Evaluation of harm in the pharmacotherapy of irritable bowel syndrome.

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. 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. 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. 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.