Amitriptyline

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

Medical uses

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

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

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

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

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

Adverse effects

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

Overdose

The symptoms and the treatment of an overdose are largely the same as for the other TCAs. The British National Formulary notes that Amitryptyline can be particularly dangerous in overdose,^[12] 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.

Pharmacology

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

Amitriptyline additionally functions as a 5-HT_2A, 5-HT_2C, 5-HT₆, 5-HT₇, α₁-adrenergic, H₁, H₂,^[15] H₄,^[16][17] and mACh receptor antagonist, and σ₁ receptor agonist.^{[18][19][20][21]} It has also been shown to be a relatively weak NMDA receptor negative allosteric modulator at the same binding site as phencyclidine.^[22] Amitriptyline inhibits sodium channels, L-type calcium channels, and K_v1.1, K_v7.2, and K_v7.3 voltage-gated potassium channels, and therefore acts as a sodium, calcium, and potassium channel blocker as well.^[23][24][25]

Recently, amitriptyline has been demonstrated to act as an agonist of the TrkA and TrkB receptors.^[26] 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.^[26][27] These are the same receptors BDNF activate, an endogenous neurotrophin with powerful antidepressant effects, and as such this property may contribute significantly to its therapeutic efficacy against depression.

History

Amitriptyline, under the brand name Elavil, was developed by Merck and approved by the FDA on April 7, 1961, for the treatment of major depression in the United States.^[28]

See also

• Tricyclic antidepressant

References

Further reading

• 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.