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Amitriptyline, sold under the brand name Elavil among others, is a tricyclic antidepressant primarily used to treat major depressive disorder, a variety of pain syndromes such as neuropathic pain, fibromyalgia, migraine and tension headaches. Due to the frequency and prominence of side effects, amitriptyline is generally considered a second-line therapy for these indications. The most common side effects are dry mouth, drowsiness, dizziness, constipation, and weight gain. Of note is sexual dysfunction, observed primarily in males. Glaucoma, liver toxicity and abnormal heart rhythms are rare but serious side effects. Blood levels of amitriptyline vary significantly from one person to another, and amitriptyline interacts with many other medications potentially aggravating its side effects. Amitriptyline was discovered in the late 1950s by scientists at Merck and approved by the US Food and Drug Administration (FDA) in 1961. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication. In 2020, it was the 81st most commonly prescribed medication in the United States, with more than 9 million prescriptions. Amitriptyline is indicated for the treatment of major depressive disorder and 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. Amitriptyline is effective for depression, but it is rarely used as a first-line antidepressant due to its higher toxicity in overdose and generally poorer tolerability. It can be tried for depression as a second-line therapy, after the failure of other treatments. For treatment-resistant adolescent depression or for cancer-related depression 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, but supporting evidence for that is lacking. Amitriptyline alleviates painful diabetic neuropathy.
Jaroslava Joniová, Veronika Huntosova
Douglas Hanahan, Ksenya Shchors, Aristea Massaras