Efficacy and side-effect profiles of lactulose, docusate sodium, and sennosides compared to PEG in opioid-induced constipation: A systematic review

Teresa Ruston, Kathleen Hunter, Greta Cummings, Adriana Lazarescu


Opioid-induced constipation (OIC) is a side effect of opioid therapy that can affect quality of life, adherence to treatment, and morbidity and possibly mortality.

Objectives: To investigate whether docusate sodium, sennosides, and lactulose have equal efficacy and side effect profiles compared to PEG in the management of OIC in adults.

Methods: A systematic review was undertaken. Randomized controlled trials of adults taking opioids for cancer or non-cancer pain were considered if they met inclusion criteria.

Conclusions: Statistical pooling was not possible as no studies met inclusion criteria. Large, well-powered, randomized controlled trials are feasible. Standard definitions of OIC would assist with the execution of these studies and contribute to their internal and external validity. Further research is strongly encouraged.

Full Text:



Annunziata, K., & Bell, T. (2006). Impact of opioid-induced constipation

on healthcare resource utilisation and patient functioning

[Abstract]. European Journal of Pain, 10(Suppl. S1) S172.

Camilleri, M. (2011). Opioid-induced constipation: Challenges and

therapeutic opportunities. American Journal of Gastroenterology,

(5), 835–842.

Caraccia-Economou, D. (2006). Bowel management: Constipation,

diarrhea, obstruction, and ascites. In B. Ferrell, & N. Coyle (Eds.),

Textbook of palliative nursing (2nd ed., pp. 219–238). New York,

NY: Oxford University Press, Inc.

Choi, Y.S., & Billings, J.A. (2002). Opioid antagonists: A review of

their role in palliative care, focusing on use in opioid-related

constipation. Journal of Pain & Symptom Management, 24(1),


Freedman, M.D., Schwartz, H.J., Roby, R., & Fleisher, S. (1997).

Tolerance and efficacy of polyethylene glycol 3350/electrolyte

solution versus lactulose in relieving opiate induced

constipation: A double-blinded placebo-controlled trial. Journal

of Clinical Pharmacology, 37(10), 904–907.

Hawley, P.H., & Byeon, J.J. (2008). A comparison of sennosidesbased

bowel protocols with and without docusate in hospitalized

patients with cancer. Journal of Palliative Medicine, 11(4),


Higgins, J., & Altman, D. (2008). Chapter 8: Assessing risk of bias

in included studies. In J. Higgins, & S. Green (Eds.), Cochrane

handbook for systematic reviews of interventions (version 5.0) ().

Chichester, UK: John Wiley & Sons, Ltd.

Hjalte, F., Berggren, A.C., Bergendahl, H., & Hjortsberg, C. (2010).

The direct and indirect costs of opioid-induced constipation.

Journal of Pain & Symptom Management, 40(5), 696–703.

Intelliware Development Inc. (2011). Shoppers drug mart: Health

watch. Toronto, ON:

Lee-Robichaud, H., Thomas, K., Morgan, J., & Nelson, R.L. (2010).

Lactulose versus polyethylene glycol for chronic constipation.

Cochrane Database of Systematic Reviews, (7), 007570.

Liberati, A, Altman, D., Tetzlaff, J., Mulrow, C., Gotzsche, P.,

Ioannidis, J., Clarke, M., … Moher, D. (2009). The PRISMA

statement for reporting systematic reviews and meta-analyses of

studies that evaluate health care interventions: Explanation and

elaboration. Annals of Internal Medicine, 151(4), W65–W94.

McNicol, E., Boyce, D.B., Schumann, R., & Carr, D. (2008). Efficacy

and safety of mu-opioid antagonists in the treatment of opioidinduced

bowel dysfunction: Systematic review and meta-analysis

of randomized controlled trials. Pain Medicine, 9(6), 634–659.

Panchal, S.J., Muller-Schwefe, P., & Wurzelmann, J.I. (2007). Opioidinduced

bowel dysfunction: Prevalence, pathophysiology

and burden. International Journal of Clinical Practice, 61(7),


Pappagallo, M. (2001). Incidence, prevalence, and management of

opioid bowel dysfunction. American Journal of Surgery, 182(5A

Suppl), 11S–18S.

Rome Foundation. (2006). Appendix A: Rome III diagnostic criteria

for functional gastrointestinal disorders. Retrieved from http://


STARD. (2008). STARD statement. Retrieved from http://www.


Swegle, J.M., & Logemann, C. (2006). Management of common

opioid-induced adverse effects. American Family Physician,

(8), 1347–1354.

Wood, J.D., & Galligan, J.J. (2004). Function of opioids in the enteric

nervous system. Neurogastroenterology & Motility, 16(Suppl 2),


Woolery, M., Bisanz, A., Lyons, H.F., Gaido, L., Yenulevich, M.,

Fulton, S., et al. (2008). Putting evidence into practice: Evidencebased

interventions for the prevention and management of

constipation in patients with cancer. Clinical Journal of Oncology

Nursing, 12(2), 317–337.

World Health Organization. (2011). WHO’s pain ladder. Retrieved

from http://www.who.int/cancer/palliative/painladder/en/



  • There are currently no refbacks.