Amitriptyline is a medication for the treatment of depression, pain, and migraine. It was being marketed under the brand name Elavil but this has now been discontinued in the U.S., where generic versions are still available.

In patients with motor neuron diseases such as spinal muscular atrophy (SMA), amitriptyline is used to reduce excessive saliva production and drooling.

How amitriptyline works

Amitriptyline has several different effects on the nervous system that explain its usefulness in the reduction of depression and pain.

Its effect on saliva production is due to its interference with the neurotransmitter acetylcholine. Neurotransmitters are small molecules that transmit signals from a nerve cell to another cell by binding to receptors found on their surface. The other cell can be another nerve cell, a muscle cell, or a gland cell. Amitriptyline blocks acetylcholine’s action by blocking its receptors.

When amitriptyline is injected into salivary glands, it blocks acetylcholine receptors in the glands that secrete saliva and therefore reduces drooling.

Amitriptyline in clinical trials

In a comparative trial with 10 patients with motor neuron disease, participants received either under-the-skin injections of 50 mg per day of amitriptyline or Botox injections. Six participants without salivary dysfunction served as controls. In both treatment groups, saliva production significantly decreased to a similar degree.

Three patients who were treated with amitriptyline experienced constipation, problems with the eyes in changing focus, dry mouth, sleepiness, and poor concentration. Upon dose reduction along with starting Botox treatment, the side effects disappeared while the decrease in saliva production was maintained.

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