The level of evidence is downgraded by study limitations (small studies with limited duration).
A Cochrane review included 6 studies with a total of 438 subjects. All studies were double-blinded comparing tramadol with placebo. Participants had experienced moderate or severe neuropathic pain for at least three months due to cancer, cancer treatment, postherpetic neuralgia, peripheral diabetic neuropathy, spinal cord injury, or polyneuropathy. The mean age was 50 to 67 years with approximately equal numbers of men and women. In each study tramadol was started at a dose of about 100 mg daily and increased over one to two weeks to a maximum of 400 mg daily or the maximum tolerated dose, and then maintained for the remainder of the study. Study duration for treatments was four to six weeks, and two studies had a cross-over design.
At least 50% pain intensity reduction was reported in three studies (265 participants, 110 events). Using a random-effects analysis, 70/132 (53%) had at least 50% pain relief with tramadol, and 40/133 (30%) with placebo; RR) 2.2 (95% CI 1.02 to 4.6), NNT was 4.4 (95% CI 2.9 to 8.8).
Participants experienced more adverse events with tramadol than placebo. Report of any adverse event was higher with tramadol (58%) than placebo (34%) (4 studies, 266 participants, 123 events; RR 1.6 (95% CI 1.2 to 2.1); NNH 4.2 (95% CI 2.8 to 8.3)). Adverse event withdrawal was higher with tramadol (16%) than placebo (3%) (6 studies, 485 participants, 45 events; RR 4.1 (95% CI 2.0 to 8.4); NNH 8.2 (95% CI 5.8 to 14)).
Five trials compared tramadol with placebo, one with clomipramine, and one with morphine. Two of studies comparing tramadol with placebo considered diabetic neuropathy, one postherpetic neuralgia, one painful polyneuropathy of any cause and one neuropathic cancer pain. For those 3 placebo-controlled trials where it was possible to evaluate the primary outcome measure, participants achieving at least 50% pain relief RR was 1.7 (95% CI 1.36 to 2.14), NNT 3.8. Two trials (neuropathic cancer pain, diabetic neuropathy) could not be included in the meta-analysis due to lack of the necessary data. The RR of side effect leading to withdrawal was 5.37 (95% Cl 1.62 to 17.75), NNH 8.3. Given the small number of participants and the non-blinded nature of the trials comparing tramadol with clomipramine or morphine it is not possible to draw conclusions about their relative efficacy.