Systematic (IUPAC) name
Clinical data
Trade names Elavil
AHFS/ monograph
MedlinePlus a682388
Pregnancy cat. D(US)
Legal status Prescription only
Routes Oral
Pharmacokinetic data
Bioavailability 30–60% due to first pass metabolism
Protein binding > 90%
Metabolism Hepatic
Half-life 10–50 hours, with an average of 15 hours
Excretion Renal
CAS number 50-48-6 YesY
549-18-8 (hydrochloride)
ATC code N06AA09
PubChem CID 2160
IUPHAR ligand 200
DrugBank APRD00227
ChemSpider 2075 YesY
UNII 1806D8D52K YesY
KEGG D07448 YesY
Chemical data
Formula C20H23N 
Mol. mass 277.403 g/mol
SMILES eMolecules & PubChem
 N(what is this?)  (verify)

Amitriptyline (Elavil, Tryptizol, Laroxyl, Sarotex, Lentizol) is a tricyclic antidepressant (TCA). It is the most widely used TCA and has at least equal efficacy against depression as the newer class of SSRIs.[1] As well as reducing depressive symptoms, these type of tricyclics also aid migraines, tension headaches, anxiety attacks and some schizophrenic symptoms.


Medical uses

Amitriptyline is used for a number of medical conditions including: depressive disorders, anxiety disorders, attention deficit hyperactivity disorder, migraine prophylaxis, eating disorders, bipolar disorder, post herpetic neuralgia, and insomnia.[2]

Amitriptyline is used in ankylosing spondylitis for pain relief. It is also used as a preventive for patients with recurring biliary dyskinesia (sphincter of Oddi dysfunction).[3]

Amitriptyline is also used in the treatment of nocturnal enuresis in children.[4]

Amitriptyline may be prescribed for other conditions such as post-traumatic stress disorder (PTSD),[5] chronic pain, tinnitus, chronic cough, carpal tunnel syndrome (CTS), fibromyalgia, vulvodynia, interstitial cystitis, male chronic pelvic pain syndrome, irritable bowel syndrome (IBS), diabetic peripheral neuropathy, neurological pain, laryngeal sensory neuropathy, chronic fatigue syndrom and painful paresthesias related to multiple sclerosis. Typically lower dosages are required for pain modification of 10 to 50 mg daily.[6]

A randomized controlled trial published in June 2005 found that amitriptyline was effective in functional dyspepsia that did not respond to a first-line treatment (famotidine or mosapride).[7]

Adverse effects

The main two side effects that occur from taking amitriptyline are drowsiness and a dry mouth. Other common side effects of using amitriptyline are mostly due to its anticholinergic activity, including: weight gain, changes in appetite, muscle stiffness, nausea, constipation, nervousness, dizziness, blurred vision, urinary retention, insomnia and changes in sexual function. Some rare side effects include seizures, tinnitus, hypotension, mania, psychosis, sleep paralysis, hypnagogia[clarification needed], hypnopompia[clarification needed], heart block, arrhythmias, lip and mouth ulcers, extrapyramidal symptoms, depression, tingling pain or numbness in the feet or hands, yellowing of the eyes or skin, pain or difficulty passing urine, confusion, abnormal production of milk in females, breast enlargement in both males and females, fever with increased sweating, and suicidal thoughts.[8] The Indianapolis Discovery Network for Dementia (IDND) [9] rates Amitriptyline as having definite 'Anticholinergic Effects'. A side effect of many commonly used drugs with such effects appears to be to increase the risks of both cognitive impairment and death in older people, according to new research led by the University of East Anglia (UEA).[10] Amitriptyline can induce hepatotoxicity.[11]


The symptoms and the treatment of an overdose are largely the same as for the other TCAs. However, the British National Formulary notes that amitryptyline is particularly dangerous in overdose, and thus does not recommend its use in depression.[12]


Amitriptyline acts primarily as a serotonin-norepinephrine reuptake inhibitor, with strong actions on the serotonin transporter, and moderate effects on the norepinephrine transporter.[13][14] It has negligible influence on the dopamine transporter and therefore does not affect dopamine reuptake, being nearly 1,000 times weaker on it than on serotonin.[14]

Amitriptyline additionally functions as a 5-HT2A, 5-HT2C, 5-HT3, 5-HT6, 5-HT7, α1-adrenergic, H1, and mACh receptor antagonist, and σ1 receptor agonist.[15][16][17][18] It has also been shown to be a relatively weak NMDA receptor negative allosteric modulator at the same binding site as phencyclidine.[19] Amitriptyline inhibits sodium channels, L-type calcium channels, and Kv1.1, Kv7.2, and Kv7.3 voltage-gated potassium channels, and therefore acts as a sodium, calcium, and potassium channel blocker as well.[20][21][22]

Recently, amitriptyline has been demonstrated to act as an agonist of the TrkA and TrkB receptors.[23] It promotes the heterodimerization of these proteins in the absence of NGF and has potent neurotrophic activity both in-vivo and in-vitro in mouse models.[23][24]


Amitriptyline, under the brand name Elavil, was developed by Merck and approved by the FDA on April 7, 1961, for the treatment of major depression in the United States.[25]

See also


  1. ^ Barbui C, Hotopf M (February 2001). "Amitriptyline v. the rest: still the leading antidepressant after 40 years of randomised controlled trials". The British Journal of Psychiatry : the Journal of Mental Science 178 (2): 129–144. doi:10.1192/bjp.178.2.129. PMID 11157426. 
  2. ^ "Amitriptyline Hydrochloride". The American Society of Health-System Pharmacists. Retrieved 3 April 2011. 
  3. ^ S. G. Hubscher et al. (2006). Functional biliary type pain syndrome. In P. J. Pasricha, W. D. Willis & G. F. Gebhart (Eds.), ' ' italics' ' Chronic Abdominal and Visceral Pain' 'italics' '. London: Informa Healthcare, pp. 459-461.
  4. ^
  5. ^ National Institute for Clinical Excellence: The Treatment of PTSD in Adults and Children
  6. ^ British National Formulary 45 (March 2003).
  7. ^ Otaka M, Jin M, Odashima M et al. (June 2005). "New strategy of therapy for functional dyspepsia using famotidine, mosapride and amitriptyline". Aliment. Pharmacol. Ther. 21 (Suppl 2): 42–46. doi:10.1111/j.1365-2036.2005.02473.x. PMID 15943846. 
  8. ^ -Connect to Better Health
  9. ^ [1]
  10. ^ [2]
  11. ^ Drug-induced liver disease By Neil Kaplowitz, Laurie D. DeLeve; pag.527;
  12. ^
  13. ^
  14. ^ a b Tatsumi; Groshan, K.; Blakely, R. D.; Richelson, E. (1997). "Pharmacological profile of antidepressants and related compounds at human monoamine transporters". European journal of pharmacology 340 (2–3): 249–258. doi:10.1016/S0014-2999(97)01393-9. PMID 9537821.  edit
  15. ^ Owens; Morgan, WN; Plott, SJ; Nemeroff, CB (1997). "Neurotransmitter receptor and transporter binding profile of antidepressants and their metabolites". The Journal of pharmacology and experimental therapeutics 283 (3): 1305–22. PMID 9400006.  edit
  16. ^ Alan F. Schatzberg, Charles B. (2006). Essentials of clinical psychopharmacology. American Psychiatric Pub. p. 7. ISBN 1585622435, 9781585622436. 
  17. ^ Rauser; Savage, J. E.; Meltzer, H. Y.; Roth, B. L. (2001). "Inverse agonist actions of typical and atypical antipsychotic drugs at the human 5-hydroxytryptamine(2C) receptor". The Journal of pharmacology and experimental therapeutics 299 (1): 83–89. PMID 11561066.  edit
  18. ^ Werling; Keller, A. .; Frank, J. .; Nuwayhid, S. . (2007). "A comparison of the binding profiles of dextromethorphan, memantine, fluoxetine and amitriptyline: treatment of involuntary emotional expression disorder". Experimental neurology 207 (2): 248–257. doi:10.1016/j.expneurol.2007.06.013. PMID 17689532.  edit
  19. ^ Sills; Loo, PS (1989). "Tricyclic antidepressants and dextromethorphan bind with higher affinity to the phencyclidine receptor in the absence of magnesium and L-glutamate". Molecular pharmacology 36 (1): 160–5. PMID 2568580.  edit
  20. ^ Pancrazio; Kamatchi, GL; Roscoe, AK; Lynch C, 3rd (1998). "Inhibition of neuronal Na+ channels by antidepressant drugs". The Journal of pharmacology and experimental therapeutics 284 (1): 208–14. PMID 9435180.  edit
  21. ^ Zahradnik, I. .; Minarovic, I. .; Zahradnikova, A. . (2008). "Inhibition of the cardiac L-type calcium channel current by antidepressant drugs". The Journal of pharmacology and experimental therapeutics 324 (3): 977–984. doi:10.1124/jpet.107.132456. PMID 18048694.  edit
  22. ^ Punke MA, Friederich P (May 2007). "Amitriptyline is a potent blocker of human Kv1.1 and Kv7.2/7.3 channels". Anesthesia and Analgesia 104 (5): 1256–1264. doi:10.1213/01.ane.0000260310.63117.a2. PMID 17456683. 
  23. ^ a b Jang; Liu, X. .; Chan, C. .; Weinshenker, D. .; Hall, R. .; Xiao, G. .; Ye, K. . (2009). "Amitriptyline is a TrkA and TrkB receptor agonist that promotes TrkA/TrkB heterodimerization and has potent neurotrophic activity". Chemistry & biology 16 (6): 644–656. doi:10.1016/j.chembiol.2009.05.010. PMC 2844702. PMID 19549602.  edit
  24. ^
  25. ^ Fangmann P, Assion HJ, Juckel G, González CA, López-Muñoz F (February 2008). "Half a century of antidepressant drugs: on the clinical introduction of monoamine oxidase inhibitors, tricyclics, and tetracyclics. Part II: tricyclics and tetracyclics". Journal of Clinical Psychopharmacology 28 (1): 1–4. doi:10.1097/jcp.0b013e3181627b60. PMID 18204333. 

Further reading