Are laxatives or methylnaltrexone (Relistor) helpful for the management of constipation in patients receiving palliative care?
There is insufficient evidence to recommend one laxative over another for the treatment of constipation in patients receiving palliative care. Methylnaltrexone can increase the frequency of bowel movements at four hours (odds ratio = 7.0; 95% confidence interval, 3.8 to 12.6) and at 24 hours (odds ratio = 5.4; 95% confidence interval, 3.1 to 9.4). Methylnaltrexone also may increase the risk of flatulence and dizziness. (Strength of Recommendation: B, based on inconsistent or limited-quality patient-oriented evidence.)
Constipation affects up to 48 percent of all patients receiving palliative care,1 and up to 87 percent of patients receiving palliative care who also are taking opioids.2 For some patients, opioid-induced constipation may be so severe that they avoid opioid therapy and choose inadequate analgesia over constipation.3 Although constipation is difficult to define or quantify because normal bowel movements can range from one to three stools per day, three sets of factors can predispose patients to constipation: lifestyle-related factors, disease-related factors, and medications that predispose to constipation. Laxatives have long been recommended for prevention and treatment of palliative care–associated constipation, and methylnaltrexone is a peripherally acting opioid antagonist that is licensed for treatment of opioid-induced constipation when usual measures are ineffective.4
To determine the effectiveness and safety of treating constipation in patients receiving palliative care, the authors searched for randomized controlled trials comparing laxatives or methylnaltrexone with another active treatment or with placebo. The authors found seven studies including 616 patients. Four trials of laxatives that included a variety of agents (i.e., senna, lactulose, misrakasneham, codanthramer, and magnesium hydroxide with liquid paraffin) found no differences in stool frequency response. In all four trials, some patients experienced vomiting and colicky pain, and some required additional interventions for constipation. Three trials evaluated methylnaltrexone and found improved stool frequency at four and 24 hours. However, methylnaltrexone was associated with increased risk of flatulence and dizziness, and one patient had severe diarrhea, dehydration, and cardiovascular collapse.
Palliative care involves balancing symptom relief with avoidance of iatrogenic adverse effects from palliative treatments. For patients with constipation, especially those with opioid-induced constipation, there is insufficient evidence to recommend one laxative over another. The choice of laxatives should be based on past patient experience, tolerability, and adverse effects. Methylnaltrexone is a newer agent that may be useful especially for patients with opioid-induced constipation that has not responded to standard laxatives, but there is limited evidence of potential adverse effects. Therefore, judicious use preceded by a discussion with patients about known risks and benefits is warranted.