Sex-specific effects of digital home-based neuromodulation combined with mindfulness-based meditation on knee osteoarthritis symptoms

OBJECTIVES: We evaluated the effects of digital home‐based transcranial direct current stimulation (tDCS) paired with audio‐delivered mindfulness‐based meditation (MBM) on knee‐specific clinical pain and symptoms in patients with symptomatic knee osteoarthritis, assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). As sex is a major source of variability in responses to tDCS and MBM, we examined treatment effects by sex. METHODS: Participants (N = 200) from a double‐blind, randomized, sham‐controlled parent trial were allocated to one of four parallel groups: (1) active tDCS + active MBM, (2) active tDCS + sham MBM, (3) sham tDCS + active MBM, or (4) sham tDCS + sham MBM. They underwent 10 20‐minute sessions of anodal tDCS (active or sham) simultaneously with MBM (active or sham). WOMAC measures were secondary outcomes in the parent trial. Linear mixed‐effects models, adjusted for baseline demographic and clinical characteristics, compared changes in WOMAC total and subscores (pain, stiffness, and physical function) across groups immediately (10 days) and three months post‐intervention. RESULTS: The sample was predominantly female (69.0%). Among females, only the active tDCS + active MBM group showed significantly greater reductions in WOMAC total scores‐particularly in physical function‐compared to the sham tDCS + sham MBM group immediately post‐intervention (p = .049). No significant immediate effects were observed among males across WOMAC outcomes. No persistent effects of active tDCS + active MBM were observed at three months in either sex. CONCLUSIONS: Although digital home‐based tDCS paired with MBM may improve knee‐specific symptoms, this effect was observed only among females and was short‐term. Furthermore, findings should be interpreted cautiously given the sex imbalance.