title: Efficacy of extended-release tramadol for treatment of prescription opioid withdrawal: a two-phase randomized controlled trial.
abstract: BACKGROUND
  Tramadol is an atypical analgesic with monoamine and modest mu opioid agonist activity. The purpose of this study was to evaluate: (1) the efficacy of extended-release (ER) tramadol in treating prescription opioid withdrawal and (2) whether cessation of ER tramadol produces opioid withdrawal.
  
  
  METHODS
  Prescription opioid users with current opioid dependence and observed withdrawal participated in this inpatient, two-phase double blind, randomized placebo-controlled trial. In Phase 1 (days 1-7), participants were randomly assigned to matched oral placebo or ER tramadol (200 or 600 mg daily). In Phase 2 (days 8-13), all participants underwent double blind crossover to placebo. Breakthrough withdrawal medications were available for all subjects. Enrollment continued until 12 completers/group was achieved.
  
  
  RESULTS
  Use of breakthrough withdrawal medication differed significantly (p<0.05) among groups in both phases; the 200mg group received the least amount in Phase 1, and the 600 mg group received the most in both phases. In Phase 1, tramadol 200mg produced significantly lower peak ratings than placebo on ratings of insomnia, lacrimation, muscular tension, and sneezing. Only tramadol 600 mg produced miosis in Phase 1. In Phase 2, tramadol 600 mg produced higher peak ratings of rhinorrhea, irritable, depressed, heavy/sluggish, and hot/cold flashes than placebo. There were no serious adverse events and no signal of abuse liability for tramadol.
  
  
  CONCLUSIONS
  ER tramadol 200mg modestly attenuated opioid withdrawal. Mild opioid withdrawal occurred after cessation of treatment with 600 mg tramadol. These data support the continued investigation of tramadol as a treatment for opioid withdrawal.
authors.affiliation: University of Kentucky (UK), Department of Psychiatry, Lexington, KY 40509, USA; UK, Department of Behavioral Science, Lexington, KY 40502, USA; UK, Center on Drug and Alcohol Research, Lexington, KY 40502, USA. Electronic address: michelle.lofwall@uky.edu.
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Lofwall
authors.forename: Shanna
authors.initials: S
authors.lastname: Babalonis
authors.forename: Paul A
authors.initials: PA
authors.lastname: Nuzzo
authors.forename: Anthony
authors.initials: A
authors.lastname: Siegel
authors.forename: Charles
authors.initials: C
authors.lastname: Campbell
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Walsh
mesh_terms: D000293:Adolescent; D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009293:Opioid-Related Disorders / Q000188:drug therapy*; D055553:Prescription Drugs / Q000009:adverse effects*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*; D014147:Tramadol / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D055553:Prescription Drugs; D014147:Tramadol
keywords: Efficacy; Opioid withdrawal; Prescription opioid dependence; Randomized clinical trial; Tramadol; Treatment