Description

Amitriptyline

Amitriptyline, sold under the brand name Elavil among others, is a medicine primarily used to treat a number of mental illnesses. These include major depressive disorder and anxiety disorders, and less commonly attention deficit hyperactivity disorder (ADHD) and bipolar disorder. Other uses include prevention of migraines, treatment of neuropathic pain such as fibromyalgia and postherpetic neuralgia, and less commonly insomnia. It is in the tricyclic antidepressant (TCA) class and its exact mechanism of action is unclear. Amitriptyline is taken by mouth.

Common side effects include blurred vision, dry mouth, low blood pressure on standing, sleepiness, and constipation. Serious side effects may include seizures, an increased risk of suicide in those less than 25 years of age, urinary retention, glaucoma, and a number of heart issues. It should not be taken with MAO inhibitors or the medication cisapride. Amitriptyline may cause problems if taken during pregnancy. Use during breastfeeding appears to be relatively safe.

Amitriptyline was discovered in 1960 and approved by the US Food and Drug Administration (FDA) in 1961. It is on the World Health Organization’s List of Essential Medicines, the safest and most effective medicines needed in a health system. It is available as a generic medication. The wholesale cost in the developing world as of 2014 was between 0.01 and US$0.04 per dose. In the United States, it costs about US$0.20 per dose. In 2016, it was the 88th most prescribed medication in the United States, with more than eight million prescriptions.

Medical uses

Amitriptyline is used for a number of medical conditions including major depressive disorder (MDD). Some evidence suggests amitriptyline may be more effective than other antidepressants, including selective serotonin reuptake inhibitors (SSRIs), although it is rarely used as a first-line antidepressant due to its higher toxicity in overdose and generally poorer tolerability, so is used as a second-line treatment when SSRIs do not work. It is used in addition to other medications for pain. A 2001 review called it “the gold-standard antidepressant”.

It is TGA-labeled in Australia for migraine prevention, also in cases of neuropathic pain disorders, fibromyalgia and nocturnal enuresis. Amitriptyline is a popular off-label treatment for irritable bowel syndrome (IBS), although it is most frequently reserved for severe cases of abdominal pain in patients with IBS because it needs to be taken regularly to work and has a generally poor tolerability profile, although a firm evidence base supports its efficacy in this indication. Amitriptyline can also be used as an anticholinergic drug in the treatment of early-stage Parkinson’s disease if depression also needs to be treated. Amitriptyline is the most widely researched agent for the prevention of frequent tension headaches.

Contraindications

The known contraindications of amitriptyline are:

  • Hypersensitivity to TCAs or to any of its excipients
  • History of myocardial infarction
  • History of arrhythmias, particularly heart block to any degree
  • Congestive heart failure
  • Coronary artery insufficiency
  • Mania
  • Severe liver disease
  • Being under seven years of age
  • Breastfeeding
  • Patients who are taking monoamine oxidase inhibitors (MAOIs) or have taken them within the last 14 days.

Side effects

Amitriptyline elicits a variety of adverse effects. Common side effects, occurring in more than 1% of users, include dizziness, headache, and weight gain. Side effects common to anticholinergics occur more often than with other TCAs such as imipramine. Cognitive side effects include delirium and confusion, as well as mood disturbances such as anxiety and agitation. Cardiovascular side effects may include orthostatic hypotension, sinus tachycardia, and QT-interval prolongation. Sexual side effects include loss of libido and impotence, while sleep disturbances may include drowsiness, insomnia, and nightmares. Of the TCAs, amitriptyline is said to have the most anticholinergic side effects and to be the most likely to produce delirium.

Overdose

Main article: Tricyclic antidepressant overdose

The symptoms and the treatment of an overdose are largely the same as for the other TCAs, including the presentation of serotonin syndrome and adverse cardiac effects. The British National Formulary notes that amitriptyline can be particularly dangerous in overdose, thus it and other TCAs 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. English folk singer Nick Drake died from an overdose of Tryptizol in 1974.

The possible symptoms of amitriptyline overdose include:

  • Drowsiness
  • Hypothermia (low body temperature)
  • Tachycardia (high heart rate)
  • Other arrhythmic abnormalities, such as bundle branch block
  • ECG evidence of impaired conduction
  • Congestive heart failure
  • Dilated pupils
  • Convulsions (e.g. seizures, myoclonus)
  • Severe hypotension (very low blood pressure)
  • Stupor
  • Coma
  • Death
  • Polyradiculoneuropathy
  • Changes in the electrocardiogram, particularly QT-interval prolongation and change in QRS axis or width
  • Agitation
  • Hyperactive reflexes
  • Muscle rigidity