title: Randomized study of tramadol/acetaminophen versus placebo in painful diabetic peripheral neuropathy.
abstract: OBJECTIVE
  To examine the efficacy and safety of tramadol/acetaminophen (APAP) for the management of painful diabetic peripheral neuropathy (DPN).
  
  
  METHODS
  Adults with painful DPN involving the lower extremities received 37.5 mg tramadol/325 mg APAP or placebo, up to 1-2 tablets four times daily, for 66 days. Subjects rated average daily pain and sleep interference from 0 ('none') to 10 ('pain as bad as you can imagine' or 'complete interference') every night. Baseline values were recorded for 7 days before starting study medication. The primary endpoint was change in mean of average daily pain scores from baseline to final week. Secondary efficacy outcomes included pain intensity, sleep interference, quality of life, mood, and global impression of change. Potential study limitations included permission to use serotonin reuptake inhibitors concomitantly (except venlafaxine or duloxetine) and the lack of a tramadol-alone or APAP-alone control group.
  
  
  RESULTS
  A total of 160 subjects received tramadol/APAP and 153 received placebo. Tramadol/APAP reduced average daily pain significantly compared to placebo from baseline to the final week (-2.71 vs. -1.83, p = 0.001). Tramadol/APAP was associated with significantly greater improvement than placebo (p < or = 0.05) for all measures of pain intensity, sleep interference, and global impression, as well as several measures of quality of life and mood. The only adverse event reported by > 10% of subjects in either the tramadol/APAP or placebo group was nausea (11.9% and 3.3%, respectively). Adverse events resulted in early study discontinuation for 8.1% and 6.5% of subjects in the tramadol/APAP and placebo groups, respectively.
  
  
  CONCLUSIONS
  Tramadol/APAP was more effective than placebo and was well tolerated in the management of painful DPN.
authors.affiliation: Center for Autonomic and Peripheral Nerve Disorders, Beth Israel-Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. rfreeman@bidmc.harvard.edu
authors.forename: Roy
authors.initials: R
authors.lastname: Freeman
authors.forename: Philip
authors.initials: P
authors.lastname: Raskin
authors.forename: David J
authors.initials: DJ
authors.lastname: Hewitt
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Vorsanger
authors.forename: Donna M
authors.initials: DM
authors.lastname: Jordan
authors.forename: Jim
authors.initials: J
authors.lastname: Xiang
authors.forename: Norman R
authors.initials: NR
authors.lastname: Rosenthal
mesh_terms: D000082:Acetaminophen / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D018712:Analgesics, Non-Narcotic / Q000627:therapeutic use*; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D000704:Analysis of Variance; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000523:psychology; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000523:psychology; D010147:Pain Measurement; D010919:Placebos; D016016:Proportional Hazards Models; D011788:Quality of Life; D012890:Sleep / Q000187:drug effects; D013607:Tablets; D014147:Tramadol / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D004338:Drug Combinations; D010919:Placebos; D013607:Tablets; D000082:Acetaminophen; D014147:Tramadol