furthermore, Rodenbeck et al. reported that sleep-promoting effects of doxepin are regulated through modulation of the hypothalamic–pituitary–adrenal axis functions (Rodenbeck et al., 2003). Doxepin has been shown to be one of the most potent H 1 R antagonists available, and the blockade of H 1 R is its principal pharmacologic effect (Hajak et al., 2001). Previous studies have shown doxepin has more than seven times greater affinity for the H 1 R than any other receptors it has been tested (Krystal et al., 2013; Stahl, 2008). "
    [Show abstract] [Hide abstract] ABSTRACT: Histaminergic neurons have been reported to play an important role in the regulation of sleep-wake behavior through the histamine H1 receptor (R, H1R). First generation H1R antagonists, such as doxepin and diphenhydramine, produce drowsiness in humans, and are occasionally used to treat insomnia. However, if H1R antagonists function via physically blocking the H1R remains unclear. In the current study, we used H1R knockout (KO) mice to investigate if the sleep-promoting effects of doxepin and diphenhydramine are dependent on blockade of the H1R. When doxepin was administered, non-rapid eye movement (NREM) sleep in wild type (WT) mice increased for 4 h, with an increase in the numbers of NREM sleep bouts of 256-512 s and 512-1024 s. These effects were not observed in the H1R KO mice. Furthermore, diphenhydramine increased NREM sleep for 6 h in WT, and not in the H1R KO mice after the injection. These results indicate that both doxepin at 15 mg/kg and diphenhydramine at 10 mg/kg induce NREM sleep through blockade of H1R. Copyright © 2014. Published by Elsevier Inc.
    Full-text · Article · Dec 2014
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