Abstract

Objective: The purpose of this meta-analysis was to investigate the antidepressant effects of repetitive transcranial magnetic stimulation (rTMS) over the prefrontal cortex (PFC) of patients with Parkinson's disease (PD) and to determine the optimal rTMS parameters, such as the intensity, frequency and the delivered pattern of rTMS stimulation.Methods: EMBASE, PubMed, Web of Science, MEDLINE, and Cochrane data bases were researched for papers published before March 12, 2018. Studies investigating the anti-depression effects of rTMS over PFC in patients with PD were considered. The main outcomes of pre- and post-rTMS treatment as well as score changes were all extracted. The mean effect size was estimated by calculating the standardized mean difference (SMD) with 95% confidence interval (CI) by using fixed or random effect models as appropriate.Results: Nine studies containing 137 PD patients with depression were included. The pooled results showed significant pre-post anti-depressive effects of rTMS over PFC in PD patients with depression (SMD = −0.80, P < 0.00001). The subgroup analyses of stimulation intensity, frequencies, and models also revealed significant effects (Intensities: 90% RMT: SMD = −1.16, P = 0.0006; >100% RMT: SMD = −0.82, P < 0.0001. Frequencies: < 1.0 Hz: SMD = −0.83, P = 0.03; 5.0 Hz: SMD = −1.10, P < 0.0001; ≥10.0 Hz: SMD = −0.55, P = 0.02. Models: Continuous: SMD = −0.79, P < 0.0001; Discontinuous: SMD = −0.84, P = 0.02). But the results of the studies with place-controlled designs were not significant (Overall: SMD = −0.27, P = 0.54. Intensities: 90% RMT: SMD = 0.27, P = 0.68; 100% RMT: SMD = −0.32, P = 0.33. Frequencies: 5.0 Hz: SMD = −0.87, P = 0.10; ≥10.0 Hz: SMD = 0.27, P = 0.66. Models: Continuous: SMD = −0.28, P = 0.68; Discontinuous: SMD = −0.32, P = 0.33). The greater effect sizes of rTMS with 90% RMT, 5.0 Hz in discontinuous days can be observed rather than the other parameters in both kinds of analyses across study design.Conclusions: rTMS may have a significant positive pre-post anti-depressive effect over PFC on patients with depression, especially by using 5.0 Hz frequency with 90% RMT intensity in discontinuous days, which may produce better effects than other parameters. The real effect, though, was not different from that of the placebo. Future studies with larger sample sizes and high-quality studies are needed to further corroborate our results and to identify the optimal rTMS protocols.

Highlights

  • Parkinson’s disease (PD) is considered a movement disorder, a significant proportion of PD patients has suffered from non-motor symptoms [1, 2]

  • The basic mechanism in using repetitive transcranial magnetic stimulation (rTMS) over the prefrontal cortex (PFC) is that left dorsolateral prefrontal cortex (DLPFC) hypo-activity has been featured as an important role in the pathophysiological process of depression [9, 10], and the improvement of its activity has been related to symptom alleviation [11]

  • We systematically searched studies that were undertaken to identify the effects of rTMS over PFC on depression in PD patients in the EMBASE, PubMed, MEDLINE, and Cochrane databases published before March 12, 2018

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Summary

Introduction

Parkinson’s disease (PD) is considered a movement disorder, a significant proportion of PD patients has suffered from non-motor symptoms [1, 2]. The severity and incidence of these symptoms rise with the development of PD—which negatively affects quality of life—the progression of overall disability [4], and are not related to the progression of motor symptoms of PD patients [5]. These nonmotor symptoms exert a vital effect on quality of life in patients, and increase caregiver burden and health care costs. Some studies have shown antidepressant effects of rTMS on major depression (MD) patients [13, 14]. We hypothesized that rTMS may have a similar antidepressant effect on depressed PD patients

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