ArticlesPharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis
Introduction
Neuropathic pain, caused by a lesion or disease affecting the somatosensory nervous system,1 has a substantial effect on quality of life and is associated with a high economic burden for the individual and society.2, 3, 4 It is now regarded as a distinct clinical entity despite a large variety of causes.5
Epidemiological surveys have shown that many patients with neuropathic pain do not receive appropriate treatment.2, 6, 7 The reasons might be low diagnostic accuracy and ineffective drugs, and perhaps also insufficient knowledge about effective drugs and their appropriate use in clinical practice.8 Evidence-based recommendations for the pharmacotherapy of neuropathic pain are therefore essential.
Over the past 10 years, a few recommendations have been proposed for the pharmacotherapy of neuropathic pain9, 10, 11 or specific neuropathic pain disorders, particularly painful diabetic neuropathies and post-herpetic neuralgia.12, 13, 14 Meanwhile, new pharmacological therapies have been developed and high-quality clinical trials have been done. Previously undisclosed and unpublished large trials can now be identified online (ClinicalTrials.gov and pharmaceutical industry websites), which, together with an analysis of publication bias, might reduce the risk of bias in reporting data. Furthermore, there were some discrepancies in previous recommendations due to inconsistencies in methods used to assess the quality of evidence.13, 15, 16 To address these inconsistencies, the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was introduced in 200017, 18 and received widespread international acceptance. Together, these reasons justify an update of the evidence-based recommendations for the pharmacotherapy of neuropathic pain.
We did a systematic review and meta-analysis of randomised controlled trials of all drug treatments for neuropathic pain published since 1966 and of unpublished trials with available results, and assessed publication bias. We used GRADE to rate the quality of evidence and the strength of recommendations.17, 18 On the basis of the updated review and meta-analysis, we revised the recommendations of the Special Interest Group on Neuropathic Pain (NeuPSIG) of the International Association for the Study of Pain for the systemic and topical pharmacological treatment of neuropathic pain.19 Non-pharmacological management strategies such as neurostimulation techniques were beyond the scope of this work.20
Section snippets
Search strategy and selection criteria
We followed the 23-item Appraisal of Guidelines for Research and Evaluation (AGREE II) for developing and reporting recommendations.21 For details of the working group, criteria for eligibility of studies for the analysis, search methods, reporting, and statistical analysis, see the appendix.
The systematic review of the literature complied with the PRISMA statement.22 We used a standardised review and data extraction protocol (unpublished, appendix). The full reports of randomised, controlled,
Results
Figure 1 shows the results of the database and registry search. 191 published reports and 21 unpublished studies were included in the quantitative synthesis. Study characteristics are summarised in the appendix. Additionally, five published and 12 unpublished studies were retrieved between April, 2013, and January, 2014. Thus, a total of 229 reports or studies were included (see appendix for details of the references).
In studies eligible for inclusion in the meta-analysis, the following drugs
Discussion
In accordance with previous reports,23 results of our meta-analysis show that the efficacy of systemic drug treatments is generally not dependent on the cause of the underlying disorder (appendix). Side-effects might, however, to some degree depend on the cause—eg, drugs with CNS-related side-effects might be tolerated less well in patients with CNS lesions.43 Pain due to HIV-related painful polyneuropathy and radiculopathy seems more refractory than other types of pain in our meta-analysis.
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