A Multicentre Clinical Trial Protocol of Shuganjieyu Capsules Combined With Fluoxetine in the Treatment of Depression.

Background  Depression is a global disease with high prevalence, recurrence, and disability rates. Currently, antidepressant chemical drug therapeutic regimens are the mainstay, but they have low recovery rates, and a significant portion of patients develop refractory depression. Consequently, traditional Chinese medicine (TCM) has emerged as a crucial alternative, with various studies investigating its potential in both standalone and adjunctive treatments for depression. Thus, this study aims to explore the efficacy and safety of an integrated TCM and Western medicine antidepressant therapeutic regimen, i.e., the combination of Shuganjieyu capsules and fluoxetine, in patients with moderate to severe depression (17-item Hamilton Rating Scale for Depression (HAMD-17) score ≥ 18 and Item 13 score ≥ 2) in the short- and long-term (8 weeks and 16 weeks, respectively). Methods  The study will be divided into a basic study period (0-8 weeks) and an extended study period (9-24 weeks). The basic study period will employ a multicentre, randomized, double-blind, placebo-parallel controlled study, in which patients with moderate to severe depression will be selected and randomly assigned at a 1:1 ratio, with 80 patients in each group. The extended study period will utilize a multicentre, open-label observational study. During the basic study period, the experimental group will receive oral fluoxetine (20 mg/dose, once daily) and Shuganjieyu capsules (two capsules/dose, twice daily, morning and evening), whereas the control group will receive fluoxetine (20 mg/dose, once daily) and a Shuganjieyu capsule simulant (two capsules/dose, twice daily, morning and evening). The dosing regimen for the extended study period will be formulated on the basis of the condition of the subjects after 8 weeks of the basic study period. The primary efficacy endpoint will be the change in the HAMD-17, and the secondary efficacy endpoint will include the change in the Hamilton Anxiety Rating Scale (HAMA), Clinical Global Impression (CGI), Patient Health Questionnaire-15 (PHQ-15), Pittsburgh Sleep Quality Index (PSQI), Dimensional Anhedonia Rating Scale (DARS), Temporal Experience of Pleasure Scale (TEPS), and Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF).  Discussion  This study aims to evaluate the efficacy and safety of the combination of TCM and Western medicine in the acute treatment of moderate to severe depression. Additionally, it seeks to explore the long-term efficacy (in terms of improving residual symptoms and preventing relapse) and safety of this combination therapy. The ultimate goal will be to develop an optimized treatment regimen for depression that combines traditional Chinese medicine and Western medicine, thereby offering more options for the clinical management of moderate to severe depression.