Amitriptyline for fibromyalgia and neuropathic pain: An Assessment

Patient Expert

Amitriptyline (once known by the brand name Elavil) is a tricyclic antidepressant that is often prescribed in low doses to treat neuropathic pain. Before there were any FDA-approved drugs to treat fibromyalgia, amitriptyline was also frequently prescribed off-label to treat FM symptoms. Although it is no longer considered a first-line treatment for fibromyalgia, a number of FM patients still find it helpful.

Because of its continued widespread use, scientists at the University of Oxford set out to assess how effective amitriptyline is in reducing pain for both chronic neuropathic pain and fibromyalgia.

Study Design and Results

The researchers reviewed every amitriptyline study they could find, from the earliest studies up to September 2012. For the purpose of this analysis, they included all randomized, double-blind studies of at least four weeks' duration that compared amitriptyline with a placebo or another active treatment for chronic neuropathic pain or fibromyalgia.

A total of 21 studies (1,437 participants) were included. The included studies were classified into two tiers:

  • The first tier used data from the studies that met current best standards, where the studies reported the outcome of at least 50% pain reduction, lasted eight to 12 weeks or longer, had a parallel-group design, and had at least 200 participants.
  • The second tier of studies used data that failed to meet this standard and were therefore considered subject to potential bias.

The individual studies included involved between 15 and 235 participants, with only four studies involving more than 100 people. The median study size was 44 participants. The median duration of the studies was six weeks. The doses of amitriptyline used generally ranged between 25 mg and 125 mg and dose escalation was common. Based on these studies, the researchers found:

  • None of the top-tier studies showed amitriptyline to be effective in treating neuropathic pain or fibromyalgia.

  • The second-tier studies did not show amitriptyline to be effective in treating cancer-related neuropathic pain or HIV-related neuropathic pain, but there was some evidence of effectiveness in treating painful diabetic neuropathy, mixed neuropathic pain, and fibromyalgia.

  • Even using the potentially biased data from the second-tier studies, only about 38% of participants benefited with amitriptyline and 16% with placebo. Most participants did not get adequate pain relief.

  • The potential benefits of amitriptyline were supported by a lower rate of participants withdrawing from the studies due to a lack of effectiveness--5% taking amitriptyline withdrew, while 12% taking a placebo withdrew.

  • At least one adverse event (side-effect) was experienced by 64% of participants taking amitriptyline and 40% taking a placebo.

The researchers concluded, "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. There is no good evidence of a lack of effect; rather our concern should be of overestimation of treatment effect.

"Amitriptyline should continue to be used as part of the treatment of neuropathic pain or fibromyalgia, but only a minority of patients will achieve satisfactory pain relief. Limited information suggests that failure with one antidepressant does not mean failure with all."

My Thoughts...

When I was first diagnosed with fibromyalgia about 16 years ago, amitriptyline was one of the few treatments being used for FM. I did not have a good reaction to it, so my experience with amitriptyline was very short-lived. My understanding at the time was that it was supposed to help me sleep better and thereby help reduce my pain. Of course, I now know that antidepressants can be quite effective at reducing certain types of pain.

Today two of the three medications with FDA-approval for treating fibromyalgia are classified as antidepressants--Cymbalta (duloxetine) and Savella (milnacipran). Both of these are selective serotonin and norepinephrine reuptake inhibitors (SSNRIs), a newer class of antidepressant that is thought to be more effective in reducing FM pain than the tricyclics like amitriptyline.

Despite the newer antidepressants, I still hear from people who continue to take amitriptyline and feel it is helping them. I'd like to hear from you. Have you ever taken amitriptyline? Are you taking it now? Has it helped reduce your pain? Has it helped with any other FM symptoms like sleep problems or fatigue?


Moore RA, et al. "." Cochrane Database of Systematic Reviews. 2012 Dec 12;12:CD008242. doi: 10.1002/14651858.CD008242.pub2.

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