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Amitryptyline is a drug of the tricyclic antidepressant group, with a wide range of applications beyond mental health, especially in pain management. Like other drugs of the group, it inhibits the enzyme catechol-O-methyl transferase, which metabolizes norepinephrine and serotonin postsynaptic neurons, thus raising their concentration and effect in the synapse.

While its effects vary with individuals, it tends to be relatively more sedating and have more anticholinergic side effects than other tricyclics. Its sedating property may be exploited in the treatment of insomnia.


When prescribed for depression, it may take three weeks or more to be effective, and the dose may have to be raised slowly to manage side effects. For depression, the typical daily dose is 75-300 mg.

Pain management

In the treatment of chronic pain smaller doses can be used then when treating depression. Amitriptyline usually acts more quickly.

Chronic pain syndromes

It has been useful in diffuse pain syndromes such as fibromyalgia.

Neurogenic pain

In a randomized controlled trial of patients with diabetic neuropathy, amitriptyline was better than fluoxetine [1] In this trial, amitriptyline was effective in patients regardless of whether they had depression, whereas fluoxetine was effective only in depressed patients.

In a randomized crossover trial of patients with diabetic neuropathy, amitriptyline provided moderate or greater pain relief in 67% of patients as compared to 52% with gabapentin. In this small study, this result was statistically insignificant.[2]

Headache prevention

A systematic review concluded that it is not clear whether any medications taken daily can prevent tension headaches.[3] However, several randomized controlled trials of antidepressant agents included in the systematic review were positive.

It has been used in the prophylaxis of migraine headache.

Side effects and toxicity


  1. Max MB, Lynch SA, Muir J, Shoaf SE, Smoller B, Dubner R (May 1992). "Effects of desipramine, amitriptyline, and fluoxetine on pain in diabetic neuropathy". N. Engl. J. Med. 326 (19): 1250–6. PMID 1560801[e]
  2. Morello CM, Leckband SG, Stoner CP, Moorhouse DF, Sahagian GA (September 1999). "Randomized double-blind study comparing the efficacy of gabapentin with amitriptyline on diabetic peripheral neuropathy pain". Arch. Intern. Med. 159 (16): 1931–7. PMID 10493324[e]
  3. Verhagen AP, Damen L, Berger MY, Passchier J, Koes BW (2010). "Lack of benefit for prophylactic drugs of tension-type headache in adults: a systematic review.". Fam Pract 27 (2): 151-65. DOI:10.1093/fampra/cmp089. PMID 20028727. Research Blogging.