Amitriptyline for Fibromyalgia & Chronic Fatigue Syndrome

Amitriptyline is a popular antidepressant that's available only in generic form in the U.S. It used to be sold under the brand name Elavil.

Amitriptyline is classified as a tricyclic antidepressant. For years, some healthcare providers have considered it a front-line treatment for fibromyalgia and chronic fatigue syndrome (ME/CFS). However, this came about more from trial-and-error use than clinical studies.

In recent years, especially with the advent of FDA-approved fibromyalgia treatments, use of amitriptyline for these illness has declined. Amitriptyline is still, however, sometimes used as a reference drug in fibromyalgia treatment studies, and many healthcare providers still prescribe it for these conditions.

A man holding his prescription
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How It Works

Amitriptyline and other tricyclic drugs are thought to increase the amount of the neurotransmitters serotonin and norepinephrine that your brain can use. They do this by slowing down a process called "reuptake," which is when specialized cells absorb used neurotransmitters so they can be re-used elsewhere.

Other antidepressants, called reuptake inhibitors, use different mechanisms to achieve a similar effect.

Serotonin and norepinephrine are believed to be dysregulated in both fibromyalgia and ME/CFS.


A 2012 review of amitriptyline for fibromyalgia had this to say on the drug's use in fibromyalgia:

"Amitriptyline has been a first-line treatment for neuropathic pain for many years. The fact that there is no supportive unbiased evidence for a beneficial effect is disappointing but has to be balanced against decades of successful treatment in many patients with neuropathic pain or fibromyalgia."

The review goes on to say that overestimation of its effectiveness is a concern because recent studies show only a minority of people who try it will have satisfactory pain relief.

Another review that year, which also included the antidepressants duloxetine and milnacipran, stated:

"A small number of patients experience a substantial symptom relief with no or minor adverse effects. However, a remarkable number of patients drop out of therapy because of intolerable adverse effects or experience only a small relief of symptoms, which does not outweigh the adverse effects."

A 2011 review concluded that amitriptyline shouldn't be regarded as the gold-standard for fibromyalgia because of the limitations of the studies that had been conducted.

However, also in 2011, a review of drug classes for fibromyalgia stated that amitriptyline was similar to the FDA-approved drugs – Lyrica (pregabalin), Cymbalta (duloxetine), and Savella (milnacipran) when it came to pain and fatigue.Some healthcare providers may prefer amitriptyline for a couple of reasons:

  • Its long history of use, and
  • Its low cost compared to FDA-approved fibromyalgia drugs.

For example, a one-month supply of generic amitriptyline can cost between about $15 and $65, depending on the dosage. Meanwhile, a one-month supply of Cymbalta (duloxetine), Lyrica (pregabalin), or Savella (milnacipran) starts at about $125 and can range up to around $180. (This may change as generic duloxetine comes on the market.)

Chronic Fatigue Syndrome

Amitriptyline has a long history of use for ME/CFS, again despite a lack of clinical studies and because of real-world observations of improvement. Very little research has been done.

A 2012 study, however, did look at amitriptyline for ME/CFS and found that it was the only one among several antidepressants tested that inhibited the mast-cell release of pro-inflammatory cytokines, which are believed to play a role in ME/CFS.


For adults, a typical amitriptyline dosage can range from 40 mg up to 150 mg per day. It's generally divided into multiple doses.

It can take as long as a month for you to notice changes due to this medication.

Be sure to follow your healthcare provider's instructions for taking this medication. If you want to quit taking it, don't just stop suddenly. Ask your healthcare provider about the proper way to wean off of this drug.

Side Effects

As with all antidepressants, it carries a warning about an increased risk of suicidal thoughts or attempts in people under 24 years old.

Amitriptyline has a long list of possible side effects. Common side effects include:

  • Unsteadiness,
  • Nightmares,
  • Nausea or vomiting,
  • Difficulty urinating,
  • Constipation,
  • Excessive sweating,
  • Changes in weight or appetite,
  • Changes in sex drive or ability to have sex,
  • Pain, burning or tingling in the hands or feet.

If you have any of the following severe side effects, you should call your healthcare provider immediately:

  • Slow speech, difficulty speaking,
  • Fainting,
  • Weakness or numbness of a limb,
  • Crushing chest pain,
  • Irregular heartbeat,
  • Severe rash or hives,
  • Swelling of the face and tongue,
  • Yellow skin or eyes,
  • Muscle spasms in the jaw, neck, and back,
  • Uncontrollable shaking,
  • Unusual bleeding or bruising,
  • Seizures,
  • Hallucinations.

Because this medication increases available amounts of serotonin, you should avoid other drugs that also increase serotonin and learn the symptoms of a potentially deadly reaction: serotonin syndrome.

As with any drug, it's important for you and your healthcare provider to weigh the risks against the benefits and decide which treatments are appropriate for you.

6 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Mease PJ. Further strategies for treating fibromyalgia: the role of serotonin and norepinephrine reuptake inhibitors. Am J Med. 2009;122(12 Suppl):S44-55. doi:10.1016/j.amjmed.2009.09.010

  2. Moore RA, Derry S, Aldington D, Cole P, Wiffen PJ. Amitriptyline for neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev. 2012;12:CD008242. doi:10.1002/14651858.CD008242.pub2

  3. Häuser W, Wolfe F, Tölle T, Uçeyler N, Sommer C. The role of antidepressants in the management of fibromyalgia syndrome: a systematic review and meta-analysis. CNS Drugs. 2012;26(4):297-307. doi:10.2165/11598970-000000000-00000

  4. Häuser W, Petzke F, Üçeyler N, Sommer C. Comparative efficacy and acceptability of amitriptyline, duloxetine and milnacipran in fibromyalgia syndrome: a systematic review with meta-analysis. Rheumatology (Oxford). 2011;50(3):532-43. doi:10.1093/rheumatology/keq354

  5. Smith B, et al. Drug Class Reviews. 2011 Apr. Drug Class Review: Drugs for Fibromyalgia: Final Original Report.

  6. Clemons A, Vasiadi M, Kempuraj D, Kourelis T, Vandoros G, Theoharides TC. Amitriptyline and prochlorperazine inhibit proinflammatory mediator release from human mast cells: possible relevance to chronic fatigue syndrome. J Clin Psychopharmacol. 2011;31(3):385-7. doi:10.1097/JCP.0b013e3182196e50

Additional Reading

By Adrienne Dellwo
Adrienne Dellwo is an experienced journalist who was diagnosed with fibromyalgia and has written extensively on the topic.