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

BackgroundFunctional 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. MethodsFD 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 2weeks of single-blind placebo treatment, 128 patients with continuous symptoms were randomly assigned to 8weeks 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 ResultsRikkunshito increased OTE compared to placebo at 8weeks (P=.019). Rikkunshito improved upper gastrointestinal symptoms (PAGI-SYM, GOS, and m-FSSG) at 8weeks, especially postprandial fullness/early satiety (P=.015 and P=.001) and bloating (P=.007 and P=.002) of the PAGI-SYM subscales at 4weeks and 8weeks. Improvement of HADS at 8weeks (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 & inferencesRikkunshito may be beneficial for FD patients to simultaneously treat gastrointestinal and psychological symptoms.