A Comparison of Tardive Dyskinesia With First- and Second-Generation Antipsychotics in Postmarket Surveillance Data

Introduction: Tardive dyskinesia (TD) is a known adverse drug reaction (ADR) of first-generation and second-generation antipsychotics. While second-generation antipsychotics are believed to pose a lower TD risk, evidence remains mixed. This study compares TD risk between first- and second-generation antipsychotics using postmarket ADR data. Study Type: Observational cross-sectional pharmacovigilance analysis. Methods: We conducted a disproportionality analysis of the FAERS database from 2012 to 2024, calculating the reporting odds ratio (OR) for TD in antipsychotic users. Individual drug ORs were pooled via meta-analysis with stratification by age and sex. Results: Significant variation in TD risk was observed across drugs; second-generation antipsychotics were not uniformly safer than first-generation agents. Stratified analyses revealed further variability by demographic factors. Notably, clozapine exhibited a lower OR compared with other antipsychotics. Conclusions: These findings challenge the assumption of uniformly decreased TD risk of second-generation antipsychotics and underscore the importance of individualized risk assessment when prescribing antipsychotics.