Amitriptyline (Elavil) Medication Facts

Basic information

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

Medical uses

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

This medication is used to treat depression, obsessive - compulsive disorders, and bed-wetting in children over 6 years of age (enuresis). This drug also may be used to treat chronic pain and eating disorders. It helps treat depression by moderating certain chemicals in the brain (like serotonin and norepinephrine) that are responsible for mood.

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) [4].
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)

Benefits

very effective antidepressant
proven analgesic efficacy [5]
well studied in post-herpetic neuralgia and diabetic neuropathy
relatively early onset of antidepressant action [11]
generic availability

Concerns

dangerous in overdose
weight gain [31, 32]
sweet craving [32]
impairment of cognitive skills and psychomotor abilities
high rate of anticholinergic effects like dry mouth, drowsiness, constipation and fatigue
high risk of cardiovascular side effects [2]
potential for weight gain [3]
cardiotoxicity
decreased amount of REM sleep [33]

Unlabeled uses

chronic and neuropathic pain [8, 9, 12, 14]
migraine prophylaxis [24, 25]
painful diabetic neuropathy [13]
postherpetic neuralgia [19, 20]
neurogenic pain syndromes
tension headache [6, 26]
chronic drug-induced headache [7]
interstitial cystitis [28, 29]
depressive disorders in children
insomnia
papnic disorder
anxiety
irritable bowel syndrome [30]
vulvodynia
fibromyalgia [21, 22, 23]

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. and some antihistamine H1 blocking activity. [34]

Amitriptyline also produces antihistaminic effects [10].

Pain management with amitriptyline

Low dose amitriptyline (75 mg) for chronic pain have a positive effect on the intensity and some other aspects of chronic pain, but that the effect is modest. However, chronic pain is a very treatment-resistant condition. Therefore, even modest positive effects may be worthwhile [14]. The results of the other study showed 25 mg amitriptyline to have a good analgesic and sleep regulatory effect in the treatment of chronic pain [8].

Amitriptyline proved to be an effective alternative treatment for chronic pain caused by temporomandibular joint disorder (TMJ) [15]. It also may produce improvement in chronic low-back pain [16]. Clinical study demonstrated that amitriptyline in combination with gabapentin is effective treatment for chronic pelvic pain [17].

Low dose amitriptyline (up to 25 mg) appears to be not effective for articular pain and tenderness in rheumatoid arthritis [18].

Amitriptyline is useful in treating postherpetic neuralgia and may not act as an antidepressant. It may provide good to excellent pain relief with the dose 75 mg. [20]

Low dose amitriptyline (25 mg at night) appears to be not effective for patients with fibromyalgia and can provide improvements in general health, pain, sleep quality and quantity, and fatigue [22, 23].

Amitriptyline 25 mg/day can significantly reduce frequency and duration of headache as well as analgesic consumption in chronic tension-type headache [27].

References

1. Kyle CJ, Petersen HE, Overo KF. Comparison of the tolerability and efficacy of citalopram and amitriptyline in elderly depressed patients treated in general practice. Depress Anxiety. 1998;8(4):147-53. PubMed
2. Jefferson JW. A review of the cardiovascular effects and toxicity of tricyclic antidepressants. Psychosom Med. 1975 Mar-Apr;37(2):160-79. PubMed
3. Fava M. Weight gain and antidepressants. J Clin Psychiatry. 2000;61 Suppl 11:37-41. PubMed
4. 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. PubMed
5. Sharav Y, Singer E, Schmidt E, Dionne RA, Dubner R. The analgesic effect of amitriptyline on chronic facial pain. Pain. 1987 Nov;31(2):199-209. PubMed
6. Go bel H, Hamouz V, Hansen C, Heininger K, Hirsch S, Lindner V, Heuss D, Soyka D. Amitriptyline in therapy of chronic tension headache. Nervenarzt. 1994 Oct;65(10):670-9. PubMed
7. 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
8. Brenne E, van der Hagen K, Maehlum E, Husebo S. Treatment chronic pain with amitriptyline. A double-blind dosage study with determination of serum levels. Tidsskr Nor Laegeforen. 1997 Oct 10;117(24):3491-4. PubMed
9. McQuay HJ, Carroll D, Glynn CJ. Dose-response for analgesic effect of amitriptyline in chronic pain. Anaesthesia. 1993 Apr;48(4):281-5. PubMed
10. Kachur JF, Allbee WE, Gaginella TS. Antihistaminic and antimuscarinic effects of amitriptyline on guinea pig ileal electrolyte transport and muscle contractility in vitro. J Pharmacol Exp Ther. 1988 May;245(2):455-9. PubMed
11. Bech P. Meta-analysis of placebo-controlled trials with mirtazapine using the core items of the Hamilton Depression Scale as evidence of a pure antidepressive effect in the short-term treatment of major depression. Int J Neuropsychopharmacol. 2001 Dec;4(4):337-45. PubMed
12. McQuay HJ, Carroll D, Glynn CJ. Low dose amitriptyline in the treatment of chronic pain. Anaesthesia. 1992 Aug;47(8):646-52. PubMed
13. 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. PubMed
14. 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. PubMed
15. Rizzatti-Barbosa CM, Nogueira MT, de Andrade ED, Ambrosano GM, de Barbosa JR. Clinical evaluation of amitriptyline for the control of chronic pain caused by temporomandibular joint disorders. Cranio. 2003 Jul;21(3):221-5. PubMed
16. 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. PubMed
17. Sator-Katzenschlager SM, Scharbert G, Kress HG, Frickey N, Ellend A, Gleiss A, Kozek-Langenecker SA. Chronic pelvic pain treated with gabapentin and amitriptyline: a randomized controlled pilot study. Wien Klin Wochenschr. 2005 Nov;117(21-22):761-8. PubMed
18. Grace EM, Bellamy N, Kassam Y, Buchanan WW. Controlled, double-blind, randomized trial of amitriptyline in relieving articular pain and tenderness in patients with rheumatoid arthritis. Curr Med Res Opin. 1985;9(6):426-9. PubMed
19. Bowsher D. Acute herpes zoster and postherpetic neuralgia: effects of acyclovir and outcome of treatment with amitriptyline. Br J Gen Pract. 1992 Jun;42(359):244-6. PubMed
20. 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. PubMed
21. 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
22. Goldenberg D, Mayskiy M, Mossey C, Ruthazer R, Schmid C. A randomized, double-blind crossover trial of fluoxetine and amitriptyline in the treatment of fibromyalgia. Arthritis Rheum. 1996 Nov;39(11):1852-9. PubMed
23. Goldenberg DL, Felson DT, Dinerman H. A randomized, controlled trial of amitriptyline and naproxen in the treatment of patients with fibromyalgia. Arthritis Rheum. 1986 Nov;29(11):1371-7. PubMed
24. Couch JR, Ziegler DK, Hassanein R. Amitriptyline in the prophylaxis of migraine. Effectiveness and relationship of antimigraine and antidepressant effects. Neurology. 1976 Feb;26(2):121-7. PubMed
25. Ziegler DK, Hurwitz A, Preskorn S, Hassanein R, Seim J. Propranolol and amitriptyline in prophylaxis of migraine. Pharmacokinetic and therapeutic effects. Arch Neurol. 1993 Aug;50(8):825-30. PubMed
26. Boline PD, Kassak K, Bronfort G, Nelson C, Anderson AV. Spinal manipulation vs. amitriptyline for the treatment of chronic tension-type headaches: a randomized clinical trial. J Manipulative Physiol Ther. 1995 Mar-Apr;18(3):148-54. PubMed
27. 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
28. Hanno PM, Buehler J, Wein AJ. Use of amitriptyline in the treatment of interstitial cystitis. J Urol. 1989 Apr;141(4):846-8. PubMed
29. 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
30. Rajagopalan M, Kurian G, John J. Symptom relief with amitriptyline in the irritable bowel syndrome. J Gastroenterol Hepatol. 1998 Jul;13(7):738-41. PubMed
31. Berilgen MS, Bulut S, Gonen M, Tekatas A, Dag E, Mungen B. Comparison of the effects of amitriptyline and flunarizine on weight gain and serum leptin, C peptide and insulin levels when used as migraine preventive treatment. Cephalalgia. 2005 Nov;25(11):1048-53. PubMed
32. Berken GH, Weinstein DO, Stern WC. Weight gain. A side-effect of tricyclic antidepressants. J Affect Disord. 1984 Oct;7(2):133-8. PubMed
33. Staner L, Kerkhofs M, Detroux D, Leyman S, Linkowski P, Mendlewicz J. Acute, subchronic and withdrawal sleep EEG changes during treatment with paroxetine and amitriptyline: a double-blind randomized trial in major depression. Sleep. 1995 Jul;18(6):470-7. PubMed
34. 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
35. U.S. Food and Drug Administration. Amitriptyline U.S. Prescribing Information. Available at (PDF format): Prescribing Information

Amitriptyline (Elavil) Facts