Abstract | BACKGROUND: AIM: METHODS: We searched the medical literature in January 2013 using MEDLINE/Pubmed, Embase, Cochrane Library, and Web of Science/Scopus for randomised, controlled trials of highly selective 5-HT4 agonists in adults with CC, with no minimum duration of therapy (maximum 12 weeks) or date limitations. Data were extracted from intention-to-treat analyses, pooled using a random-effects model, and reported as relative risk (RR), mean differences, or standardised mean differences with 95% confidence intervals (CI). RESULTS: Main outcomes included stool frequency, Patient-Assessment of Constipation Quality of Life (PAC-QOL), PAC of symptoms (PAC-SYM) and adverse events. Thirteen eligible trials were identified: 11 prucalopride, 1 velusetrag, 1 naronapride. Relative to control, treatment with highly selective 5-HT4 agonists was superior for all outcomes: mean ≥3 spontaneous complete bowel movements (SCBM)/week (RR = 1.85; 95% CI 1.23-2.79); mean ≥1 SCBM over baseline (RR = 1.57; 95% CI 1.19, 2.06); ≥1 point improvement in PAC-QOL and PAC-SYM scores. The only active comparator trial of prucalopride and PEG3350 suggested PEG3350 is more efficacious for some end points. Adverse events were more common with highly selective 5-HT4 agonists, but were generally minor; headache was the most frequent. Most trials studied prucalopride. CONCLUSION: Demonstration of efficacy on patient-important outcomes and a favourable safety profile support the continued use and development of highly selective 5-HT4 agonists in the treatment of chronic constipation.
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Authors | A Shin, M Camilleri, G Kolar, P Erwin, C P West, M H Murad |
Journal | Alimentary pharmacology & therapeutics
(Aliment Pharmacol Ther)
Vol. 39
Issue 3
Pg. 239-53
(Feb 2014)
ISSN: 1365-2036 [Electronic] England |
PMID | 24308797
(Publication Type: Journal Article, Meta-Analysis, Review, Systematic Review)
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Copyright | © 2013 John Wiley & Sons Ltd. |
Chemical References |
- Azabicyclo Compounds
- Benzamides
- Benzofurans
- Quinuclidines
- Serotonin 5-HT4 Receptor Agonists
- TD-5108
- ATI 7505
- prucalopride
- Polyethylene Glycols
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Topics |
- Adult
- Azabicyclo Compounds
(adverse effects, pharmacology, therapeutic use)
- Benzamides
(adverse effects, pharmacology, therapeutic use)
- Benzofurans
(adverse effects, pharmacology, therapeutic use)
- Chronic Disease
- Constipation
(drug therapy, physiopathology)
- Defecation
(drug effects)
- Humans
- Polyethylene Glycols
(therapeutic use)
- Quality of Life
- Quinuclidines
(adverse effects, pharmacology, therapeutic use)
- Serotonin 5-HT4 Receptor Agonists
(adverse effects, therapeutic use)
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