Meta-analysis of the therapeutic effect and safety of repetitive transcranial magnetic stimulation combined with pramipexole in Parkinson's disease.

Abstract

<h4>Background</h4>The motor and non-motor symptoms of PD severely impair the quality of life of PD patients. rTMS improves neuroplasticity by modulating cortical striatal pathways and provides a new strategy for non-pharmacological interventions, but its synergistic effect and optimal combination with pharmacological therapies have not been clarified. Meta-analysis was used to assess the clinical efficacy and safety of rTMS combined with pramipexole in the treatment of PD.<h4>Methods</h4>A comprehensive search was conducted in the CNKI, VIP, Wanfang, CBM, PubMed, Web of Science, and Cochrane Library databases for clinical randomized controlled trials (RCTs) on the combined use of rTMS and pramipexole for the treatment of PD. The literature was in Chinese and English. Researchers used the Cochrane risk of bias assessment tool to determine the quality of the included literature, as well as the GRADE to assess the quality of the data. The primary outcome measure was the UPDRS, and the secondary outcome measures were: HAMD, FAQ, STEF, BBS, MAS, MMSE, MoCA, PDSS, PDQ-39, NMSQuest, SCOPA-AUT, Adverse Event Rate. The analysis of autonomic nervous system function used a random effects model, while the rest used a fixed-effects model. Furthermore, we performed trial sequential analysis. Due to the small sample size, sensitivity analysis was performed by excluding individual RCTs 2 by 1.<h4>Results</h4>Twelve studies, all RCTs, ultimately included 995 patients. Meta-analysis results showed: rTMS combined with pramipexole had a higher overall effective rate in treating PD patients than the control group, and significantly reduced the UPDRS total score (OR = 4.58, 95% CI: 2.91-7.19, P < .0001). Based on our validation through trial sequential analysis, this result is decisive and robust. rTMS with pramipexole treatment showed overall improvement in PD (OR = 4.58, 95% CI: 2.91-7.19, P < .0001), improvement in cognitive functioning (MD = 2.23, 95% CI: 1.91-2.54, P < .0001), improvement in depression level (MD = -2.22, 95% CI: -2.71 to -1.72, P < .0001), improvement in social functioning (MD = -2.64, 95% CI: -3.09 to -2.19, P < .00001), improvement in non-motor symptoms (MD = -1.29, 95% CI: -1.97 to -0.60, P = .0002), gait improvement (MD = 6.34, 95% CI: 2.66-10.02, P < .00001; MD = 4.59, 95% CI: 2.37-6.80, P < .0001; MD = -0.14, 95% CI: -0.19 to -0.09, P < .00001) and other significant efficacy. Safety analysis showed that the rTMS combined with pramipexole group had a lower incidence of adverse effects during treatment (OR = 0.77, 95% CI: 0.40-1.46, P = .42). The GRADE assessment showed two outcomes as moderate-quality evidence, 6 as low-quality evidence, and 3 as very-low-quality evidence. In terms of heterogeneity analyses, the heterogeneity of the analyses was relatively low, except for significant heterogeneity in autonomic function and sleep quality. Also, funnel plot analyses were performed without significant publication bias.<h4>Conclusion</h4>rTMS combined with pramipexole treatment can significantly control the symptoms of PD, accelerate the healing of the disease, better than the single pramipexole treatment of the clinical effect, and the safety of the use of the drug is higher.