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


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


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


METHODS
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.


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


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.


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.
Marie Curie Palliative Care Research Unit, Department of Mental Health Sciences, Royal Free & University College Medical School, Hampstead Campus, Rowland Hill Street, London, UK, NW3 2PF.
Bridget
B
Candy
Louise
L
Jones
Margaret Lynn
ML
Goodman
Robyn
R
Drake
Adrian
A
Tookman
D000701:Analgesics, Opioid / Q000009:adverse effects; D000880:Anthraquinones / Q000627:therapeutic use; D002400:Cathartics / Q000009:adverse effects / Q000627:therapeutic use*; D003248:Constipation / Q000139:chemically induced / Q000188:drug therapy*; D006801:Humans; D007792:Lactulose / Q000627:therapeutic use; D008276:Magnesium Hydroxide / Q000627:therapeutic use; D009271:Naltrexone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010166:Palliative Care; D010232:Paraffin / Q000627:therapeutic use; D000644:Quaternary Ammonium Compounds / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012676:Senna Extract / Q000627:therapeutic use
D000701:Analgesics, Opioid; D000880:Anthraquinones; D002400:Cathartics; D000644:Quaternary Ammonium Compounds; C032257:methylnaltrexone; D007792:Lactulose; D009271:Naltrexone; D010232:Paraffin; D012676:Senna Extract; D008276:Magnesium Hydroxide; C004315:danthron