We compared the effectiveness and harms of anticonvulsants, tricyclic antidepressants, serotonin–norepinephrine reuptake inhibitors (SNRIs), and the lidocaine patchin adults with neuropathic pain.
To identify published studies, we searched MEDLINE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, and reference lists of included studies. We also searched the US Food and Drug Administration Center for Drug Evaluation and Research website for additional unpublished data and dossiers of information submitted by 5 pharmaceutical manufacturers.
Study selection, data abstraction, validity assessment, grading the strength of the evidence, and data synthesis were all carried out according to standard Drug Effectiveness Review Project review methods.
Overall, the strength of evidence evaluating the comparative benefits or harms of these drugs to treat neuropathic pain was low to moderate. Based on a small number of short-term trials directly comparing the drugs in patients with painful diabetic neuropathy and postherpetic neuralgia, the evidence did not support a statistically significant difference in response (50% reduction in pain) or withdrawal due to adverse events with gabapentin, pregabalin, and lamotrigine compared with tricyclic antidepressants. Oralpregabalin was similar to lidocaine 5% medicated patchin rate of response, but resulted in more patients withdrawing due to an adverse event. Adjusted indirect comparisons of placebo-controlled trials suggested that duloxetine, pregabalin, and gabapentin were superior to lacosamide and lamotrigine, but no difference in withdrawal from study due to adverse events was found. In these analyses, differences were not found between pregabalin, duloxetine, and gabapentin or comparisons of 5% lidocaine patch and amitriptyline or gabapentin. Tricyclic antidepressants caused more dry mouth than pregabalin or gabapentin while gabapentin and pregabalin resulted in higher rates of ataxia. In patients with cancer-related neuropathic pain who were taking opioids, there was no difference in pain relief with low-dose gabapentin compared with low-dose imipramine. Monotherapy with either drug was insufficient for pain relief. In patients with spinal cord injury, gabapentin was more effective for pain relief than amitriptyline. The difference was significant only in the subgroup of patients with the highest levels of depression. In patients with central poststroke pain, there was no difference between amitriptyline and carbamazepine. There was no direct evidence in patients with HIV-associated neuropathic pain, multiple sclerosis, complex regional pain syndrome, postmastectomy pain syndrome, phantom limb pain, or traumatic nerve injury pain. Evidence for comparative effectiveness in patients with types of neuropathic pain other than diabetic or postherpetic was insufficient to assess comparative safety. Post hoc analyses have not found older age to have an impact on response or treatment-emergent adverse events with duloxetine. Combination therapy with duloxetine and pregabalin; lidocaine patch and pregabalin; or gabapentin with imipramine, nortriptyline, or venlafaxine may have had a potential benefit compared with monotherapy, but there was an increased risk of adverse events.
