Am Fam Physician. 2000 Jun 1;61(11):3452.
Analgesia is often achieved with opioid treatment, but a common side effect is constipation. Because methylnaltrexone does not cross the blood-brain barrier, it does not antagonize the central nervous system effects of opioids but may decrease the peripheral effects of opioids. Yuan and colleagues studied the efficacy of methylnaltrexone, an opioid receptor antagonist, in the management of constipation associated with chronic methadone use.
Twenty-two adults who had been in a methadone maintenance program for at least one month, who had a diagnosis of methadone-induced constipation and who were not currently using laxatives were included in the study. Patients with significant medical conditions or significant findings on physical examination were excluded. Patients continued to receive their normal dosage of methadone during the study. Oral-cecal transit time was measured. The morning after an overnight fast each participant received 10 g of lactulose and intravenous placebo (saline). In the evening, each subject received placebo or methylnaltrexone (up to 0.365 mg per kg) in four syringes. Each syringe was administered intravenously over nine minutes. The four syringes were given consecutively, and the syringes containing the study drug contained gradually larger doses of methylnaltrexone. If defecation occurred within one minute after infusion of the syringe's contents, further administration was stopped. Each person received a fiber-free meal that evening, fasted overnight and again received lactulose to measure oral-cecal transit time. The frequency and consistency of stools were recorded by each participant and confirmed by a nurse. Subjects also completed an opioid withdrawal symptom questionnaire, which included questions about yawning, tearing, perspiration, rhinorrhea, tremor and restlessness.
Mean stool frequency before the study was 1.5 times per week. The placebo administered on day 1 had no effect on any of the participants. None of the 11 patients who were subsequently randomized to the placebo group had any laxation response during the study period. Ten of the 11 people in the active treatment group had an immediate laxation response after the first afternoon treatment, and all of them had an immediate response on the morning of the second day. All participants who received the active drug reported mild to moderate abdominal cramping but no discomfort. None of the patients reported opioid withdrawal symptoms or significant adverse effects. All of the patients who received the study drug reported that they were satisfied with the bowel movement activity. The mean transit time was reduced from 132.3 minutes to 54.5 minutes in the patients who received the active drug.
The authors conclude that patients who have methadone-induced constipation are highly sensitive to the laxation effects of low-dose methylnaltrexone. The authors believe that this effect may also be helpful in other patients who experience opioid-induced constipation.
Yuan CS, et al. Methylnaltrexone for reversal of constipation due to chronic methadone use. A randomized controlled trial. JAMA. January 19, 2000;283:367–72.
Copyright © 2000 by the American Academy of Family Physicians.
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