Direct Current Stimulation of Prefrontal Cortex Is Not Effective in Progressive Supranuclear Palsy: A Randomized Trial

Background Progressive supranuclear palsy (PSP) is a rare 4R‐tauopathy. Transcranial direct current stimulation (tDCS) may improve specific symptoms. Objectives This randomized, double‐blinded, sham‐controlled trial aimed at verifying the short‐, mid‐, and long‐term effect of multiple sessions of anodal tDCS over the left dorsolateral prefrontal cortex (DLPFC) cortex in PSP. Methods Twenty‐five patients were randomly assigned to active or sham stimulation (2 mA for 20 minute) for 5 days/week for 2 weeks. Participants underwent assessments at baseline, after the 2‐week stimulation protocol, then after 45 days and 3 months from baseline. Primary outcomes were verbal and semantic fluency. The efficacy was verified with analysis of covariance. Results We failed to detect a significant effect of active stimulation on primary outcomes. Stimulation was associated to worsening of specific behavioral complaints. Conclusions A 2‐week protocol of anodal left DLPFC tDCS is not effective in PSP. Specific challenges in running symptomatic clinical trials with classic design are highlighted. © 2024 International Parkinson and Movement Disorder Society.