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Chapter 1 18 be managed by a tailored therapy that can be adapted when the predominant symptom switches. 20 Drugs that can reduce symptoms of bloating include rifaximin, some probiotics, eluxadoline in case of accompanying diarrhea, and linaclotide, plecanatide, or tenapanor in case of accompanying constipation. 5,87,89 Pharmaceuticals that have shown some efficacy in treatment of abdominal pain, the most important hallmark of IBS, include tricyclic antidepressants, selective serotonin reuptake inhibitors, and antispasmodic drugs. 76 Despite the large therapeutic array and advances in the management of IBS in recent years, a considerable proportion of patients remain refractory to currently licensed pharmacological therapies. Furthermore, the therapeutic gain over placebo is a mere 8 to 20% for most drugs available for IBS 76 and treatment efficacy of the most cardinal symptom in particular, abdominal pain, is often unsatisfactory. Factors that further complicate the search for better treatments are the generally high placebo response in patients with IBS in clinical trials ( i.e. approximately 30%) 90 , and the chronic relapse- remitting and heterogeneous nature of IBS. In addition, it is difficult to capture treatment response since treatment effects cannot be monitored with biomarkers and end-of-day symptom diaries are often hindered by fake adherence. 91 More research into the underlying pathophysiological mechanisms, appropriate symptom assessment tools, but also new therapeutic compounds or alternative formulations of existing drugs are warranted to optimize future treatment of patients with IBS. In addition, because IBS imposes such a significant socioeconomic burden, it is important that therapies are not only effective, but associated costs should also be justifiable ( i.e. cost-effectiveness). A drug of particular interest that is low in costs and was found to have a promising number needed to treat of 3-4 in meta-analyses is peppermint oil. 22 Peppermint oil is a pharmacological compound of herbal origin that has been used to treat IBS for many years. Peppermint oil has an antispasmodic, smooth muscle relaxing effect by blocking calcium influx in the sarcolemma of the intestinal smooth muscle cells. 92 Furthermore, menthol, the main constituent of peppermint oil, is thought to have direct analgesic properties through interaction with previously described intestinal TRPM8 and TRPA1 receptors. 93 Other mechanisms of action include 5- hydroxytryptamine antagonism 94,95 , antimicrobial and antifungal effects 96-99 , and ĸ-opioid receptor agonism. 100 Currently, capsules that release the peppermint oil in the small intestine are available as an over-the-counter drug. Placebo controlled randomized trials using this small-intestinal release peppermint oil formulation in patients with IBS support