Are solifenacin and ramosetron really ideal to treat irritable bowel syndrome?

TO THE EDITOR: Apart from the annoying bowel symptoms, irritable bowel syndrome (IBS) patients usually have various extra-intestinal co-morbidities in terms of insomnia, depression, chronic fatigue syndrome, fibromyalgia, chronic pelvic pain and lower urinary tract symptoms.1,2 Accordingly, a concept of central sensitivity syndromes (CSS) has been addressed to include IBS and its extra-intestinal co-morbidies because these disorders share an evident biopsychosocial disturbance, eg, interstitial cystitis is one of CSS components.3 Besides, it remains unknown whether overactive bladder (OAB), another lower urinary tract disorder, should be enrolled in the CSS family because literature do not indicate their closed association. Based on an open-labeled and cross-over trial, Fukushima et al4 in the July 2012 issue of this journal indicated that solifenacin, an agent recommended to treat OAB,5 was very effective in relieving IBS overall symptoms with an efficacy not inferior to ramosetron. I agreed that solifenacin in the present study was obviously off-labeled and used to explore its applicableness on IBS patients since antispasmodics have long been recommended to treat IBS, as this OAB agent also exhibits antispasmodic ability.5,6

Overall, several issues in this article remain debatable. Regarding the assessment of IBS overall improvement, the authors pointed out that both agents reached up to 80%-90%. It looks very dramatic with an efficacy almost doubling others. For example, a large-scaled and open-labeled trial conducted on Korean IBS patients indicated that both ramosetron and mebeverin displayed a comparable responded efficacy around 38%.7 Our previous antispasmodic study also reported the limited efficacies of otilonium bromide and mebeverin in treating IBS main symptoms.8 It seems that the authors should clearly address what was the definition to assess IBS overall improvement among their trial. Alternatively, their excellent efficacy showed a superiority exceeding the well-accepted data for treating IBS. Unlike other cross-over trials, present study did not design an allowable washout period when the treatment was immediately switched from solifenacin to ramosetron.9 Did the authors ignore the possible solifenacin residual pharmacological impact on the early days of ramosetron treatment? Third, solifenacin to treat OAB often has the constipation side effect with an odds ratio of 3.02.5 It is controversial whether the result of diminished bowel movement frequency was the solifenacin side effect or true therapeutic effect. Finally, Figure 2C depicts the duration of pain during various visits, and why is the y-axis labeled as "scores" rather than the recorded number of days?