Amitriptyline is a medication for the treatment of depression, pain, and migraines. It was being marketed under the brand name Elavil but this has now been discontinued in the U.S., where generic versions of the treatment 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 which help to reduce 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 surfaces. The other cell can be another nerve cell, a muscle cell, or a gland cell. Amitriptyline inhibits acetylcholine’s action by blocking its receptors.

When amitriptyline is taken orally, it blocks acetylcholine receptors in the salivary glands and thereby reduces drooling.

Amitriptyline in clinical trials

No studies have investigated the use of amitriptyline in patients with SMA specifically but it is sometimes prescribed to reduce drooling in this group of patients.

The treatment has, however, been tested in people with other neurodegenerative diseases. For example, in a comparative trial in 10 patients with motor neuron disease, participants received either under-the-skin injections of 50 mg per day of amitriptyline or dysport (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, eye problems when changing focus, dry mouth, sleepiness, and poor concentration. In these patients, the dose of amitriptyline was reduced and given in conjunction with dysport (Botox), which removed the side effects without an increase in salivation. The study stated that dysport cannot be used instead of amitryptiline in this patient population to reduce drooling, but it can be used with a reduced dose of amitryptiline if the regular dose causes side effects.

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