What is the role of sedating antidepressants in the treatment of insomnia?

Updated: Sep 11, 2018
  • Author: Jasvinder Chawla, MD, MBA; Chief Editor: Selim R Benbadis, MD  more...
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Although there is a paucity of clinical data on the use of sedating antidepressants for the treatment of primary insomnia without mood disorders, these agents are still sometimes used. Sedating tricyclic antidepressants, such as amitriptyline, nortriptyline, and doxepin, and the tetracyclic drug mirtazapine have been used.

Many clinicians believe that sedating antidepressants have fewer adverse effects than nonbenzodiazepine receptor agonists; however, this is not the case. Tricyclic drugs and mirtazapine can cause daytime sedation, weight gain, dry mouth, postural hypotension, and cardiac arrhythmias. Trazodone can cause priapism in men, daytime sedation, and hypotension.

The efficacy and safety of low-dose doxepin have been demonstrated in 2 randomized, double-blind, parallel-group, placebo-controlled trials. Low-dose doxepin is thought to be a hypnotic that primarily works through an antihistaminic effect.

Roth et al reported that low-dose doxepin (6 mg) provided significant improvements in sleep onset, maintenance, duration, and quality, as well as appearing to reduce early morning awakenings. These researchers used a first-night effect combined with a 3-hour phase advance to induce transient insomnia in healthy adults. The incidence of adverse events was comparable to placebo. [89] .

In a 12-week study of elderly patients with chronic primary insomnia, Krystal et al reported that a nightly 1-mg or 3-mg dose of doxepin resulted in significant and sustained improvements in most insomnia endpoints, including sleep maintenance and early morning awakenings. There was no evidence of next-day residual sedation or other significant adverse effects. Efficacy was assessed using polysomnography, patient reports, and clinician ratings. [90]

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