Exploring the Risk of Adverse Drug Events in Combination with antiparkinsonics and antipsychotics - a two-decade real-world pharmacovigilance analysis based on the FAERS database

Abstract Background The combination of antiparkinsonics and antipsychotic drugs (AP) can improve the motor and mental symptoms of Parkinson's disease (PD) and reduce the actual burden of chronic disease care. To explore the adverse drug events (ADEs) worthy of attention in this treatment management process, we conducted a real-world pharmacovigilance analysis based on the FDA Adverse Event Reporting System (FAERS) database. Method The Standard pharmacotherapy for PD include Levodopa/Carbidopa, Entacapone, Rasagiline, Pramipexole, Ropinirole, Rotigotine, Apomorphine and Amantadine, etc. AP includes Quetiapine, Clozapine and Pimavanserin. We collected the ADEs reports of FAERS that conformed to the combination regimens of anti-Parkinson's drugs and AP during the 20-year period from the third quarter of 2004 to the second quarter of 2024. Disproportionate analysis and subgroup analysis were conducted through five algorithms, namely Ω shrinkage measure, additive model, multiplicative model, Combination risk ratio, and Chi-square. The Time to onset (TTO) analysis was used to predict the variation of the risk size of ADEs occurrence over time. Finally, we explored the correlation between population characteristics and the occurrence of ADEs through Logistic regression. Result We collected a total of 6,297 cases, including 38,316 ADEs records. The results of the disproportionate analysis show that The ADEs with the highest occurrence frequency include hallucination, general physical health deterioration, somnolence, stoma site discharge, urinary tract infection and memory impairment, etc. The TTO analysis results showed that the median TTO for all ADEs was 657.50 days, the median TTO for infection and inflammation was 716.00 days, and the median TTO for psychiatric symptoms was 823.00 days. All median TTOs conform to the early failure curve. The results of Logistic regression showed that gender was correlated with the occurrence of infection and inflammation, and the female population was more inclined to have IME related to infection and inflammation. Conclusion During the combined application of antiparkinsonics and AP, in addition to ADEs such as movement disorders and emerging mental symptoms, the risks of infection and inflammation should also be given key attention. Long-term follow-up should run through the entire process of disease diagnosis and treatment, and attention should be paid to the influence of drug dosage forms and dosages. The medication plan should be adjusted in a timely manner when ADEs occur.