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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Pharmacotherapy for neuropathic pain in adults: systematic review, meta-analysis and updated NeuPSIG recommendations</title>
<author><name sortKey="Finnerup, Nanna B" sort="Finnerup, Nanna B" uniqKey="Finnerup N" first="Nanna B" last="Finnerup">Nanna B. Finnerup</name>
<affiliation><nlm:aff id="A1">Danish Pain Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Attal, Nadine" sort="Attal, Nadine" uniqKey="Attal N" first="Nadine" last="Attal">Nadine Attal</name>
<affiliation><nlm:aff id="A2">INSERM U-987, Centre d’Evaluation et de Traitement de la Douleur, Hôpital Ambroise Paré, APHP, Boulogne-Billancourt, France</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">Université Versailles Saint-Quentin, France</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Haroutounian, Simon" sort="Haroutounian, Simon" uniqKey="Haroutounian S" first="Simon" last="Haroutounian">Simon Haroutounian</name>
<affiliation><nlm:aff id="A4">Division of Clinical and Translational Research, Department of Anesthesiology, Washington University Scool of Medicine, St Louis, MO, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Mcnicol, Ewan" sort="Mcnicol, Ewan" uniqKey="Mcnicol E" first="Ewan" last="Mcnicol">Ewan Mcnicol</name>
<affiliation><nlm:aff id="A5">Departments of Anesthesiology and Pharmacy, Tufts Medical Center, Boston, MA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Baron, Ralf" sort="Baron, Ralf" uniqKey="Baron R" first="Ralf" last="Baron">Ralf Baron</name>
<affiliation><nlm:aff id="A6">Division of Neurological Pain Research and Therapy, Department of Neurology, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Germany</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Dworkin, Robert H" sort="Dworkin, Robert H" uniqKey="Dworkin R" first="Robert H" last="Dworkin">Robert H. Dworkin</name>
<affiliation><nlm:aff id="A7">Department of Anesthesiology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA and Department of Neurology, Center for Human Experimental Therapeutics, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Gilron, Ian" sort="Gilron, Ian" uniqKey="Gilron I" first="Ian" last="Gilron">Ian Gilron</name>
<affiliation><nlm:aff id="A8">Department of Anesthesiology & Perioperative Medicine and Biomedical & Molecular Sciences, Queen’s University, Kingston, Canada</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Haanpaa, Maija" sort="Haanpaa, Maija" uniqKey="Haanpaa M" first="Maija" last="Haanpaa">Maija Haanpaa</name>
<affiliation><nlm:aff id="A9">Department of Neurosurgery, Helsinki University Central Hospital, Helsinki, Finland; Mutual Insurance Company Etera, Helsinki, Finland</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hansson, Per" sort="Hansson, Per" uniqKey="Hansson P" first="Per" last="Hansson">Per Hansson</name>
<affiliation><nlm:aff id="A10">Dept. of Pain Management and Research, Oslo University Hospital, Oslo, Norway and Dept. of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Jensen, Troels S" sort="Jensen, Troels S" uniqKey="Jensen T" first="Troels S" last="Jensen">Troels S. Jensen</name>
<affiliation><nlm:aff id="A1">Danish Pain Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A11">Department of Neurology, Aarhus University Hospital, Aarhus, Denmark</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kamerman, Peter R" sort="Kamerman, Peter R" uniqKey="Kamerman P" first="Peter R" last="Kamerman">Peter R. Kamerman</name>
<affiliation><nlm:aff id="A12">Brain Function Research Group, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, South Africa</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Lund, Karen" sort="Lund, Karen" uniqKey="Lund K" first="Karen" last="Lund">Karen Lund</name>
<affiliation><nlm:aff id="A1">Danish Pain Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Moore, Andrew" sort="Moore, Andrew" uniqKey="Moore A" first="Andrew" last="Moore">Andrew Moore</name>
<affiliation><nlm:aff id="A13">Nuffield Division of Anaesthetics, Nuffield Department of Clinical Neurosciences, Pain Research, The Churchill, Oxford, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Raja, Srinivasa N" sort="Raja, Srinivasa N" uniqKey="Raja S" first="Srinivasa N" last="Raja">Srinivasa N. Raja</name>
<affiliation><nlm:aff id="A14">Johns Hopkins School of Medicine, Division of Pain Medicine, Department of Anesthesiology and Critical Care Medicine, Baltimore, MD, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Rice, Andrew Sc" sort="Rice, Andrew Sc" uniqKey="Rice A" first="Andrew Sc" last="Rice">Andrew Sc Rice</name>
<affiliation><nlm:aff id="A15">Pain Research, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, UK and Hon. Consultant in Pain Medicine, Chelsea and Westminster Hospital NHS Foundation Trust, London, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Rowbotham, Michael" sort="Rowbotham, Michael" uniqKey="Rowbotham M" first="Michael" last="Rowbotham">Michael Rowbotham</name>
<affiliation><nlm:aff id="A16">California Pacific Medical Center Research Institute and UCSF Pain Management Center, San Francisco, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Sena, Emily" sort="Sena, Emily" uniqKey="Sena E" first="Emily" last="Sena">Emily Sena</name>
<affiliation><nlm:aff id="A17">Division of Clinical Neurosciences, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK and Florey Institute of Neuroscience and Mental Health, Melbourne, Australia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Siddall, Philip" sort="Siddall, Philip" uniqKey="Siddall P" first="Philip" last="Siddall">Philip Siddall</name>
<affiliation><nlm:aff id="A18">Department of Pain Management, Greenwich Hospital, HammondCare, Sydney NSW Australia; and Kolling Institute, Sydney Medical School-Northern, University of Sydney, Sydney NSW Australia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Smith, Blair H" sort="Smith, Blair H" uniqKey="Smith B" first="Blair H" last="Smith">Blair H. Smith</name>
<affiliation><nlm:aff id="A19">Division of Population Health Sciences, University of Dundee, Ninewells Hospital and Medical School, Dundee, Scotland</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wallace, Mark" sort="Wallace, Mark" uniqKey="Wallace M" first="Mark" last="Wallace">Mark Wallace</name>
<affiliation><nlm:aff id="A20">Division of Pain Medicine, Department of Anesthesiology, University of California, San Diego, USA</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">25575710</idno>
<idno type="pmc">4493167</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4493167</idno>
<idno type="RBID">PMC:4493167</idno>
<idno type="doi">10.1016/S1474-4422(14)70251-0</idno>
<date when="2015">2015</date>
<idno type="wicri:Area/Pmc/Corpus">001E09</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001E09</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Pharmacotherapy for neuropathic pain in adults: systematic review, meta-analysis and updated NeuPSIG recommendations</title>
<author><name sortKey="Finnerup, Nanna B" sort="Finnerup, Nanna B" uniqKey="Finnerup N" first="Nanna B" last="Finnerup">Nanna B. Finnerup</name>
<affiliation><nlm:aff id="A1">Danish Pain Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Attal, Nadine" sort="Attal, Nadine" uniqKey="Attal N" first="Nadine" last="Attal">Nadine Attal</name>
<affiliation><nlm:aff id="A2">INSERM U-987, Centre d’Evaluation et de Traitement de la Douleur, Hôpital Ambroise Paré, APHP, Boulogne-Billancourt, France</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">Université Versailles Saint-Quentin, France</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Haroutounian, Simon" sort="Haroutounian, Simon" uniqKey="Haroutounian S" first="Simon" last="Haroutounian">Simon Haroutounian</name>
<affiliation><nlm:aff id="A4">Division of Clinical and Translational Research, Department of Anesthesiology, Washington University Scool of Medicine, St Louis, MO, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Mcnicol, Ewan" sort="Mcnicol, Ewan" uniqKey="Mcnicol E" first="Ewan" last="Mcnicol">Ewan Mcnicol</name>
<affiliation><nlm:aff id="A5">Departments of Anesthesiology and Pharmacy, Tufts Medical Center, Boston, MA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Baron, Ralf" sort="Baron, Ralf" uniqKey="Baron R" first="Ralf" last="Baron">Ralf Baron</name>
<affiliation><nlm:aff id="A6">Division of Neurological Pain Research and Therapy, Department of Neurology, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Germany</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Dworkin, Robert H" sort="Dworkin, Robert H" uniqKey="Dworkin R" first="Robert H" last="Dworkin">Robert H. Dworkin</name>
<affiliation><nlm:aff id="A7">Department of Anesthesiology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA and Department of Neurology, Center for Human Experimental Therapeutics, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Gilron, Ian" sort="Gilron, Ian" uniqKey="Gilron I" first="Ian" last="Gilron">Ian Gilron</name>
<affiliation><nlm:aff id="A8">Department of Anesthesiology & Perioperative Medicine and Biomedical & Molecular Sciences, Queen’s University, Kingston, Canada</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Haanpaa, Maija" sort="Haanpaa, Maija" uniqKey="Haanpaa M" first="Maija" last="Haanpaa">Maija Haanpaa</name>
<affiliation><nlm:aff id="A9">Department of Neurosurgery, Helsinki University Central Hospital, Helsinki, Finland; Mutual Insurance Company Etera, Helsinki, Finland</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hansson, Per" sort="Hansson, Per" uniqKey="Hansson P" first="Per" last="Hansson">Per Hansson</name>
<affiliation><nlm:aff id="A10">Dept. of Pain Management and Research, Oslo University Hospital, Oslo, Norway and Dept. of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Jensen, Troels S" sort="Jensen, Troels S" uniqKey="Jensen T" first="Troels S" last="Jensen">Troels S. Jensen</name>
<affiliation><nlm:aff id="A1">Danish Pain Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A11">Department of Neurology, Aarhus University Hospital, Aarhus, Denmark</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kamerman, Peter R" sort="Kamerman, Peter R" uniqKey="Kamerman P" first="Peter R" last="Kamerman">Peter R. Kamerman</name>
<affiliation><nlm:aff id="A12">Brain Function Research Group, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, South Africa</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Lund, Karen" sort="Lund, Karen" uniqKey="Lund K" first="Karen" last="Lund">Karen Lund</name>
<affiliation><nlm:aff id="A1">Danish Pain Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Moore, Andrew" sort="Moore, Andrew" uniqKey="Moore A" first="Andrew" last="Moore">Andrew Moore</name>
<affiliation><nlm:aff id="A13">Nuffield Division of Anaesthetics, Nuffield Department of Clinical Neurosciences, Pain Research, The Churchill, Oxford, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Raja, Srinivasa N" sort="Raja, Srinivasa N" uniqKey="Raja S" first="Srinivasa N" last="Raja">Srinivasa N. Raja</name>
<affiliation><nlm:aff id="A14">Johns Hopkins School of Medicine, Division of Pain Medicine, Department of Anesthesiology and Critical Care Medicine, Baltimore, MD, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Rice, Andrew Sc" sort="Rice, Andrew Sc" uniqKey="Rice A" first="Andrew Sc" last="Rice">Andrew Sc Rice</name>
<affiliation><nlm:aff id="A15">Pain Research, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, UK and Hon. Consultant in Pain Medicine, Chelsea and Westminster Hospital NHS Foundation Trust, London, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Rowbotham, Michael" sort="Rowbotham, Michael" uniqKey="Rowbotham M" first="Michael" last="Rowbotham">Michael Rowbotham</name>
<affiliation><nlm:aff id="A16">California Pacific Medical Center Research Institute and UCSF Pain Management Center, San Francisco, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Sena, Emily" sort="Sena, Emily" uniqKey="Sena E" first="Emily" last="Sena">Emily Sena</name>
<affiliation><nlm:aff id="A17">Division of Clinical Neurosciences, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK and Florey Institute of Neuroscience and Mental Health, Melbourne, Australia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Siddall, Philip" sort="Siddall, Philip" uniqKey="Siddall P" first="Philip" last="Siddall">Philip Siddall</name>
<affiliation><nlm:aff id="A18">Department of Pain Management, Greenwich Hospital, HammondCare, Sydney NSW Australia; and Kolling Institute, Sydney Medical School-Northern, University of Sydney, Sydney NSW Australia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Smith, Blair H" sort="Smith, Blair H" uniqKey="Smith B" first="Blair H" last="Smith">Blair H. Smith</name>
<affiliation><nlm:aff id="A19">Division of Population Health Sciences, University of Dundee, Ninewells Hospital and Medical School, Dundee, Scotland</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wallace, Mark" sort="Wallace, Mark" uniqKey="Wallace M" first="Mark" last="Wallace">Mark Wallace</name>
<affiliation><nlm:aff id="A20">Division of Pain Medicine, Department of Anesthesiology, University of California, San Diego, USA</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">The Lancet. Neurology</title>
<idno type="ISSN">1474-4422</idno>
<idno type="eISSN">1474-4465</idno>
<imprint><date when="2015">2015</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><title>Summary</title>
<sec id="S1"><title>Background</title>
<p id="P1">Neuropathic pain is difficult to treat. New treatments, clinical trials and standards of quality for assessing evidence justify an update of evidence-based recommendations for its pharmacological treatment.</p>
</sec>
<sec id="S2"><title>Methods</title>
<p id="P2">The Neuropathic Pain Special Interest Group (NeuPSIG) of the International Association for the Study of Pain conducted a systematic review of randomised double-blind studies of oral and topical pharmacotherapy for neuropathic pain, including unpublished trials (retrieved from clinicaltrials.gov and pharmaceutical websites). Meta-analysis used Numbers Needed to Treat (NNT) for 50 % pain relief as primary measure and assessed publication bias. Recommendations used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE).</p>
</sec>
<sec id="S3"><title>Findings</title>
<p id="P3">In total 229 studies were included. Analysis of publication bias suggested a 10% overstatement of treatment effects. Studies published in peer-review journals reported greater effects than online studies (R<sup>2</sup>
=9·3%, p<0·01). Trial outcomes were generally modest even for effective drugs : in particular NNTs were 3·6 (95 % CI 3·0–4·4) for tricyclic antidepressants (TCAs), 6·4 (95 % CI 5·2–8·4) for serotonin- noradrenaline reuptake inbibitor (SNRI) antidepressants duloxetine and venlafaxine, 7·7 (95 % CI 6·5–9·4) for pregabalin and 6·3 (95 % CI 5·0–8·3) for gabapentin. NNTs were higher for gabapentin ER/enacarbil and capsaicin high concentration patches, lower for opioids and botulinum toxin A (BTX-A) and undetermined for lidocaine patches. Final quality of evidence was lower for lidocaine patches and BTX-A. Tolerability/safety and values/preferences were high for lidocaine patches and lower for opioids and TCAs. This permitted a strong GRADE recommendation for use and proposal as first line for TCAs, SNRIs, pregabalin, gabapentin and gabapentin ER/enacarbil in neuropathic pain, a weak recommendation for use and proposal as second line for lidocaine patches, capsaicin patches and tramadol, and a weak recommendations for use and proposal as third line for strong opioids (particularly oxycodone and morphine) and BTX-A. Data for cannabinoids, tapentadol, drug combinations, and several other antiepileptics, antidepressants and topical drugs were inconclusive.</p>
</sec>
<sec id="S4"><title>Interpretation</title>
<p id="P4">Limited efficacy, large placebo responses, inadequate diagnostic criteria and poor phenotypic profiling probably account for modest trial outcomes and should be taken into account in future studies.</p>
</sec>
<sec id="S5"><title>Funding</title>
<p id="P5">This study was funded by NeuPSIG.</p>
</sec>
</div>
</front>
</TEI>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">101139309</journal-id>
<journal-id journal-id-type="pubmed-jr-id">30413</journal-id>
<journal-id journal-id-type="nlm-ta">Lancet Neurol</journal-id>
<journal-id journal-id-type="iso-abbrev">Lancet Neurol</journal-id>
<journal-title-group><journal-title>The Lancet. Neurology</journal-title>
</journal-title-group>
<issn pub-type="ppub">1474-4422</issn>
<issn pub-type="epub">1474-4465</issn>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">25575710</article-id>
<article-id pub-id-type="pmc">4493167</article-id>
<article-id pub-id-type="doi">10.1016/S1474-4422(14)70251-0</article-id>
<article-id pub-id-type="manuscript">NIHMS702730</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Pharmacotherapy for neuropathic pain in adults: systematic review, meta-analysis and updated NeuPSIG recommendations</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Finnerup</surname>
<given-names>Nanna B</given-names>
</name>
<degrees>MD</degrees>
<xref rid="FN2" ref-type="author-notes">*</xref>
<xref ref-type="aff" rid="A1">a</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Attal</surname>
<given-names>Nadine</given-names>
</name>
<degrees>MD</degrees>
<xref rid="FN2" ref-type="author-notes">*</xref>
<xref ref-type="aff" rid="A2">b</xref>
<xref ref-type="aff" rid="A3">c</xref>
<xref rid="FN1" ref-type="author-notes">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Haroutounian</surname>
<given-names>Simon</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="A4">d</xref>
</contrib>
<contrib contrib-type="author"><name><surname>McNicol</surname>
<given-names>Ewan</given-names>
</name>
<degrees>MS</degrees>
<xref ref-type="aff" rid="A5">e</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Baron</surname>
<given-names>Ralf</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A6">f</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Dworkin</surname>
<given-names>Robert H</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="A7">g</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Gilron</surname>
<given-names>Ian</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A8">h</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Haanpaa</surname>
<given-names>Maija</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A9">i</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hansson</surname>
<given-names>Per</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A10">j</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Jensen</surname>
<given-names>Troels S</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A1">a</xref>
<xref ref-type="aff" rid="A11">k</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kamerman</surname>
<given-names>Peter R</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="A12">l</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lund</surname>
<given-names>Karen</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A1">a</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Moore</surname>
<given-names>Andrew</given-names>
</name>
<degrees>DSc</degrees>
<xref ref-type="aff" rid="A13">m</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Raja</surname>
<given-names>Srinivasa N</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A14">n</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Rice</surname>
<given-names>Andrew SC</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A15">o</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Rowbotham</surname>
<given-names>Michael</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A16">p</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Sena</surname>
<given-names>Emily</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="A17">q</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Siddall</surname>
<given-names>Philip</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A18">r</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Smith</surname>
<given-names>Blair H</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A19">s</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Wallace</surname>
<given-names>Mark</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A20">t</xref>
</contrib>
</contrib-group>
<aff id="A1"><label>a</label>
Danish Pain Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark</aff>
<aff id="A2"><label>b</label>
INSERM U-987, Centre d’Evaluation et de Traitement de la Douleur, Hôpital Ambroise Paré, APHP, Boulogne-Billancourt, France</aff>
<aff id="A3"><label>c</label>
Université Versailles Saint-Quentin, France</aff>
<aff id="A4"><label>d</label>
Division of Clinical and Translational Research, Department of Anesthesiology, Washington University Scool of Medicine, St Louis, MO, USA</aff>
<aff id="A5"><label>e</label>
Departments of Anesthesiology and Pharmacy, Tufts Medical Center, Boston, MA, USA</aff>
<aff id="A6"><label>f</label>
Division of Neurological Pain Research and Therapy, Department of Neurology, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Germany</aff>
<aff id="A7"><label>g</label>
Department of Anesthesiology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA and Department of Neurology, Center for Human Experimental Therapeutics, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA</aff>
<aff id="A8"><label>h</label>
Department of Anesthesiology & Perioperative Medicine and Biomedical & Molecular Sciences, Queen’s University, Kingston, Canada</aff>
<aff id="A9"><label>i</label>
Department of Neurosurgery, Helsinki University Central Hospital, Helsinki, Finland; Mutual Insurance Company Etera, Helsinki, Finland</aff>
<aff id="A10"><label>j</label>
Dept. of Pain Management and Research, Oslo University Hospital, Oslo, Norway and Dept. of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden</aff>
<aff id="A11"><label>k</label>
Department of Neurology, Aarhus University Hospital, Aarhus, Denmark</aff>
<aff id="A12"><label>l</label>
Brain Function Research Group, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, South Africa</aff>
<aff id="A13"><label>m</label>
Nuffield Division of Anaesthetics, Nuffield Department of Clinical Neurosciences, Pain Research, The Churchill, Oxford, UK</aff>
<aff id="A14"><label>n</label>
Johns Hopkins School of Medicine, Division of Pain Medicine, Department of Anesthesiology and Critical Care Medicine, Baltimore, MD, USA</aff>
<aff id="A15"><label>o</label>
Pain Research, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, UK and Hon. Consultant in Pain Medicine, Chelsea and Westminster Hospital NHS Foundation Trust, London, UK</aff>
<aff id="A16"><label>p</label>
California Pacific Medical Center Research Institute and UCSF Pain Management Center, San Francisco, USA</aff>
<aff id="A17"><label>q</label>
Division of Clinical Neurosciences, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK and Florey Institute of Neuroscience and Mental Health, Melbourne, Australia</aff>
<aff id="A18"><label>r</label>
Department of Pain Management, Greenwich Hospital, HammondCare, Sydney NSW Australia; and Kolling Institute, Sydney Medical School-Northern, University of Sydney, Sydney NSW Australia</aff>
<aff id="A19"><label>s</label>
Division of Population Health Sciences, University of Dundee, Ninewells Hospital and Medical School, Dundee, Scotland</aff>
<aff id="A20"><label>t</label>
Division of Pain Medicine, Department of Anesthesiology, University of California, San Diego, USA</aff>
<author-notes><corresp id="FN1"><label>1</label>
Corresponding author: Nadine ATTAL, INSERM U 987 and Centre d’Evaluation et de Traitement de La Douleur, Hospital Ambroise Pare, Boulogne-Billancourt, France Tel.: 0033149094433 ; <email>nadine.attal@apr.aphp.fr</email>
</corresp>
<fn id="FN2" fn-type="equal"><label>*</label>
<p>N Attal and NB Finnerup contributed equally to this work.</p>
</fn>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>25</day>
<month>6</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="epub"><day>07</day>
<month>1</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="ppub"><month>2</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>01</day>
<month>2</month>
<year>2016</year>
</pub-date>
<volume>14</volume>
<issue>2</issue>
<fpage>162</fpage>
<lpage>173</lpage>
<pmc-comment>elocation-id from pubmed: 10.1016/S1474-4422(14)70251-0</pmc-comment>
<abstract><title>Summary</title>
<sec id="S1"><title>Background</title>
<p id="P1">Neuropathic pain is difficult to treat. New treatments, clinical trials and standards of quality for assessing evidence justify an update of evidence-based recommendations for its pharmacological treatment.</p>
</sec>
<sec id="S2"><title>Methods</title>
<p id="P2">The Neuropathic Pain Special Interest Group (NeuPSIG) of the International Association for the Study of Pain conducted a systematic review of randomised double-blind studies of oral and topical pharmacotherapy for neuropathic pain, including unpublished trials (retrieved from clinicaltrials.gov and pharmaceutical websites). Meta-analysis used Numbers Needed to Treat (NNT) for 50 % pain relief as primary measure and assessed publication bias. Recommendations used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE).</p>
</sec>
<sec id="S3"><title>Findings</title>
<p id="P3">In total 229 studies were included. Analysis of publication bias suggested a 10% overstatement of treatment effects. Studies published in peer-review journals reported greater effects than online studies (R<sup>2</sup>
=9·3%, p<0·01). Trial outcomes were generally modest even for effective drugs : in particular NNTs were 3·6 (95 % CI 3·0–4·4) for tricyclic antidepressants (TCAs), 6·4 (95 % CI 5·2–8·4) for serotonin- noradrenaline reuptake inbibitor (SNRI) antidepressants duloxetine and venlafaxine, 7·7 (95 % CI 6·5–9·4) for pregabalin and 6·3 (95 % CI 5·0–8·3) for gabapentin. NNTs were higher for gabapentin ER/enacarbil and capsaicin high concentration patches, lower for opioids and botulinum toxin A (BTX-A) and undetermined for lidocaine patches. Final quality of evidence was lower for lidocaine patches and BTX-A. Tolerability/safety and values/preferences were high for lidocaine patches and lower for opioids and TCAs. This permitted a strong GRADE recommendation for use and proposal as first line for TCAs, SNRIs, pregabalin, gabapentin and gabapentin ER/enacarbil in neuropathic pain, a weak recommendation for use and proposal as second line for lidocaine patches, capsaicin patches and tramadol, and a weak recommendations for use and proposal as third line for strong opioids (particularly oxycodone and morphine) and BTX-A. Data for cannabinoids, tapentadol, drug combinations, and several other antiepileptics, antidepressants and topical drugs were inconclusive.</p>
</sec>
<sec id="S4"><title>Interpretation</title>
<p id="P4">Limited efficacy, large placebo responses, inadequate diagnostic criteria and poor phenotypic profiling probably account for modest trial outcomes and should be taken into account in future studies.</p>
</sec>
<sec id="S5"><title>Funding</title>
<p id="P5">This study was funded by NeuPSIG.</p>
</sec>
</abstract>
<kwd-group><kwd>neuropathic pain</kwd>
<kwd>pharmacotherapy</kwd>
<kwd>systematic review</kwd>
<kwd>meta-analysis</kwd>
<kwd>evidence-based</kwd>
<kwd>recommendations</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
</record>
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