Abstract: We found six randomised, double-blind trials of at least two weeks' duration eligible for inclusion. These trials included 460 participants with neuropathic pain, with most participants having painful diabetic neuropathy. Four studies were of cross-over design and two were parallel trials. Only one trial was both parallel design and placebo-controlled. Mean age of participants ranged from 48 to 59 years. In three studies (Forssell 2004, Jia 2006 and Tasmuth 2002), only mean data were reported. Comparators included placebo, imipramine, and carbamazepine and duration of treatment ranged from two to eight weeks. The risk of bias was considerable overall in the review, especially due to the small size of most studies and due to attrition bias. Four of the six studies reported some positive benefit for venlafaxine. In the largest study by Rowbotham, 2004, 56% of participants receiving venlafaxine 150 to 225 mg achieved at least a 50% reduction in pain intensity versus 34% of participants in the placebo group and the number needed to treat for an additional beneficial outcome was 4.5. However, this study was subject to significant selection bias. Known adverse effects of venlafaxine, including somnolence, dizziness, and mild gastrointestinal problems, were reported in all studies but were not particularly problematic and, overall, adverse effects were equally prominent in placebo or other active comparator groups. We found little compelling evidence to support the use of venlafaxine in neuropathic pain. While there was some third-tier evidence of benefit, this arose from studies that had methodological limitations and considerable risk of bias. Placebo effects were notably strong in several studies. Given that effective drug treatments for neuropathic pain are in current use, there is no evidence to revise prescribing guidelines to promote the use of venlafaxine in neuropathic pain. Although venlafaxine was generally reasonably well tolerated, there was some evidence that it can precipitate fatigue, somnolence, nausea, and dizziness in a minority of people.

Plain-language summary: In detailed searches of the medical literature, we found six trials that were suitable for inclusion in our analysis, that together included 460 adults. All six trials were conducted in an approved statistical manner (randomised and double-blinded); however, all had limitations that could lead to an overestimation of efficacy in treating this type of pain. Four were of very small size and five were of short duration, both of which can bias the results of chronic pain trials. Although it was not possible to combine the results of all trials to make an overall conclusion, individually they did all show some, albeit moderate, benefit for venlafaxine in treating neuropathic pain. Usually this benefit was achieved at doses of 75 to 225 mg per day. Known side effects of venlafaxine, including sleepiness, dizziness, and mild gastrointestinal problems, were reported by some studies, but were not particularly problematic. Overall, there is currently an inadequate amount of information available to warrant any change in current prescribing practice and we cannot recommend venlafaxine as a first-line treatment for neuropathic pain. However, it is a reasonably well-tolerated drug and may be of some benefit in people who cannot tolerate other antidepressants or anticonvulsant drugs that are more widely prescribed to people with neuropathic pain. Larger clinical trials may provide more robust evidence for the effectiveness of venlafaxine in treating neuropathic pain.