Therapy of replenishing and regulating for manic episode in bipolar disorder: study protocol for a prospective, double-blind, randomized controlled trial.

Bipolar disorder (BD) is a chronic and recurrent disorder characterized by biphasic mood episodes of mania or hypomania and depression. It affects more than 1% of the global population and is a leading cause of disability in young people. Currently available treatments for BD are still fairly limited in terms of efficacy, with high rates of non-adherence, non-response, and undesirable side effects. Traditional Chinese medicine (TCM) has a long history and rich experience in stabilizing mania and improving quality of life. Aiming at rebalancing and in BD, therapy of replenishing and regulating (RYRY therapy) has been in clinical use for years in China. The present prospective, double-blind, randomized controlled trial is designed to investigate the efficacy and safety of RYRY therapy for bipolar mania and its possible mechanism from the point of regulating gut microbiota and anti-inflammation. A total of 60 eligible participants will be recruited from Beijing Anding Hospital. They will be randomized to either the study group or the control group in a ratio of 1∶1. Participants allocated to the study group will receive RYRY granule, while placebo granule will be applied in the control group. Participants in both groups will be prescribed conventional therapy for manic episode in BD. Four scheduled visits will be conducted over 4 weeks. Outcome measurements include Young Mania Rating Scale, TCM Symptom Pattern Rating Scale, Treatment Emergent Symptom Scale, levels of C-reactive protein, interleukin-6 and tumor necrosis factor-α and the gut microbial community profile of stool samples. Safety outcomes and adverse events will also be recorded. In this study, we set a number of scientific and objective assessments to evaluate the efficacy of RYRY therapy and study into its possible mechanism, hopefully offering clinicians an alternative approach to BD.