Amitriptyline for Multiple Sclerosis

Last updated July 19, 2022, by Marisa Wexler, MS

Fact-checked by Inês Martins, PhD

What is amitriptyline for MS?

Amitriptyline is an oral therapy approved by the U.S. Food and Drug Administration to treat depression. In people with multiple sclerosis (MS), it’s sometimes used off-label to help ease neuropathic pain, or pain caused by damage to the nervous system.

Amitriptyline has been sold in the U.S. under brand names such as Elavil, Endep, and Vanatrip, but these have been discontinued by the manufacturers for reasons unrelated to the therapy’s safety or effectiveness. Generic versions of amitriptyline remain available.

How does amitriptyline work?

Inflammation in MS may cause damage to nerve cells involved in perceiving physical sensations. Common symptoms of such neuronal damage include chronic pain, or painful altered sensations, such as pins and needles, numbness, or a feeling of burning or stabbing in the skin, which have a significant impact on the quality of life.

Amitriptyline belongs to a class of medications called tricyclic antidepressants. It works by modulating the activity of certain neurotransmitters, which are molecules nerve cells release to communicate with each other. In doing so, it can help to normalize abnormal nervous system activity that gives rise to depression or nerve pain.

Specifically, amitriptyline affects two neurotransmitters called serotonin and norepinephrine. Normally, these molecules are released by a nerve cell to signal to a neighboring cell and then specialized proteins on the original nerve take the neurotransmitter back in. Amitriptyline blocks this re-uptake, which ultimately increases serotonin and norepinephrine levels outside the cell, boosting their signaling power.

The resulting increase in serotonin has a potent analgesic effect that helps ease nerve pain in people with neurologic conditions.

Who should not use amitriptyline?

Amitriptyline should not be used by:

  • anyone with a known allergy to the therapy
  • individuals in the acute recovery phase after myocardial infarction (heart attack)
  • children under 12 years old

Amitriptyline also is not recommended for use in combination with monoamine oxidase inhibitors (another class of antidepressant) or with the heartburn medication cisapride.

How is amitriptyline administered in MS?

Amitriptyline is available in film-coated tablets, taken orally, that come in six dosage strengths:

  • 10 mg pink tablets
  • 25 mg light green tablets
  • 50 mg brown tablets
  • 75 mg purple tablets
  • 100 mg orange tablets
  • 150 mg light green or peach tablets

Generally, a low dose is used initially, and then increased until symptoms are adequately controlled. The maximum recommended dose is 150 mg/day, although the medication typically is used to treat nerve pain at much lower doses.

Because the medicine may cause drowsiness, it’s typically recommended that amitriptyline be taken at bedtime.

Common side effects of amitriptyline

Common side effects of amitriptyline include:

  • weight gain
  • drowsiness
  • digestive complaints (e.g., constipation)
  • dry mouth
  • dizziness
  • headache

Suicidal ideation and behavior

Amitriptyline carries a boxed warning stating that, like other antidepressants, that it may increase the risk of suicidal thoughts and actions in children and young adults. The treatment also may worsen psychotic symptoms in people with schizophrenia, and it can prompt a shift toward mania in those with bipolar disorder.

Patients taking antidepressants like amitriptyline should be monitored for any worrisome mood changes or worsening psychiatric issues.

Pregnancy and breastfeeding

Amitriptyline has not been thoroughly studied in those who are pregnant or breastfeeding. Animal studies have suggested that it may cause harm to a developing fetus and there have been reports of babies born with notable health problems after being exposed to amitriptyline in the womb. Amitriptyline is secreted in human breast milk.

It is broadly recommended that amitriptyline should only be used during pregnancy or while breastfeeding if the potential benefits of treatment outweigh these risks.

Overdose and interactions with alcohol

Overdosing on tricyclic antidepressants such as amitriptyline can be fatal and medical attention should be sought immediately if an overdose occurs.

Amitriptyline can potentiate the effects of alcohol — in other words, alcohol’s normal effects (impairing coordination, reducing inhibitions, etc.) are generally more powerful and pronounced in those taking amitriptyline.


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