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Amitriptyline (Elavil) Facts
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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
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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.
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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)
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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
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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]
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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]
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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].
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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].
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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
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PubMed
- 10. Kachur JF, Allbee WE, Gaginella TS. Antihistaminic and
antimuscarinic effects of amitriptyline on guinea pig ileal
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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
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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.
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- 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
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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.
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- 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
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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.
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- 35. U.S. Food and Drug Administration. Amitriptyline U.S.
Prescribing Information. Available at (PDF format): Prescribing
Information
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Interesting Amitriptyline facts
- Between 1960 and 1980 tricyclic antidepressants (TCAs) represented
the major pharmacological treatment for depression.
- They remained the first line of treatment for depression through
the 1980s, before newer SSRI antidepressants arrived.
- Amitriptyline is a strong antihistamine.
- In multiple sclerosis, Amitriptyline is frequently used to treat
pain in the arms and legs (e.g., burning sensations, pins and needles,
stabbing pains) caused by damage to the pain regulating pathways
of the brain and spinal cord.
- It has also been found to be helpful for treating fibromyalgia
and symptoms related to chronic pain. Amitriptyline is also used
as a preventative (prophylaxis) medication for patients with frequent
migraines.
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