BackgroundDopamine receptor agonists (DAs) are widely used as first-line therapeutic agents for Parkinson's disease. However, comparative clinical trials assessing their safety profiles are limited. This study aims to compare adverse event (AE) data across various DAs to inform personalized treatment strategies.MethodsAE reports with DAs as the "primary suspicion (PS)" were extracted from the FDA Adverse Event Reporting System (FAERS) database, covering 67 quarters from the second quarter of 2007 to the fourth quarter of 2023. Four disproportionality analysis methods, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN) and multi-item gamma Poisson shrinker (MGPS), were employed to evaluate the risk of AEs.ResultsA total of 19,745,533 DA-related AEs reports were analyzed. The six DAs-pramipexole, ropinirole, cabergoline, rotigotine, bromocriptine and apomorphine-generated 269, 246, 202, 163, 146, and 135 preferred terms positive signals, respectively. Non-ergot DAs (pramipexole, ropinirole, rotigotine and apomorphine) were primarily associated with psychiatric disorders and reported more hallucinations than ergot-derived dopamine agonists (ergot-DAs), with ropinirole showing a slightly higher signal intensity than pramipexole (ROR = 15.76 vs. 11.23). Pramipexole demonstrated the most significant signal for impulse control disorders (ICDs). Compared with pramipexole and ropinirole, rotigotine generally exhibits milder signals in terms of psychiatric disorders such as hallucinations, ICDs, and sleep-related AEs. Administration site-related AEs were more prominent in rotigotine and apomorphine users. Ergot-DAs exhibited higher signal intensities for cardiac disorders, with cabergoline also showing a notable signal for amnestic symptoms (ROR = 340.54), which is not mentioned in the drug label.ConclusionThis study elucidates the distinct safety profiles of six DAs. Non-ergot DAs are primarily associated with psychiatric AEs, while administration-related AEs are more notable for rotigotine and apomorphine. Ergot-DAs present a higher risk for cardiac valvulopathies. These findings highlight the importance of individualized treatment considerations in clinical practice, emphasizing the need to formulate appropriate treatment plans on patients' specific conditions.