The Medical Letter on Drugs and Therapeutics
In Brief: Off-Label Amitriptyline for Insomnia
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Med Lett Drugs Ther. 2023 Mar 20;65(1672):48   doi:10.58347/tml.2023.1672d
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  • Mark Abramowicz, M.D., President has disclosed no relevant financial relationships.
  • Jean-Marie Pflomm, Pharm.D., Editor in Chief has disclosed no relevant financial relationships.
  • Brinda M. Shah, Pharm.D., Consulting Editor has disclosed no relevant financial relationships.
Upon completion of this activity, the participant will be able to:
  1. Discuss the efficacy and safety of off-label use of amitriptyline for treatment of insomnia.
 Select a term to see related articles  amitriptyline   antidepressants   doxepin   insomnia   mirtazapine   Silenor   trazodone   tricylic antidepressants 

In our article on Drugs for Chronic Insomnia, we said there is little evidence that antidepressants such as trazodone, mirtazapine, or amitriptyline are effective in treating insomnia not associated with depression.1 We received a comment from a reader who has prescribed the tricyclic antidepressant amitriptyline for insomnia, particularly for patients with headache disorders, and finds that most patients are satisfied with the treatment.

Amitriptyline has sedative effects, which may improve sleep latency and sleep maintenance (it has a long half-life); it may also improve sleep indirectly by treating headache or mood disorders. The drug has been used off-label for treatment of insomnia for many years, but data from large controlled trials are lacking, and insomnia treatment guidelines do not recommend its use.2

Anticholinergic and antihistaminic adverse effects (e.g., urinary retention, constipation, dry mouth, blurred vision, orthostatic hypotension) are common with amitriptyline. Amitriptyline also can cause QT-interval prolongation and cardiac conduction delays. Chronic use of anticholinergic drugs has been associated with an increased risk of dementia and is not recommended for older patients.3

Amitriptyline doses used for treatment of insomnia are lower than the usual antidepressant doses (10-50 mg vs 100-300 mg) and may be better tolerated, but data are lacking.

The tricyclic antidepressant doxepin (Silenor, and generics) is FDA-approved for treatment of sleepmaintenance insomnia in low doses (3-6 mg, compared to 75-300 mg for depression).4 It has been shown to provide a hypnotic effect without causing anticholinergic and other typical tricyclic adverse effects and is generally preferred over amitriptyline and other antidepressants for such use.

  1. Drugs for chronic insomnia. Med Lett Drugs Ther 2023; 65:1.
  2. MJ Sateia et al. Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med 2017; 13:307. doi:10.5664/jcsm.6470
  3. 2019 American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2019 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc 2019; 67:674. doi:10.1111/jgs.15767
  4. Low-dose doxepin (Silenor) for insomnia. Med Lett Drugs Ther 2010; 52:79.
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