Editing Amitriptyline (section)

==Medical uses==
Amitriptyline is [[indicated]] for the treatment of [[major depressive disorder]], [[neuropathic pain]], and for the prevention of [[migraine]] and chronic [[tension headache]]. It can be used for the treatment of [[nocturnal enuresis]] in children older than 6 after other treatments have failed.<ref name = EMC/>

===Depression===
Amitriptyline is effective for depression,<ref name="pmid23235671"/> but it is rarely used as a first-line antidepressant due to its higher toxicity in overdose and generally poorer tolerability.<ref name = "AMH">{{cite book | title = Australian Medicines Handbook | year = 2013 | publisher = The Australian Medicines Handbook Unit Trust | isbn = 978-0-9805790-9-3 | edition = 2013 | place = Adelaide | veditors = Rossi S }}</ref> It can be tried for depression as a second-line therapy, after the failure of other treatments.<ref name= top100drugs>{{cite book | vauthors = Hitchings A, Lonsdale D, Burrage D, Baker E |title=Top 100 drugs : clinical pharmacology and practical prescribing |date=2015 |isbn=978-0-7020-5516-4 |page=50|publisher=Churchill Livingstone }}</ref> For [[treatment-resistant depression|treatment-resistant]] adolescent depression<ref name="pmid25433401">{{cite journal | vauthors = Zhou X, Michael KD, Liu Y, Del Giovane C, Qin B, Cohen D, Gentile S, Xie P | title = Systematic review of management for treatment-resistant depression in adolescents | journal = BMC Psychiatry | volume = 14 | pages = 340 | date = November 2014 | pmid = 25433401 | pmc = 4254264 | doi = 10.1186/s12888-014-0340-6 | doi-access = free }}</ref> or for cancer-related depression<ref name="pmid24950919">{{cite journal | vauthors = Riblet N, Larson R, Watts BV, Holtzheimer P | title = Reevaluating the role of antidepressants in cancer-related depression: a systematic review and meta-analysis | journal = General Hospital Psychiatry | volume = 36 | issue = 5 | pages = 466–473 | date = 2014 | pmid = 24950919 | doi = 10.1016/j.genhosppsych.2014.05.010 }}</ref> amitriptyline is no better than placebo; however, the number of treated patients in both studies was small. It is sometimes used for the treatment of depression in [[Parkinson's disease]],<ref>{{cite web | url= http://www.merckmanuals.com/home/brain_spinal_cord_and_nerve_disorders/movement_disorders/parkinsons_disease.html |title= Parkinson's disease| website= merckmanuals.com| archive-url= https://web.archive.org/web/20131118154550/http://www.merckmanuals.com/home/brain_spinal_cord_and_nerve_disorders/movement_disorders/parkinsons_disease.html |archive-date=18 November 2013 | publisher= Merck Sharp & Dohme Corp.| date= August 2007| access-date= 22 December 2013}}</ref> but supporting evidence for that is lacking.<ref name="pmid22021174">{{cite journal | vauthors = Seppi K, Weintraub D, Coelho M, Perez-Lloret S, Fox SH, Katzenschlager R, Hametner EM, Poewe W, Rascol O, Goetz CG, Sampaio C | title = The Movement Disorder Society Evidence-Based Medicine Review Update: Treatments for the non-motor symptoms of Parkinson's disease | journal = Movement Disorders | volume = 26 | issue = Supply 3 | pages = S42–S80 | date = October 2011 | pmid = 22021174 | pmc = 4020145 | doi = 10.1002/mds.23884 }}</ref>

===Pain===
Amitriptyline alleviates painful [[diabetic neuropathy]]. It is recommended by a variety of guidelines as a first or second-line treatment.<ref name="pmid32040849">{{cite journal | vauthors = Alam U, Sloan G, Tesfaye S | title = Treating Pain in Diabetic Neuropathy: Current and Developmental Drugs | journal = Drugs | volume = 80 | issue = 4 | pages = 363–384 | date = March 2020 | pmid = 32040849 | doi = 10.1007/s40265-020-01259-2 | s2cid = 211074023 }}</ref> It is as effective for this indication as [[gabapentin]] or [[pregabalin]] but less well tolerated.<ref name="pmid33145709">{{cite journal | vauthors = Liampas A, Rekatsina M, Vadalouca A, Paladini A, Varrassi G, Zis P | title = Pharmacological Management of Painful Peripheral Neuropathies: A Systematic Review | journal = Pain and Therapy | volume = 10 | issue = 1 | pages = 55–68 | date = June 2021 | pmid = 33145709 | pmc = 8119529 | doi = 10.1007/s40122-020-00210-3 | doi-access = free }}</ref> Amitriptyline is as effective at relieving pain as [[duloxetine]]. [[Combination therapy|Combination treatment]] of amitriptyline and pregabalin offers additional pain relief for people whose pain is not adequately controlled with one medication and is usually safe.<ref>{{cite journal |date=6 April 2023 |title=Combination therapy for painful diabetic neuropathy is safe and effective |url=https://evidence.nihr.ac.uk/alert/combination-therapy-for-painful-diabetic-neuropathy-is-safe-and-effective/ |journal=NIHR Evidence |language=en |doi=10.3310/nihrevidence_57470 |s2cid=258013544 |access-date=28 April 2023 |archive-date=28 April 2023 |archive-url=https://web.archive.org/web/20230428104720/https://evidence.nihr.ac.uk/alert/combination-therapy-for-painful-diabetic-neuropathy-is-safe-and-effective/ |url-status=live |url-access=subscription }}</ref><ref>{{cite journal | vauthors = Tesfaye S, Sloan G, Petrie J, White D, Bradburn M, Julious S, Rajbhandari S, Sharma S, Rayman G, Gouni R, Alam U, Cooper C, Loban A, Sutherland K, Glover R, Waterhouse S, Turton E, Horspool M, Gandhi R, Maguire D, Jude EB, Ahmed SH, Vas P, Hariman C, McDougall C, Devers M, Tsatlidis V, Johnson M, Rice AS, Bouhassira D, Bennett DL, Selvarajah D | title = Comparison of amitriptyline supplemented with pregabalin, pregabalin supplemented with amitriptyline, and duloxetine supplemented with pregabalin for the treatment of diabetic peripheral neuropathic pain (OPTION-DM): a multicentre, double-blind, randomised crossover trial | journal = Lancet | volume = 400 | issue = 10353 | pages = 680–690 | date = August 2022 | pmid = 36007534 | pmc = 9418415 | doi = 10.1016/s0140-6736(22)01472-6 }}</ref> Amitriptyline in certain formulations may also induce the level of [[sciatic]]-nerve blockade needed for local [[anesthesia]] therein.<ref name="pmid12749958">{{cite journal | vauthors = Sudoh Y, Cahoon EE, Gerner P, Wang GK | title = Tricyclic antidepressants as long-acting local anesthetics | journal = Pain | volume = 103 | issue = 1–2 | pages = 49–55 | date = May 2003 | pmid = 12749958 | doi = 10.1016/s0304-3959(02)00375-5 | s2cid = 24955042 }}</ref> Here, it has been demonstrated to be of superior potency to [[bupivacaine]], a customary long-acting local anesthetic.

Low doses of amitriptyline moderately improve sleep disturbances and reduce pain and fatigue associated with [[fibromyalgia]].<ref name="pmid28493231" /> It is recommended for fibromyalgia accompanied by depression by [[Association of the Scientific Medical Societies in Germany]]<ref name="pmid28493231">{{cite journal | vauthors = Sommer C, Alten R, Bär KJ, Bernateck M, Brückle W, Friedel E, Henningsen P, Petzke F, Tölle T, Üçeyler N, Winkelmann A, Häuser W | title = [Drug therapy of fibromyalgia syndrome : Updated guidelines 2017 and overview of systematic review articles] | language = de | journal = Schmerz | volume = 31 | issue = 3 | pages = 274–284 | date = June 2017 | pmid = 28493231 | doi = 10.1007/s00482-017-0207-0 | s2cid = 195671256 }}</ref> and as a second-line option for fibromyalgia, with exercise being the first line option, by [[European League Against Rheumatism]].<ref name="pmid27377815">{{cite journal | vauthors = Macfarlane GJ, Kronisch C, Dean LE, Atzeni F, Häuser W, Fluß E, Choy E, Kosek E, Amris K, Branco J, Dincer F, Leino-Arjas P, Longley K, McCarthy GM, Makri S, Perrot S, Sarzi-Puttini P, Taylor A, Jones GT | title = EULAR revised recommendations for the management of fibromyalgia | journal = Annals of the Rheumatic Diseases | volume = 76 | issue = 2 | pages = 318–328 | date = February 2017 | pmid = 27377815 | doi = 10.1136/annrheumdis-2016-209724 | hdl-access = free | doi-access = free | hdl = 2164/8814 }}</ref> Combinations of amitriptyline and [[fluoxetine]] or [[melatonin]] may reduce fibromyalgia pain better than either medication alone.<ref name="pmid29457627">{{cite journal | vauthors = Thorpe J, Shum B, Moore RA, Wiffen PJ, Gilron I | title = Combination pharmacotherapy for the treatment of fibromyalgia in adults | journal = The Cochrane Database of Systematic Reviews | volume = 2 | issue = 2 | pages = CD010585 | date = February 2018 | pmid = 29457627 | pmc = 6491103 | doi = 10.1002/14651858.CD010585.pub2 }}</ref>

There is some (low-quality) evidence that amitriptyline may reduce pain in cancer patients. It is recommended only as a second-line therapy for non-chemotherapy-induced neuropathic or mixed neuropathic pain if [[opioid]]s did not provide the desired effect.<ref name="pmid27207115">{{cite journal | vauthors = van den Beuken-van Everdingen MH, de Graeff A, Jongen JL, Dijkstra D, Mostovaya I, Vissers KC | title = Pharmacological Treatment of Pain in Cancer Patients: The Role of Adjuvant Analgesics, a Systematic Review | journal = Pain Practice | volume = 17 | issue = 3 | pages = 409–419 | date = March 2017 | pmid = 27207115 | doi = 10.1111/papr.12459 | s2cid = 37418010 }}</ref>

Moderate evidence exists in favor of amitriptyline use for [[atypical facial pain]].<ref name="pmid33037835">{{cite journal | vauthors = Do TM, Unis GD, Kattar N, Ananth A, McCoul ED | title = Neuromodulators for Atypical Facial Pain and Neuralgias: A Systematic Review and Meta-Analysis | journal = The Laryngoscope | volume = 131 | issue = 6 | pages = 1235–1253 | date = June 2021 | pmid = 33037835 | doi = 10.1002/lary.29162 | s2cid = 222256076 }}</ref> Amitriptyline is ineffective for HIV-associated neuropathy.<ref name="pmid33145709"/>

In multiple sclerosis, it is frequently used to treat painful paresthesias 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.<ref>{{cite web |title=Elavil for MS |url=https://www.nationalmssociety.org/Treating-MS/Medications/Elavil |access-date=7 July 2023 |website=nationalmssociety.org |archive-date=7 July 2023 |archive-url=https://web.archive.org/web/20230707205228/https://www.nationalmssociety.org/Treating-MS/Medications/Elavil |url-status=dead }}</ref>

===Headache===
Amitriptyline is probably effective for the prevention of periodic [[migraine]] in adults. Amitriptyline is similar in efficacy to [[venlafaxine]] and [[topiramate]] but carries a higher burden of adverse effects than topiramate.<ref name="pmid22529202">{{cite journal | vauthors = Silberstein SD, Holland S, Freitag F, Dodick DW, Argoff C, Ashman E | title = Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society | journal = Neurology | volume = 78 | issue = 17 | pages = 1337–1345 | date = April 2012 | pmid = 22529202 | pmc = 3335452 | doi = 10.1212/WNL.0b013e3182535d20 }}</ref> For many patients, even very small doses of amitriptyline are helpful, which may allow for minimization of side effects.<ref name="pmid30137671">{{cite journal | vauthors = Loder E, Rizzoli P | title = Pharmacologic Prevention of Migraine: A Narrative Review of the State of the Art in 2018 | journal = Headache | volume = 58 | issue = Suppl 3 | pages = 218–229 | date = November 2018 | pmid = 30137671 | doi = 10.1111/head.13375 | s2cid = 52071815 }}</ref> Amitriptyline is not significantly different from placebo when used for the prevention of migraine in children.<ref name="pmid31413170">{{cite journal | vauthors = Oskoui M, Pringsheim T, Billinghurst L, Potrebic S, Gersz EM, Gloss D, Holler-Managan Y, Leininger E, Licking N, Mack K, Powers SW, Sowell M, Victorio MC, Yonker M, Zanitsch H, Hershey AD | title = Practice guideline update summary: Pharmacologic treatment for pediatric migraine prevention: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Headache Society | journal = Neurology | volume = 93 | issue = 11 | pages = 500–509 | date = September 2019 | pmid = 31413170 | pmc = 6746206 | doi = 10.1212/WNL.0000000000008105 }}</ref>

Amitriptyline may reduce the frequency and duration of chronic [[tension headache]], but it is associated with worse adverse effects than [[mirtazapine]]. Overall, amitriptyline is recommended for tension headache [[prophylaxis]], along with lifestyle advice, which should include avoidance of analgesia and caffeine.<ref name="pmid26859719">{{cite journal | vauthors = Ghadiri-Sani M, Silver N | title = Headache (chronic tension-type) | journal = BMJ Clinical Evidence | volume = 2016 | date = February 2016 | pmid = 26859719 | pmc = 4747324 }}</ref>

===Other indications===
Amitriptyline is effective for the treatment of [[irritable bowel syndrome]]; however, because of its side effects, it should be reserved for select patients for whom other agents do not work.<ref name="pmid24992947">{{cite journal | vauthors = Trinkley KE, Nahata MC | title = Medication management of irritable bowel syndrome | journal = Digestion | volume = 89 | issue = 4 | pages = 253–267 | date = 2014 | pmid = 24992947 | doi = 10.1159/000362405 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Ford AC, Wright-Hughes A, Alderson SL, Ow PL, Ridd MJ, Foy R, Bianco G, Bishop FL, Chaddock M, Cook H, Cooper D, Fernandez C, Guthrie EA, Hartley S, Herbert A, Howdon D, Muir DP, Nath T, Newman S, Smith T, Taylor CA, Teasdale EJ, Thornton R, Farrin AJ, Everitt HA | title = Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment in primary care (ATLANTIS): a randomised, double-blind, placebo-controlled, phase 3 trial | journal = Lancet | volume = 402 | issue = 10414 | pages = 1773–1785 | date = November 2023 | pmid = 37858323 | doi = 10.1016/s0140-6736(23)01523-4 | doi-access = free }}</ref><ref>{{Cite journal |date=26 March 2024 |title=Irritable bowel syndrome: low-dose antidepressant improves symptoms |url=https://evidence.nihr.ac.uk/alert/irritable-bowel-syndrome-low-dose-antidepressant-improves-symptoms/ |journal=NIHR Evidence |publisher=National Institute for Health and Care Research (NIHR) |doi=10.3310/nihrevidence_62555 |access-date=12 April 2024 |archive-date=18 May 2024 |archive-url=https://web.archive.org/web/20240518164652/https://evidence.nihr.ac.uk/alert/irritable-bowel-syndrome-low-dose-antidepressant-improves-symptoms/ |url-status=live |url-access=subscription }}</ref> There is insufficient evidence to support its use for abdominal pain in children with functional gastrointestinal disorders.<ref>{{cite journal | vauthors = de Bruijn CM, Rexwinkel R, Gordon M, Benninga M, Tabbers MM | title = Antidepressants for functional abdominal pain disorders in children and adolescents | journal = The Cochrane Database of Systematic Reviews | volume = 2 | issue = 2 | pages = CD008013 | date = February 2021 | pmid = 33560523 | pmc = 8094232 | doi = 10.1002/14651858.CD008013.pub3 }}</ref>

[[Tricyclic antidepressants]] decrease the frequency, severity, and duration of [[cyclic vomiting syndrome]] episodes. Amitriptyline, as the most commonly used of them, is recommended as a first-line agent for its therapy.<ref name="pmid31241819">{{cite journal | vauthors = Venkatesan T, Levinthal DJ, Tarbell SE, Jaradeh SS, Hasler WL, Issenman RM, Adams KA, Sarosiek I, Stave CD, Sharaf RN, Sultan S, Li BU | title = Guidelines on management of cyclic vomiting syndrome in adults by the American Neurogastroenterology and Motility Society and the Cyclic Vomiting Syndrome Association | journal = Neurogastroenterology and Motility | volume = 31 | issue = Suppl 2 | pages = e13604 | date = June 2019 | pmid = 31241819 | pmc = 6899751 | doi = 10.1111/nmo.13604 }}</ref>

Amitriptyline may improve pain and urgency intensity associated with [[bladder pain syndrome]] and can be used in the management of this syndrome.<ref name="pmid29972328">{{cite journal | vauthors = Giusto LL, Zahner PM, Shoskes DA | title = An evaluation of the pharmacotherapy for interstitial cystitis | journal = Expert Opinion on Pharmacotherapy | volume = 19 | issue = 10 | pages = 1097–1108 | date = July 2018 | pmid = 29972328 | doi = 10.1080/14656566.2018.1491968 | s2cid = 49674883 }}</ref><ref name="pmid32904438">{{cite journal | vauthors = Colemeadow J, Sahai A, Malde S | title = Clinical Management of Bladder Pain Syndrome/Interstitial Cystitis: A Review on Current Recommendations and Emerging Treatment Options | journal = Research and Reports in Urology | volume = 12 | pages = 331–343 | date = 2020 | pmid = 32904438 | pmc = 7455607 | doi = 10.2147/RRU.S238746 | doi-access = free }}</ref> Amitriptyline can be used in the treatment of nocturnal [[enuresis]] in children. However, its effect is not sustained after the treatment ends. Alarm therapy gives better short- and long-term results.<ref name="pmid26789925">{{cite journal | vauthors = Caldwell PH, Sureshkumar P, Wong WC | title = Tricyclic and related drugs for nocturnal enuresis in children | journal = The Cochrane Database of Systematic Reviews | volume = 2016 | issue = 1 | pages = CD002117 | date = January 2016 | pmid = 26789925 | pmc = 8741207 | doi = 10.1002/14651858.CD002117.pub2 }}</ref>

In the US, amitriptyline is commonly used in children with [[ADHD]] as an adjunct to stimulant medications without any evidence or guideline supporting this practice.<ref name="pmid30630642">{{cite journal | vauthors = Klein T, Woo TM, Panther S, Odom-Maryon T, Daratha K | title = Somnolence-Producing Agents: A 5-Year Study of Prescribing for Medicaid-Insured Children With Attention Deficit Hyperactivity Disorder | journal = Journal of Pediatric Health Care | volume = 33 | issue = 3 | pages = e1–e8 | date = 2019 | pmid = 30630642 | doi = 10.1016/j.pedhc.2018.10.002 | s2cid = 58577978 }}</ref> Many physicians in the UK (and the US also) commonly prescribe amitriptyline for [[insomnia]];<ref name="pmid24567616">{{cite journal | vauthors = Everitt H, McDermott L, Leydon G, Yules H, Baldwin D, Little P | title = GPs' management strategies for patients with insomnia: a survey and qualitative interview study | journal = The British Journal of General Practice | volume = 64 | issue = 619 | pages = e112–e119 | date = February 2014 | pmid = 24567616 | pmc = 3905408 | doi = 10.3399/bjgp14X677176 }}</ref> however, [[Cochrane (organization)|Cochrane]] reviewers were not able to find any randomized controlled studies that would support or refute this practice.<ref name="pmid29761479">{{cite journal | vauthors = Everitt H, Baldwin DS, Stuart B, Lipinska G, Mayers A, Malizia AL, Manson CC, Wilson S | title = Antidepressants for insomnia in adults | journal = The Cochrane Database of Systematic Reviews | volume = 2018 | issue = 5 | pages = CD010753 | date = May 2018 | pmid = 29761479 | pmc = 6494576 | doi = 10.1002/14651858.CD010753.pub2 }}</ref> Similarly, a major [[systematic review]] and [[network meta-analysis]] of medications for the treatment of insomnia published in 2022 found little evidence to inform the use of amitriptyline for insomnia.<ref name="pmid35843245">{{cite journal | vauthors = De Crescenzo F, D'Alò GL, Ostinelli EG, Ciabattini M, Di Franco V, Watanabe N, Kurtulmus A, Tomlinson A, Mitrova Z, Foti F, Del Giovane C, Quested DJ, Cowen PJ, Barbui C, Amato L, Efthimiou O, Cipriani A | title = Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and network meta-analysis | journal = Lancet | volume = 400 | issue = 10347 | pages = 170–184 | date = July 2022 | pmid = 35843245 | doi = 10.1016/S0140-6736(22)00878-9 | hdl-access = free | s2cid = 250536370 | doi-access = free | hdl = 11380/1288245 }}</ref> The well-known sedating effects of amitriptyline, however, bear understanding on and arguable justification for this practice. It may function similarly to [[doxepin]] in this regard, although the evidence for [[doxepin]] is more robust.<ref name="pmid29487083">{{cite journal | vauthors = Atkin T, Comai S, Gobbi G | title = Drugs for Insomnia beyond Benzodiazepines: Pharmacology, Clinical Applications, and Discovery | journal = Pharmacological Reviews | volume = 70 | issue = 2 | pages = 197–245 | date = April 2018 | pmid = 29487083 | doi = 10.1124/pr.117.014381 }}</ref> [[Trimipramine]] may be a more novel alternative given its tendency to not suppress but brighten R.E.M. sleep.<ref name="pmid2693052">{{cite journal | vauthors = Pecknold JC, Luthe L | title = Trimipramine, anxiety, depression and sleep | journal = Drugs | volume = 38 | issue = Suppl 1 | pages = 25–31; discussion 49–50 | date = 1989 | pmid = 2693052 | doi = 10.2165/00003495-198900381-00007 }}</ref><ref name="pmid12237787">{{cite journal | vauthors = Riemann D, Voderholzer U, Cohrs S, Rodenbeck A, Hajak G, Rüther E, Wiegand MH, Laakmann G, Baghai T, Fischer W, Hoffmann M, Hohagen F, Mayer G, Berger M | title = Trimipramine in primary insomnia: results of a polysomnographic double-blind controlled study | journal = Pharmacopsychiatry | volume = 35 | issue = 5 | pages = 165–74 | date = September 2002 | pmid = 12237787 | doi = 10.1055/s-2002-34119 }}</ref><ref name="pmid8863001">{{cite journal | vauthors = Berger M, Gastpar M | title = Trimipramine: a challenge to current concepts on antidepressives | journal = European Archives of Psychiatry and Clinical Neuroscience | volume = 246 | issue = 5 | pages = 235–9 | date = 1996 | pmid = 8863001 | doi = 10.1007/BF02190274 }}</ref>