Abstract
Objective
Current treatment options for irritable bowel syndrome are limited and often poorly
studied. A select few drugs have been studied in irritable bowel syndrome, and the
number needed to treat is frequently used to assess the relative efficacy of these
treatments. However, side effects are an important consideration in the clinical decision
on which particular treatment to use. This study examines trials of subjects with
irritable bowel syndrome with diarrhea and constipation who are receiving a drug intervention
deemed of merit by the American College of Gastroenterology task force and compares
these therapies to examine the number needed to harm using a systematic review and
meta-analysis approach.
Methods
Potential studies of irritable bowel syndrome treatments were identified through a
search of MEDLINE (1950 to April 2011), EMBASE (1980 to April 2011), the Cochrane
central register of controlled trials, and the bibliography of recent meta-analyses.
Clinical trials of pharmacotherapy for irritable bowel syndrome were eligible for
inclusion only if a description of adverse events and the number of patients who discontinued
treatment because of adverse events were reported. The relative risk of experiencing
an adverse event requiring discontinuation of treatment was used to determine the
number needed to harm. In addition, the number and severity of adverse events were
summarized.
Results
Twenty-six clinical trials (4 with selective serotonin reuptake inhibitors, 3 with
lubiprostone, 6 with tricyclic antidepressants, 8 with alosetron, and 5 with rifaximin)
were included. Lubiprostone was safe with insignificant harm in one combined phase
III trial. Selective serotonin reuptake inhibitors did not have enough data for a
reliable meta-analysis of harm but seemed to be safe. More rigorous data were available
for tricyclic antidepressants, alosetron, and rifaximin; the numbers needed to harm
were 18.3, 19.4, and 8971, respectively, and the numbers needed to treat were 8, 7.5,
and 10.6, respectively. For tricyclic antidepressant and alosetron, an adverse event
resulting in discontinuation of the study medication occurred for every 2.3 and 2.6
patients who benefited from a drug, respectively. For rifaximin, this number was 846
patients. In addition, adverse events were more common with tricyclic antidepressants
and alosetron.
Conclusion
In irritable bowel syndrome with diarrhea, tricyclic antidepressants and alosetron
are associated with a significant number needed to harm compared with rifaximin. Apart
from lubiprostone, treatment of irritable bowel syndrome with constipation is limited
to small studies (with poor descriptions of side effects), although lubiprostone and
selective serotonin reuptake inhibitors appear safe.
Keywords
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Article info
Footnotes
Funding: Beatrice and Samuel A. Seaver Foundation.
Conflict of Interest: Eric Shah, Sharon Kim, and Kelly Chong have no conflicts to report. Anthony Lembo is a consultant for Prometheus, Forrest, Alkermes, and Salix Pharmaceuticals. Mark Pimentel is a consultant for Salix Pharmaceuticals. Cedars-Sinai Medical Center has a licensing agreement with Salix Pharmaceuticals.
Authorship: All authors had access to the data and played a role in writing this manuscript. Kelly Chong performed the meta-analyses.
Identification
Copyright
© 2012 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
