Siemens, W., Gaertner, J., & Becker, G. (2015). Advances in pharmacotherapy for opioid-induced constipation–A systematic review. Expert Opinion on Pharmacotherapy, 16, 515–532. 

DOI Link

Purpose

STUDY PURPOSE: To evaluate the efficacy and safety of drugs reported in randomized controlled trial for the management of opioid-induced constipation

TYPE OF STUDY: Systematic review

Search Strategy

DATABASES USED: Medline; Medline In-Process and Other Non-Indexed Citations; Cochrane Central Register of Controlled Trials; PubMed; EMBASE
 
KEYWORDS: constipation, gastrointestinal transit, bowel dysfunction, opiate alkaloids, analgesics, opioid
 
INCLUSION CRITERIA: Primary study aim was improvement of opiod-induced constipation (OIC). Study type: Phase II and III RCTs and randomized dose-ranging studies. Full text. Primary intervention: Pharmacological interventions against OIC. Objective outcome measures, bowel movement (BM) within four hours, time to first BM.
 
EXCLUSION CRITERIA: Open-label (extension) phases with single- or double-blind phase

Literature Evaluated

TOTAL REFERENCES RETRIEVED: N = 869 retrieved, 540 screened 
 
EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Two independent reviewers screened abstracts. Items extracted: study ID, author, publication year, article type, study aim, population, inclusion criteria, exclusion criteria, intervention, control group, primary outcome, secondary outcome, results for objective outcome measures (OOM), dropouts adverse events and comments. Risk: fixed effects model with Mantel-Haenszel method

Sample Characteristics

  • FINAL NUMBER STUDIES INCLUDED = 21 studies included in qualitative synthesis, 14 analyzed in quantitative synthesis 
  • TOTAL PATIENTS INCLUDED IN REVIEW: methylnaltexone: 1760, naloxone: 798, alvimopan: 1525, naloxegol: 1545, lubiprostone: 877, CB-5945: 131, prucalopride: 196
  • KEY SAMPLE CHARACTERISTICS: Opioid constipation

Phase of Care and Clinical Applications

PHASE OF CARE: Active antitumor treatment
 
APPLICATIONS: Palliative care

Results

Efficacy: Methylnaltrexone OOM were examined in seven studies. Averaged over all the studies, responder rated reached 30%. Median time to rescue-free bowel movement (RFBM) was shortest for doses 0.15 mg/kg and 0.3 mg/kg compared to placebo. Naloxone: Four studies' group differences were significant, but the mean difference of less than or equal to 0.5 and the one-week and four-week comparison was small.  Noloxegel: Three studies with responder rates after 12 weeks of treatment were significantly higher for the 25 mg group, and there was no difference between noloxegel and the placebo group at 12.5 mg. Lubiprostone: Two RCTs showed results not consistent across studies. CB-5945: One study and statistical significant results for all BM frequency only in 0.25 mg bid versus placebo group. Pruclopride: One study with little statistical significance.  Alvimopan: Three studies; after 12 weeks there were spontaneous bowel movement (SBM) in both intervention groups with statistical significance and improvement also.

Conclusions

Seven novel drugs for OIC were reviewed. Effectiveness was shown for all drugs, but BM frequency measures hindered comparison of the studies and the drugs.

Limitations

The authors used different terms in their inclusion criteria for outcome analysis. Seven drugs were included in the review. Comparing seven drugs made comparisons difficult and conclusions limited.

Nursing Implications

Improvement in management of OIC could improve patient experience, reduce hospital stays, and decrease patient suffering. Nurses should ensure preventive and proactice measure for their patients on opioids.

Legacy ID

5736