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Analysis of Amitriptyline’s Effectiveness for Fibromyalgia and Neuropathic Pain

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Amitriptyline for neuropathic pain and fibromyalgia in adults.
– Source: “Cochrane Database of Systematic Reviews”, December 12, 2012

By R.A. Moore, et al.


Background: Amitriptyline is a tricyclic antidepressant that is widely used to treat chronic neuropathic pain (pain due to nerve damage) and fibromyalgia, and is recommended in many guidelines. These types of pain can be treated with antidepressant drugs in doses below those at which the drugs act as antidepressants.

Objectives: To assess the analgesic efficacy of amitriptyline for chronic neuropathic pain and fibromyalgia.To assess the adverse events associated with the clinical use of amitriptyline for chronic neuropathic pain and fibromyalgia.

Search Methods: We searched CENTRAL, MEDLINE, and EMBASE to September 2012, together with reference lists of retrieved papers, previous systematic reviews, and other reviews; we also used our own handsearched database for older studies.

Selection Criteria: We included randomised, double-blind studies of at least four weeks’ duration comparing amitriptyline with placebo or another active treatment in chronic neuropathic pain or fibromyalgia.

Data Collection and Analysis: We extracted efficacy and adverse event data, and two study authors examined issues of study quality independently. We performed analysis using two tiers of evidence.

  • The first tier used data meeting current best standards, where studies reported the outcome of at least 50% pain intensity reduction over baseline (or its equivalent), without the use of last observation carried forward (LOCF) or other imputation method for dropouts, reported an intention-to-treat (ITT) analysis, lasted 8 to 12 weeks or longer, had a parallel-group design, and where there were at least 200 participants in the comparison.

  • The second tier used data that failed to meet this standard and were therefore subject to potential bias.

Main Results: Twenty-one studies (1437 participants) were included; they individually involved between 15 and 235 participants, only four involved over 100 participants, and the median study size was 44 participants. The median duration was six weeks. Ten studies had a cross-over design. Doses of amitriptyline were generally between 25 mg and 125 mg, and dose escalation was common.

  • There was no top-tier evidence for amitriptyline in treating neuropathic pain or fibromyalgia.

  • Second-tier evidence indicated no evidence of effect in cancer-related neuropathic pain or HIV-related neuropathic pain, but some evidence of effect in painful diabetic neuropathy (PDN), mixed neuropathic pain, and fibromyalgia.

  • Combining the classic neuropathic pain conditions of PDN, postherpetic neuralgia (PHN) and post-stroke pain with fibromyalgia for second-tier evidence, in eight studies and 687 participants, there was a statistically significant benefit (risk ratio (RR) 2.3, 95% confidence interval (CI) 1.8 to 3.1) with a number needed to treat (NNT) of 4.6 (3.6 to 6.6). The analysis showed that even using this potentially biased data, only about 38% of participants benefited with amitriptyline and 16% with placebo; most participants did not get adequate pain relief.

  • Potential benefits of amitriptyline were supported by a lower rate of lack of efficacy withdrawals; 8/153 (5%) withdrew because of lack of efficacy with amitriptyline and 14/119 (12%) with placebo.

  • More participants experienced at least one adverse event; 64% of participants taking amitriptyline and 40% taking placebo.

  • The RR was 1.5 (95% CI 1.4 to 1.7) and the number needed to treat to harm was 4.1 (95% CI 3.2 to 5.7).

  • Adverse event and all-cause withdrawals were not different.

Authors’ Conclusions: 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.

It is unlikely that any large randomised trials of amitriptyline will be conducted in specific neuropathic pain conditions or in fibromyalgia to prove efficacy.

Source: “Cochrane Database of Systematic Reviews”, December 12, 2012. By R.A. Moore, S. Derry, D. Aldington, P. Cole, and P.J. Wiffen. Pain Research and Nuffield Department of Clinical Neurosciences, University of Oxford, Pain Research Unit, Churchill Hospital, Oxford, Oxfordshire, UK, OX3 7LE.

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3 thoughts on “Analysis of Amitriptyline’s Effectiveness for Fibromyalgia and Neuropathic Pain”

  1. roge says:

    why are we still wasting limited research dollars on studying amitrypyline for FM – lets stop beating a dead horse – this is not 1991, it is 2013 almost.

  2. rosedale says:

    I ‘ve had fibro for 18 years, and it was awful for a long time. There were no meds like Lyrica (which does not faze my pain) and while Aleve helped, with my past history of stomach ulcers I could take it infrequently. Epsom salt baths and homeopathic arnica, and physical therapy, helped, but my life was and is changed. About 6 months ago my doc gave me amytriptylline 25 mg. at bedtime to see if it wouls help me sleep since I have had insomnia for 9 or 10 years. I started sleeping and was able to stop taking temazepam, which was making me feel drunk and have nightmares. Then- surprise! I have had a gradual improvement of fibro pain with no other changes that could be affecting it. I used to take amytriptylline in the ’80’s for depression in a much larger dose with side effects but no real effect on the depression. So, you never know what might help you. It’s worth a try- just give it some time. I will never be well, after all these years, but I feel better, and that’s a good thing.

  3. ME/Fibro says:

    Since being diagnosed with Fibromyalgia (I have had ME for many more years), I tried Nortripyline on the advice of a good doctor of my acquaintance. I started at 5mg, increased to 10mg, and have maintained this for several years.

    For comparison, I tried going off it a few years ago. I found my stiffness and pain increased immediately, and I became crankier than usual.

    I went back onto it and those symptoms cleared up quite well. It is not perfect, but it definitely helps. A high dose multi mineral also helps just as much.

    Some people can’t handle the frequent urination Nortriptyline causes. One person is on Gabapentin. I Googled it and found it can cause aggressive vociferousness, which it definitely does.

    It’s best to be healthy. If you’re not, something like this might be needed.

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