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

Department of Psychiatry and Psychotherapy, Georg-August-University of Göttingen, Germany.
The Journal of Clinical Psychiatry (Impact Factor: 5.5). 07/2001; 62(6):453-63. DOI: 10.4088/JCP.v62n0609
Source: PubMed


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.

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    • "Doxepin is used to treat depression and anxiety disorders and low doses of it are used to treat sleep disorders. Doxepin also has been known as second-line therapy for chronic urticaria.[20] Various properties of doxepin have been reported; among them we can mention the anticonvulsant effects. "
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    ABSTRACT: Studies have shown that Doxepin has anti-inflammatory effects and reduces oxidative stress. Due to the fact that other tricyclic antidepressants have been shown to have neuroprotective effects, this study aimed to investigate the effects of different doses of doxepin on passive avoidance learning in rats. Old male Wistar rats were used in this study. Doxepin was administered intraperitoneally (1, 5 and 10 mg/kg) for 21 days. Passive avoidance learning test was used for evaluation of learning and memory. Rats received foot electrical shock on fifteen day, and step through latencies were evaluated one week after the electrical shock in retention phase. Administration of Doxepin considerably increased the step through latencies in the rats that received the doses of 1 and 5 mg/kg (P < 0.05). However, in the dose of 10 mg/kg, there wasn't any significant change comparing to control group. These results indicate that Doxepin has desirable effects on cognitive functions in low doses. Therefore, Doxepin can be considered as memory enhancers that understanding the underling mechanisms need further investigation.
    09/2013; 2:66. DOI:10.4103/2277-9175.115823
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    • "ism may also contribute . There are no controlled studies of hypnotic efficacy of low - dose amitriptyline in insomnia , and tricyclics are more likely to be lethal than licensed hypnotics in overdose ( Nutt , 2005a ) . Controlled trials have demon - strated an effect of doxepin in insomnia at low dose ( 25 mg ) for 4 weeks with rebound insomnia ( Hajak et al . , 2001 ) , and very low ' microdose ' studies using 1 , 2 or 6 mg for two nights in adult ( Roth et al . , 2007 ) and elderly insomnia patients ( Scharf et al . , 2008 ) have shown sleep improvement ; at this dose the antihistamine action is paramount . Trazodone is an antagonist at 5HT1a , 5HT2 and a1 adre - nergic receptors as well as a weak"
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    ABSTRACT: Sleep disorders are common in the general population and even more so in clinical practice, yet are relatively poorly understood by doctors and other health care practitioners. These British Association for Psychopharmacology guidelines are designed to address this problem by providing an accessible up-to-date and evidence-based outline of the major issues, especially those relating to reliable diagnosis and appropriate treatment. A consensus meeting was held in London in May 2009. Those invited to attend included BAP members, representative clinicians with a strong interest in sleep disorders and recognized experts and advocates in the field, including a representative from mainland Europe and the USA. Presenters were asked to provide a review of the literature and identification of the standard of evidence in their area, with an emphasis on meta-analyses, systematic reviews and randomized controlled trials where available, plus updates on current clinical practice. Each presentation was followed by discussion, aimed to reach consensus where the evidence and/or clinical experience was considered adequate or otherwise to flag the area as a direction for future research. A draft of the proceedings was then circulated to all participants for comment. Key subsequent publications were added by the writer and speakers at draft stage. All comments were incorporated as far as possible in the final document, which represents the views of all participants although the authors take final responsibility for the document.
    Journal of Psychopharmacology 11/2010; 24(11):1577-601. DOI:10.1177/0269881110379307 · 3.59 Impact Factor
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    • "trials and conclusions as to whether insomnia is reactive to placebo interventions remain mitigated (Bixler et al., 1995; Hajak et al., 2001; McCall et al., 2003; McCall et al., 2005; Roehrs et al., 1985; Roehrs et al., 1990; Walsh et al., 2000). Results of a recent meta-analysis assessing the magnitude of sleep changes from baseline in the placebo arms of five hypnotic clinical trials show that sleep parameters [sleep onset latency (SOL) and total sleep time (TST)] significantly improve during placebo administration (McCall et al., 2003). "
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    ABSTRACT: A meta-analysis assessing the magnitude of sleep changes from baseline in placebo-treated (psychological and pharmacological placebo) and untreated groups issued from independent trials was conducted. Comparisons were then performed to assess if the magnitude of sleep changes in the placebo control groups were significantly different than those of the untreated group. Medline, PsychInfo and Current Contents databases (1990-2004) were searched for primary insomnia treatment studies using a randomized controlled parallel-group design. Effect sizes were computed for each end-point variable based on subjective (patient-reported) and polysomnographic measures. Thirty-four studies (n = 1392 subjects) met inclusion criteria; twenty-three used a pharmacological placebo (n = 1163), four used a psychological placebo (n = 81), and seven used a waitlist condition (n = 148). Between-group comparisons were performed using a random effects model analysis. Significant pre-post changes were observed in the pharmacological placebo condition on several sleep parameters, both on objectively and subjectively measured outcomes [objective and subjective sleep onset latency (SOL) and total sleep time (TST) and subjective wake after sleep onset]. Although a tendency was observed for objective SOL, only the changes on subjective SOL and TST in the pharmacological placebo condition were significantly different from the corresponding changes in the untreated group. No differences were significant for the psychological placebo groups. Although the present findings suggest that sleep may significantly change in response to a pharmacological placebo, conclusions remain tentative because of possible confounds that may arise when comparing groups issued from different trials. Further research directly comparing placebo groups and untreated groups from the same randomized trials remains necessary.
    Journal of Sleep Research 04/2007; 16(1):77-84. DOI:10.1111/j.1365-2869.2007.00566.x · 3.35 Impact Factor
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