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Physician Resource
Untitled 1

Amitriptyline. Find out the true side Amitriptyline effects. Amitriptyline side effects, warnings, Amitriptyline precautions, Amitriptyline adverse effects, Amitriptyline overdose, Amitriptyline withdrawal symptoms and  Amitriptyline natural alternatives. Before you begin the spiral down with Amitriptyline, try giving your body what it really wants.

Amitriptyline 
Brand name (Elavil and Endep)

Amitriptyline Clinical Trials

Disputed case of homicide by smothering due to severe amitriptyline intoxication of the victim.

Stiakakis I, Belivanis SD, Tzatzarakis MN, Fragoulis M, Tsatsakis AM.

J Forensic Leg Med. 2009 Jul;16(5):280-283. Epub 2009 Jan 13.

PMID: 19481712 [PubMed - as supplied by publisher]

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A rapid and reliable method for the quantitation of tricyclic antidepressants in serum using HPLC-MS/MS.

Breaud AR, Harlan R, Kozak M, Clarke W.

Clin Biochem. 2009 May 20. [Epub ahead of print]

PMID: 19463806 [PubMed - as supplied by publisher]

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Successful treatment of refractory pudendal neuralgia with pulsed radiofrequency.

Rhame EE, Levey KA, Gharibo CG.

Pain Physician. 2009 May-Jun;12(3):633-8.

PMID: 19461829 [PubMed - in process]

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Two different doses of Amitriptyline ER in the prophylaxis of migraine: long-term results and predictive factors.

Lampl C, Huber G, Adl J, Luthringshausen G, Franz G, Marecek S, Weber J, Baumhackl U, Mueller T.

Eur J Neurol. 2009 Apr 23. [Epub ahead of print]

PMID: 19456855 [PubMed - as supplied by publisher]

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Mirtazapine: a review of its use in major depression and other psychiatric disorders.

Croom KF, Perry CM, Plosker GL.

CNS Drugs. 2009;23(5):427-52. doi: 10.2165/00023210-200923050-00006.

PMID: 19453203 [PubMed - in process]

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Pharmacokinetics and efficacy of fluvoxamine and amitriptyline in depression.

Vezmar S, Miljkovic B, Vucicevic K, Timotijevic I, Prostran M, Todorovic Z, Pokrajac M.

J Pharmacol Sci. 2009 May;110(1):98-104.

PMID: 19444001 [PubMed - in process]

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[Application of liquid chromatography coupled with mass spectrometry (LC/MS) to determine antidepressants in blood samples]

Pufal E, Sykutera M.

Arch Med Sadowej Kryminol. 2009 Oct-Dec;58(4):171-6. Polish.

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Does adenosine A(1) receptor stimulation causes QRS prolongation by blocking beta adrenergic receptors in amitriptyline poisoning?

Akgun Arici MA, Kalkan S, Demir O, Hocaoglu Aksay N, Gidener S, Tuncok Y.

Toxicol Lett. 2009 Apr 25;186(2):130-8. Epub 2009 Jan 20.

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Amitriptyline suppresses neuroinflammation-dependent interleukin-10-p38 mitogen-activated protein kinase-heme oxygenase-1 signaling pathway in chronic morphine-infused rats.

Tai YH, Tsai RY, Lin SL, Yeh CC, Wang JJ, Tao PL, Wong CS.

Anesthesiology. 2009 Jun;110(6):1379-89.

PMID: 19417613 [PubMed - in process]

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The histamine H4 receptor is functionally expressed on neurons in the mammalian CNS.

Connelly WM, Shenton FC, Lethbridge N, Leurs R, Waldvogel HJ, Faull RL, Lees G, Chazot PL.

Br J Pharmacol. 2009 May;157(1):55-63.

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Amitriptyline inhibits the activity of the rat glutamate transporter EAAT3 expressed in Xenopus oocytes.

Baik HJ, Lee SA, Washington JM, Zuo ZY.

J Pharm Pharmacol. 2009 May;61(5):577-81.

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Diagnostic and therapeutic trajectory of cluster headache patients in Flanders.

Van Alboom E, Louis P, Van Zandijcke M, Crevits L, Vakaet A, Paemeleire K.

Acta Neurol Belg. 2009 Mar;109(1):10-7.

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Serotoninergic and non-serotoninergic effects of two tricyclic antidepressants on visceral nociception in a rat model.

Bechmann LP, Best J, Haag S, Leineweber K, Gerken G, Holtmann G.

Scand J Gastroenterol. 2009;44(6):680-6.

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Topiramate versus amitriptyline in migraine prevention: a 26-week, multicenter, randomized, double-blind, double-dummy, parallel-group noninferiority trial in adult migraineurs.

Dodick DW, Freitag F, Banks J, Saper J, Xiang J, Rupnow M, Biondi D, Greenberg SJ, Hulihan J; CAPSS-277 Investigator Group.

Clin Ther. 2009 Mar;31(3):542-59.

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A case report of amitriptyline poisoning successfully treated with the application of plasma exchange.

Belen B, Akman A, Yüksel N, Dilsiz G, Yenicesu I, Olguntürk R.

Ther Apher Dial. 2009 Apr;13(2):147-9.

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A study on electrocardiographic changes secondary to the use of tricyclic antidepressants in patients with chronic pain.

da Cunha RJ Jr, Barrucand L, Verçosa N.

Rev Bras Anestesiol. 2009 Jan-Feb;59(1):50-5, 46-50. English, Portuguese.

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The effect of amitriptyline on ectopic discharge of primary afferent fibers in the L5 dorsal root in a rat model of neuropathic pain.

Su X, Liang AH, Urban MO.

Anesth Analg. 2009 May;108(5):1671-9.

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Central poststroke pain: a review of pathophysiology and treatment.

Kumar B, Kalita J, Kumar G, Misra UK.

Anesth Analg. 2009 May;108(5):1645-57. Review.

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Coenzyme Q(10) and alpha-tocopherol protect against amitriptyline toxicity.

Cordero MD, Moreno-Fernández AM, Gomez-Skarmeta JL, de Miguel M, Garrido-Maraver J, Oropesa-Ávila M, Rodríguez-Hernández A, Navas P, Sánchez-Alcázar JA.

Toxicol Appl Pharmacol. 2009 Jan 19. [Epub ahead of print]

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Sertraline versus other antidepressive agents for depression.

Cipriani A, La Ferla T, Furukawa TA, Signoretti A, Nakagawa A, Churchill R, McGuire H, Barbui C.

Cochrane Database Syst Rev. 2009 Apr 15;(2):CD006117. Review.

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Benign clinical picture after ingestion of 780 milligrams of aripiprazole and 1050 milligrams of amitriptyline.

Prakash R, Munda S, Pattojoshi A, Choudhary PP.

Indian J Med Sci. 2009 Feb;63(2):77-80. No abstract available.

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[Observation on therapeutic effect of herb-partitioned moxibustion on fibromyalgia syndrome]

Zhao RH, Zhu YB.

Zhongguo Zhen Jiu. 2009 Mar;29(3):200-2. Chinese.

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Bioavailability of a controlled-release cyclobenzaprine tablet and influence of a high fat meal on bioavailability.

Gai MN, Costa E, Arancibia A.

Int J Clin Pharmacol Ther. 2009 Apr;47(4):269-74.

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Gender differences in the association between antidepressant use and restless legs syndrome.

Baughman KR, Bourguet CC, Ober SK.

Mov Disord. 2009 Apr 7;24(7):1054-1059. [Epub ahead of print]

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Efficacy of tricyclic antidepressants in irritable bowel syndrome: a meta-analysis.

Rahimi R, Nikfar S, Rezaie A, Abdollahi M.

World J Gastroenterol. 2009 Apr 7;15(13):1548-53.

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Evaluation of the effect of locally administered amitriptyline gel as adjunct to local anesthetics in irreversible pulpitis pain.

Moghadamnia AA, Partovi M, Mohammadianfar I, Madani Z, Zabihi E, Hamidi MR, Baradaran M.

Indian J Dent Res. 2009 Jan-Mar;20(1):3-6.

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[Antidepressant properties of afobazole in Porsolt and Nomura tests]

Seredenin SB, Molodavkin GM, Voronin MV, Voronina TA.

Eksp Klin Farmakol. 2009 Jan-Feb;72(1):19-21. Russian.

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[Prevention of migraine: a pharmacoepidemiological study.]

López Hernández N, Morera J, Medrano Martínez V, Fernández Izquierdo S, Pérez Sempere A.

Neurologia. 2009 Mar;24(2):98-101. Spanish.

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Peripheral neuropathy in HIV-positive patients at an antiretroviral clinic in Lilongwe, Malawi.

Beadles WI, Jahn A, Weigel R, Clutterbuck D.

Trop Doct. 2009 Apr;39(2):78-80.

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Preventive migraine treatment.

Silberstein SD.

Neurol Clin. 2009 May;27(2):429-43.

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Clinical, electrocardiographic, and laboratory findings in children with amitriptyline intoxication.

Olgun H, Yildirim ZK, Karacan M, Ceviz N.

Pediatr Emerg Care. 2009 Mar;25(3):170-3.

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Amitriptyline treatment under chronic stress conditions: effect on circulating catecholamines and anxiety in early maternally separated rats.

Cotella EM, Lascano IM, Levin GM, Suarez MM.

Int J Neurosci. 2009;119(5):664-80.

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Paediatric painful bladder syndrome/interstitial cystitis: diagnosis and treatment.

Sea J, Teichman JM.

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1-(m-Chlorophenyl)piperazine induces depressogenic-like behaviour in rodents by stimulating the neuronal 5-HT(2A) receptors: proposal of a modified rodent antidepressant assay.

Rajkumar R, Pandey DK, Mahesh R, Radha R.

Eur J Pharmacol. 2009 Apr 17;608(1-3):32-41. Epub 2009 Mar 6.

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Guidelines on the management of fibromyalgia syndrome - A systematic review.

Häuser W, Thieme K, Turk DC.

Eur J Pain. 2009 Mar 3. [Epub ahead of print]

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Coenzyme Q10 and alpha-tocopherol protect against amitriptyline toxicity.

Cordero MD, Moreno-Fernández AM, Gomez-Skarmeta JL, de Miguel M, Garrido-Maraver J, Oropesa-Avila M, Rodríguez-Hernández A, Navas P, Sánchez-Alcázar JA.

Toxicol Appl Pharmacol. 2009 Mar 15;235(3):329-37.

PMID: 19263520 [PubMed - indexed for MEDLINE]

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Clinical, Electrocardiographic, and Laboratory Findings in Children With Amitriptyline Intoxication.

Olgun H, Yldrm ZK, Karacan M, Ceviz N.

Pediatr Emerg Care. 2009 Feb 28. [Epub ahead of print]

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Neuropathic pain: quality-of-life impact, costs and cost effectiveness of therapy.

O'Connor AB.

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Short-term outcomes of tension type and migraine headache in children.

Sri-udomkajorn S, Ruangsuwan S.

J Med Assoc Thai. 2008 Oct;91 Suppl 3:S104-8.

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Pleiotropic effects of amitriptyline ameliorate renal fibrosis.

Morrissey JJ.

Kidney Int. 2009 Mar;75(6):583-4.

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A pharmacokinetic comparison of single doses of once-daily cyclobenzaprine extended-release 15 mg and 30 mg: a randomized, double-blind, two-period crossover study in healthy volunteers.

Darwish M, Chang S, Hellriegel ET.

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Cost effectiveness of venlafaxine compared with generic fluoxetine or generic amitriptyline in major depressive disorder in the UK.

Lenox-Smith A, Greenstreet L, Burslem K, Knight C.

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Effect of food on the pharmacokinetics of once-daily cyclobenzaprine extended-release 30 mg: a randomized, open-label, crossover, single-centre study.

Darwish M, Xie F.

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Herpes simplex virus vector-mediated gene delivery for the treatment of lower urinary tract pain.

Goins WF, Goss JR, Chancellor MB, de Groat WC, Glorioso JC, Yoshimura N.

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Dynamic optimization of chronic migraine treatment: current and future options.

Mathew NT.

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Antidepressant-induced mood conversions in bipolar disorder: a retrospective study of tricyclic versus non-tricyclic antidepressant drugs.

Koszewska I, Rybakowski JK.

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Comparison of the single-dose pharmacokinetics of once-daily cyclobenzaprine extended-release 30 mg and cyclobenzaprine immediate-release 10 mg three times daily in the elderly: a randomized, open-label, crossover study.

Darwish M, Xie F.

Drugs Aging. 2009;26(2):95-101. doi: 10.2165/0002512-200926020-00001.

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Location of the antidepressant binding site in the serotonin transporter: importance of Ser-438 in recognition of citalopram and tricyclic antidepressants.

Andersen J, Taboureau O, Hansen KB, Olsen L, Egebjerg J, Strřmgaard K, Kristensen AS.

J Biol Chem. 2009 Apr 10;284(15):10276-84. Epub 2009 Feb 12.

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Effect of selected antidepressant drugs on cytochrome P450 2B (CYP2B) in rat liver. An in vitro and in vivo study.

Haduch A, Wójcikowski J, Daniel WA.

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Olfactory bulbectomy and amitriptyline treatment influences mGlu receptors expression in the mouse brain hippocampus.

Wierońska JM, Legutko B, Dudys D, Pilc A.

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Meta-analysis of duloxetine vs. pregabalin and gabapentin in the treatment of diabetic peripheral neuropathic pain.

Quilici S, Chancellor J, Löthgren M, Simon D, Said G, Le TK, Garcia-Cebrian A, Monz B.

BMC Neurol. 2009 Feb 10;9:6.

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Antidepressant-associated mood elevations in bipolar II disorder compared with bipolar I disorder and major depressive disorder: a systematic review and meta-analysis.

Bond DJ, Noronha MM, Kauer-Sant'Anna M, Lam RW, Yatham LN.

J Clin Psychiatry. 2008 Oct;69(10):1589-601. Review.

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Kinetic and pharmacological properties of [(3)H]-histamine transport into cultured type 1 astrocytes from neonatal rats.

Osredkar D, Burnik-Papler T, Pecavar B, Kralj-Iglic V, Krzan M.

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Self-management, amitriptyline, and amitripyline plus triamcinolone in the management of vulvodynia.

Brown CS, Wan J, Bachmann G, Rosen R.

J Womens Health (Larchmt). 2009 Feb;18(2):163-9.

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Clinical diagnosis and treatment of suspected neuropathic pain in three dogs.

Cashmore RG, Harcourt-Brown TR, Freeman PM, Jeffery ND, Granger N.

Aust Vet J. 2009 Jan-Feb;87(1):45-50.

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[Stylocarotid syndrome: a case report]

Petrović B, Radak D, Kostić V, Covicković-Sternić N.

Srp Arh Celok Lek. 2008 Nov-Dec;136(11-12):650-3. Serbian.

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Effective prophylactic treatments of migraine lower plasma glutamate levels.

Ferrari A, Spaccapelo L, Pinetti D, Tacchi R, Bertolini A.

Cephalalgia. 2009 Apr;29(4):423-9. Epub 2008 Dec 11.

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Persistence with migraine prophylactic treatment and acute migraine medication utilization in the managed care setting.

Yaldo AZ, Wertz DA, Rupnow MF, Quimbo RM.

Clin Ther. 2008 Dec;30(12):2452-60.

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Review of pediatric migraine headaches refractory to medical management.

Kung TA, Totonchi A, Eshraghi Y, Scher MS, Gosain AK.

J Craniofac Surg. 2009 Jan;20(1):125-8.

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How do general practitioners in Thailand diagnose and treat patients presenting with anxiety and depression?

Lotrakul M, Saipanish R.

Psychiatry Clin Neurosci. 2009 Feb;63(1):37-42.

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Insulin-like growth factor-I (IGF-I) serum concentrations in depressed patients: relationship to saliva cortisol and changes during antidepressant treatment.

Weber-Hamann B, Blum WF, Kratzsch J, Gilles M, Heuser I, Deuschle M.

Pharmacopsychiatry. 2009 Jan;42(1):23-8. Epub 2009 Jan 19.

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Evaluation of risk factors for elevated tricyclic antidepressant plasma concentrations.

Billups SJ, Delate T, Dugan D.

Pharmacoepidemiol Drug Saf. 2009 Mar;18(3):253-7.

PMID: 19148878 [PubMed - indexed for MEDLINE]

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Anticholinergic esotropia.

Anderson JM, Brodsky MC.

J Neuroophthalmol. 2008 Dec;28(4):359-60. No abstract available.

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Psychotropic drugs associated with corrected QT interval prolongation.

van Noord C, Straus SM, Sturkenboom MC, Hofman A, Aarnoudse AJ, Bagnardi V, Kors JA, Newton-Cheh C, Witteman JC, Stricker BH.

J Clin Psychopharmacol. 2009 Feb;29(1):9-15.

PMID: 19142100 [PubMed - indexed for MEDLINE]

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Treatment of severe amitriptyline intoxication with plasmapheresis.

Kolsal E, Tekin IO, Piskin E, Aydemir C, Akyüz M, Cabuk H, Eldes N, Numanoglu V.

J Clin Apher. 2009;24(1):21-4.

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Extraction and determination of some psychotropic drugs in urine samples using dispersive liquid-liquid microextraction followed by high-performance liquid chromatography.

Xiong C, Ruan J, Cai Y, Tang Y.

J Pharm Biomed Anal. 2009 Feb 20;49(2):572-8. Epub 2008 Dec 3.

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Antidepressants reveal differential effect against 1-methyl-4-phenylpyridinium toxicity in differentiated PC12 cells.

Han YS, Lee CS.

Eur J Pharmacol. 2009 Feb 14;604(1-3):36-44. Epub 2008 Dec 24.

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Pharmacoeconomics of antidepressants in moderate-to-severe depressive disorder in Colombia.

Machado M, Lopera MM, Diaz-Rojas J, Jaramillo LE, Einarson TR; Universidad Nacional de Colombia Pharmacoeconomics Group.

Rev Panam Salud Publica. 2008 Oct;24(4):233-9.

PMID: 19133171 [PubMed - indexed for MEDLINE]

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Irritable bowel syndrome. Don't forget amitriptyline.

Leeds JS, Leeds CM, Sanders DS.

BMJ. 2009 Jan 6;338:a3150. doi: 10.1136/bmj.a3150. No abstract available.

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Unexplained seizures in an infant.

Astuto M, Minardi C, Rizzo G, Gullo A.

Lancet. 2009 Jan 3;373(9657):94. No abstract available.

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Effective use of topical amitriptyline hydrochloride 2.5% and ketamine hydrochloride 0.5% for analgesia in refractory proctodynia.

Lehman JS, Sciallis GF.

J Drugs Dermatol. 2008 Sep;7(9):887-9.

PMID: 19112806 [PubMed - indexed for MEDLINE]

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Anxiolytic and antidepressant characteristics of impaza.

Voronina TA, Molodavkin GM, Zhavbert ES, Tarasov SA, Kheyfets IA, Dugina JL, Sergeeva SA, Epstein OI.

Bull Exp Biol Med. 2008 Jun;145(6):735-7.

PMID: 19110564 [PubMed - indexed for MEDLINE]

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Evaluating the effectiveness of exposure and acceptance strategies to improve functioning and quality of life in longstanding pediatric pain--a randomized controlled trial.

Wicksell RK, Melin L, Lekander M, Olsson GL.

Pain. 2009 Feb;141(3):248-57. Epub 2008 Dec 23.

PMID: 19108951 [PubMed - indexed for MEDLINE]

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Metabolic acidosis in a patient with type 1 diabetes mellitus complicated by methanol and amitriptyline intoxication.

Celik U, Celik T, Avci A, Annagur A, Yilmaz HL, Kucukosmanoglu O, Topaloglu AK, Daglioglu N.

Eur J Emerg Med. 2009 Feb;16(1):45-8.

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Management of neuropathic cancer pain following WHO analgesic ladder: a prospective study.

Mishra S, Bhatnagar S, Gupta D, Nirwani Goyal G, Jain R, Chauhan H.

Am J Hosp Palliat Care. 2008 Dec-2009 Jan;25(6):447-51.

PMID: 19106278 [PubMed - indexed for MEDLINE]

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Fracture risks of antidepressants.

Vestergaard P.

Expert Rev Neurother. 2009 Jan;9(1):137-41.

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Lower facial contouring with botulinum toxin type A.

Tartaro G, Rauso R, Santagata M, Santillo V, Itro A.

J Craniofac Surg. 2008 Nov;19(6):1613-7.

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Potential utility of histamine H3 receptor antagonist pharmacophore in antipsychotics.

von Coburg Y, Kottke T, Weizel L, Ligneau X, Stark H.

Bioorg Med Chem Lett. 2009 Jan 15;19(2):538-42. Epub 2008 Sep 7.

PMID: 19091563 [PubMed - indexed for MEDLINE]

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Serotonin syndrome in a patient taking Lexapro and Flexeril: a case report.

Day LT, Jeanmonod RK.

Am J Emerg Med. 2008 Nov;26(9):1069.e1-3.

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[Neuro- and psychotropic activity of N-uronoylamino acids and N-uronoylpeptides]

Ravaeva MIu, Koreniuk II, Kur'ianov VO, Chupakhina TA, Chirva VIa.

Bioorg Khim. 2008 Nov-Dec;34(6):734-8. Russian.

PMID: 19088745 [PubMed - indexed for MEDLINE]

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Influence of amitriptyline on eryptosis, parasitemia and survival of Plasmodium berghei-infected mice.

Brand V, Koka S, Lang C, Jendrossek V, Huber SM, Gulbins E, Lang F.

Cell Physiol Biochem. 2008;22(5-6):405-12. Epub 2008 Dec 9.

PMID: 19088422 [PubMed - indexed for MEDLINE]

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Pharmacological treatment of a patient with first-bite syndrome.

Phillips TJ, Farquhar-Smith WP.

Anaesthesia. 2009 Jan;64(1):97-8. No abstract available.

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Is amitriptyline really effective in diarrhoea-predominant irritable bowel syndrome?

Chassany O, Duracinsky M.

Aliment Pharmacol Ther. 2008 Aug 1;28(3):371-2; author reply 372-3. No abstract available.

PMID: 19086238 [PubMed - in process]

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Hypnic headache associated with medication overuse: case report.

Baykan B, Ertaş M.

Agri. 2008 Jul;20(3):40-3.

PMID: 19085181 [PubMed - indexed for MEDLINE]

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[Nummular headache: 21 new cases and therapeutic results]

Zhu KY, Huang Y, Zhong SS, Bao ZY, Tian XL.

Zhonghua Yi Xue Za Zhi. 2008 Nov 11;88(41):2935-7. Chinese.

PMID: 19080105 [PubMed - indexed for MEDLINE]

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Serum concentrations of antidepressant drugs in a naturalistic setting: compilation based on a large therapeutic drug monitoring database.

Reis M, Aamo T, Spigset O, Ahlner J.

Ther Drug Monit. 2009 Feb;31(1):42-56.

PMID: 19077925 [PubMed - indexed for MEDLINE]

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Pharmacology

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Indications

In the drug management of depressive illness.

Amitriptyline may be used in depressive illness of psychotic or endogenous nature and in selected patients with neurotic depression. Endogenous depression is more likely to be alleviated than are other depressive states. Amitriptyline, because of its sedative action, is also of value in alleviating the anxiety component of depression.

As with other tricyclic antidepressants, amitriptyline may precipitate hypomanic episodes in patients with bipolar depression. These drugs are not indicated in mild depressive states and depressive reactions.


Contraindications   Back to top of page

In patients who have shown prior hypersensitivity to it. It should not be given concomitantly with a MAO inhibiting compound. Hyperpyretic crises, severe convulsions, and deaths have occurred in patients receiving tricyclic antidepressant and MAO inhibiting drugs simultaneously. When it is desired to substitute amitriptyline for a MAO inhibitor, a minimum of 14 days should be allowed to elapse after the latter is discontinued. Amitriptyline should then be initiated cautiously with gradual increase in dosage until optimum response is achieved.

This drug is not recommended for use during the acute recovery phase following myocardial infarction and in the presence of acute congestive heart failure.

See Pregnancy under Warnings.


Warnings   Back to top of page

Amitriptyline should be used with caution in patients with a history of seizures, impaired liver function, a history of hepatic damage or blood dyscrasias and, because of its atropine-like action, in patients with a history of urinary retention, or with narrow-angle glaucoma or increased intraocular pressure. In patients with narrow-angle glaucoma, even average doses may precipitate an attack.

There has been a report of fatal dysrhythmia occurring as late as 56 hours after amitriptyline overdose.

Patients with cardiovascular disorders should be watched closely. Tricyclic antidepressant drugs, including amitriptyline, particularly when given in high doses, have been reported to produce arrhythmias, sinus tachycardia, and prolongation of the conduction time.

A few instances of unexpected deaths have been reported in patients with cardiovascular disorders. Myocardial infarction and stroke have also been reported with drugs of this class. Therefore, these drugs should be used with caution in patients with a history of cardiovascular disease, such as myocardial infarction and congestive heart failure.

Concurrent administration of amitriptyline and electroshock therapy may increase the hazards of therapy. Such treatment should be limited to patients for whom it is essential.

Close supervision is required when amitriptyline is given to hyperthyroid patients or those receiving thyroid medication.

Occupational Hazards:   Back to top of page

May impair mental and/or physical abilities required for performance of hazardous tasks, such as operating machinery or driving a motor vehicle.

Pregnancy:
There are no well-controlled studies in pregnant women; therefore, in administering the drug to pregnant patients or women who may become pregnant, the potential benefits must be weighed against the possible hazards to mother and child.

Lactation:
Amitriptyline is detectable in breast milk. Because of the potential for serious adverse reactions in infants from amitriptyline, a decision should be made whether to discontinue nursing or discontinue the drug.

Children:
In view of the lack of experience with the use of this drug in the treatment of depression in children, amitriptyline is not recommended for depressed patients under 12 years of age.


Precautions   Back to top of page

The potency of amitriptyline is such that addition of other antidepressant drugs generally does not result in any additional therapeutic benefit. Untoward reactions have been reported after the combined use of antidepressant agents having varying modes of activity. Accordingly, combined use of amitriptyline and other antidepressant drugs should be undertaken only with due recognition of the possibility of potentiation and with a thorough knowledge of the pharmacology of both drugs. There has been no reports of untoward events when patients receiving amitriptyline were changed immediately to protriptyline or vice versa.

When amitriptyline is used to treat the depressive component of schizophrenia, activation or aggravation of existing psychotic manifestation may occur. Likewise, manic depressive patients may experience hypomanic or manic episodes and hyperactive or agitated patients may become overstimulated. Paranoid delusions, with or without associated hostility, may be exaggerated. A reduction in dose or discontinuation of amitriptyline may be indicated and administration of a neuroleptic such as a phenothiazine, be considered under these circumstances.

Seriously depressed patients should be carefully supervised. The possibility of suicide in depressed patients remains during treatment. Patients should not have access to large quantities of this drug during treatment.

Discontinue the drug several days before elective surgery if possible.

Drug Interactions:   Back to top of page

Amitriptyline may block the antihypertensive action of guanethidine or similarly acting compounds.

When amitriptyline is given with anticholinergic agents or sympathomimetic drugs, including epinephrine combined with local anesthetics, close supervision and careful adjustment of dosage are required. Paralytic ileus may occur in patients taking tricyclic antidepressants in combination with anticholinergic-type drugs.

Since amitriptyline, in combination with anticholinergic type drugs, may give rise to paralytic ileus, particularly in elderly or hospitalized patients, appropriate measures should be taken if constipation occurs in these patients.

Cimetidine is reported to reduce hepatic metabolism of certain tricyclic antidepressants.

Caution is advised if patients receive large doses of ethchlorvynol concurrently. Transient delirium has been reported in patients who were treated with 1 g of ethchlorvynol and 75 to 150 mg of amitriptyline.

Amitriptyline may enhance the response to alcohol and the effects of barbiturates and other CNS depressants. Delirium has been reported with concurrent administration of amitriptyline and disulfiram.

Note:
Included in this listing which follows are a few adverse reactions which have not been reported with this specific drug. However, pharmacological similarities among the tricyclic antidepressant drugs require that each of the reactions be considered when amitriptyline is administered.

Behavioral:
Drowsiness, fatigue, activation of latent schizophrenia, disorientation, confusional states, hallucinations, delusions, hypomanic reactions, disturbed concentration, nightmares, insomnia, restlessness, agitation, excitement, jitteriness, anxiety, giddiness.

Neurological:
Epileptiform seizures, coma, dizziness, tremors, numbness, tingling, paresthesias of the extremities, peripheral neuropathy, headache, ataxia, alteration in EEG patterns, extrapyramidal symptoms including abnormal involuntary movements and tardive dyskinesia, dysarthria, tinnitus, incoordination, and slurred speech.

Anticholinergic:
Urinary retention, dilatation of the urinary tract, constipation, paralytic ileus, especially in the elderly, hyperpyrexia, dry mouth, blurred vision, disturbance of accommodation, increased intraocular pressure, precipitation of latent glaucoma, aggravation of existing glaucoma, and mydriasis.

Cardiovascular:
Quinidine-like effect and other non-specific ECG changes and changes in AV conduction, prolonged conduction time, asystole, hypotension, syncope, hypertension, palpitation, arrhythmias, heart block, ventricular tachycardia, fibrillation, myocardial infarction, stroke, unexpected death in patients with cardiovascular disorders.

Hematologic:
Bone marrow depression, including agranulocytosis, leukopenia, eosinophilia, purpura, thrombocytopenia.

Allergic:
Skin rash, urticaria, photosensitization, edema of the face and tongue, itching.

Gastrointestinal:
Nausea, epigastric distress, heartburn, vomiting, hepatitis (including altered liver function and jaundice), anorexia, stomatitis, peculiar taste, diarrhea, parotid swelling, black tongue may occur.

Endocrine:
Testicular swelling, gynecomastia and impotence in the male, breast enlargement and galactorrhea in the female, increased or decreased libido, elevation and lowering of blood sugar levels, syndrome of inappropriate ADH (antidiuretic hormone) secretion.

Miscellaneous:
Weakness, increased perspiration, edema, urinary frequency, alopecia, increased appetite, weight gain, weight loss.

Withdrawal Symptoms:
Abrupt cessation of treatment after prolonged administration may produce nausea, headache, and malaise. Gradual dosage reduction has been reported to produce, within 2 weeks, transient symptoms including irritability, restlessness, and dream and sleep disturbance. These symptoms are not indicative of addiction. Rare instances have been reported of mania or hypomania occurring within 2 to 7 days following cessation of chronic therapy with tricyclic antidepressants.

Overdose  

Symptoms:
High doses may cause temporary confusion, disturbed concentration, or transient visual hallucinations. Overdosage may cause drowsiness, hypothermia, tachycardia and other arrhythmic abnormalities, such as bundle branch block, ECG evidence of impaired conduction, congestive heart failure, disorders of ocular motility, convulsions, severe hypotension, stupor, coma, polyradiculoneuropathy and constipation. Other symptoms may be agitation, hyperactive reflexes, muscle rigidity, vomiting, hyperpyrexia, or any of those listed under Adverse Effects.

In patients with glaucoma, even average doses may precipitate an attack.

Treatment:
Treatment is symptomatic and supportive. Cardiac arrhythmias and CNS involvement pose the greatest threat and may occur suddenly even when initial symptoms appear to be mild. Therefore, patients who may have ingested an overdosage of amitriptyline, particularly children, should be hospitalized and kept under close surveillance. Induced emesis and gastric lavage are recommended in the alert and conscious patient. Following gastric lavage, activated charcoal may be administered. Twenty to 30 g of activated charcoal may be given every 4 to 6 hours during the first 24 to 48 hours after ingestion. It may be helpful to leave the tube in the stomach, with irrigation (with an electrolyte balanced fluid) and continual aspiration of stomach contents possibly promoting more rapid elimination of the drug from the body. If the patient is not alert, a cuffed endotracheal tube should be inserted before lavage is performed, and emesis should not be induced. An open airway should be maintained. Standard measures (oxygen, i.v. fluids, corticosteroids) may be used to manage circulatory shock and metabolic acidosis. Norepinephrine or other pressor agents (but no epinephrine) by i.v. drop infusion under continuous monitoring may be used if necessary. Failing respiration must be maintained by artificial means, but respiratory stimulants should not be used. Regulate body temperature. Hyperpyrexia should be controlled by external measures, such as ice packs and cooling sponge baths. Catheterization should be performed in the unconscious patient. Continuous cardiac monitoring should be instituted in all patients, particularly in the presence of ECG abnormalities and should be maintained for several days after the cardiac rhythm has returned to normal. Because of its effects on cardiac conduction, digitalis should be used only with caution. If rapid digitalization is required for the treatment of congestive heart failure, special care should be exercised in using the drug.

It has been reported that i.v. administration of physostigmine salicylate may reverse some of the CNS and cardiovascular effects of tricyclic antidepressants. The dosage that has been recommended for adults is 1 to 2 mg in very slow i.v. injection. In children, the initial dosage should not exceed 0.5 mg and should be adjusted to age and response. Since physostigmine has a short duration of action, administration may have to be repeated at 30 to 60 minute intervals particularly in life-threatening signs such as arrhythmias, convulsions, and deep coma recur or persist after the initial dose of physostigmine. Because physostigmine itself may be toxic, it is not recommended for routine use.

The room should be darkened, with a minimal amount of external stimulation, to reduce the tendency to convulsions. If convulsions occur, they should preferably be controlled by non-barbiturate sedatives, such as chlordiazepoxide or diazepam, or by an inhalation anesthetic (amitriptyline increases the CNS depressant but not the anticonvulsant action of barbiturates). Deaths by deliberate or accidental overdosage have occurred with this class of drugs. Since the propensity for suicide is high in depressed patients, a suicide attempt by other means may occur during the recovery phase. The possibility of simultaneous ingestion of other drugs should also be considered. Dialysis has not been found to be of value for intoxication by amitriptyline alone due to low plasma concentrations of the drug.


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