Efficacy of extended-release tramadol for treatment of prescription opioid withdrawal: A two-phase randomized controlled trial

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 200. mg group received the least amount in Phase 1, and the 600. mg group received the most in both phases. In Phase 1, tramadol 200. mg 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 200. mg 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.