Mining of Pharmacovigilance Signals for Adverse Events of Drug-induced Parkinsonism Based on FAERS Database

OBJECTIVE  To conduct data mining on drugs causing drug-induced Parkinsonism(DIP) based on the FDA adverse event reporting system(FAERS).

METHODS Collect adverse event reports of DIP from the FAERS database for a total of 81 quarters from Q1 2004 to Q1 2024. Using reporting odds ratio(ROR), proportional reporting ratio, Bayesian confidence propagation neuralnetwork, and muti-item gamma poisson shrinker methods for signal mining.

RESULTS The final number of reports included in the analysis was 405755. There were more females(239269 cases, 58.97%) than males(135094 cases, 33.29%). Among patients of known age, the 45–64 age group had the highest proportion(23.83%), followed by elderly people aged 65 and above(20.75%). The intersection of four methods resulted in 107 DIP signal drugs, involving 183258 cases. Among them, the most commonly used drugs involve the nervous system, accounting for 73. The drugs found to cause adverse event of Parkinson's disease with the strongest signal were metoclopramideOR=67.85, 95% CI(67.03−68.67) and carbidopa & levodopaOR=12.05, 95% CI(11.87−12.23), valbenazineOR=16.14, 95% CI(15.68−16.62), haloperidolOR=12.30, 95% CI(11.90−12.71). Clinical outcome: 84.03% of cases experienced serious adverse events; most DIP events manifest within 30 d after the first use of medication(17.39%), with a median onset time of 9 d. The clinical outcomes were as follows: a total of 12 062 cases resulted in death(2.97%), 13 852 cases were life-threatening(3.41%), and 35 309 cases led to disability(8.70%).

CONCLUSION First-generation antipsychotics, metoclopramide, and Parkinson's medications containing levodopa are prone to inducing DIP, mostly occured within 30 d, with a high risk of severe adverse reactions. Second-generation antipsychotics and antidepressants may also lead to DIP, but their potential risks still require clinical verification.