Research Progress on the Application and Mechanisms of Baihe Dihuang Decoction in Major Depressive Disorder

The treatment of major depressive disorder (MDD) is often plagued by inadequate therapeutic efficacy, high relapse rates, and adverse drug effects. Baihe Dihuang Decoction (BHDH, Lily Bulb and Rehmannia Decoction), a classic Traditional Chinese Medicine (TCM) formula, shows promise for depression, but a comprehensive synthesis of modern evidence is warranted. This study aimed to review the clinical efficacy, pharmacological mechanisms, and safety profile of BDD for MDD to inform its clinical application and guide future research.

A systematic literature search was conducted in both English (PubMed, Web of Science) and Chinese (CNKI, Wanfang) databases from inception to June 2025. For clinical evidence, the search focused on "Baihe Dihuang Decoction", "major depressive disorder/depression", and "randomized controlled trial". Supplementary searches using terms like "chemical constituents" and "pharmacological action" were performed for mechanistic studies. Relevant literature was subsequently summarized and analyzed.

Current evidence suggests that BHDH, as an adjunct to conventional antidepressants, can improve the overall clinical response rate, reduce Hamilton Depression Rating Scale scores, and potentially alleviate adverse reactions. Its active constituents may exert antidepressant effects via multiple pathways, including monoaminergic neurotransmission modulation, neuroinflammation inhibition, hypothalamic-pituitary-adrenal axis regulation, hippocampal neuron protection, and gut microbiota modulation. However, its efficacy as a monotherapy and long-term safety profile require further validation through high-quality clinical trials.

BHDH possesses a multi-target pharmacological basis for antidepressant activity. Existing clinical evidence supports its effectiveness and relative safety as an adjunctive therapy for MDD. To better define its clinical role and advance TCM modernization, future research should prioritize rigorous randomized controlled trials, elucidate its formula compatibility mechanisms, and identify its key bioactive components.