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.