Digestive Diseases and Sciences

, Volume 64, Issue 1, pp 39–49 | Cite as

Pharmacological Treatment of Opioid-Induced Constipation Is Effective but Choice of Endpoints Affects the Therapeutic Gain

  • Salman NusratEmail author
  • Taseen Syed
  • Rabia Saleem
  • Shari Clifton
  • Klaus Bielefeldt



Widespread opioid use has led to increase in opioid-related adverse effects like constipation. We examined the impact of study endpoints on reported treatment benefits.


Using MEDLINE, EMBASE, and, we searched for randomized control trials targeting chronic opioid-induced constipation (OIC) and subjected them to meta-analysis. Data are given with 95% confidence intervals.


Thirty trials met our inclusion criteria. Combining all dichotomous definitions of responders, active drugs were consistently more effective than placebo, with an odds ratio (OR): 2.30 [2.01–2.63; 15 studies], independent of the underlying drug mechanism. The choice of endpoints significantly affected the therapeutic gain. When time from drug administration to defecation was used, the OR decreased from 4.74 [2.71–4.74] at 6 h or less to 2.46 [1.80–3.30] at 24 h (P < 0.05). Using other response definitions, the relative benefit over placebo was 2.10 [1.77–2.50; 12 studies] for weekly bowel frequency, 2.03 [1.39–2.95; 9 studies] for symptom scores, 2.21 [1.25–3.90; 4 studies] for global assessment scales, and 1.27 [0.79–2.03; 7 studies] for rescue laxative use.


While treatment of OIC with active drugs is more effective than placebo, the relative gain depends on the choice of endpoints. The commonly used time-dependent response definition is associated with the highest response rate but is of questionable relevance in a chronic disorder. The limited data do not clearly demonstrate a unique advantage of the peripherally restricted opioid antagonists, suggesting that treatment with often cheaper agents should be optimized before shifting to these novel expensive agents.


Opioid-induced constipation Opioid antagonists Laxative use Naloxegol Methylnaltrexone 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Salman Nusrat
    • 1
    Email author
  • Taseen Syed
    • 2
  • Rabia Saleem
    • 2
  • Shari Clifton
    • 3
    • 4
  • Klaus Bielefeldt
    • 5
  1. 1.Neurogastroenterology and Motility Program, Division of Digestive Diseases and NutritionUniversity of Oklahoma Health Sciences CenterOklahoma CityUSA
  2. 2.Department of Internal MedicineUniversity of Oklahoma Health Sciences CenterOklahoma CityUSA
  3. 3.Health Sciences Library and Information Management, Graduate CollegeUniversity of Oklahoma Health Sciences CenterOklahoma CityUSA
  4. 4.Reference and Instructional Services, Robert M. Bird Health Sciences LibraryUniversity of Oklahoma Health Sciences CenterOklahoma CityUSA
  5. 5.Section of GastroenterologyGeorge E. Wahlen VAMCSalt Lake CityUSA

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