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

Abstract 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. 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. 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. 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. CTRI/2024/03/064632.