Laxatives or methylnaltrexone for the management of constipation in palliative care patients

Candy B, Jones L, Goodman ML, Drake R, Tookman A

Published Online:

August 10, 2011

Palliative care patients commonly experience constipation. This is as a result of the use of medications (in particular opioids) for pain control, as well as disease, dietary and mobility factors. This review aimed to determine the effectiveness of laxatives for the management of constipation in palliative care patients. Two review authors assessed study quality and extracted data. Seven studies involving 616 people were included. The drugs evaluated were lactulose, senna, danthron combined with poloxamer, misrakasneham and magnesium hydroxide combined with liquid paraffin. Methylnaltrexone, a drug only recently licensed, was also evaluated for this updated review. There is some evidence that methylnaltrexone is effective (in comparison with a placebo) at inducing laxation (bowel relaxation) in patients taking opioids who have not had a good response to conventional laxatives. The evidence in the other studies was more limited due to lack of overlap in laxatives evaluated. Further rigorous, independent trials with longer follow up are needed to evaluate the effectiveness of laxatives, including methylnaltrexone.

Abstract (click to read)

Background:

Constipation is common in palliative care; it can generate considerable suffering due to the unpleasant physical symptoms. In the first Cochrane Review on effectiveness of laxatives for the management of constipation in palliative care patients, published in 2006, no conclusions could be drawn because of the limited number of evaluations. This article describes the first update of this review.

Objectives:

To determine the effectiveness of laxatives or methylnaltrexone for the management of constipation in palliative care patients.

Search strategy:

We searched databases including MEDLINE and CENTRAL (The Cochrane Library) in 2005 and in the update to August 2010.

Selection criteria:

Randomised controlled trials (RCTs) evaluating laxatives for constipation in palliative care patients. In the update we also included RCTs on subcutaneous methylnaltrexone; an opioid-receptor antagonist that is now licensed for the treatment of opioid-induced constipation in palliative care when response to usual laxative therapy is insufficient.

Data collection and analysis:

Two authors assessed trial quality and extracted data. The appropriateness of combining data from the studies depended upon clinical and outcome measure homogeneity.

Main results:

We included seven studies involving 616 participants; all under-reported methodological features. In four studies the laxatives lactulose, senna, co-danthramer, misrakasneham, and magnesium hydroxide with liquid paraffin were evaluated. In three methylnaltrexone.

In studies comparing the different laxatives evidence was inconclusive. Evidence on subcutaneous methylnaltrexone was clearer; in combined analysis (287 participants) methylnaltrexone, in comparison with a placebo, significantly induced laxation at 4 hours (odds ratio 6.95; 95% confidence interval 3.83 to 12.61). In combined analyses there was no difference in the proportion experiencing side effects, although participants on methylnaltrexone suffered more flatulence and dizziness. No evidence of opioid withdrawal was found. In one study severe adverse events, commonly abdominal pain, were reported that were possibly related to methylnaltrexone. A serious adverse event considered to be related to the methylnaltrexone also occurred; this involved a participant having severe diarrhoea, subsequent dehydration and cardiovascular collapse.

Authors' conclusions:

The 2010 update found evidence on laxatives for management of constipation remains limited due to insufficient RCTs. However, the conclusions of this update have changed since the original review publication in that it now includes evidence on methylnaltrexone. Here it found that subcutaneous methylnaltrexone is effective in inducing laxation in palliative care patients with opioid-induced constipation and where conventional laxatives have failed. However, the safety of this product is not fully evaluated. Large, rigorous, independent trials are needed.

This record should be cited as:

Candy B, Jones L, Goodman ML, Drake R, Tookman A. Laxatives or methylnaltrexone for the management of constipation in palliative care patients. Cochrane Database of Systematic Reviews 2011, Issue 1. Art. No.: CD003448. DOI: 10.1002/14651858.CD003448.pub3

Assessed as up to date:

December 6, 2010

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Primary Review Group:

Pain, Palliative and Supportive Care Group

Health topics:

Cancer > Palliative and supportive care > Symptomatic relief

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

Laxatives or methylnaltrexone for the management of constipation in palliative care patients

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