A personalized, integrative approach in treating major depressive disorder: N-of-1 study with plasma proteome and physicochemical analysis of homeopathic preparations

This is the authors' abstract. We don't add key points for this paper.

Major Depressive Disorder (MDD) treatment remains challenging. This N-of-1 study evaluated a personalized integrative homeopathic protocol for MDD. Methods: A 28-week, double-blind, randomized, placebo-controlled crossover trial assessed Sulphur fifty-millesimal potencies (LM4–7) effectiveness and safety in a 45-year-old female with MDD. The primary outcomes were Beck Depression Inventory-II (BDI-II) scores, and secondary outcomes included SF-12 and Clinical Global Impression Scale scores. We conducted Plasma proteomics and physicochemical analyses (SEM, DLS, ICP-MS) of Sulphur LM2–7. BDI-II scores increased significantly in the placebo group (P = 0.017), whereas no significant change was observed in the Sulphur -treated group (P = 0.243). Overall symptom improvement with homeopathy compared to placebo, controlling for baseline, was 78 % (p < 0.05). MCS-12 significantly decreased during placebo (P = 0.008) but remained stable during homeopathic treatment (P = 0.542). No significant PCS-12 changes were observed (P > 0.2). CGI-I scores improved during the run-in treatment but showed no further change during the N-of-1 trial. Sulfur-loaded LM formulations presented nanoparticles, as confirmed by SEM analysis, demonstrated distinct particle size characteristics via DLS, and exhibited quantifiable sulfur concentrations detected through ICP-MS. Proteomic analysis suggested that Sulphur treatment modulates immune response pathways, highlighting a potential mechanism underlying its antidepressant-like effects. This personalized integrative homeopathic protocol demonstrated superior effectiveness to placebo in the studied individual. The physicochemical characteristics and proteomic findings indicate potential immunomodulatory effects mediated by nanomedicine mechanisms. However, further research involving larger cohorts is warranted to confirm these preliminary observations.