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Drug Class Review: Neuropathic Pain

Final Update 1 Report

Drug Class Reviews

, MD, , MPH, , PhD, , MPA:HA, , BA, and , PharmD.

Portland (OR): Oregon Health & Science University; .

Structured Abstract


We compared the effectiveness and harms of anticonvulsants, tricyclic antidepressants, serotonin–norepinephrine reuptake inhibitors (SNRIs), and the lidocaine patchin adults with neuropathic pain.

Data Sources:

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 We also searched the US Food and Drug Administration Center for Drug Evaluation and Research website for additional unpublished data and dossiers of information submitted by 5 pharmaceutical manufacturers.

Review Methods:

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.

Results and Conclusions:

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.


Original Report: October 2007

The medical literature relating to this topic is scanned periodically. (See for description of scanning process). Prior versions of this report can be accessed at the DERP website.

Drug Effectiveness Review Project, Marian McDonagh, PharmD, Principal Investigator, Oregon Evidence-based Practice Center.
Mark Helfand, MD, MPH, Director, Oregon Health & Science University

Acknowledgments: We thank Leah Williams, our publications editor, for putting this report into its present form for you to read. We also thank Theresa Nguyen for retrieval of articles and assistance with editing and formatting during the production of the original report.

Authors of previous updates: Original Report authors: Roger Chou, MD, Susan L. Norris, MD MPH, Susan Carson, MPH, and Benjamin K.S. Chan, MS

Funding: The Drug Effectiveness Review Project, composed of 12 organizations including 11 state Medicaid agencies, and the Canadian Agency for Drugs and Technology in Health commissioned and funded for this report. These organizations selected the topic of the report and had input into its Key Questions. The content and conclusions of the report were entirely determined by the Evidence-based Practice Center researchers. The authors of this report have no financial interest in any company that makes or distributes the products reviewed in this report.

Suggested citation:

Selph S, Carson S, Fu R, Thakurta S, Low A, McDonagh M. Drug class review: Neuropathic pain. Update 1 final report. Prepared by the Oregon Evidence-based Practice Center for the Drug Effectiveness Review Project. Oregon Health & Science University. Portland, OR. 2011. Available at:

The Agency for Healthcare Research and Quality has not yet seen or approved this report

The purpose of Drug Effectiveness Review Project reports is to make available information regarding the comparative clinical effectiveness and harms of different drugs. Reports are not usage guidelines, nor should they be read as an endorsement of or recommendation for any particular drug, use, or approach. Oregon Health & Science University does not recommend or endorse any guideline or recommendation developed by users of these reports.

Copyright © 2011 by Oregon Health & Science University.
Bookshelf ID: NBK61823PMID: 21977547


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