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Selph S, Carson S, Fu R, et al. Drug Class Review: Neuropathic Pain: Final Update 1 Report [Internet]. Portland (OR): Oregon Health & Science University; 2011 Jun.

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Drug Class Review: Neuropathic Pain: Final Update 1 Report [Internet].

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Strength of Evidence

The results of this review are summarized in Table 17, below, and Appendix E summarizes the strength of the evidence for each key question. The strongest evidence in neuropathic pain trials was in patients with painful diabetic neuropathy. Even within this group, there was no high-strength, comparative evidence available for this review. Evidence of the direct comparison between gabapentin and pregabalin compared with tricyclic antidepressants in patients with either painful diabetic neuropathy or postherpetic neuralgia was moderate. Evidence of indirect comparisons of duloxetine, pregabalin, and gabapentin compared with both lacosamide and lamotrigine in the same population was also moderate. In comparisons involving drugs limited to a single study (lamotrigine, lidocaine, venlafaxine, carbamazepine, and duloxetine), the strength of evidence was generally low to insufficient. There was no direct evidence concerning the effectiveness of 4 drugs (divalproex, oxcarbazepine, lacosamide, and topiramate) in the diabetic or postherpetic neuralgia population.

Table 17. Summary of the evidence by key question.

Table 17

Summary of the evidence by key question.

Limitations of this Report

As with other types of research, the limitations of this systematic review are important to recognize. These can be divided into 2 groups: those relating to generalizability of the results and those relating to methodology within the scope of this review. The generalizability of the results are limited by the scope of the key questions and inclusion criteria and by the generalizability of the studies included. Most studies included narrowly defined populations of patients who met strict criteria for case definition, had fewer comorbidities, and used fewer concomitant medications than many neuropathic pain patients not participating in trials. Minorities, young adults, and the least healthy were under represented as were patients whose pain was less severe or unrelated to diabetes.

Methodological limitations of the review within the defined scope included the exclusion of studies published in languages other than English and lack of a specific search for unpublished studies. Few direct head-to-head comparisons of many of the included drugs have been conducted, which limited our conclusions to indirect comparison of placebo-controlled trials for many of the outcomes. This also limited the strength of the evidence due to heterogeneity of trial populations, interventions, and outcomes assessment. One potential limitation to the applicability of this review is it relates to a narrower range of drugs than are available in clinical practice.


Based on the scope of this review the evidence presented and synthesized here is applicable to a somewhat limited group of patients. Patients in direct comparison trials included in this review were most often from Europe or Asia, female (53%), 60 years old, and had diabetes or postherpetic neuralgia for 7 years (mean range 4–13 years). Only 1 trial was based in the United States; this trial consisted of 26 United States military veterans who included 25 males and 23 Caucasians. Therefore, it is difficult to know whether the results presented here apply equally well to African Americans, Hispanics, or to Caucasians in the United States. The selection of drugs included in this review was influenced by the specific programmatic interests of the organizations participating in the Drug Effectiveness Review Project and were not meant to be read as a usage guideline. Of the drugs studied, trials differed with respect to dosing regimens limiting any conclusions about optimal dose. While evidence on how the drugs compared directly was the goal, the evidence with direct comparison is limited; much of the evidence consisted of placebo-controlled trials. Given that neuropathic pain is a chronic condition, the applicability of results from short-term trials such as those included in this report may be limited. Outcomes studied were primarily measures of pain, with multiple methods used to assess pain response. Neuropathic pain may impact a patient ’s life in other ways as well, such as causing fatigue, depression, lack of ability to have full employment, or reduced quality of life. These outcomes were not well studied, and the evidence does not provide insight here.

Studies Pending Review

The following unpublished studies were identified just after completion of this report (summaries of these studies can be found at and/or and will be considered for inclusion in the next update: NCT01117766, NCT00570310, NCT00424372, NCT01138124, NCT00552175, NCT00385671, NCT00408993, NCT00654940, NCT00232141, NCT00159705, GSK-PXN110448.

Copyright © 2011 by Oregon Health & Science University.
Bookshelf ID: NBK61819


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