In a small randomized, sham-controlled crossover trial of 25 mild-to-moderate PD patients, two brief sessions of left DLPFC HD-tDCS improved depressive, cognitive, and other non-motor symptom scores versus sham with good tolerability.

This study supports a safe, non-pharmacologic, symptomatic intervention for PD non-motor symptoms with translational potential for clinical management and trial design, but its small size and lack of mechanistic insight limit its value for disease-modifying therapeutic discovery.

OBJECTIVES: To explore the effect of two sessions of high-definition transcranial direct current stimulation (HD-tDCS) at a 30-minute interval on depressive and other non-motor symptoms in patients with Parkinson's disease (PD). METHODS: Consecutive patients aged ≥18 years with mild-to-moderate idiopathic PD who had depressive symptoms, were right-handed, had no or mild cognitive impairment, and were receiving stable doses of anti-Parkinsonian drugs for at least 1 month were invited to participate. Participants were randomly assigned to either the active-first or sham-first group. Intervention consisted of two sessions (separated by a 30-minute interval) of 20-minute anodal stimulation targeting the left dorsolateral prefrontal cortex. Participants were assessed at baseline and 1 week after intervention using the Montgomery-Asberg Depression Rating Scale, Montreal Cognitive Assessment, Movement Disorder Society Unified Parkinson's Disease Rating Scale Parts 1 to 3, and EuroQol 5-Dimension 5-Level Scale. Adverse effects of HD-tDCS and any subjective change in emotional state were assessed immediately after intervention. Subsequently, participants crossed over to the alternate group after a 1-week washout period. Participants were asked after each session to guess the type of stimulation received. RESULTS: In total, 25 patients were included in the analysis. Significant time × group interactions were observed for Montgomery-Asberg Depression Rating Scale (p = 0.02), Montreal Cognitive Assessment (p < 0.01), Movement Disorder Society Unified Parkinson's Disease Rating Scale Part 1 (p = 0.02), Part 2 (p < 0.01), Part 3 (p < 0.01), and EuroQol 5-Dimension 5-Level Scale (p = 0.05). Common adverse effects included itching and burning sensations at the stimulation site. Subjective mood change was reported by 72% of participants in the active group and 48% of those in the sham group. The active and sham groups did not differ significantly in terms of correct identification of the stimulation type (96% vs 20%, p = 0.18). CONCLUSION: Two-session HD-tDCS at a 30-minute interval targeting the left dorsolateral prefrontal cortex is a safe, well-tolerated, and potentially effective intervention for depressive and cognitive symptoms in patients with mild-to-moderate PD.