Wellbutrin XL
Celexa (Citalopram)
Zoloft (Sertraline)
Effexor XR (Venlafaxine)

Amitriptyline (Elavil)

  • 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 in a class of drugs called tricyclic antidepressants. It is a potent antidepressant with strong sedative properties. The brand name, before it was discontinued, was Elavil.

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.

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 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
  • cardiotoxicity: high risk of cardiovascular side effects, including orthostatic hypotension, changes in heart rhythm and conduction [1]
  • decreased amount of REM sleep [21]
Unlabeled uses
  • chronic and neuropathic pain [4, 8, 9, 10]
  • migraine prophylaxis [14]
  • painful diabetic neuropathy [7]
  • postherpetic neuralgia [11]
  • headache [3, 15]
  • interstitial cystitis, painful bladder syndrome [16, 17]
  • depressive disorders in children
  • panic disorder
  • irritable bowel syndrome [18]
  • vulvodynia
  • fibromyalgia [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].

Amitriptyline for Pain management

Amitriptyline is widely used to treat chronic pain problems. When used to treat pain, the dose of amitriptyline is typically much lower than that used for treating depression. In the United States, amitriptyline is not approved for the management of pain, although it is proven to be safe and effective by numerous medical studies.

Low dose amitriptyline (75 mg) may improve intensity and some other aspects of chronic pain, but the usefulness is modest. However, chronic pain is a very treatment-resistant condition. Therefore, even modest positive results may be worthwhile [8]. The results of the study showed amitriptyline to be good in the treatment of chronic pain and regulating sleep [4].

Interstitial cystitis/Painful bladder syndrome
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.

Temporomandibular joint disorder
Amitriptyline proved to be an effective alternative symptomatic treatment for temporomandibular joint disorder (TMJ) [9].

Low-back pain
Clinical study demonstrated that it may produce improvement in chronic low-back pain [10].

Postherpetic neuralgia
Amitriptyline is useful in postherpetic neuralgia and may not act as an antidepressant. It may provide good to excellent pain relief with the dose 75 mg [11].

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].

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.

Amitriptyline 25 mg/day can significantly reduce frequency and duration of headache [15].

Unlike other painkillers, Amitriptyline will only work if taken regularly and not on a "when needed" basis. It will not work to reduce pain as soon as you take it. You need to take it for two or three weeks before the effects begin to show and for about six weeks to get the peak effect. On the other hand, its effect on improving the quality of sleep is usually noticed much sooner, often after the first dose.

  • 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 naïve 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.

Last updated: February 10, 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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