|Systematic (IUPAC) name|
|Trade names||Amitrip, Elavil, Endep, Levate|
|Licence data||US FDA:|
|Bioavailability||30–60% due to first pass metabolism|
|Half-life||22.4 hr (26 hr for active metabolite, nortriptyline)|
|Molecular mass||277.403 g/mol|
|(what is this?)|
Amitriptyline // (Elavil, Endep, Levate, and many others) is the most widely used tricyclic antidepressant (TCA). Amitriptyline is chemically basic and is in the form of hydrochloride salt (pKa 9.4) in the market. It is used to treat a number of mental disorders, including major depressive disorder and anxiety, and less commonly psychosis, attention deficit hyperactivity disorder, and bipolar disorder. Other uses include prevention of migraines, postherpetic neuralgia, neuropathic pain such as fibromyalgia, and less commonly insomnia.
Side effects may include seizures, an increased risk of suicide in those less than 25 years of age, urinary retention, and a number of heart issues. They should not be taken with MAO inhibitors or cisapride. In the United States and Australia, they are pregnancy category C which means that may cause problems during pregnancy. Use during breastfeeding does not appear to be a problem.
It was originally developed by Merck, first synthesized in 1960 and first approved by the US Food and Drug Administration (FDA) on 7 April 1961. It is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system.
- 1 Medical uses
- 2 Adverse effects
- 3 Mechanism of action
- 4 Pharmacokinetics
- 5 Pharmacogenetics
- 6 Brand names
- 7 Synthesis
- 8 See also
- 9 Notes
- 10 References
- 11 Further reading
Amitriptyline is used for a number of medical conditions including major depressive disorder (MDD) which is its only FDA-labeled indication. This is also a TGA- and MHRA-labelled indication. Some evidence suggests amitriptyline may have superior efficacy compared to other antidepressants, including the selective serotonin reuptake inhibitors (SSRIs), although it is rarely used as a first-line antidepressant nowadays due to its high degree of toxicity in overdose and generally poorer tolerability than the newer antidepressants such as the SSRIs and serotonin-norepinephrine reuptake inhibitors.
It is TGA-labeled for migraine prophylaxis, also in cases of neuropathic pain disorders, fibromyalgia and nocturnal enuresis. Amitriptyline is a popular off-label treatment for irritable bowel syndrome (IBS). Although it is most frequently reserved for severe cases of abdominal pain in patients with IBS because it needs to be taken regularly to work and has a generally poor tolerability profile, although a firm evidence base supports its efficacy in this indication. Amitriptyline can also be used as an anticholinergic drug in the treatment of early-stage Parkinson's disease if depression also needs to be treated.
- Eating disorders: The few randomized controlled trials investigating its efficacy in eating disorders have been discouraging.
- Insomnia: Owing to the development of tolerance and the potential for adverse effects such as constipation, its use in the elderly for this indication is recommended against.
- Urinary incontinence. An accepted use for amitriptyline in Australia is the treatment of urinary urge incontinence.
- Cyclic vomiting syndrome
- Chronic cough
- Preventive treatment for patients with recurring biliary dyskinesia (sphincter of Oddi dysfunction)
- Attention deficit/hyperactivity disorder (in addition to, or sometimes in place of ADHD stimulant drugs)
Common (≥1% frequency)
- Weight gain
- Anticholinergic side effects (it tends to produce more anticholinergic effects than the other TCAs) such as:
- Somnolence (drowsiness) it tends to be a more sedating TCA.
- Decreased lacrimation
- Orthostatic hypotension
- Sinus tachycardia
- Loss of libido
- Other sexual adverse effects
Uncommon (0.1–1% frequency)
Rare (<0.1% frequency)
- Liver failure
- Lupus-like syndrome (migratory arthritis, positive ANA and rheumatoid factor)
- Hypotension (low blood pressure)
- Syncope (fainting)
- Myocardial infarction
- Heart block
- Neuroleptic malignant syndrome
- Skin rash
- Urticaria (hives)
- Testicular swelling
- Increased or decreased libido
- Urinary retention
- Dilatation of the urinary tract
- Disturbance of accommodation[clarification needed]
- Increased intraocular pressure
- Paralytic ileus
- Epigastric distress
- Peculiar taste
- Parotid swelling
- Black tongue
- Alopecia (hair loss)
- Urinary frequency
- Weight loss
- Increased perspiration
- Urinary frequency
- Confusional states
- Peripheral neuropathy
- Extrapyramidal symptoms
- Tardive dyskinesia
- Disturbed concentration
- Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
- Tinnitus (ringing in the ears)
- Alteration in EEG patterns
The known contraindications of amitriptyline are:
- Hypersensitivity to tricyclic antidepressants or to any of its excipients
- History of myocardial infarction
- History of arrhythmias, particularly heart block to any degree
- Congestive heart failure
- Coronary artery insufficiency
- Severe liver disease
- Children under 7 years
- Breast feeding
- Patients who are taking monoamine oxidase inhibitors (MAOIs) or have taken them within the last 14 days.
Amitriptyline is known to interact with:
- Monoamine oxidase inhibitors as it can potentially induce a serotonin syndrome
- CYP2D6 inhibitors and substrates such as fluoxetine due to the potential for an increase in plasma concentrations of the drug to be seen
- Guanethidine as it can reduce the antihypertensive effects of this drug
- Anticholinergic agents such as benztropine, hyoscine (scopolamine) and atropine, because the two might exacerbate each other's anticholinergic effects, including paralytic ileus and tachycardia
- Antipsychotics due to the potential for them to exacerbate the sedative, anticholinergic, epileptogenic and pyrexic (fever-promoting) effects. Also increases the risk of neuroleptic malignant syndrome
- Cimetidine due to the potential for it to interfere with hepatic metabolism of amitriptyline and hence increasing steady-state concentrations of the drug
- Disulfiram due to the potential for the development of delirium
- ECT may increase the risks associated with this treatment
- Antithyroid medications may increase the risk of agranulocytosis
- Thyroid hormones have a potential for increased adverse effects such as CNS stimulation and arrhythmias.
- Analgesics, such as tramadol, due to the potential for an increase in seizure risk
- Medications subject to gastric inactivation (e.g. levodopa) due to the potential for amitriptyline to delay gastric emptying and reduce intestinal motility
- Medications subject to increased absorption given more time in the small intestine (e.g. anticoagulants)
- Serotoninergic agents such as the SSRIs and triptans due to the potential for serotonin syndrome.
The symptoms and the treatment of an overdose are largely the same as for the other TCAs, including the presentation of serotonin syndrome and adverse cardiac effects. The British National Formulary notes that amitriptyline can be particularly dangerous in overdose, thus it and other tricyclic antidepressants are no longer recommended as first-line therapy for depression. Alternative agents, SSRIs and SNRIs, are safer in overdose, though they are no more efficacious than TCAs. English folk singer Nick Drake died from an overdose of Tryptizol in 1974.
The possible symptoms of amitriptyline overdose include:
- Hypothermia (low body temperature)
- Tachycardia (high heart rate)
- Other arrhythmic abnormalities, such as bundle branch block
- ECG evidence of impaired conduction
- Congestive heart failure
- Dilated pupils
- Convulsions (e.g. seizures, myoclonus)
- Severe hypotension (very low blood pressure)
- Changes in the electrocardiogram, particularly in QRS axis or width
- Hyperactive reflexes
- Muscle rigidity
The treatment of overdose is mostly supportive as no specific antidote for amitriptyline overdose is available. Activated charcoal may reduce absorption if given within 1–2 hours of ingestion. If the affected person is unconscious or has an impaired gag reflex, a nasogastric tube may be used to deliver the activated charcoal into the stomach. ECG monitoring for cardiac conduction abnormalities is essential and if one is found close monitoring of cardiac function is advised. Body temperature should be regulated with measures such as heating blankets if necessary. Likewise, cardiac arrhythmias can be treated with propranolol and should heart failure occur, digitalis may be used. Cardiac monitoring is advised for at least five days after the overdose. Amitriptyline increases the CNS depressant action, but not the anticonvulsant action of barbiturates; therefore, an inhalation anaesthetic or diazepam is recommended for control of convulsions. Dialysis is of no use due to the high degree of protein binding with amitriptyline.
Mechanism of action
|Receptor||Ki [nM][Note 1]
|Ki [nM][Note 2]
Amitriptyline acts primarily as a serotonin-norepinephrine reuptake inhibitor, with strong actions on the serotonin transporter and moderate effects on the norepinephrine transporter. 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. It is metabolised to nortriptyline — a more potent and selective norepinephrine reuptake inhibitor — which may complement its effects on norepinephrine reuptake.
Amitriptyline additionally functions as a 5-HT2A, 5-HT2C, 5-HT3, 5-HT6, 5-HT7, α1-adrenergic, H1, H2, H4, and mACh receptor antagonist, and σ1 receptor agonist. It has also been shown to be a relatively weak NMDA receptor negative allosteric modulator at the same binding site as phencyclidine. 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.
Recently, amitriptyline has been demonstrated to act as an agonist of the TrkA and TrkB receptors. 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. These are the same receptors BDNF activates, an endogenous neurotrophin with powerful antidepressant effects, and as such this property may contribute significantly to its therapeutic efficacy against depression. Amitriptyline also acts as a functional inhibitor of acid sphingomyelinase.
Amitriptyline is readily absorbed from the gastrointestinal tract and is extensively metabolised on first pass through the liver. It is metabolised mostly by CYP2D6, CYP3A4, and CYP2C19-mediated N-demethylation into nortriptyline, which is another tricyclic antidepressant in its own right. It is 96% bound to plasma proteins, nortriptyline is 93-95% bound to plasma proteins. It is mostly excreted in the urine (around 30-50%) as metabolites either free or as glucuronide and sulfate conjugates. Small amounts are also excreted in feces.
Since amitriptyline is primarily metabolized by CYP2D6 and CYP2C19, genetic variations within the genes coding for these enzymes can affect its metabolism, leading to changes in the concentrations of the drug in the body. Increased concentrations of amitriptyline may increase the risk for side effects, including anticholinergic and nervous system adverse effects, while decreased concentrations may reduce the drug's efficacy.
Individuals can be categorized into different types of CYP2D6 or CYP2C19 metabolizers depending on which genetic variations they carry. These metabolizer types include poor, intermediate, extensive, and ultrarapid metabolizers. Most individuals (about 77-92%) are extensive metabolizers, and have "normal" metabolism of amitriptyline. Poor and intermediate metabolizers have reduced metabolism of the drug as compared to extensive metabolizers; patients with these metabolizer types may have an increased probability of experiencing side effects. Ultrarapid metabolizers use amitriptyline much faster than extensive metabolizers; patients with this metabolizer type may have a greater chance of experiencing pharmacological failure.
The Clinical Pharmacogenetics Implementation Consortium recommends avoiding amitriptyline in patients who are CYP2D6 ultrarapid or poor metabolizers, due to the risk for a lack of efficacy and side effects, respectively. The consortium also recommends considering an alternative drug not metabolized by CYP2C19 in patients who are CYP2C19 ultrarapid metabolizers. A reduction in starting dose is recommended for patients who are CYP2D6 intermediate metabolizers and CYP2C19 poor metabolizers. If use of amitriptyline is warranted, therapeutic drug monitoring is recommended to guide dose adjustments. The Dutch Pharmacogenetics Working Group also recommends selecting an alternative drug or monitoring plasma concentrations of amitriptyline in patients who are CYP2D6 poor or ultrarapid metabolizers, and selecting an alternative drug or reducing initial dose in patients who are CYP2D6 intermediate metabolizers.
- Amirol (NZ)
- Amit (IN)
- Amitone (IN)
- Amitor (IN)
- Amitrip (AU,† IN, NZ)
- Amitriptyline (UK)
- Amitriptyline Hydrochloride Caraco (US)
- Amitriptyline Hydrochloride Mutual (US)
- Amitriptyline Hydrochloride Mylan (US)
- Amitriptyline Hydrochloride Sandoz (US)
- Amitriptyline Hydrochloride Vintage (US)
- Amitriptyline Hydrochloride (UK)
- Amitrol† (AU)
- Amrea (IN)
- Amypres (IN)
- Apo-Amitriptyline (CA, HK, SG)
- Crypton (IN)
- Elavil (CA, UK†, US†)
- Eliwel (IN)
- Endep (AU, HK]]† , ZA†, US†)
- Enovil† (US)
- Gentrip (IN)
- Kamitrin (IN)
- Latilin (IN)
- Levate (US)
- Maxitrip (IN)
- Mitryp (IN)
- Mitryp-10 (IN)
- Odep (IN)
- Qualitriptine (HK)
- Sandoz Amitriptyline (ZA)
- Saroten (CH)
- Sarotena (IN)
- Tadamit (IN)
- Trepiline (ZA)
- Tripta (SG)
- Tryptanol (ZA)
- Tryptomer (IN)
- These Ki values are averaged binding affinities towards cloned human receptors when available.
- As with amitriptyline, these Kivalues are averaged binding affinities towards cloned human receptors when available.
- "AMITRIPTYLINE HYDROCHLORIDE tablet, film coated [Dispensing Solutions, Inc.]". DailyMed. Dispensing Solutions, Inc. September 2013. Retrieved 1 December 2013.
- "Levate (amitriptyline), dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 1 December 2013.
- "Endep Amitriptyline hydrochloride" (PDF). TGA eBusiness Services. Alphapharm Pty Limited. 10 December 2012. Retrieved 1 December 2013.
- "Amitriptyline Tablets BP 50mg - Summary of Product Characteristics (SPC)". electronic Medicines Compendium. Actavis UK Ltd. 24 March 2013. Retrieved 1 December 2013.
- Oxford Dictionary: Definition of amitriptyline (British & World English)
- A.S. Yazdi, N. Razavi, S.R. Yazdinejad. Separation and determination of amitriptyline and nortriptyline by dispersive liquid–liquid microextraction combined with gas chromatography flame ionization detection. Talanta, 75 (2008), pp. 1293–1299
- "Amitriptyline Hydrochloride". The American Society of Health-System Pharmacists. Retrieved Sep 25, 2014.
- "Prescribing medicines in pregnancy database". Australian Government. 3 March 2014. Retrieved 22 April 2014.
- "Amitriptyline Levels and Effects while Breastfeeding". drugs.com. Sep 8, 2014. Retrieved 25 September 2014.
- 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.
- Leucht, C; Huhn, M; Leucht, S (December 2012). "Amitriptyline versus placebo for major depressive disorder.". The Cochrane Database of Systematic Reviews 12: CD009138. doi:10.1002/14651858.CD009138.pub2. PMID 23235671.
- "WHO Model List of Essential Medicines". World Health Organization. October 2013. Retrieved 22 April 2014.
- Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.
- Joint Formulary Committee (2013). British National Formulary (BNF) (65 ed.). London, UK: Pharmaceutical Press. ISBN 978-0-85711-084-8.
- 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.
- Anderson IM (April 2000). "Selective serotonin reuptake inhibitors versus tricyclic antidepressants: a meta-analysis of efﬁcacy and tolerability". Journal of Affective Disorders 58 (1): 19–36. doi:10.1016/S0165-0327(99)00092-0. PMID 10760555.
- Moore RA, Derry S, Aldington D, Cole P, Wiffen PJ (2012). Moore, RA, ed. "Amitriptyline for neuropathic pain and fibromyalgia in adults". Cochrane Database of Systematic Reviews 12: CD008242. doi:10.1002/14651858.CD008242.pub2. PMID 23235657.
- Kennea, NL; Evans, JHC (June 2000). "Drug Treatment of Nocturnal Enuresis" (PDF). Paediatric and Perinatal Drug Therapy (Informa Healthcare) 4 (1): 12–18. doi:10.1185/1463009001527679.
- Viera AJ, Hoag S, Shaughnessy J (2002). "Management of irritable bowel syndrome". Am Fam Physician 66 (10): 1867–74. PMID 12469960.
- Parkinson's disease. Merck Sharp & Dohme Corp. August 2007. Retrieved on 2013-12-22.
- Flament MF, Bissada H, Spettigue W (March 2012). "Evidence-based pharmacotherapy of eating disorders". International Journal of Neuropsychopharmacology 15 (2): 189–207. doi:10.1017/S1461145711000381. PMID 21414249.
- Sim Y-J, Kim J-M, Kwon S, Choe B-H (2009). "Clinical experience with amitriptyline for management of children with cyclic vomiting syndrome". Korean Journal of Pediatrics 52 (5): 538–43. doi:10.3345/kjp.2009.52.5.538.
- Boles RG, Lovett-Barr MR, Preston A, Li BU, Adams K (2010). "Treatment of cyclic vomiting syndrome with co-enzyme Q10 and amitriptyline, a retrospective study". BMC Neurol 10: 10. doi:10.1186/1471-2377-10-10. PMC 2825193. PMID 20109231.
- Chung, KF (2008). "Currently available cough suppressants for chronic cough.". Lung. 186 Suppl 1: S82–7. PMID 17909897.
- Wald, Arnold (2006). "Functional biliary type pain syndrome". In Pasricha, Pankaj Jay; Willis, William D.; Gebhart, G. F. Chronic Abdominal and Visceral Pain. London: Informa Healthcare. pp. 453–62. ISBN 978-0-8493-2897-8.
- Taylor D, Paton C, Shitij K (2012). The Maudsley prescribing guidelines in psychiatry. West Sussex: Wiley-Blackwell. ISBN 978-0-470-97948-8.
- Brunton, L; Chabner, B; Knollman, B (2010). Goodman and Gilman's The Pharmacological Basis of Therapeutics (12th ed.). New York: McGraw-Hill Professional. ISBN 978-0-07-162442-8.
- Roth, BL; Driscol, J (12 January 2011). "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 1 December 2013.
- "Potency of antidepressants to block noradrenaline reuptake". CNS Forum. Retrieved 2013-02-16.
- Tatsumi M, Groshan K, Blakely RD, Richelson E (December 1997). "Pharmacological profile of antidepressants and related compounds at human monoamine transporters". Eur. J. Pharmacol. 340 (2–3): 249–58. doi:10.1016/S0014-2999(97)01393-9. PMID 9537821.
- Albert Ellis; Gwynn Pennant Ellis (1 January 1987). Progress in Medicinal Chemistry. Elsevier. p. 56. ISBN 978-0-444-80876-9. Retrieved 27 November 2011.
- Nguyen T, Shapiro DA, George SR, Setola V, Lee DK, Cheng R, Rauser L, Lee SP, Lynch KR, Roth BL, O'Dowd BF (March 2001). "Discovery of a novel member of the histamine receptor family". Molecular Pharmacology 59 (3): 427–33. PMID 11179435.
- D. Sriram & P. Yogeeswari (1 September 2010). Medicinal Chemistry. Pearson Education India. p. 299. ISBN 978-81-317-3144-4. Retrieved 27 November 2011.
- Owens MJ, Morgan WN, Plott SJ, Nemeroff CB (December 1997). "Neurotransmitter receptor and transporter binding profile of antidepressants and their metabolites". J. Pharmacol. Exp. Ther. 283 (3): 1305–22. PMID 9400006.
- Alan F. Schatzberg, Charles B. (2006). Essentials of clinical psychopharmacology. American Psychiatric Pub. p. 7. ISBN 978-1-58562-243-6.
- Rauser L, Savage JE, Meltzer HY, Roth BL (October 2001). "Inverse agonist actions of typical and atypical antipsychotic drugs at the human 5-hydroxytryptamine(2C) receptor". J. Pharmacol. Exp. Ther. 299 (1): 83–9. PMID 11561066.
- Werling LL, Keller A, Frank JG, Nuwayhid SJ (October 2007). "A comparison of the binding profiles of dextromethorphan, memantine, fluoxetine and amitriptyline: treatment of involuntary emotional expression disorder". Exp. Neurol. 207 (2): 248–57. doi:10.1016/j.expneurol.2007.06.013. PMID 17689532.
- Sills MA, Loo PS (July 1989). "Tricyclic antidepressants and dextromethorphan bind with higher affinity to the phencyclidine receptor in the absence of magnesium and L-glutamate". Mol. Pharmacol. 36 (1): 160–5. PMID 2568580.
- Pancrazio JJ, Kamatchi GL, Roscoe AK, Lynch C (January 1998). "Inhibition of neuronal Na+ channels by antidepressant drugs". J. Pharmacol. Exp. Ther. 284 (1): 208–14. PMID 9435180.
- 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.
- Jang SW, Liu X, Chan CB, Weinshenker D, Hall RA, Xiao G, Ye K (June 2009). "Amitriptyline is a TrkA and TrkB receptor agonist that promotes TrkA/TrkB heterodimerization and has potent neurotrophic activity". Chem. Biol. 16 (6): 644–56. doi:10.1016/j.chembiol.2009.05.010. PMC 2844702. PMID 19549602.
- "Pharmaceutical Information - AMITRIPTYLINE". RxMed. Retrieved 2013-02-16.
- Kornhuber J, Muehlbacher M, Trapp S, Pechmann S, Friedl A, Reichel M, Mühle C, Terfloth L, Groemer TW, Spitzer GM, Liedl KR, Gulbins E, Tripal P (2011). Riezman, Howard, ed. "Identification of novel functional inhibitors of acid sphingomyelinase". PLoS ONE 6 (8): e23852. doi:10.1371/journal.pone.0023852. PMC 3166082. PMID 21909365.
- The Pharmaceutical Codex. 1994. Principles and practice of pharmaceutics, 12th edn. Pharmaceutical press
- Hansch C, Leo A, Hoekman D. 1995. Exploring QSAR.Hydrophobic, electronic and steric constants. Washington, DC: American Chemical Society.
- Amitriptyline. Martindale: The Complete Drug Reference (London, UK: Pharmaceutical Press). 30 January 2013. Retrieved 2 December 2013.
- "Pamelor, Aventyl (nortriptyline) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 2 December 2013.
- Rudorfer MV, Potter WZ (1999). "Metabolism of tricyclic antidepressants". Cell Mol Neurobiol 19 (3): 373–409. PMID 10319193.
- Stingl JC, Brockmoller J, Viviani R (2013). "Genetic variability of drug-metabolizing enzymes: the dual impact on psychiatric therapy and regulation of brain function". Mol Psychiatry 18 (3): 273–87. doi:10.1038/mp.2012.42. PMID 22565785.
- Kirchheiner J, Seeringer A (2007). "Clinical implications of pharmacogenetics of cytochrome P450 drug metabolizing enzymes". Biochim Biophys Acta 1770 (3): 489–94. doi:10.1016/j.bbagen.2006.09.019. PMID 17113714.
- Hicks JK, Swen JJ, Thorn CF, Sangkuhl K, Kharasch ED, Ellingrod VL, Skaar TC, Muller DJ, Gaedigk A, Stingl JC (2013). "Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants". Clinical Pharmacology & Therapeutics 93 (5): 402–8. doi:10.1038/clpt.2013.2. PMC 3689226. PMID 23486447.
- Swen JJ, Nijenhuis M, de Boer A, Grandia L, Maitland-van der Zee AH, Mulder H, Rongen GA, van Schaik RH, Schalekamp T, Touw DJ, van der Weide J, Wilffert B, Deneer VH, Guchelaar HJ (2011). "Pharmacogenetics: from bench to byte--an update of guidelines". Clinical Pharmacology & Therapeutics 89 (5): 662–73. doi:10.1038/clpt.2011.34. PMID 21412232.
- "Amitriptyline". Drugs.com. Retrieved 2 December 2013.
- Hoffsommer, R. D.; Taub, D.; Wendler, N. L. (1965). "Coupling Reactions in the Synthesis of Amitriptyline". Journal of Medicinal Chemistry 8 (4): 555. doi:10.1021/jm00328a042. PMID 5884168.
- Hoffsommer, R. D.; Taub, D.; Wendler, N. L. (1962). "The Homoallylic Rearrangement in the Synthesis of Amitriptyline and Related Systems". The Journal of Organic Chemistry 27 (12): 4134. doi:10.1021/jo01059a004.
- Hoffsommer, R. D.; Taub, D.; Wendler, N. L. (1963). "Synthesis of Amitriptyline and Related Substances. Hydroboration of 5-Allylidene-5H-dibenzo[a,d]-10,11-dihydrocycloheptene". The Journal of Organic Chemistry 28 (7): 1751. doi:10.1021/jo01042a004.
- PubChem Substance Summary: Amitriptyline National Center for Biotechnology Information.
- TREPILINE-10 TABLETS; TREPILINE-25 TABLETS South African Electronic Package Inserts. 12 May 1978. Revised February 2004.
- SAROTEN RETARD 25 mg Capsules; SAROTEN RETARD 50 mg Capsules South African Electronic Package Inserts. December 1987. Updated May 2000.
- AMITRIP Amitriptyline hydrochloride 10 mg, 25 mg and 50 mg Capsules Medsafe NZ Physician Data Sheet. November 2004.
- Endep Consumer Medicine Information, Australia. December 2005.
- MedlinePlus Drug Information: Amitriptyline. US National Institutes of Health. January 2008.