Homeopathy as a Personalised Adjuvant Approach in Treating Major Depressive Disorder: An N-of-1 Study and Physicochemical Analysis of Homeopathic Preparations

Background: Major depressive disorder (MDD) is difficult to treat pharmacologically, highlighting the need for personalised approaches like homeopathy. This study examines the efficacy and safety of a standardised homeopathy protocol for MDD through N-of-1 trials. Findings from the first participant are reported, along with an analysis of the medications used. Methods: A 28-week crossover, double-blind, placebo-controlled N-of-1 trial was conducted. The participant, diagnosed with a major depressive episode, showed a 50% reduction in baseline depressive symptoms during homeopathic treatment ( Sulphur LM2 and LM3). Three treatment blocks were completed, each with masked periods ( Sulphur LM4–7 or placebo) lasting 2, 4, and 8 weeks. Primary outcomes were depressive symptom progression, assessed using the Beck Depression Inventory, Second Edition (BDI-II). Secondary outcomes included clinical global impression severity (CGI-S) and improvement (CGI-I) scores and the mental (MCS-12) and physical (PCS-12) components of the SF-12 health survey. Adverse events were monitored. The composition of Sulphur LM2–7 was analysed using scanning electron microscopy (SEM), dynamic light scattering (DLS), and inductively coupled plasma-mass spectrometry (ICP-MS). Results: Linear regression showed a significant increase in BDI-II scores during placebo periods, but not with homeopathic treatment. MCS-12 scores decreased during placebo, in-line with the BDI-II findings. No significant trends appeared in PCS-12 scores. CGI-S scores improved from “markedly ill” to “borderline mentally ill” during the run-in period and remained stable. CGI-I scores improved to “very much improved” and remained unchanged throughout the trial. SEM identified nanoparticles in Sulphur LM4, while DLS and ICP-MS confirmed nanomaterials in Sulphur LM2–7. Conclusion: Preliminary findings suggest the homeopathic protocol is more effective than placebo in treating MDD. Homeopathy may be considered a form of personalised nanomedicine.