Miles, C.L., Fellowes, D., Goodman, M.L., & Wilkinson, S. (2006). Laxatives for the management of constipation in palliative care patients. Cochrane Database of Systematic Reviews, 4, CD003448.

To determine the effectiveness of laxative administration for constipation in patients receiving palliative care; to differentiate among laxatives being used regarding efficacy for constipation management.

Databases searched were Medline, Embase, CANCERLIT, PubMed, CINAHL, System for Information on Grey Literature in Europe (SIGLE), National Technical Information Service (NTIS), Department of Health and Social Security (DHSS-DATA), Science Citation Index, Cochrane Central Register of Controlled Trials (CENTRAL), Dissertation Abstracts, and the Index to Scientific and Technical Proceedings. Conference proceedings and references of articles reviewed were also hand searched.

Search keywords were palliative care, cathartics (adverse effects; therapeutic use), constipation (drug therapy), and randomized controlled trial as topic. 

Studies were included in the review if they

• Were a randomized controlled trial (RCT) of the efficacy of laxatives in palliative care patients
• Reported on a sample of adult patients receiving palliative care interventions who reported constipation
• Involved the use of any oral or rectal laxatives
• Included the outcome measures patient-reported relief of constipation in terms of frequency and ease of defecation, relief of related symptoms such as distension, appetite improvement, and improvement of quality of life.

Studies were excluded if they included healthy volunteers, patients with constipation as a result of drug misuse, patients with bowel obstruction, or other interventions such as opioid antagonists.

Two hundred twelve studies were initially retrieved. After removal of duplicates and studies that did not meet inclusion criteria, three studies were finally included. Study quality was assessed using the Jadad scale and additional criteria identified including issues of accrual, homogeneity, attrition, interventions, quality of outcome measurement, and clarity of results presentation. The review provided extensive detail on quality assessment findings and rationale for study exclusion. Included studies used senna, lactulose, danthron combined with poloxamer, misrakasneham, and magnesium hydroxide combined with liquid paraffin.

The final sample of three studies involved a total of 162 patients, with study samples ranging from 36 to 75.

• One study found no differences between groups taking senna and lactulose.
• One study found no difference between patients with advanced cancer taking misrakasneham and senna.
• One study of hospice patients with cancer found that those taking lactulose plus senna had significantly higher stool frequency than those using danthron and poloxamer. This pattern was true in patients at varied levels of opioid use. This study used a crossover design and showed that significantly fewer patients reported constipation when taking lactulose plus senna.
• One study in hospice patients with cancer found no difference between patients taking lactulose plus senna versus those taking magnesium hydroxide and liquid paraffin. In patients taking different levels of opioids, a trend to less constipation existed in the lactulose plus senna group, but the trend was not statistically significant.
• No significant differences were found between opioid-level groups in terms of laxative results.
• Diarrhea was reported as an adverse effect in studies for both senna and lactulose.
• Where patient preference was reported, no differences were found between most combinations. Patients preferred lactulose plus senna over magnesium hydroxide and liquid paraffin. The basis of preference was usually taste.
• The authors included a general literature review of constipation treatments.

The treatment of constipation in palliative care patients is not based on sufficient data from RCTs. Recommendations for laxatives may be based as much on cost as on efficacy. Polyethylene glycols are widely used in palliative care despite lack of evidence. The authors did not note evidence in this area in other patient populations that may be applicable.

This review and included studies did not provide sufficient information to draw conclusions about the laxatives in terms of weighing effectiveness versus adverse side effects.

• Little research exists in this area, and very few direct comparisons have been done between laxative classes and combinations to compare efficacy.
• Because of the lack of evidence in this area, determining most effective treatments is difficult.

This area could benefit from research to compare effects and cost effectiveness. Some findings suggested effect and preference for lactulose combinations, whereas lactulose tends to be much more expensive than alternatives.