Modified sini powder for the management of postoperative depression in non-small cell lung cancer patients: a multicenter, randomized, double-blind, placebo-controlled trial protocol.

BACKGROUND

Postoperative depression is a common complication following non-small cell lung cancer (NSCLC) resection, which adversely affects quality of life and may impede long-term survival. Modified Sini Powder (MSNP), a modified traditional Chinese medicine formula derived from classical Sini Powder, has been used in clinical practice to alleviate depressive symptoms. However, comprehensive evidence from well-designed clinical trials remains insufficient. This protocol describes a study designed to evaluate the efficacy and safety of MSNP in managing postoperative mild-to-moderate depression in patients with NSCLC and to characterize its biological mechanisms.

METHODS

In this multicenter, randomized, double-blind, placebo-controlled trial, 468 postoperative patients with NSCLC and mild-to-moderate depression will be recruited across nine tertiary medical centers. Participants will be stratified by concomitant paroxetine use and randomized in a 1:1 ratio within each stratum to receive an MSNP-containing intervention or the corresponding placebo control for 6 weeks. The primary outcome is the total effective rate at the end of treatment, defined as a ≥25% reduction in the 17-item Hamilton Depression Rating Scale score from baseline. Secondary outcomes include measures of anxiety, sleep quality, fear of cancer recurrence, quality of life, and survival. Safety will be monitored through adverse event reporting and laboratory examinations. Mechanistic explorations will integrate analyses of inflammatory cytokines, hypothalamic-pituitary-adrenal axis hormones, neurotransmitters, brain-derived neurotrophic factor, serum metabolomics, and gut microbiota profiles.

DISCUSSION: This trial aims to provide robust clinical evidence for the integration of MSNP into the management of postoperative mild-to-moderate depression in patients with NSCLC. Furthermore, multi-omics analyses are expected to elucidate the multi-target and multi-pathway mechanisms of MSNP, offering insights into personalized and integrative therapeutic strategies.

TRIAL REGISTRATION: Registered on September 1, 2025, at the International Traditional Medicine Clinical Trial Registration Center (https://itmctr.ccebtcm.org.cn/mgt/project/view/1962361959055753216; Identifier: ITMCTR2025001642).