Amitriptyline for spinal muscular atrophy

Last updated Jan. 30, 2025, by Margarida Maia, PhD
Fact-checked by Jose Lopes, PhD

What is amitriptyline for SMA?

Amitriptyline, or amitriptyline hydrochloride, is an anticholinergic medication that can be taken by mouth for treating symptoms of depression. It’s also used off-label to treat anxiety, difficulty falling or staying asleep, and pain, including migraine.

Sometimes, it’s used off-label to reduce excessive drooling when a motor neuron disease like spinal muscular atrophy (SMA) weakens the muscles around the mouth and throat, causing difficulty swallowing and leading to saliva pooling until it overflows as drool. In SMA, muscle weakness gets progressively worse over time.

In the U.S., the therapy is available as generics in the form of oral tablets. It was once also marketed under brand names such as Amitid, Amitril, Elavil, and Endep, but these have been discontinued and are no longer available.

Therapy snapshot

How does amitriptyline work?

SMA causes weakness in the skeletal muscles used for movement. It can also cause bulbar weakness, which affects the muscles around the mouth and throat. Bulbar weakness can make it difficult to swallow. This can lead to sialorrhea, or drooling, which occurs when too much saliva builds up and spills out of the mouth. In some cases, excess saliva can enter the lungs, causing choking or pneumonia.

Like many medications that reduce the amount of saliva produced by the salivary glands, amitriptyline is an anticholinergic. It works by blocking the effects of the parasympathetic nervous system, which controls bodily functions such as heartbeat. It does this by competing with acetylcholine, a chemical messenger that nerve cells release to communicate with other cells. Amitriptyline prevents acetylcholine from activating its receptors on the salivary glands, reducing excessive drooling.

Amitriptyline also increases the amount of serotonin and norepinephrine in the brain. These chemical messengers help regulate mood. Along with being used to reduce excessive drooling, amitriptyline is also sometimes used to treat anxiety arising from breathing difficulties caused by SMA.

How is amitriptyline administered?

Amitriptyline is available as oral tablets of 10, 25, 50, 75, 100, or 150 mg. While amitriptyline is not indicated for treating SMA, the initial dose recommended for treating symptoms of depression in the outpatient setting is 75 or 100 mg daily, which can be increased to 150 mg per day. Hospitalized patients may need as much as 300 mg a day.

A maintenance dose is usually 40 to 100 mg daily at bedtime. A lower dose is recommended for adolescents, ages 12 and older, and elderly patients.

There have been no studies on the use of amitriptyline to reduce excessive drooling in patients with SMA. However, data from the ALS CARE program showed that patients with amyotrophic lateral sclerosis (ALS), another progressive neuromuscular disease, may benefit from 25 to 50 mg of amitriptyline at bedtime.

In a study that compared amitriptyline against Dysport (botulinum toxin type A), an injection treatment to smooth wrinkles and reduce muscle spasms, in 10 patients with motor neuron diseases and sialorrhea, both reduced excessive drooling when used at mean therapeutic doses.

Common side effects of amitriptyline

Common side effects occurring with amitriptyline at the recommended dose for the approved indication include:

• dry mouth
• drowsiness or sleepiness (sedation)
• fatigue.

Other side effects include:

• vision changes
• appetite or weight changes
• constipation
• diarrhea
• nausea and vomiting.

Suicidal thinking and behavior

In the U.S., amitriptyline comes with a boxed warning for risk of suicide because it can increase suicidal thinking and behavior in adolescents and young adults with symptoms of depression. As such, the use of amitriptyline for depression must weigh clinical needs and risk.

SMA News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.