Description

Simple

A medication used to treat symptoms of depression and anxiety that can be related to depression.

Clinical

A tricyclic antidepressant indicated in the treatment of depressive illness, either endogenous or psychotic, and to relieve depression associated anxiety.

Overview

Amitriptyline hydrochloride, also known as _Elavil_, is a tricyclic antidepressant (TCA) with analgesic properties, widely used to treat depression and neuropathic pain [5]. It was originally approved by the FDA in 1977 and manufactured by Sandoz [11].

Pharmacology

Indication

This drug in indicated for the following conditions [FDA label]:

Major depressive disorder in adults

Management of neuropathic pain in adults

Prophylactic treatment of chronic tension-type headache (CTTH) in adults

Prophylactic treatment of migraine in adults

Treatment of nocturnal en... Read more

Pharmacodynamic

**Effects in pain and depression**

Amitriptyline is a tricyclic antidepressant and an analgesic. It has anticholinergic and sedative properties [FDA label].
Clinical studies have shown that oral amitriptyline achieves, at a minimum, good to moderate response in up to 2/3 of patients diagnosed w... Read more

Mechanism of action

The mechanism of action of this drug is not fully elucidated. It is suggested that amitriptyline inhibits the membrane pump mechanism responsible for the re-uptake of transmitter amines, such as norepinephrine and serotonin, thereby increasing their concentration at the synaptic clefts of the brain... Read more

Absorption

Rapidly absorbed following oral administration (bioavailability is 30-60% due to first pass metabolism). Peak plasma concentrations are reached 2-12 hours after oral or intramuscular administration [FDA label]. Steady-state plasma concentrations vary greatly and this variation may be due to genetic... Read more

Protein binding

Very highly protein bound (95%) in plasma and tissues [FDA Label].

Volume of distribution

The apparent volume of distribution (Vd)β estimated after intravenous administration is 1221 L±280 L; range 769-1702 L (16±3 L/kg) [FDA Label]. It is found widely distributed throughout the body [ Read more

Clearance

The mean systemic clearance (Cls) is 39.24 ± 10.18 L/h (range: 24.53-53.73 L/h) [FDA Label]. No clear effect of older age on the pharmacokinetics of amitriptyline has been determined, although it is possible that clearance may be decreased [ Read more

Half life

The elimination half-life (t1⁄2 β) amitriptyline after peroral administration is about 25 hours (24.65 ± 6.31 hours; range 16.49-40.36 hours) [FDA Label].

Route of elimination

Amitriptyline and its metabolites are mainly excreted in the urine. Virtually the entire dose is excreted as glucuronide or sulfate conjugate of metabolites, with approximately 2% of unchanged drug appearing in the urine [FDA Label]. 25-50% of a single orally administered dose is excreted in urine a... Read more

Toxicity

**Toxicity Data**: Oral TDLO (child): 4167 μg/kg; Oral TDLO (man): 714 μg/kg/1D (intermittent); Oral TDLO (woman): 10 mg/kg [12].

Ingestion of 750 mg or more by an adult may result in severe toxicity. The effects in ov... Read more

Adverse Effects

Contraindications

  • Regions: US
  • Below Age:
    • Amount: 6
    • Unit: year
  • Regions: US
  • Patient Conditions:
      • Name: Severe liver disease
      • Drugbank Id: DBCOND0108367
      • Modification Of:
        • Base:
          • Name: Liver Disease
          • Drugbank Id: DBCOND0028338
        • Severity:
          • Includes:
            • severe
  • Regions: US
  • With Categories:
      • Name: Monoamine Oxidase Inhibitors
      • Drugbank Id: DBCAT001004
      • Mesh Id: D008996
  • Regions: US
  • Patient Conditions:
      • Name: Coronary Artery Insufficiency
      • Drugbank Id: DBCOND0033888
  • Regions: US
  • Patient Conditions:
      • Name: Cardiac Rhythm Disorders
      • Drugbank Id: DBCOND0055728
  • Regions: US
  • Patient Conditions:
      • Name: Heart Block
      • Drugbank Id: DBCOND0032425
  • Regions: US
  • Patient Conditions:
      • Name: Recent Myocardial Infarction
      • Drugbank Id: DBCOND0043731
  • Regions: US
  • Patient Conditions:
      • Name: Hypersensitivity to the active substance or to any of the excipients
      • Drugbank Id: DBCOND0117394
  • Regions: US
  • With Categories Coadmin:
      • Name: Monoamine Oxidase Inhibitors
      • Drugbank Id: DBCAT001004
      • Mesh Id: D008996
  • Regions: US
  • With Drugs Coadmin:
      • Name: Cisapride
      • Drugbank Id: DB00604

Food Interactions

  • Avoid alcohol.
  • Avoid St. John's Wort.
  • Limit caffeine intake.
  • Take with food. Food reduces irritation.

Interactions

Type in a drug name to check for interaction with Amitriptyline
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  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
(R)-warfarin
The metabolism of (R)-warfarin can be decreased when combined with Amitriptyline.
(S)-Warfarin
The metabolism of (S)-Warfarin can be decreased when combined with Amitriptyline.
1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine
The metabolism of Amitriptyline can be decreased when combined with 1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine.
1-benzylimidazole
The risk or severity of hypertension can be increased when Amitriptyline is combined with 1-benzylimidazole.
1,10-Phenanthroline
The therapeutic efficacy of Amitriptyline can be decreased when used in combination with 1,10-Phenanthroline.
2,4-thiazolidinedione
Amitriptyline may decrease the hypoglycemic activities of 2,4-thiazolidinedione.
2,5-Dimethoxy-4-ethylamphetamine
The therapeutic efficacy of Amitriptyline can be decreased when used in combination with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamine
The therapeutic efficacy of Amitriptyline can be decreased when used in combination with 2,5-Dimethoxy-4-ethylthioamphetamine.
4-Bromo-2,5-dimethoxyamphetamine
The therapeutic efficacy of Amitriptyline can be decreased when used in combination with 4-Bromo-2,5-dimethoxyamphetamine.
4-Bromo-2,5-dimethoxyphenethylamine
The therapeutic efficacy of 4-Bromo-2,5-dimethoxyphenethylamine can be decreased when used in combination with Amitriptyline.
4-hydroxycoumarin
The risk or severity of adverse effects can be increased when Amitriptyline is combined with 4-hydroxycoumarin.
4-Methoxyamphetamine
The metabolism of 4-Methoxyamphetamine can be decreased when combined with Amitriptyline.
5-methoxy-N,N-dimethyltryptamine
The metabolism of 5-methoxy-N,N-dimethyltryptamine can be decreased when combined with Amitriptyline.
6-Deoxyerythronolide B
The metabolism of Amitriptyline can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanine
The metabolism of 6-O-benzylguanine can be decreased when combined with Amitriptyline.
7-ethyl-10-hydroxycamptothecin
The metabolism of Amitriptyline can be decreased when combined with 7-ethyl-10-hydroxycamptothecin.
7-Nitroindazole
The risk or severity of adverse effects can be increased when Amitriptyline is combined with 7-Nitroindazole.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the serotonergic activities of Amitriptyline.
8-azaguanine
The metabolism of 8-azaguanine can be decreased when combined with Amitriptyline.
8-chlorotheophylline
The metabolism of 8-chlorotheophylline can be decreased when combined with Amitriptyline.
13 References
  1. 1 . Otaka M, Jin M, Odashima M, Matsuhashi T, Wada I, Horikawa Y, Komatsu K, Ohba R, Oyake J, Hatakeyama N, Watanabe S: New strategy of therapy for functional dyspepsia using famotidine, mosapride and amitriptyline. Aliment Pharmacol Ther. 2005 Jun;21 Suppl 2:42-6.PubMed: 15943846
  2. 2 . Hisaoka K, Tsuchioka M, Yano R, Maeda N, Kajitani N, Morioka N, Nakata Y, Takebayashi M: Tricyclic antidepressant amitriptyline activates fibroblast growth factor receptor signaling in glial cells: involvement in glial cell line-derived neurotrophic factor production. J Biol Chem. 2011 Jun 17;286(24):21118-28. doi: 10.1074/jbc.M111.224683. Epub 2011 Apr 22.PubMed: 21515689
  3. 3 . Yan L, Wang Q, Fu Q, Ye Q, Xiao H, Wan Q: Amitriptyline inhibits currents and decreases the mRNA expression of voltage-gated sodium channels in cultured rat cortical neurons. Brain Res. 2010 Jun 8;1336:1-9. doi: 10.1016/j.brainres.2010.04.016. Epub 2010 Apr 14.PubMed: 20398637
  4. 4 . Olesen OV, Linnet K: Metabolism of the tricyclic antidepressant amitriptyline by cDNA-expressed human cytochrome P450 enzymes. Pharmacology. 1997 Nov;55(5):235-43. doi: 10.1159/000139533.PubMed: 9399333
  5. 5 . Lawson K: A Brief Review of the Pharmacology of Amitriptyline and Clinical Outcomes in Treating Fibromyalgia. Biomedicines. 2017 May 17;5(2). pii: biomedicines5020024. doi: 10.3390/biomedicines5020024.PubMed: 28536367
  6. 6 . Bryson HM, Wilde MI: Amitriptyline. A review of its pharmacological properties and therapeutic use in chronic pain states. Drugs Aging. 1996 Jun;8(6):459-76. doi: 10.2165/00002512-199608060-00008.PubMed: 8736630
  7. 7 . Guaiana G, Barbui C, Hotopf M: Amitriptyline versus other types of pharmacotherapy for depression. Cochrane Database Syst Rev. 2003;(2):CD004186. doi: 10.1002/14651858.CD004186 .PubMed: 12804503
  8. 8 . Nishishinya B, Urrutia G, Walitt B, Rodriguez A, Bonfill X, Alegre C, Darko G: Amitriptyline in the treatment of fibromyalgia: a systematic review of its efficacy. Rheumatology (Oxford). 2008 Dec;47(12):1741-6. doi: 10.1093/rheumatology/ken317. Epub 2008 Aug 12.PubMed: 18697829
  9. 9 . Moret C, Briley M: The importance of norepinephrine in depression. Neuropsychiatr Dis Treat. 2011;7(Suppl 1):9-13. doi: 10.2147/NDT.S19619. Epub 2011 May 31.PubMed: 21750623
  10. 10 . Gupta SK, Shah JC, Hwang SS: Pharmacokinetic and pharmacodynamic characterization of OROS and immediate-release amitriptyline. Br J Clin Pharmacol. 1999 Jul;48(1):71-8.PubMed: 10383563
  11. 11 . Amitriptyline FDA information, Approval Link
  12. 12 . Elavil Monograph File
  13. 13 . Safety data sheet, amitriptyline File