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Amitriptyline HCL (Elavil) for Insomnia

  • Generic name: Amitriptyline Hydrochloride
  • Brand names: Amitrol, Elavil, Endep, Levate, Tryptizol, Vanatrip
  • Dosages: 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 150 mg tablets
  • Pharmacologic category: Tricyclic antidepressant, Tertiary amine
  • Habit forming? No
  • Pregnancy risk factor: C

Medical uses

Amitriptyline hcl is an old tertiary amine tricyclic antidepressant indicated for the treatment of major depressive disorder. It is a potent antidepressant with strong sedative properties.

Amitriptyline is used to treat depression, mainly melancholic, endogenous, or when anxiety or insomnia coexist. It helps treat depression by moderating certain chemicals in the brain (like serotonin and norepinephrine) that are responsible for mood. Amitriptyline is also used to treat obsessive-compulsive disorders, chronic pain, and bed-wetting in children over 6 years of age (enuresis). Amitriptyline plus perphenazine works well in psychotic depression.

Amitriptyline is widely used in the management of chronic pain syndromes such as migraines, headaches, vulvodynia, fibromyalgia, and irritable bowel syndrom.

Pharmacological characteristics

  • Absorption: appears in plasma within 30 to 60 minutes after oral ingestion and 5 to 10 minutes after intramuscular injection.
  • Elimination half-life: varies from 9 to 27 hours (average: 15 hours); nortriptyline, the most important metabolite, has a half-life of 38 hours (18-60 hours) [2].
  • Metabolism: demethylated in the liver to its primary active metabolite, nortriptyline; Metabolism may be impaired in the elderly.
  • Excretion: urine (18% as unchanged drug), feces (small amounts)


  • Very effective antidepressant [6]
  • Frequently used to treat symptoms such as burning sensations, pins and needles, and stabbing pains caused by damage to the pain regulating pathways of the brain and spinal cord
  • Well studied in post-herpetic neuralgia and diabetic neuropathy
  • Relatively early onset of antidepressant action
  • Low cost and generic availability


  • Dangerous in overdose -- may cause convulsions, cardiac arrhythmias, severe hypotension.
  • May increase appetite and cause sweet craving [20]
  • Potential for weight gain [19, 20]
  • Impairment of cognitive skills and psychomotor abilities
  • Poor tolerability -- the burden of anticholinergic effects like dry mouth, drowsiness, constipation and fatigue. Being the is the most anticholinergic tricyclic antidepressant amitriptyline is most likely to produce delirium.
  • Cardiotoxicity: high risk of cardiovascular side effects, including orthostatic hypotension, changes in heart rhythm and conduction [1]
  • Decreased amount of REM sleep [21]

Amitriptyline for Sleep

Insomnia is an insufficient amount of night sleep or a non-restorative, poor-quality sleep. Once the problem has lasted longer than 30 days, the patient is considered to have chronic insomnia. Although sleeping pills may help fall asleep quicker and increase total time asleep, they may not improve the actual quality of sleep.

Amitriptyline is not licenced for insomnia and there is only limited evidence from clinical trials of its effectiveness. However, amitriptyline is commonly prescribed by doctors for sleep problems, particularly when insomnia is associated with anxiety, depression, or other psychiatric disorders. It is also effective for sleep problems related to pain. Amitriptyline is generally considered an effective sleep aid and suitable for long-term use28.

Amitriptyline is as effective as lorazepam (Ativan) for insomnia due to opiate withdrawal29.

The principal advantage of amitriptyline over traditional hypnotics is lack of abuse potential. On the other hand daytime sleepiness and sedation are significant problem with amitriptyline.

Amitriptyline dosage for insomnia:

Amitriptyline is commonly used at doses 10 or 25 mg to promote sleep27. At this dose the drug is probably acting mostly as a histamine H1 receptor antagonist.

Reasons to avoid Amitriptyline as a sleep aid:

  • Cardiac arrhythmias, myocardial infarction, and other cardiovascular problems
  • Children <12 years of age
  • Use of MAOIs
  • Elderly with risk of falls
  • Persons at high risk of overdose.

Unlabeled uses

  • Migraine prophylaxis [14]
  • Painful diabetic neuropathy [7]
  • Panic disorder
  • Irritable bowel syndrome [18]
  • Vulvodynia
  • Nocturnal enuresis
  • Low-back pain [10]
  • Headache: amitriptyline 25 mg/day significantly reduces frequency and duration of headaches [3, 15].
  • Interstitial cystitis/Painful bladder syndrome [16, 17]
    Amitriptyline is often used in patients with IC/PBS to regulate bladder pain and urgency. It may increase bladder capacity, possibly through effects on beta-adrenergic receptors located on the bladder26. Recent research, however, has demonstrated that amitriptyline relieves pain and reduces bladder spasms at doses higher than 50 mg per day 25.
  • Facial pain
    Low dose amitriptyline (10mg daily) is effective in the management of mid-facial segmental tension-type pain and work better in combination with pindolol24.
  • Temporomandibular joint disorder (TMJ) [9]
  • Postherpetic neuralgia -- amitriptyline may provide good to excellent pain relief with the dose 75 mg [11].
  • Fibromyalgia -- low dose amitriptyline (25 mg at night) appears to be effective for patients with fibromyalgia and can provide improvements in general health, pain, sleep quality and quantity, and fatigue [12, 13].

Mechanism of action

Amitriptyline increases the synaptic concentration of serotonin and norepinephrine in the central nervous system by inhibition of their reuptake by the presynaptic neuronal membrane [22].

The medication also produces antimuscarinic and antihistaminic effects by blocking histamine H1 receptors [5].



  • 1. Jefferson JW. A review of the cardiovascular toxicity of tricyclic antidepressants. Psychosomatic Medicine 1975 Mar-Apr;37(2):160-79.
  • 2. Ghose K. Decreased tyramine sensitivity after discontinuation of amitriptyline therapy. An index of pharmacodynamic half-life. Eur J Clin Pharmacol. 1980 Aug;18(2):151-17.
  • 3. Descombes S, Brefel-Courbon C, Thalamas C, Albucher JF, Rascol O, Montastruc JL, Senard JM. Amitriptyline treatment in chronic drug-induced headache: a double-blind comparative pilot study. Headache. 2001 Feb;41(2):178-82. PubMed
  • 4. Brenne E, van der Hagen K, Maehlum E, Husebo S. Amitriptyline for chronic pain: a double-blind study with determination of serum levels. Tidsskr Nor Laegeforen. 1997 Oct 10;117(24):3491-4.
  • 5. Kachur JF, Allbee WE, Gaginella TS. Antihistaminic and antimuscarinic effects of amitriptyline on guinea pig ileal electrolyte transport and in vitro. J Pharmacology Experimental Therapeutics 1988 May;245(2):455-9.
  • 6. Guaiana G, Barbui C, Hotopf M. Amitriptyline for depression. Cochrane Database Systematic Rev. 2007 Jul 18;(3):CD004186.
  • 7. Max MB, Culnane M, Schafer SC, Gracely RH, Walther DJ, Smoller B, Dubner R. Amitriptyline relieves diabetic neuropathy pain in patients with normal or depressed mood. Neurology. 1987 Apr;37(4):589-96.
  • 8. Zitman FG, Linssen AC, Edelbroek PM, Stijnen T. Low dose amitriptyline in chronic pain: the gain is modest. Pain. 1990 Jul;42(1):35-42.
  • 9. Rizzatti-Barbosa CM, Nogueira MT, de Andrade ED, Ambrosano GM, de Barbosa JR. Clinical evaluation of amitriptyline for temporomandibular joint disorders. Cranio. 2003 Jul;21(3):221-5.
  • 10. Pheasant H, Bursk A, Goldfarb J, Azen SP, Weiss JN, Borelli L. Amitriptyline and chronic low-back pain. A randomized double-blind crossover study. Spine. 1983 Jul-Aug;8(5):552-7.
  • 11. Watson CP, Evans RJ, Reed K, Merskey H, Goldsmith L, Warsh J. Amitriptyline versus placebo in postherpetic neuralgia. Neurology. 1982 Jun;32(6):671-3.
  • 12. Jaeschke R, Adachi J, Guyatt G, Keller J, Wong B. Clinical usefulness of amitriptyline in fibromyalgia: the results of 23 N-of-1 randomized controlled trials. J Rheumatol. 1991 Mar;18(3):447-51. PubMed
  • 13. Goldenberg DL, Felson DT, Dinerman H. A randomized, controlled trial of amitriptyline and naproxen in the treatment of fibromyalgia. Arthritis Rheum. 1986 Nov;29(11):1371-7.
  • 14. Couch JR, Ziegler DK, Hassanein R. Amitriptyline in the prophylaxis of migraine. Neurology. 1976 Feb;26(2):121-7
  • 15. Cerbo R, Barbanti P, Fabbrini G, Pascali MP, Catarci T. Amitriptyline is effective in chronic but not in episodic tension-type headache: pathogenetic implications. Headache. 1998 Jun;38(6):453-7. PubMed
  • 16. Hertle L, van Ophoven A. Long-term results of amitriptyline treatment for interstitial cystitis. Aktuelle Urol. 2010 Jan; 41 Suppl 1:S61-5
  • 17. van Ophoven A, Pokupic S, Heinecke A, Hertle L. A prospective, randomized, placebo-controlled, double-blind study of amitriptyline for the treatment of interstitial cystitis. J Urol. 2004 Aug;172(2):533-6. PubMed
  • 18. Rajagopalan M, Kurian G, John J. Symptom relief with amitriptyline in the irritable bowel syndrome. J Gastroenterol Hepatol. 1998 Jul;13(7):738-41.
  • 19. Berilgen MS, Bulut S, Gonen M, Tekatas A, Dag E, Mungen B. Comparison of amitriptyline and flunarizine on weight gain and serum leptin, C peptide and insulin levels. Cephalalgia. 2005 Nov;25(11):1048-53.
  • 20. Berken GH, Weinstein DO, Stern WC. Weight gain. A side-effect of tricyclic antidepressants. J Affect Disord. 1984 Oct;7(2):133-8. PubMed
  • 21. Riemann D, Velthaus S, Laubenthal S, Müller WE, Berger M. REM-suppressing effects of amitriptyline and amitriptyline-N-oxide in healthy volunteers: results of two uncontrolled pilot trials. Pharmacopsychiatry. 1990 Nov;23(6):253-8.
  • 22. Hyttel J, Christensen AV, Fjalland B. Neuropharmacological properties of amitriptyline, nortriptyline and their metabolites. Acta Pharmacol Toxicol (Copenh). 1980 Jul;47(1):53-7. PubMed
  • 23. Amitriptyline Hydrochloride Monograph from American Society of Health-System Pharmacists
  • 24. Agius AM, Jones NS, Muscat R. A Randomized Controlled Trial comparing the efficacy of low-dose amitriptyline, amitriptyline with pindolol and surrogate placebo in the treatment of chronic tension-type facial pain. Rhinology. 2013 Jun;51(2):143-53.
  • 25. Foster HE Jr, Hanno PM, Nickel JC, Payne CK, et al. Effect of amitriptyline on symptoms in treatment patients with interstitial cystitis/painful bladder syndrome. J Urol. 2010 May PubMed
  • 26. Hanno PM. Painful bladder syndrome/interstitial cystitis and related disorders. In: Wein AJ, editor. Campbell-Walsh Urology. 9th ed. Philadelphia: Saunders; 2007. pp. 330-70.
  • 27. Wilson S, Nutt D. Management of insomnia: treatments and mechanisms. Br J Psychiatry. 2007;191:195–197.
  • 28. Everitt H, McDermott L, Leydon G, Yules H, Baldwin D, Little P. GPs’ management strategies for patients with insomnia: a survey and qualitative interview study. Br J Gen Pract. 2014 Feb;64(619):e112-9.
  • 29. Srisurapanont M, Jarusuraisin N. Amitriptyline vs. lorazepam in the treatment of opiate-withdrawal insomnia: a randomized double-blind study. Acta Psychiatr Scand. 1998 Mar;97(3):233-5. PubMed

Written by, October 2009.
Last updated: May, 2015

Interesting facts

Amitriptyline Hydrochloride

  • Many doctors prefer amitriptyline to other TCAs for the treatment of chronic pain. However, many TCAs may be effective for chronic pain.
  • They remained the first line of treatment for depression through the 1980s, before newer SSRI antidepressants arrived.
  • Amitriptyline is a strong antihistamine.

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