Efficacy and Safety of Rotigotine Transdermal Patch on Neuropsychiatric Symptoms of Parkinson's Disease: An Updated Meta-Analysis and Systematic Review

Objective: The effects of rotigotine transdermal patch (RTG) on the neuropsychiatric symptoms of Parkinson's disease (PD) outcomes remain controversial. The aim of this review was to determine the efficacy and safety of RTG on the neuropsychiatric symptoms of PD.Methods: In this systematic review and meta-analysis, PubMed, Cochrane Library, EMBASE, and Web of Science were searched for randomized controlled trials comparing RTG and placebo in PD up to May 10, 2021. We analyzed the data using Review Manager 5.2 software. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation Approach. In order to avoid false-positive results caused by random error, we use TSA software for trial sequential analysis (TSA).Results: We included 10 studies (1,844 patients). The meta-analysis showed that, compared with placebo, RTG can significantly improve the scores for Apathy Scale (MD = −1.68, 95% confidence interval, CI: −2.74 to −0.62, P = 0.002; moderate certainty), Beck Depression Inventory-II (MD = −1.19, 95% CI: −2.26 to −0.11, P = 0.03; moderate certainty), the Non-Motor Symptoms Scale (MD = −3. 66, 95% CI: −4. 30 to −3.01, P < 0.00001; moderate certainty), the sleep/fatigue domains of the Parkinson's Disease Non-motor Symptom Assessment Scale (MD = −2.03, 95% CI: −3.08 to −0.98, P = 0.0001; moderate certainty), the mood/apathy domains of the Non-motor Symptom Scale (MD = −2.48, 95% CI: −4.07 to −0.89, P = 0.002; high certainty), the eight-item Parkinson's Disease Questionnaire (MD = −4. 93, 95% CI: −6.79 to −3.07, P < 0.00001; moderate certainty), and the 39-item Parkinson's Disease Questionnaire (MD = −3.52, 95% CI: −5.25 to −1.79, P < 0.0001; high certainty). However, there was no statistically significant difference on the Snaith–Hamilton Pleasure Scale (MD = −0.12, 95% CI: −0.58 to 0.34, P = 0.61). Our results showed that RTG exerts a positive effect on sleep. According to the TSA, the results implied that, except for the Beck Depression Inventory-II, conclusive evidence have been obtained in the RTG group. It has been proven in our meta-analysis that rotigotine has good safety and tolerability.Conclusions: RTG can effectively improve the neuropsychiatric symptoms, sleep quality, and quality of life in patients with PD.

A Study for Expanding Application Sites for Rotigotine Transdermal Patch

The rotigotine transdermal patch (RTP) is a dopamine agonist used to treat Parkinson’s disease (PD). Some PD patients cannot continue RTP treatment due to application site reactions. We explored sites for RTP where application site reactions are less severe than those in the six approved application sites. Thirty PD patients (12 men, mean age = 76 years) who underwent RTP at the approved sites and had some application site reactions were enrolled in this study. When applying the RTP to the approved application sites for more than four weeks (pre-RTP) and then on the shin for the following four weeks (post-RTP), skin reactions, itching evaluated using the skin irritation score, motor symptoms, clinical global impressions scale, and plasma rotigotine concentration were examined. The mean visual analogue scale and skin irritation score in the post-RTP group were significantly lower than those in the pre-RTP group. The mean Movement Disorder Society-Unified Parkinson’s Disease Rating Scale part III score in the post-RTP group was slightly but significantly lower than that in the pre-RTP group. Plasma rotigotine concentration in the post-RTP group was slightly but significantly lower than that in the pre-RTP group. These results indicate that the shin can be a useful application site for RTP.