Randomized Trial of Repetitive Transcranial Magnetic Stimulation for Apathy and Depression in Parkinson?s Disease

Abstract

Objective: Repetitive transcranial magnetic stimulation (rTMS) has been reported to improve motor function and depression in Parkinson’s disease (PD) patients, but there has been only one randomized controlled trial for apathy. We evaluated the efficacy of rTMS for apathy and depression in Parkinson’s disease. Methods: Fifteen PD patients received real rTMS (5 Hz, 500 pulses/day) and placebo stimulation over the supplementary motor area (SMA) for each 5 days with total amount of 2500 real pulses and 2500 placebo pulses, using a randomized real-first or placebo-first protocol. The modified apathy scale, the Zung Self-rating Depression Scale (SDS) and Unified Parkinson’s Disease Rating Scale (UPDRS) were used to assess apathy, depression and clinical status before and after each stimulative treatment. Results: Real rTMS improved the apathy score by 3 points (P<0.05) compared to the baseline, while placebo stimulation produced no improvement, irrespective of the order of treatment. Real rTMS also improved the depression scale, SDS by 5 points (P<0.05) compared to the baseline, while placebo stimulation was ineffective. Combined analysis confirmed that real rTMS was significantly superior to placebo stimulation in apathy and depression (p<0.05). Real rTMS also improved UPDRS by 10 points (P=0.001), while placebo stimulation was ineffective. No side effects were observed in either real rTMS or placebo stimulation. Clinical factors including age, gender, disease duration, UPDRS score pre-rTMS, and daily dose of L-DOPA did not influence the improvement of UPDRS and apathy scores by real rTMS. Conclusions: rTMS over the SMA appears to be effective for treatment of apathy and depression in PD patients in addition to UPDRS.