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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.

It is TGA-labeled 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 prevention of frequent tension headaches. 

Investigational uses

The few randomized controlled trials investigating its efficacy in eating disorders have been discouraging.

As of 2004, amitriptyline was the most commonly prescribed off-label prescription sleep aid in the United States. Owing to the development of tolerance and the potential for adverse effects such as constipation, its use in the elderly for this indication is recommended against.

(in addition to, or sometimes in place of ADHD stimulant drugs)

Especially after the anti-reflux procedure Nissen fundoplication

Usual Adult Dose for Depression

Outpatients:
Usual dose: 75 mg orally per day in divided doses; this may be increased to a total of 150 mg per day if needed
Alternate dose: 40 to 100 mg orally as a single dose at bedtime; this may be increased by 25 or 50 mg as needed at bedtime to a total of 150 mg per day
Maximum dose: 150 mg orally per day

Inpatients:
Initial dose: 100 mg orally per day
Maintenance dose: 40 to 100 mg orally as a single dose at bedtime
Maximum dose: 300 mg orally per day

Comments:
-Dosage should be reduced to the lowest amount that will maintain relief of symptoms, when satisfactory improvement has been obtained.
-Dose increases should preferably be made in the late afternoon or at bedtime due to the sedative effect.
-The full therapeutic effect may take as long as 30 days to develop.
-Maintenance therapy should be continued for 3 months or longer to lessen the possibility of relapse.

Use: Relief of symptoms of depression

Usual Geriatric Dose for Depression

10 mg orally 3 times a day with 20 mg at bedtime

Comments:
-The full therapeutic effect may take as long as 30 days to develop.
-Elderly patients should be monitored carefully and serum levels obtained as clinically appropriate.
-Dose adjustments should be made according to clinical response.

Use: Relief of symptoms of depression

Common (≥1% frequency) side effects include dizziness, headache, weight gain, side effects common to anticholinergics, but more such effects than other TCAs, cognitive effects such as delirium and confusion, mood disturbances such as anxiety and agitation, cardiovascular side effects such as orthostatic hypotension, sinus tachycardia, and QT-interval prolongation, sexual side effects such as loss of libido and impotence, and sleep disturbances such as drowsiness, insomnia and nightmares.