The level of evidence is downgraded by study quality and imprecise results.

A Cochrane review ¹ included 17 studies with 1342 participants in seven neuropathic pain conditions. Five studies evaluated amitriptyline in postherpetic neuralgia (PHN); none involved more than 62 participants. The duration of the studies varied from five to eight weeks. All studies were active controlled, comparing amitriptyline (25 to 200 mg daily) with fluphenazine, lorazepam, desipramine, fluoxetine, maprotiline, and nortriptyline. Two studies also included a placebo treatment arm. The estimate of exposure to interventions was 227 for amitriptyline, 53 to placebo, and 148 to other interventions. There was no convincing evidence that amitriptyline at various daily doses was better than nortriptyline, maprotiline, desipramine, or fluoxetine. Two studies pointed to amitriptyline being better than placebo, but based on only 84 participants in the comparison. Amitriptyline was possibly better than lorazepam, but not desipramine, maprotiline, or nortriptyline.

More participants experienced at least one adverse event; 55% of participants taking amitriptyline and 36% taking placebo. The RR was 1.5 (95% 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.

Clinical comment: 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 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 but the treatment effect may be overestimated. 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.