Psychiatric adverse events associated with semaglutide, liraglutide and tirzepatide: a pharmacovigilance analysis of individual case safety reports submitted to the EudraVigilance database.

BACKGROUND: Semaglutide, liraglutide and tirzepatide are glucagon-like peptide-1 (GLP-1) receptor agonists that are effective for weight reduction. Recent reports of patients experiencing suicidal thoughts and other psychiatric adverse events while using GLP-1 agonists have raised concerns about the potential risk of self-harm and led the European Medicines Agency to investigate these medications. AIM: To identify and analyse the psychiatric adverse events associated with semaglutide, liraglutide and tirzepatide. METHOD: All individual case safety reports for semaglutide, liraglutide, and tirzepatide reported to the EudraVigilance database from 01/01/2021 to 30/05/2023 were analysed. Descriptive statistics were used to explore study population characteristics. RESULTS: During the study period, 31,444 adverse event reports were identified: semaglutide (n = 13,956; 44.4%), liraglutide (n = 16,748; 53.2%), and tirzepatide (n = 740; 2.3%). There were 372 reports with psychiatric adverse event reports (n = 372; 1.18%) with a total of 481 adverse events. Women accounted for 65% (n = 242) of these reports. Depression was the most commonly reported adverse event (n = 187; 50.3%), followed by anxiety (n = 144; 38.7%) and suicidal ideation (n = 73; 19.6%). Nine deaths (8 with liraglutide and 1 with semaglutide) and 11 life-threatening outcomes (4 associated with liraglutide and 7 with semaglutide) were reported. The fatal outcomes occurred primarily among men (8 out of 9) resulting from completed suicidal attempts and depression. CONCLUSION: Psychiatric adverse events comprised only 1.2% of the total reports for semaglutide, liraglutide, and tirzepatide. However, the severity and fatal outcomes of some of these reports warrant further investigation.

Thrombotic Adverse Events Reported for Moderna, Pfizer and Oxford-AstraZeneca COVID-19 Vaccines: Comparison of Occurrence and Clinical Outcomes in the EudraVigilance Database.

Vaccination against COVID-19 is the cornerstone of controlling and mitigating the ongoing pandemic. Thrombotic adverse events linked to Moderna, Pfizer and the Oxford-AstraZeneca vaccine have been documented and described as extremely rare. While the Oxford-AstraZeneca vaccine has received much of the attention, the other vaccines should not go unchallenged. This study aimed to determine the frequency of reported thrombotic adverse events and clinical outcomes for these three COVID-19 vaccines, namely, Moderna, Pfizer and Oxford-AstraZeneca. A retrospective descriptive analysis was conducted of spontaneous reports for Moderna, Pfizer and Oxford-AstraZeneca COVID-19 vaccines submitted to the EudraVigilance database in the period from 17 February to 14 June 2021. There were 729,496 adverse events for the three vaccines, of which 3420 were thrombotic, mainly Oxford-AstraZeneca (n = 1988; 58.1%) followed by Pfizer (n = 1096; 32.0%) and Moderna (n = 336; 9.8%). As serious adverse events, there were 705 reports of pulmonary embolism for the three vaccines, of which 130 reports (18.4%) were for Moderna, 226 reports (32.1%) for Pfizer and 349 (49.5%) for Oxford-AstraZeneca vaccines. The occurrence of pulmonary embolism is significantly associated with a fatal outcome (p ≤ 0.001). Sixty-three fatalities were recorded (n = 63/3420; 1.8%), of which Moderna (n = 6), Pfizer (n = 25) and Oxford-AstraZeneca (n = 32).

Analysis of Thrombotic Adverse Reactions of COVID-19 AstraZeneca Vaccine Reported to EudraVigilance Database.

The development of safe, effective, affordable vaccines against COVID-19 remains the cornerstone to mitigating this pandemic. Early in December 2020, multiple research groups had designed potential vaccines. From 11 March 2021, several European countries temporarily suspended the use of the Oxford-AstraZeneca vaccine amid reports of blood clot events and the death of a vaccinated person, despite the European Medicines Agency (EMA) and the World Health Organization's assurance that there was no indication that vaccination was linked. This study aimed to identify and analyse the thrombotic adverse reactions associated with the Oxford-AstraZeneca vaccine. This was a retrospective descriptive study using spontaneous reports submitted to the EudraVigilance database in the period from 17 February to 12 March 2021. There were 54,571 adverse reaction reports, of which 28 were associated with thrombotic adverse reactions. Three fatalities were related to pulmonary embolism; one fatality to thrombosis. With 17 million people having had the AstraZeneca vaccine, these are extremely rare events The EMA's Pharmacovigilance Risk Assessment Committee (18 March 2021) concluded that the vaccine was safe, effective and the benefits outweighed the risks. Conducting further analyses based on more detailed thrombotic adverse event reports, including patients' characteristics and comorbidities, may enable assessment of the causality with higher specificity.

Adequate levels of adherence with controller medication is associated with increased use of rescue medication in asthmatic children.

BACKGROUND: The role of asthma controller medication adherence and the level of asthma control in children is poorly defined. AIMS: To assess the association between asthma controller medication adherence and asthma control in children using routinely acquired prescribing data. METHODS: A retrospective observational study of children aged 0-18 years prescribed inhaled corticosteroids only (ICS), leukotriene receptors antagonists (LTRA), or long-acting ß2 agonists (LABA) and ICS prescribed as separate or combined inhalers, between 01/09/2001 and 31/08/2006, registered with primary care practices contributing to the Practice Team Information database. The medication possession ratio (MPR) was calculated and associations with asthma control explored. Poor asthma control was defined as the issue of prescriptions for ≥ 1 course of oral corticosteroids (OCS) and/or ≥ 6 short-acting ß2 agonists (SABA) canisters annually. RESULTS: A total of 3172 children prescribed asthma controller medication were identified. Of these, 15-39% (depending on controller medication) demonstrated adequate MPR. Adequate MPR was associated with male gender, good socio-economic status, and oral LTRA therapy. Adequate MPR was more likely to be associated with increased use of rescue medication. However logistic regression only identified a significant relationship for ICS only (odds ratio [OR], 1.89; 95% confidence interval [CI], 1.35-2.48; p<0.001), LTRA (OR, 2.11; 95% CI, 1.27-3.48; p = 0.004) and LABA/ICS (OR, 2.85; 95% CI, 1.62-5.02; p<0.001). CONCLUSION: Poor adherence was observed for all asthma controller medications, although was significantly better for oral LRTA. In this study adequate adherence was not associated with the use of less rescue medication, suggesting that adherence is a complex issue.

Changes in primary care prescribing patterns for paediatric asthma: a prescribing database analysis.

BACKGROUND: Little is known about the impact of British asthma management guideline revisions. Concerns about the use of high dose inhaled corticosteroids (ICS) in children have resulted in the promotion of add-on therapy. AIMS: To assess prescribing patterns of asthma medication in children in the primary care setting. METHODS: Retrospective observational study of asthma prescribing in children aged 0-18 years using primary care database from 2001 to 2006. RESULTS: The proportion of children prescribed oral corticosteroids increased significantly (from 6% in 2001-2002 to 16% in 2005-2006, p<0.001), while the proportion of children prescribed an ICS dose of >400 mcg decreased from 16.2% to 11.7% (P<0.001). The proportion of children prescribed an add-on therapy and an ICS dose >400 µg, increased from 38.8 % in 2001-2002 to 61.2% in 2005-2006 (p<0.001). CONCLUSIONS: Although adherence with asthma management guidelines is not optimal, this study has identified improved adherence in primary care.