Zsa Zsa Weerts

Chapter 7 158 part of our population was recruited from primary care, patients had to fulfill the Rome IV diagnostic criteria for IBS 2 , and had to have an objectified mean worst abdominal score of at least 3 (on an 11-point NRS). Finally, the overall quality of evidence achieved thus far could explain the conflicting findings throughout the literature. Peppermint oil was evaluated in numerous clinical trials that were hindered by methodological limitations including lack of description of allocation concealment or of randomization method used, no description of how blinding was handled, no usage of validated endpoints, or treatment periods of one month or shorter. 37,41 As such, treatment effects may have been biased or overestimated, complicating the ability to draw firm conclusions. Since measuring treatment response in IBS patients is based on self-reported symptoms, defining optimal outcome measures in IBS trials has been subject of ongoing debate. It has been postulated that the current recommended provisional FDA/EMA endpoints are limited in their ability to capture all multidimensional aspects of IBS symptoms and treatment response due to the over-focus on certain main symptoms and the dichotomization of continuous responses. 42,43 It is therefore important to take into account various appropriate endpoints to distinguish between clinically relevant and non-relevant responses, in particular when these are used for clinical decision-making. For instance, the small-intestinal, but not ileocolonic release peppermint oil group had a significantly greater reduction in abdominal pain, discomfort, and IBS symptom severity scores, compared to placebo. Furthermore, adherence to study treatment was excellent and discontinuation due to headache, belching, or other AEs was low (6.4%). In addition, all AEs were mild and transient and the most common one, i.e . belching, subsided after the second week of treatment. This indicates a rather good tolerability of peppermint oil when administered with a gradual titration schedule for the first week. Thereby, the current results show, in our opinion, that small-intestinal release peppermint oil does have a moderate efficacy in patients with IBS and should not be ignored as a treatment option in everyday practice. We had hypothesized that a targeted ileocolonic release of peppermint oil would have led to an augmented efficacy of treatment owing to a more local colonic anti-nociceptive effect based on recent experimental evidence suggesting the involvement of TRP channels on colonic sensory afferents. 8 In the current study, however, we found no evidence of symptomatic benefits of ileocolonic release peppermint oil over placebo. In addition, although upper GI adverse events were indeed diminished compared with the small-intestinal release peppermint oil, the novel formulation resulted in more severe abdominal cramping in the beginning of the treatment period. Our findings therefore,