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

FRANÇAIS :
La méthylnaltrexone, antagoniste des récepteurs opioïdes périphériques, a été testée chez 13 personnes en traitement de maintenance à la méthadone pour ses effets contre la constipation. Des injections intraveineuses de méthylnaltrexone ont eu un effet laxatif et ont diminué le temps de transit intestinal. Aucun symptôme de sevrage et aucun effet secondaire n'a été observé durant l'étude.
ENGLISH :
Context: Constipation is themost common chronic adverse effect of opioid pain medications in patients who require long-term opioid administration, such as patients with advanced cancer, but conventional measures for ameliorating constipation often are insufficient. Objective: To evaluate the efficacy of methylnaltrexone, the first peripheral opioid receptor antagonist, in treating chronic methadone-induced constipation. 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 in a methadone maintenance program and having methadone-induced constipation. Main Outcome Measures: Laxation response, oral-cecal transit time, and central opioid withdrawal symptoms were compared between the 2 groups. Results: The 11 subjects in the placebo group showed no laxation response, and all 11 subjects in the intervention group had laxation response after intravenous meth ylnaltrexone administration (P<.001). The oral-cecal transit times at baseline for sub jects in the methylnaltrexone and placebo groups averaged 132.3 and 126.8 minutes, respectively. The average (SD) change in the methylnaltrexone-treated group was -77.7 (37.2) minutes, significantly greater than the average change in the placebo group (-1.4 [12.0] minutes; P<.001). No opioid withdrawal was observed in any subject, and no significant adverse effects were reported by the subjects during the study. Conclusions: Our data demonstrate that intravenous methylnaltrexone can induce laxation and reverse slowing of oral cecal-transit time in subjects taking high opioid dosages. Low-dosage methylnaltrexone may have clinical utility in managing opioid- induced constipation. (Author' s abstract)