Rikkunshito simultaneously improves dyspepsia correlated with anxiety in patients with functional dyspepsia: A randomized clinical trial (the DREAM study)

Abstract Background Functional dyspepsia ( FD ), a heterogeneous disorder, involves multiple pathogenetic mechanisms. Developing treatments for FD has been challenging. We performed a randomized, placebo‐controlled, double‐blind clinical trial to determine the efficacy of rikkunshito, a Japanese herbal medicine, in FD patients. Methods FD patients (n = 192) who met the Rome III criteria without Helicobacter pylori infection, predominant heartburn, and depression were enrolled at 56 hospitals in Japan. After 2 weeks of single‐blind placebo treatment, 128 patients with continuous symptoms were randomly assigned to 8 weeks of rikkunshito (n = 64) or placebo (n = 61). The primary efficacy endpoint was global assessment of overall treatment efficacy ( OTE ). The secondary efficacy endpoints were improvements in upper gastrointestinal symptoms evaluated by the Patient Assessment of Upper Gastrointestinal Disorders‐Symptom Severity Index ( PAGI ‐ SYM ), the Global Overall Symptom scale ( GOS ), and the modified Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (m‐ FSSG ), and psychological symptoms evaluated by the Hospital Anxiety and Depression Scale ( HADS ). Key Results Rikkunshito increased OTE compared to placebo at 8 weeks ( P = .019). Rikkunshito improved upper gastrointestinal symptoms ( PAGI ‐ SYM , GOS , and m‐ FSSG ) at 8 weeks, especially postprandial fullness/early satiety ( P = .015 and P = .001) and bloating ( P = .007 and P = .002) of the PAGI ‐ SYM subscales at 4 weeks and 8 weeks. Improvement of HADS at 8 weeks ( P = .027) correlated with those of PAGI ‐ SYM ( r = .302, P = .001), GOS ( r = .186, P = .044), and m‐ FSSG ( r = .462, P < .001), postprandial fullness/early satiety ( r = .226, P = .014), dyspepsia ( r = .215, P = .019), and PDS ( r = .221, P = .016). Conclusion & inferences Rikkunshito may be beneficial for FD patients to simultaneously treat gastrointestinal and psychological symptoms.