High-Frequency Repetitive Transcranial Magnetic Stimulation Can Improve Depression in Parkinson's Disease: A Randomized, Double-Blind, Placebo-Controlled Study

Abstract

Background: A recent evidence-based guideline demonstrated that bilateral repetitive transcranial magnetic stimulation (rTMS) over the motor cortex (M1) can improve motor symptoms of Parkinson's disease (PD). We conducted a randomized, double-blind, placebo-controlled study to evaluate the impact of bilateral M1 rTMS on depression in PD. Methods: Forty-six patients with PD and mild-to-moderate depression were randomly assigned to active (n = 23) and sham (n = 23) rTMS. Two patients in the sham group did not complete the protocol because of reasons unrelated to the study. High-frequency rTMS was applied over the primary motor cortex bilaterally for 10 days. An investigator blinded to the treatment performed three video-taped examinations on each patient: before stimulation (baseline), and 1 day (short-term effect) and 30 days after the treatment session ended (long-term effect). The primary end point was the changes in depression, while secondary end points included health-related quality of life scales and Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Results: In the actively treated group, not only did the severity of depression improve (from 17 to 7 points, Montgomery-Åsberg Depression Rating Scale, median values, p < 0.001), but also the health-related quality of life (from 25.4 to 16.9 points, PDQ-39 summary index, median values, p < 0.001). Besides, we could also demonstrate an improvement in MDS-UPDRS Motor Examination (from 26 to 20 points, median values, p < 0.05). In the sham-treated group, none of the examined tests and scales improved significantly after treatment. Conclusions: Our results demonstrate the beneficial effects of high-frequency bilateral M1 rTMS on depression and health-related quality of life in PD. However, this effect of rTMS should also be confirmed in patients with severe depression by further clinical trials.

Update on treatments for nonmotor symptoms of Parkinson's disease—an evidence‐based medicine review

“…rTMS was evaluated in 2 new high‐quality studies for the treatment of depression in PD, which were discrepant regarding depression outcome . Therefore, there is insufficient evidence for rTMS to be rated for the treatment of depression in PD.…”

“…There is growing evidence that rTMS is efficacious for the treatment of depression in the general population, and it was approved by the Food and Drug Administration (FDA) in 2008 for the treatment of major depressive disorder. Moreover, some beneficial effects on the different depression outcome measures used in the different trials have been reported in PD patients . Therefore, the practice implication is “ possibly useful,” although it should be kept in mind that the treatment effect is short term, and treatment would need to be repeated at regular intervals.…”

“…A total of 6 new studies were evaluated. 9,11,[16][17][18][19] We excluded trials not fulfilling the inclusion criteria for review 43,44,55 and where depression was not an inclusion criterion. 59,60,62,78 See Table 2 for recommendations.…”

“…rTMS was evaluated in 2 new high-quality studies for the treatment of depression in PD, which were discrepant regarding depression outcome. 17,18 Therefore, there is insufficient evidence for rTMS to be rated for the treatment of depression in PD. There is growing evidence that rTMS is efficacious for the treatment of depression in the general population, 83,84 and it was approved by the Food and Drug Administration (FDA) in 2008 for the treatment of major depressive disorder.…”

“…Moreover, some beneficial effects on the different depression outcome measures used in the different trials have been reported in PD patients. 2,18 Therefore, the practice implication is "possibly useful," although it should be kept in mind that the treatment effect is short term, and treatment would need to be repeated at regular intervals.…”