There have been reports of cases of myocarditis and pericarditis as rare complications following mRNA COVID-19 vaccinations among young adults. While most reported cases are mild, this potential vaccine safety signal should be closely monitored. Using data from the CDC and the Vaccine Adverse Event Reporting System (VAERS), we calculated the combined reporting rate of myocarditis and pericarditis stratified by age group, sex, vaccine dose, and manufacturer, and compared these rates to the crude background incidence rates. Compared to the general population prior to the administration of the first COVID-19 vaccines in December 2020, we identified a higher-than-expected reporting rate of myocarditis and pericarditis following mRNA vaccination; the risk was higher after a second vaccine dose, higher in males than in females, and decreased with age. The highest risk was seen in males 12–17 years of age with approximately 6 cases per 100,000 second doses. Our findings suggest an increased risk of myocarditis and pericarditis in young males following a second dose of an mRNA COVID-19 vaccine. Since these findings are based on safety signals derived from passive surveillance data, confirmatory epidemiological studies should be undertaken.

Concerns remain regarding the rare cardiovascular adverse events, myocarditis and pericarditis (myo/pericarditis), particularly in younger individuals following mRNA COVID-19 vaccination. Our study aimed to comprehensively assess potential safety signals related to these cardiac events following the primary and booster doses, with a specific focus on younger populations, including children as young as 6 months of age. Using the Vaccine Adverse Events Reporting System (VAERS), the United States national passive surveillance system, we conducted a retrospective pharmacovigilance study analyzing spontaneous reports of myo/pericarditis. We employed both frequentist and Bayesian methods and conducted subgroup analyses by age, sex, and vaccine dose. We observed a higher reporting rate of myo/pericarditis following the primary vaccine series, particularly in males and mainly after the second dose. However, booster doses demonstrated a lower number of reported cases, with no significant signals detected after the fourth or fifth doses. In children and young adults, we observed notable age and sex differences in the reporting of myo/pericarditis cases. Males in the 12–17 and 18–24-year-old age groups had the highest number of cases, with significant signals for both males and females after the second dose. We also identified an increased reporting for a spectrum of cardiovascular symptoms such as chest pain and dyspnea, which increased with age, and were reported more frequently than myo/pericarditis. The present study identified signals of myo/pericarditis and related cardiovascular symptoms after mRNA COVID-19 vaccination, especially among children and adolescents. These findings underline the importance for continued vaccine surveillance and the need for further studies to confirm these results and to determine their clinical implications in public health decision-making, especially for younger populations.

Objectives: To evaluate reports of diabetic ketoacidosis (DKA) associated with antipsychotic drug (APD) use submitted to the U.S. Food and Drug Administration’s Adverse Event Reporting System (FAERS). Methods: A retrospective pharmacovigilance analysis was conducted using FAERS data from January 2000 to December 2022. DKA cases were identified using the MedDRA preferred term “diabetic ketoacidosis” in reports listing antipsychotic drugs as suspect medications. Disproportionality analyses, including the proportional reporting ratio (PRR) and empirical Bayes geometric mean (EBGM), were used to assess reporting patterns. Multiple analyses were performed, including those restricted to primary suspect listed drugs only, expanded to incorporate secondary suspect drugs, and sensitivity analyses excluding reports submitted by legal professionals. Results: Among 19,961 DKA reports in FAERS, 2489 (12.5%) listed atypical antipsychotics as the primary suspect drug, whereas reports involving typical APDs were rare. The majority of reports were submitted by healthcare professionals (74.1%), and nearly half originated from the United States (45.4%). Hospitalization was a frequent outcome, reported in 74.3% of cases. Quetiapine and olanzapine were the most frequently reported atypical APDs, with disproportionality analyses demonstrating strong safety signals when compared to all other drugs in FAERS: olanzapine PRR 13.2 (95% CI: 12.4–14.2) and quetiapine PRR 11.8 (95% CI: 11.1–12.5). The findings remained consistent across multiple sensitivity analyses, including incorporating secondary suspect drugs, when the comparator group was restricted to only psychotropic drugs, and excluding reports submitted by lawyers. Conclusions: This pharmacovigilance analysis highlights a potential safety signal for DKA with atypical antipsychotic drugs, notably quetiapine and olanzapine. While these findings do not establish causality, they underscore the need for further investigation using clinical and epidemiological data.

Background/Objective: In recent years, epidemiological and clinical evidence has suggested an association between the use of second-generation antipsychotics (SGAs) and hyperglycemic complications: notably, diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS). However, the role of first-generation antipsychotics (FGAs) remains less well understood. To conduct a systematic review of evidence established in case reports (CRs) on adverse drug reactions, specifically DKA and HHS, associated with the use of both FGAs and SGAs in order to identify patterns that may inform clinical awareness and future research. Methods: Pertinent bibliographic databases (MEDLINE, EMBASE, PsycINFO and the Cochrane Central Register of Controlled Trials (CENTRAL)) were searched using index phrases and keywords up until 17 October 2025. Eligible CRs discussed exposure to at least one US FDA-approved antipsychotic drug (APD) and assessed either DKA or HHS. Results: A total of 151 CRs were included in the systematic review (DKA, n = 121; HHS, n = 28; both conditions, n = 2). Patients aged 30 to 39 years accounted for the highest number of emergencies (n = 49, 32.5%), which occurred mostly in males (n = 108, 71.5%). The most common mental health diagnosis was schizophrenia (n = 77, 51%), followed by bipolar disorder (n = 26, 17.2%). Olanzapine was associated with the highest number of DKA cases (n = 53, 43.1%), followed by clozapine (n = 24, 19.5%). The average blood glucose at presentation was 842.8 mg/dL for DKA patients and 1252.8 mg/dL for HHS patients. The average hemoglobin A1c levels (HbA1c) were 11.5% and 12%, respectively, for these two conditions. Of the 12 reported fatalities, treatment with olanzapine was noted in four DKA cases and in one HHS case. Conclusions: This analysis provides additional evidence of an association between the use of atypical APDs and DKA or HHS. Clinicians should continue to monitor metabolic risk factors for these conditions, as well as educating patients about the prevention of acute diabetic complications.

This study evaluated long-term trends in the prevalence of use of atypical and typical antipsychotic drugs (APDs), both as classes of drugs and as individual drugs, among adult inpatients in the United States (US). The Health Facts^® database developed by Cerner Corporation was used to analyze the prevalence of APD use among adult inpatients aged 18 years or older who were administered at least one antipsychotic medication order during hospitalization between 1 January 2000 and 31 December 2016. The prevalence of APD use was standardized by age, sex, race, and census region. Typical and atypical antipsychotic treatment patterns in the US differed over this period. While the use of atypical APDs increased overall, the use of typical antipsychotic medications decreased, but remained more prevalent. Overall, haloperidol and prochlorperazine were the two most administered antipsychotic medications throughout the study period. From 2000 to 2011, prochlorperazine and haloperidol were the first- and second-most prescribed typical APDs, respectively; haloperidol became the most administered antipsychotic of this class as of 2012. Quetiapine was the most administered atypical antipsychotic medication, followed by risperidone and olanzapine until 2014, after which olanzapine was the second-most administered atypical APD. There was a notable decline in the use of atypical antipsychotics medications between 2005 and 2008, which may reflect the impact of the Food and Drug Administration’s warnings and the American Diabetes Association’s consensus position, but only for a short time. The usage patterns observed in this study support existing evidence of substantial off-label use of antipsychotic drugs in the US.