Individualized Homeopathic Medicines in Treating Depression, Anxiety, and Stress in Adults with Osteoarthritis of the Knee: A Double-Blind, Randomized, Placebo-Controlled Trial.

BACKGROUND: Knee osteoarthritis (OA) is frequently accompanied by depression, anxiety and stress, worsening pain, disability and quality of life. Evidence for individualized homeopathic medicines (IHMs) in addressing these co-existing psychological and physical burdens remains limited. This trial aimed to evaluate the efficacy and safety of IHMs compared with placebo in adults with knee OA and co-morbid depression, anxiety and/or stress. METHODS: A double-blind, randomized (2:1), placebo-controlled, clinical trial was conducted at a teaching hospital in Kolkata, India. One hundred and ten participants aged between 50 and 70 years with knee OA (American College of Rheumatology [ACR] criteria) and mild-to-moderate depression (DASS-21) were randomized to receive IHMs plus concomitant care (CC) or placebo plus concomitant care for 3 months. Remedies were individualized through standardized homeopathic case-taking. Outcomes (DASS-21, Knee Injury and Osteoarthritis Outcome Score [KOOS], WOMAC, and Measure Yourself Medical Outcome Profile version 2 [MYMOP-2]) were assessed monthly for 3 months. Efficacy was assessed using multivariate linear mixed-effects models (primary test: Intervention × time interaction). Area under the curve analyses, effect sizes, and sensitivity analyses using Generalized Estimating Equations, and responder analyses were performed. Adjusted p-values used the Holm-Bonferroni method. RESULTS: A significant group-by-time interaction favored IHMs for DASS-21 depression (p < 0.001), anxiety, and stress, alongside clinically meaningful improvements in KOOS and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, function, and quality of life (most adjusted p < 0.001). Responder rates were higher with IHMs (59% vs. 11%). Mediation analysis indicated that pain reduction partially explained improvements in depression. No adverse events were reported. CONCLUSION: IHMs produced significant improvements in both psychological symptoms and physical outcomes related to knee OA compared with placebo, reflecting a holistic therapeutic effect without adverse events. TRIAL REGISTRATION: CTRI/2024/03/064632.