Second-Generation Antipsychotic-Associated Serious Adverse Events in Women: An Analysis of a National...

Women have historically been underrepresented in second-generation antipsychotic (SGA) clinical trials, accounting for less than 35% of participants, which raises concerns about the generalizability of the safety profile for these medications.

The US adverse event reporting system was queried for the dates January 1, 2019, to July 8, 2024, to examine the following 6 SGAs: aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone. Reports were excluded if patients were under 18 years old, contained an unknown age or gender, or were duplicated. Five adverse events were examined: Torsades de pointes (TdP), neuroleptic malignant syndrome (NMS), tardive dyskinesia (TD), agranulocytosis (AG), and cerebrovascular adverse events (CVAE). Counts of these events were noted, and reporting odds ratios (ROR) were calculated.

The total study cohort was 87,356 reports, consisting of aripiprazole (n = 10,715, 12.2%), clozapine (n = 25,096, 28.7%), olanzapine (n = 11,587, 13.3%), quetiapine (n = 28,746, 32.9%), risperidone (n = 10,467, 12%), and ziprasidone (n = 745, 0.9%). The cohort's mean age was 48.6 ± 18.5 years and comprised 42,584 females (48.7%). Most cases were reported by healthcare professionals (74,836, 85.7%). A total of 3,754 reports contained at least 1 of the 5 adverse events. The RORs among females compared to males for TdP (5.55, 95% confidence interval [CI] = 3.78-8.47), NMS (0.59, 95% CI = 0.53-0.65), TD (0.88, 95% CI = 0.76-1.02), AG (0.59, 95% CI = 0.51-0.70), and CVAE (1.12, 95% CI = 0.89-1.41) were observed. Females had a significantly higher odds of hospitalization or death with TdP compared to males (ROR = 3.09, 95% CI = 1.36-7.01).

Our findings suggest higher odds of TdP and worse TdP-associated outcomes among females exposed to SGAs compared to males. Further studies are needed to confirm these preliminary findings.