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Objective: Catatonia is a life-threatening psychomotor syndrome that occurs in approximately 10% of patients with acute psychiatric illnesses. Although some case reports have argued that first generation antipsychotics (FGAs) are more likely to induce catatonia than second generation antipsychotics (SGAs), no large observational study has confirmed this hypothesis. We investigated whether FGAs were associated with an increased risk of reporting catatonia when compared with SGAs., Methods: A pharmacovigilance study was performed within VigiBase to compare the cases of catatonia syndromes reported in patients exposed to FGAs with those reported in patients exposed to SGAs. This approach is similar in concept to case-control study, but adapted to a pharmacovigilance database, and allows the estimation of reporting odds ratios (RORs) with 95% confidence intervals., Results: We identified 60,443 adverse effects reported in patients who received FGAs and 253,067 adverse effects reported in patients treated with SGAs. Compared with SGAs, the use of FGAs was associated with an increased risk of reporting catatonia syndromes (ROR = 2.2; 95% CI, 2.0-2.3). Consistent results were observed when the analysis was restricted to reports generated from physicians, reports from the US, and reports with the highest completeness score. The highest RORs were found for molindone (6.0; 95% CI, 3.1-10.4) and haloperidol (3.8; 95% CI, 3.5-4.0)., Conclusions: In this large pharmacovigilance study of patients exposed to antipsychotics, the use of FGAs was associated with an increased risk of reporting catatonia syndromes compared to the use of SGAs. This increased risk is consistent with the pharmacodynamic hypothesis of antipsychotic-induced catatonia. Our results warrant replication in population-based studies., (© Copyright 2022 Physicians Postgraduate Press, Inc.)