First generation antipsychotic-associated serious adverse events in women: a retrospective analysis of a pharmacovigilance database.

BACKGROUND: Women have been under-represented in trials of antipsychotic medications. AIM: Our primary objective was to evaluate five adverse events (AE) associated with first-generation antipsychotics (FGAs) among women relative to men through an analysis of the FDA Adverse Event Reporting System (FAERS). METHOD: We queried 24.6 million AE reports from 2000 to 2023 involving FGAs. The study cohort consisted of chlorpromazine (n = 3317), fluphenazine (n = 1124), haloperidol (n = 16,709), loxapine (n = 3151), perphenazine (n = 816), thioridazine (n = 665), thiothixene (n = 244), and trifluoperazine (n = 360). Cases of neuroleptic malignant syndrome (NMS), tardive dyskinesia (TD), Torsades de Pointes (TdP), agranulocytosis (AG), and cerebrovascular adverse events (CVAE) were identified. Reporting odds ratios (ROR) and associated 95% confidence intervals (CI) were calculated with logistic regression for each AE among women relative to men. RESULTS: A total of 2,857 serious AEs were evaluated in the study cohort (NMS = 1810, TD = 434, TdP = 260, AG = 149, CVAE = 204). The ROR for women compared to men was 0.79 (95% CI, 0.71-0.87) for NMS, 0.83 (0.68-1.01) for TD, 1.21 (0.94-1.53) for TdP, 0.71 (0.51-0.98) for AG, and 0.91 (0.68-1.19) for CVAE. A secondary analysis revealed a higher odds in women compared to men of hospitalization associated with reports of TD (ROR = 1.95, 1.29-2.94) and death associated with reports of AG (ROR = 2.46, 1.15-5.24). A subgroup analysis of haloperidol revealed an ROR = 1.67 (1.26-2.21) for women relative to men for TdP. CONCLUSION: The subgroup analysis of haloperidol AEs revealed a significantly higher reporting odds ratio for TdP. Additionally, the secondary study findings suggest that women were more vulnerable to worse outcomes associated with certain AEs of FGAs.

Pain management considerations in patients living with both pain syndromes and cardiovascular diseases and disorders.

Concomitant pain syndromes and cardiovascular disease (CVD) and disorders are associated with significant morbidity, impaired quality of life, and neuropsychiatric disorders. There is an interplay between the mechanisms of pathophysiology of both CVD and pain syndromes. Patients with CVD (and/or disorders) as well as pain syndromes have an increased propensity for drug-drug/disease interactions. Therefore, an understanding of how to use pharmacotherapy to treat pain syndromes, in the context of patients who have diagnoses of CVD and/or disorders, is paramount to patients' success in achieving adequate pain control and appropriately managing CVD and/or disorders, all while decreasing the risk of adverse events (AEs) both from pharmacotherapy to treat pain and CVD (and/or disorders). Based on the appraisal of literature and authors' clinical expertise, it was determined that gabapentinoids, opioids, skeletal muscle relaxants, tricyclic antidepressants, clonidine, serotonin norepinephrine-reuptake inhibitors, dronabinol, carbamazepine, second-generation antipsychotics, non-steroidal anti-inflammatory drugs, aspirin, corticosteroids, and topical anesthetics have the most evidence for use in patients with CVD and/or disorders. However, the literature surrounding the use of pharmacotherapy for pain management is limited to retrospective studies and there is a lack of well-designed, prospective, randomized trials; this also includes head-to-head comparator studies. Unlike many CVD-related pharmacotherapy studies, data studying pain management in patients with CVD lacks standardized outcomes that are consistent among the pool of data. Overall, the decision to prescribe specific pain management therapies in patients with CVD and/or disorders should include assessment of pain severity, type of pain, drug-drug/disease interactions, adjuvant therapies required, and the risk or presence of AEs.

Newer Antiseizure Medications and Suicidality: Analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS) Database.

BACKGROUND: The association between antiseizure medications (ASMs) and suicidality remains controversial. Analyses of additional datasets are needed to further elucidate the complex relationship between antiseizure medications and suicidality. OBJECTIVE: The aim of this study was to compare the safety profile of newer ASMs with older ASMs through an analysis of the US Food and Drug Administration Adverse Event Reporting System (FAERS) database, with a focus on suicidality. METHODS: We queried over 17 million reports in the FAERS database from 2012 to 2021 and identified cases involving ASMs. After removing incomplete and duplicate reports, the study cohort consisted of lacosamide (n = 7593), perampanel (n = 1813), clobazam (n = 3827), brivaracetam (n = 1166), and vigabatrin (n = 5293) compared with a control group of older ASMs (topiramate, lamotrigine, valproic acid, carbamazepine, levetiracetam; n = 71,535). Cases of suicidality (completed suicide, suicidal ideation, attempted suicide, suicidal behavior, suicidal depression) were identified in each group. Adjusted (age and sex) odds ratios (aOR) and associated 95% confidence intervals (CI) were calculated using logistic regression analysis for each new drug when compared with the control group of older ASM drugs. RESULTS: A total of 6309 cases of suicidality were identified among reports with ASMs. Most reports were sourced from healthcare professionals (5516, 87.4%). The proportion of reports involving suicidality were 210/7593 (2.8%) for lacosamide, 185/1813 (10.2%) for perampanel, 108/3827 (2.8%) for clobazam, 57/1166 (4.9%) for brivaracetam, 14/5293 (0.3%) for vigabatrin, and 5735/71,535 (8.0%) for older ASMs. Compared with older ASMs, the aOR for suicidality was 0.33 (95% CI 0.28-0.38) for lacosamide, 1.34 (95% CI 1.15-1.56) for perampanel, 0.35 (95% CI 0.29-0.43) for clobazam, 0.60 (95% CI 0.45-0.77) for brivaracetam, and 0.03 (95% CI 0.02-0.05) for vigabatrin. CONCLUSION: When compared with older ASMs, four newer ASMs (lacosamide, clobazam, brivaracetam, and vigabatrin) were found to have significantly lower odds of suicidality, while perampanel was found to significantly increase the odds of suicidality. Pronounced variability (greater than 30 fold) in the proportion of FAERS reports associated with suicidality among the drugs studied was identified. The results of this case control study of FDA adverse event reports spanning 10 years and 6309 cases of suicidality expand our understanding of the safety profile of newer ASMs.

Aspirin for primary prevention of cardiovascular disease: a review of recent literature and updated guideline recommendations.

INTRODUCTION: Recent clinical trials evaluating the efficacy of aspirin in primary prevention of atherosclerotic cardiovascular disease (ASCVD) have suggested the risk of aspirin may outweigh its benefit in individuals once thought to be candidates for aspirin therapy. These results led to the publication of updated guideline recommendations in 2019 for aspirin use in primary prevention of cardiovascular disease from the American College of Cardiology (ACC) and American Heart Association (AHA). AREAS COVERED: Recent clinical trials and guidelines relevant to aspirin for primary prevention of ASCVD were identified using PubMed® (July 1, 2016 to April 1, 2019). Studies were limited to randomized, controlled clinical trials. The most current clinical practice guidelines were prioritized. EXPERT OPINION: Recent clinical trials demonstrated an increased risk of bleeding associated with aspirin use, which often outweighed cardiovascular risk reduction. In light of this new evidence, the ACC/AHA guidelines recommend aspirin for primary prevention in patients 40-70 years of age at a high ASCVD risk and low bleeding risk, who are unable to optimally control modifiable ASCVD risk factors.

Exploring the Effectiveness of Team-based Enablement Interventions to Improve Antibiotic Prescribing within a Psychiatric Hospital.

Background: Antimicrobial resistance threatens the effective prevention and treatment of many types of infections. Infection occurs more frequently in patients diagnosed with psychiatric illness due to a number of risk factors. Urinary tract infections (UTI) are among the most common infections in this patient population. Currently, there is little information available offering guidance on how to treat infections commonly reported in patients with psychiatric illnesses, nor are there specific recommendations on how to provide efficient and effective educational interventions to prescribers who typically are not infectious disease specialists yet are responsible for treating infections within a psychiatric hospital. This study aims to determine 1) whether psychiatric inpatients were appropriately treated for a urinary tract infection (UTI) prior to educational interventions, and 2) whether there is a relationship between different modes of educational interventions and increased knowledge attainment and retention among healthcare clinicians regarding UTI treatment. This study also sought to determine if 3) health-team teaching used as an enablement method improves antibiotic prescribing and if 4) the number of appropriate UTI treatment regimens increased following educational intervention compared to baseline (prior to educational intervention). Methods: A 10-question pre-test survey focusing on UTIs was administered to clinicians in various healthcare disciplines who were later randomly assigned to receive UTI educational interventions either as a live lecture or independent study with identical content. The same 10-question survey was administered as a post-test, 6 to 7 weeks following the educational intervention. Antibiotic prescribing prior to and following educational interventions was assessed to note prescribing trends. Results: Analysis showed that healthcare providers who received live education scored higher on the post-test survey versus those who received directions for self-directed review of educational material presented at the live educational intervention (p<0.001). Following educational interventions, the number of urine samples collected for suspected UTI decreased, resulting in a decrease of unnecessary antibiotic treatment. The number of appropriately prescribed antibiotic treatment regimens increased following educational efforts. Conclusion: These enablement educational intervention strategies resulted in significantly improved antibiotic prescribing, indicating that andragogical teaching methods, reinforced through printed material and verbal communication of prescribing deficits, promotes knowledge retention and improved care for patients hospitalized with psychiatric illness.