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Review
, 2015 (7), CD008242

Amitriptyline for Neuropathic Pain in Adults

Affiliations
Review

Amitriptyline for Neuropathic Pain in Adults

R Andrew Moore et al. Cochrane Database Syst Rev.

Abstract

Background: This is an updated version of the original Cochrane review published in Issue 12, 2012. That review considered both fibromyalgia and neuropathic pain, but the effects of amitriptyline for fibromyalgia are now dealt with in a separate review.Amitriptyline is a tricyclic antidepressant that is widely used to treat chronic neuropathic pain (pain due to nerve damage). It is recommended as a first line treatment in many guidelines. Neuropathic 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 relief of chronic neuropathic pain, and the adverse events associated with its use in clinical trials.

Search methods: We searched CENTRAL, MEDLINE, and EMBASE to March 2015, together with two clinical trial registries, and the reference lists of retrieved papers, previous systematic reviews, and other reviews; we also used our own hand searched 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 conditions.

Data collection and analysis: We performed analysis using three tiers of evidence. First tier evidence derived from data meeting current best standards and subject to minimal risk of bias (outcome equivalent to substantial pain intensity reduction, intention-to-treat analysis without imputation for dropouts; at least 200 participants in the comparison, 8 to 12 weeks' duration, parallel design), second tier from data that failed to meet one or more of these criteria and were considered at some risk of bias but with adequate numbers in the comparison, and third tier from data involving small numbers of participants that were considered very likely to be biased or used outcomes of limited clinical utility, or both.

Main results: We included 15 studies from the earlier review and two new studies (17 studies, 1342 participants) in seven neuropathic pain conditions. Eight cross-over studies with 302 participants had a median of 36 participants, and nine parallel group studies with 1040 participants had a median of 84 participants. Study quality was modest, though most studies were at high risk of bias due to small size.There was no first-tier or second-tier evidence for amitriptyline in treating any neuropathic pain condition. Only third-tier evidence was available. For only two of seven studies reporting useful efficacy data was amitriptyline significantly better than placebo (very low quality evidence).More participants experienced at least one adverse event; 55% of participants taking amitriptyline and 36% taking placebo. The risk ratio (RR) was 1.5 (95% confidence interval (CI) 1.3 to 1.8) and the number needed to treat for an additional harmful outcome was 5.2 (3.6 to 9.1) (low quality evidence). Serious adverse events were rare. Adverse event and all-cause withdrawals were not different, but were rarely reported (very low quality evidence).

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 people with neuropathic pain. 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, but only a minority of people will achieve satisfactory pain relief. Limited information suggests that failure with one antidepressant does not mean failure with all.

Conflict of interest statement

SD has no conflicts relating to this review or any similar product.

PW has no conflicts relating to this review or any similar product.

RAM has no conflicts relating to this review or any similar product.

DA has no conflicts relating to this review or any similar product.

PC has received research support from industry sources at various times but none related to this review.

For transparency SD, PW, and RAM have received research support from charities, government, and industry sources at various times, but none relate to this review. We are funded by the NIHR for work on a series of reviews informing the unmet need of chronic pain and providing the evidence for treatments of pain.

Figures

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Flow diagram.
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'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
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'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
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Forest plot of comparison: 1 Amitriptyline versus placebo, outcome: 1.1 Third‐tier efficacy.
1.1
1.1
Comparison 1 Amitriptyline versus placebo, Outcome 1 Third‐tier efficacy.
1.2
1.2
Comparison 1 Amitriptyline versus placebo, Outcome 2 At least 1 adverse event.
1.3
1.3
Comparison 1 Amitriptyline versus placebo, Outcome 3 All‐cause withdrawal.
1.4
1.4
Comparison 1 Amitriptyline versus placebo, Outcome 4 Adverse event withdrawal.

Update of

  • Amitriptyline for Neuropathic Pain and Fibromyalgia in Adults
    RA Moore et al. Cochrane Database Syst Rev 12, CD008242. PMID 23235657. - Review
    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 disap …

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