Sequence Symmetry Analysis of the Interrelationships Between Ramelteon and Parkinson's Disease

Parkinson's disease is the second most frequent neurodegenerative disease after Alzheimer's disease, and the most common neurodegenerative disease that causes movement dysfunction. Without innovations in prevention and treatment, the incidence and prevalence of Parkinson's disease is projected to increase by > 30% by 2030, making the development of new treatments an urgent priority. We previously investigated the association between melatonin receptor agonists and Parkinson's disease using the US Food and Drug Administration's Adverse Event Reporting System (FAERS). The results showed that ramelteon may reduce the incidence of Parkinson's disease. However, since the US FAERS relies on spontaneous reports, which are susceptible to reporting bias, further validation using real-world data is required. This study investigated the association between ramelteon use and risk of developing Parkinson's disease using the DeSC database, a Japanese claims database reported to be representative of the general Japanese population. The association was evaluated using sequence symmetry analysis, with the adjusted sequence ratio (ASR) serving as the evaluation index. Our DeSC database analysis showed a negative association between ramelteon use and Parkinson's disease (ASR: 0.959, 95% confidence interval: 0.955-0.964). Our results support previous reports suggesting that ramelteon may help suppress the onset of Parkinson's disease. However, even though this study used real-world data, these results should be interpreted with caution, as a sequence symmetry analysis cannot be adjusted for covariates. Therefore, additional pharmacoepidemiological studies are needed to further verify the potential risk of Parkinson's disease associated with ramelteon use.