Risk Of Neuropsychiatric Events Research Articles

Use of Leukotriene-Receptor Antagonists During Pregnancy and Risk of Neuropsychiatric Events in Offspring

This cohort study examines the association of the use of leukotriene-receptor antagonists during pregnancy with the risk of neuropsychiatric events in offspring.

LTRA-related risk of neuropsychiatric events in paediatric patients

LTRA-related risk of neuropsychiatric events in paediatric patients

Leukotriene receptor antagonists and risk of neuropsychiatric events in children, adolescents and young adults: a self-controlled case series.

Leukotriene receptor antagonists (LTRAs) are widely used for asthma and allergic rhinitis (AR), but concerns about the risk of neuropsychiatric events (NPEs) have been raised since the first Drug Safety Communication by the US Food and Drug Administration in 2008. This study evaluates the association between LTRA use and NPEs in children, adolescents and young adults with asthma or AR. A self-controlled case series study was conducted using the Korean National Health Insurance Service claims database from two 3-year observation periods (observation period 1 (Obs1): 2005-2007; observation period 2 (Obs2): 2016-2018). Asthma or AR patients aged 3-30 years who were prescribed LTRAs and diagnosed with NPEs were included. The incidence rate ratios (IRRs) for the exposed period and risk periods (1-3, 4-7, 8-14, 15-30, 31-90 and >90 days from initiation of LTRA) compared with unexposed periods were calculated using conditional Poisson regression. Subgroup analysis according to age group, type of NPEs and indication of LTRA was performed. Among 17 001 included patients, the risk of NPEs increased in Obs2 (IRR 1.11, 95% CI 1.00-1.22), but did not increase in Obs1. Risk was increased during risk periods 4-7 days (IRR 2.36, 95% CI 1.99-2.76) and 8-14 days (IRR 1.78, 95% CI 1.46-2.15) after initiation of LTRA, particularly in adolescents (IRR 1.28, 95% CI 1.05-1.55) and young adults (IRR 1.14, 95% CI 1.02-1.28), while risk was decreased in children (3-11 years). Risk was not increased for any single type of NPE. AR patients were at increased risk (IRR 1.19, 95% CI 1.01-1.39), but not those with asthma. Overall, risk of NPEs with LTRA use differed between risk periods and subgroups. Physicians should prescribe LTRAs according to indications and inform patients about possible NPEs.

Neuraminidase inhibitors for treatment of influenza.

Neuraminidase inhibitors (NAIs) are commonly used in the prevention and treatment of influenza. Previous studies and reviews have demonstrated a questionable and modest benefit of their use while demonstrating potential adverse effects.1,2.

A Boxed Warning for Montelukast: The FDA Perspective

The U.S. Food and Drug Administration (FDA) became aware of postmarketing reports of neuropsychiatric adverse events with Singulair (montelukast) use in 2007. Over the years, the FDA has conducted reviews of the clinical trial safety data, focused analyses of postmarketing reports, and reviews of the published literature. These activities have resulted in successive labeling updates and public communications. However, there has been continued concern among stakeholders about the risk of neuropsychiatric events and the lack of awareness among prescribers and patients/caregivers. On the basis of these concerns, the FDA embarked on another comprehensive review and also conducted a new observational study using claims data in the Sentinel Distributed Database. In September 2019, the FDA held a public Advisory Committee meeting to discuss its review and solicit recommendations from the panel regarding labeling and communication strategies. After careful consideration of the available data and feedback received during the FDA Advisory Committee meeting, the FDA required a boxed warning and a revision specifically for the allergic rhinitis indication to reserve use of montelukast to patients who have an inadequate response or intolerance to alternative therapies. Based on benefit-risk considerations, the asthma indication was not changed. To provide insight into the process and rationale for the required labeling changes, we provide an overview of the decision-making framework we used.

Oseltamivir and the Risk of Neuropsychiatric Events: A National, Population-based Study.

Reports of serious neuropsychiatric events (NPEs), specifically suicide/suicide attempts, following the use of oseltamivir have led to public concerns. Our aim in this study was to determine whether an association exists between oseltamivir use and NPEs. This study was a population-based, retrospective, cohort study on a random sample of 50% of individuals in the Korean National Health Insurance Service (KNIS) database aged ≥8 years who were diagnosed with influenza between 2009 and 2017. The primary exposure was oseltamivir prescription at the time of influenza diagnosis, whereas the primary outcome was a diagnosis of an NPE within 30 days after the influenza diagnosis. Information on oseltamivir prescription, diagnoses of NPEs, demographic characteristics, comorbidities, drugs prescribed within the year before influenza diagnosis, and healthcare utilization were extracted from the KNIS database. Of 3 352 015 individuals included in the analysis, 1 266 780 (37.8%) were prescribed oseltamivir. The incidence of NPEs was 0.86% and 1.16% in patients who were and were not prescribed oseltamivir, respectively (hazard ratio [HR], 0.74; 95% confidence interval [CI], .73 to .75; P < .001). Oseltamivir use was not associated with a difference in the overall risk of NPEs in the adjusted model (HR, 0.98; 95% CI, .96 to 1.01; P = .16), but the incidence of moderate-to-severe NPEs was significantly lower in those prescribed oseltamivir (HR, 0.92; 95% CI, .88-.96; P < .001). Treating influenza with oseltamivir does not increase the risk of NPEs. Thus, public concern regarding its use is unwarranted.

Asthma Treatments and Mental Health Visits After a Food and Drug Administration Label Change for Leukotriene Inhibitors

PurposeIn 2009, the US Food and Drug Administration (FDA) mandated a label change for leukotriene inhibitors (LTIs) to include neuropsychiatric adverse events (eg, depression and suicidality) as a precaution. This study investigated how this label change affected the use of LTIs and other asthma controller medications, mental health visits, and suicide attempts. MethodsWe analyzed data (2005-2010) from 5 large health plans in the US Population-Based Effectiveness in Asthma and Lung Diseases (PEAL) Network. The study cohort included children and adolescents (n = 30,000), young adults (n = 20,000), and adults (n = 90,000) with asthma. We used interrupted time series to examine changes in rates of LTI dispensings, non-LTI dispensings, mental health visits, and suicide attempts (using a validated algorithm based on a combination of diagnoses of injury or poisoning and psychiatric conditions). FindingsThe label change was associated with abrupt reductions in LTI use among all age groups (relative reductions of 8.3%, 15.1%, and 6.0% among adolescents, young adults, and adults, respectively, compared with expected rates at 1 year after the warnings). Although we detected immediate offset increases in non-LTI asthma medication use, these increases were not sustained among adolescents and young adults. There were small increases in mental health visits among LTI users. ImplicationsThe FDA label change for LTIs communicated possible risk of neuropsychiatric events. Communication and enhanced awareness may have increased reporting of mental health symptoms among young adults and adults. It is important to assess intended and unintended consequences of FDA warnings and label changes.