Methylnaltrexone for reversal of constipation due to chronic methadone use- A randomized controlled trial

Context Constipation is the most common chronic adverse effect of opioid pa in medications in patients who require long-term opioid administration, suc h as patients with advanced cancer, but conventional measures for ameliorat ing constipation often are insufficient, Objective To evaluate the efficacy of methylnaltrexone, the first periphera l opioid receptor antagonist, in treating chronic methadone-induced constip ation. Design Double-blind, randomized, placebo-controlled trial conducted between May 1997 and December 1998, Setting Clinical research center of a university hospital. Participants Twenty-two subjects (9 men and 13 women; mean [SD] age, 43.2 [ 5.5] years) enrolled iq a methadone maintenance program and having methadon e-induced constipation. Main Outcome Measures Laxation response, oral-cecal transit time, and centr al opioid withdrawal symptoms were compared between the 2 groups. Results The 11 subjects in the placebo group showed no laxation response, a nd all 11 subjects in the intervention group had laxation response after in travenous methylnaltrexone administration (P<.001). The oral-cecal transit times at baseline for subjects in the methylnaltrexone and placebo groups a veraged 132.3 and 126.8 minutes, respectively. The average (SD) change in t he methylnaltrexone-treated group was -77.7 (37.2) minutes, significantly g reater than the average change in the placebo group (-1.4 [12.0] minutes; P <.001), No opioid withdrawal was observed in any subject, acid no significa nt adverse effects were reported by the subjects during the study. Conclusions Our data demonstrate that intravenous methylnaltrexone can indu ce laxation and reverse slowing of oral cecal-transit time in subjects taki ng high opioid dosages, Low-dosage methylnaltrexone may have clinical utili ty in managing opioid-induced constipation.