Comparative efficacy and safety of seven Chinese patent medicines combined with SSRIs for depressive disorder: a systematic review and network meta-analysis

Background Depressive disorder is a leading cause of disability worldwide, and selective serotonin reuptake inhibitors (SSRIs) remain first-line pharmacotherapy. However, the efficacy and safety of adding Chinese patent medicines (CPMs) as adjunctive therapy to SSRIs have not been systematically evaluated in a network meta-analysis. Objective To compare and rank seven CPMs combined with SSRIs for depressive disorder in terms of HAMD improvement, clinical response rate, and adverse drug reactions (ADRs) rate. Methods We searched MEDLINE, EMBASE, PsycINFO, CENTRAL, CNKI, WanFang, and VIP from inception to April 1, 2026. Trials comparing any CPM + SSRI versus the same SSRI alone in adults with depressive disorder were included. Two authors independently extracted data and assessed risk of bias (RoB 2.0). Pairwise meta-analysis and network meta-analysis (using both netmeta and getmc packages) were performed; cumulative probability (SUCRA) rankings were derived from Bayesian analysis with getmc. Confidence in evidence was evaluated with CINeMA. Results Sixty-five trials involving 5,975 patients were included. Compared with SSRIs alone, all CPM + SSRI combinations significantly improved HAMD score (MD range –2.60 to –6.20) and clinical response rate (OR range 1.8–5.0). For HAMD, JYW+SSRIs showed the highest SUCRA ranking, followed by BJTGT+SSRIs and SGJY+SSRIs, though these rankings are probabilistic. For response rate, BJTGT+SSRIs showed the highest SUCRA ranking, but statistically unconfirmed. For safety, TM+SSRIs showed the highest SUCRA ranking, though no ADR comparison reached significance; YXQN+SSRIs ranked second in SUCRA analysis, based on one small trial. Egger’s test indicated no publication bias for HAMD (p = 0.5753) but potential bias for clinical response rate (p = 0.0002). Sensitivity analysis excluding small studies confirmed the robustness of HAMD findings. Conclusion Adding CPMs to SSRIs may enhance efficacy and reduce ADRs. Although the rankings suggest promising efficacy, they are probabilistic in nature, and the effect estimates and their confidence intervals should be given greater weight in interpretation. No ADR comparisons reached statistical significance, and evidence supporting the safety and efficacy of some CPMs remains limited. Findings should be interpreted with caution, and future studies should further evaluate the safety and efficacy of combined therapy. Systematic review registration https://www.crd.york.ac.uk/prospero/ , identifier CRD420261299414.