Abstract
First-line neuropathic pain drugs, including tricyclic antidepressants, are not always effective, and opioids have been recommended as second line. This trial evaluates a nortriptyline-morphine combination, compared with each monotherapy. In this randomized, double-blind crossover trial, patients with neuropathic pain were enrolled at 1 site between January 25, 2010, and May 22, 2014, and randomized in a 1:1:1 ratio using a balanced Latin square design to receive oral nortriptyline, morphine, and their combination. During each of three 6-week periods, doses were titrated toward maximal tolerated dose (MTD). The primary outcome was average daily pain at MTD, and secondary outcomes included other pain, mood and quality of life measures, and adverse effects. Sixty-two patients were screened, 52 enrolled, and 39 completed at least 2 treatment periods. Average daily pain (0-10) at baseline was 5.3 and at MTD was 2.6 for combination vs 3.1 for nortriptyline (P = 0.046) and 3.4 for morphine (P = 0.002). Brief Pain Inventory scores for average and present pain were also significantly lower for combination vs each monotherapy. Combination treatment resulted in moderate-severe constipation in 43% vs 46% with morphine (P = 0.82) and 5% wi...Continue Reading
References
Aug 1, 1987·Pain·Ronald Melzack
Jul 1, 1973·Psychophysiology·E HoddesW C Dement
Oct 16, 1999·Scandinavian Journal of Gastroenterology·L FrankP Miner
Apr 17, 2001·Annals of Internal Medicine·D G AltmanUNKNOWN CONSORT GROUP (Consolidated Standards of Reporting Trials)
Nov 3, 2001·Pain·J T FarrarR M Poole
Nov 21, 2002·The Clinical Journal of Pain·Dennis C Turk
Mar 28, 2003·The New England Journal of Medicine·Michael C RowbothamDavid Mohr
Mar 20, 2004·Pain·Didier BouhassiraFrançois Boureau
Apr 24, 2004·The Journal of Pain : Official Journal of the American Pain Society·Ariel BergerGerry Oster
Oct 21, 2004·Pain·Stephen F ButlerRobert N Jamison
Dec 29, 2004·Pain·Robert H DworkinUNKNOWN IMMPACT
Mar 1, 2005·Pain·Didier BouhassiraEric Vicaut
Apr 1, 2005·The New England Journal of Medicine·Ian GilronRobyn L Houlden
Dec 22, 2006·Pain·Suzan KhoromiMitchell B Max
Mar 10, 2007·Pain·Yueh-Hua TaiChih-Shung Wong
Aug 3, 2007·Family Practice·Nicola TorranceMichael I Bennett
Nov 16, 2007·Neurology·R-D TreedeJ Serra
Oct 3, 2009·Lancet·Ian GilronRobyn L Houlden
Mar 17, 2010·Mayo Clinic Proceedings·Kenneth E SchmaderBrett Stacey
Mar 9, 2010·Pain·Robert H DworkinJames Witter
Apr 21, 2010·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·N AttalT Nurmikko
Jul 16, 2010·Pain·C MaierD-R Treede
Sep 21, 2010·The Journal of Pain : Official Journal of the American Pain Society·Jianren MaoMiroslav Misha Backonja
Oct 16, 2010·Nature Medicine·Clifford J Woolf
Dec 15, 2010·Pain·Robert H DworkinWendy R Sanhai
Jul 19, 2011·Pain·Troels S JensenRolf-Detlef Treede
Feb 15, 2012·BMJ : British Medical Journal·Rafael Zambelli PintoBart Koes
Mar 8, 2012·BMC Neurology·Ariel BergerGerry Oster
Mar 8, 2013·Pain Practice : the Official Journal of World Institute of Pain·R AndrewCeri J Phillips
Jun 5, 2013·Pain·Solomon TesfayeRainer Freynhagen
Aug 15, 2013·Pain Practice : the Official Journal of World Institute of Pain·Robert Andrew MoorePaul Emery
Oct 1, 2013·Lancet Neurology·Ian GilronAnthony H Dickenson
May 29, 2014·Pain·Jennifer S GewandterRichard E White
Dec 6, 2014·Pain Research & Management : the Journal of the Canadian Pain Society = Journal De La Société Canadienne Pour Le Traitement De La Douleur·Dwight MoulinUNKNOWN Canadian Pain Society
Jan 13, 2015·Lancet Neurology·Nanna B FinnerupMark Wallace
Citations
Apr 14, 2015·Pain·Michael C Rowbotham
Feb 13, 2016·Basic & Clinical Pharmacology & Toxicology·Hugo F MirandaFernando Sierralta
Aug 16, 2016·The American Journal of Emergency Medicine·Zhengqi PanLiaobin Chen
Aug 1, 2016·Oral and Maxillofacial Surgery Clinics of North America·Glenn T ClarkRaymond Dionne
Aug 25, 2016·Experimental Neurology·Jicheng LiHua Zhao
Jan 27, 2016·Expert Opinion on Pharmacotherapy·Jana Sawynok, Celia Zinger
Jan 10, 2017·The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques·Lauren M MaiDwight E Moulin
Mar 30, 2017·JMIR Research Protocols·Ian GilronChristopher Gray
May 26, 2017·Anesthesia and Analgesia·Wenli MiJianren Mao
May 23, 2017·The Cochrane Database of Systematic Reviews·Tess E CooperR Andrew Moore
Aug 3, 2018·Fundamental & Clinical Pharmacology·Hugo F MirandaJuan C Prieto
Jun 13, 2017·Palliative Medicine·Chris M KaneMichael I Bennett
Mar 23, 2017·Pain·Ulrike KaiserRainer Sabatowski
Dec 19, 2018·JAMA : the Journal of the American Medical Association·Jason W BusseGordon H Guyatt
Jan 8, 2019·Clinical Obstetrics and Gynecology·Noor AbualnadiLauren Schiff
Nov 13, 2018·Anesthesia and Analgesia·Rishi Vashishta, Samir M Kendale
Feb 11, 2020·Drugs·Uazman AlamSolomon Tesfaye
Nov 19, 2019·Pain·Rodrigo BenavidesLuda Diatchenko
Apr 14, 2016·Pharmacology Research & Perspectives·Eimear O'NeillAndrew Harkin
Apr 1, 2016·Scandinavian Journal of Pain·Asbjørn M DrewesLona L Christrup
Oct 5, 2019·Pain Reports·Claudia M CampbellSrinivasa Raja
Feb 9, 2017·Pain Medicine : the Official Journal of the American Academy of Pain Medicine·Jian LiHong-Bin Yuan
Jan 17, 2020·Frontiers in Neuroscience·Lidia BravoJuan Antonio Micó
Feb 29, 2020·Global Advances in Health and Medicine : Improving Healthcare Outcomes Worldwide·Chao Hsing YehLeorey N Saligan
Sep 21, 2018·American Society of Clinical Oncology Educational Book·Deanna TeohNick M Spirtos
Jun 10, 2017·JMIR Research Protocols·Ian GilronRoumen Milev
Aug 11, 2020·Pain·Ian GilronChristopher Gray
Aug 5, 2019·Pain Management Nursing : Official Journal of the American Society of Pain Management Nurses·Carla R JungquistRosemary C Polomano
Nov 3, 2020·Pain Reports·Gursharan SohiIan Gilron
Apr 12, 2020·Revue neurologique·X MoissetN Attal
Oct 3, 2020·Best Practice & Research. Clinical Anaesthesiology·Ivan UritsOmar Viswanath
Oct 16, 2018·Revue neurologique·N Attal
May 15, 2021·Pain Research & Management : the Journal of the Canadian Pain Society = Journal De La Société Canadienne Pour Le Traitement De La Douleur·Giulia Di StefanoAndrea Truini
Aug 28, 2021·Journal of Clinical Medicine·Ancor Serrano AfonsoSebastià Videla Cés
Oct 13, 2021·Postgraduate Medicine·Ryan Patel, Anthony H Dickenson