{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T16:15:23Z","timestamp":1791648923011,"version":"4.3.4"},"reference-count":33,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Diabetes"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>There is a need for newer therapies for chronic painful diabetic neuropathy as the existing drugs have their own limitations. Clinical trials on low\u2010dose naltrexone (1\u20105\u2009mg\/d) showed efficacy and safety in certain chronic painful conditions, but not in painful diabetic neuropathy. Hence the present study was planned.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Sixty\u2010seven participants with painful diabetic neuropathy were randomized to receive either 2\u2009mg naltrexone or 10\u2009mg amitriptyline daily following a 2\u2010week run\u2010in period. The participants were followed up every 2\u2009weeks for a total of 6\u2009weeks. Up\u2010titration was done (to 4\u2009mg naltrexone or 25\/50\u2009mg amitriptyline) if the pain reduction was less than 20% on the visual analog scale (VAS) during the next follow\u2010up visit. Efficacy was assessed using the change in VAS score at the end of 6\u2009weeks from baseline. Safety was evaluated at each follow\u2010up visit. After 2\u2009weeks of washout period, the participants were crossed over to receive the comparator drug for another 6\u2009weeks with similar evaluations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The difference (confidence interval) in the change in VAS score between groups from baseline was 1.64 (\u22120.92 to 4.20) in per\u2010protocol analysis and 1.5 (\u22121.11 to 4.13) in intention\u2010to\u2010treat analysis. Eight and fifty\u2010two adverse events were reported in the naltrexone and amitriptyline groups, respectively (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.001). The most common adverse events were mild diarrhea with naltrexone and somnolence with amitriptyline.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Low\u2010dose naltrexone exhibited similar efficacy and a superior safety profile compared with amitriptyline in painful diabetic neuropathy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1753-0407.13202","type":"journal-article","created":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T11:49:20Z","timestamp":1621511360000},"page":"770-778","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Efficacy and safety of low\u2010dose naltrexone in painful diabetic neuropathy: A randomized, double\u2010blind, active\u2010control, crossover clinical trial"],"prefix":"10.1111","volume":"13","author":[{"given":"Anand","family":"Srinivasan","sequence":"first","affiliation":[{"name":"Department of Pharmacology All India Institute of Medical Sciences  Bhubaneswar India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinaki","family":"Dutta","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Postgraduate Institute of Medical Education and Research  Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dipika","family":"Bansal","sequence":"additional","affiliation":[{"name":"Department of Clinical Research National Institute of Pharmaceutical Education and Research  SAS Nagar India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amitava","family":"Chakrabarti","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Postgraduate Institute of Medical Education and Research  Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil Kumar","family":"Bhansali","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Postgraduate Institute of Medical Education and Research  Chandigarh 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