Alan B Ettinger's research while affiliated with Winthrop University Hospital and other places

Objective: While studies have focused on identifying potential school shooters, little is known about the mental health and other characteristics of the overall group of students who make threats. This study describes these students and factors prompting psychiatric interventions and treatment recommendations. Method: Child and adolescent psychiatry threat assessment evaluations of 157 consecutive school-referred youths in grades K-12, seen over a 22-year period between 1998 and 2019 were reviewed for demographics, reasons for referral, nature of the threat, psychiatric diagnosis, and psychiatric and educational recommendations. Predictors of recommendations for psychiatric interventions were modeled using multivariable logistic regression as a function of above-mentioned covariates. Results: Mean age of referred students was 13.37 years (sd 2.79), 88.5% male; 79.7% White, 11.6% Hispanic,10.1% Black, 2.5% Asian. 51.6% were receiving special education services. 80% made a verbal threat and 29.3% brought a weapon to school. A history of being bullied was present in 43.4%, traumatic family events in 52.2%, physical abuse in 5.1%, sexual abuse in 5.7%, verbal abuse in 36.3%. Frequently encountered psychiatric diagnoses were ADHD, learning, depressive, anxiety, and autism spectrum disorders, usually in combinations. A history of medication treatment was reported in 79 (50.3%) and psychotherapeutic interventions in 57 (36.3%). Recommendations to return the student to their prior school were made for 63.1%. Recommendations for psychotherapy were made for 79.9%, medication in 88.5% and for both in 70.1%. Therapeutic school settings or psychiatric hospitalization were more likely recommended (with statistical significance) with a prior threat history (OR 5.47 95%CI=1.91-15.70), paranoid symptoms (OR 5.72 95% CI=1.55 to 21.14, p=0.009), autism spectrum disorders (OR=3.45 95%C1.32-9.00), mood disorder (OR=5.71 95% CI=1.36-23.96), personality disorder (OR=9.47 95% CI1.78-50.55), or when psychotherapy was recommended (OR=4.84 95% CI=1.08-21.75). Conclusion: Students who make threats have diverse psychiatric profiles and warrant treatments. A trauma and/or abuse history is common. Evaluations of youths who make threats, need to go beyond simply assessing the threat itself and should include identifying underlying psychiatric problems. Psychiatric evaluation of students who issue threats of any type can lead to revelations about psychiatric diagnoses, and crucial treatment and educational recommendations. Diversity & inclusion statement: The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.

Purpose To review psychiatric and behavioural events in a study conducted to evaluate the efficacy and safety of adjunctive perampanel in patients with uncontrolled primary generalised tonic-clonic seizures (PGTCS). Method Following baseline (4 or 8 weeks), patients aged ≥12 years were randomised to double-blind treatment with perampanel or placebo (titration 4 weeks; maintenance 13 weeks; maximum dose 8 mg). Treatment-emergent adverse events (TEAEs) were evaluated using MedDRA search terms for psychiatric disorders and MedDRA SMQs for hostility/aggression-related events. Results In the Safety Analysis Set (perampanel n=81; placebo n=82), psychiatric TEAEs occurred in 20 (24.7%) perampanel- and 16 (19.5%) placebo-treated patients. Most TEAEs were of mild or moderate intensity. Frequency of TEAEs related to hostility/aggression was 18.5% for perampanel and 4.9% for placebo, largely due to a higher rate of irritability with perampanel (11.1%) versus placebo (2.4%). Incidences of serious adverse events and discontinuations due to TEAEs related to hostility/aggression for perampanel versus placebo were 1.2% versus 0% and 3.7% versus 1.2%, respectively. Conclusion Consistent with results from Phase III trials in partial epilepsy, hostility/aggression-related TEAEs occurred at a higher rate in perampanel-treated patients with PGTCS than in those treated with placebo, driven mainly by irritability. Supported by Eisai Inc.

Antiepileptic drugs (AEDs) have many benefits but also many side effects, including aggression, agitation, and irritability, in some patients with epilepsy. This article offers a comprehensive summary of current understanding of aggressive behaviors in patients with epilepsy, including an evidence-based review of aggression during AED treatment. Aggression is seen in a minority of people with epilepsy. It is rarely seizure related but is interictal, sometimes occurring as part of complex psychiatric and behavioral comorbidities, and it is sometimes associated with AED treatment. We review the common neurotransmitter systems and brain regions implicated in both epilepsy and aggression, including the GABA, glutamate, serotonin, dopamine, and noradrenaline systems and the hippocampus, amygdala, prefrontal cortex, anterior cingulate cortex, and temporal lobes. Few controlled clinical studies have used behavioral measures to specifically examine aggression with AEDs, and most evidence comes from adverse event reporting from clinical and observational studies. A systematic approach was used to identify relevant publications, andwe present a comprehensive, evidence-based summary of available data surrounding aggression-related behaviors with each of the currently available AEDs in both adults and in children/adolescents with epilepsy. A psychiatric history and history of a propensity toward aggression/anger should routinely be sought from patients, family members, and carers; its presence does not preclude the use of any specific AEDs, but those most likely to be implicated in these behaviors should be used with caution in such cases.

The purpose of this study was to measure health-care resource utilization and costs in treatment-adherent, previously seizure-free patients with epilepsy who were treated in the inpatient/emergency room (ER) setting for new-onset seizures, compared with matched controls. The study used a retrospective case/control study design using administrative claims from the IMS PharMetrics™ database. We identified adult patients with epilepsy with 1+ ER visit/hospitalization with primary diagnosis of epilepsy between 1/1/2006 and 3/31/2011, preceded by 6months of seizure-free activity and antiepileptic drug (AED) treatment adherence (≥80% of days covered by any AED); the first observed seizure defined the "breakthrough" seizure/index event. Treatment-adherent patients with epilepsy without any ER/hospital admission for seizures served as controls: an outpatient epilepsy-related medical claim within the selection window was chosen at random as the index date. The following were continuous enrollment requirements for all patients: ≥12-month pre- and ≥6-month postindex. Each case matched 1:1 to a control using propensity score matching. All-cause and epilepsy-related (epilepsy/convulsion diagnosis, AED pharmacy) resource utilization and unadjusted and adjusted direct health-care costs (per person, 2012 US dollars (USD)) were assessed in a 6-month follow-up period. There were 5729 cases and 14,437 controls eligible. The final sample comprised 5279 matched case/control pairs. In unadjusted analyses, matched cases had significantly higher rates of all-cause hospitalization and ER visits compared to controls and significantly higher total all-cause direct health-care costs (median $12,714 vs. $5095, p<0.001) and total epilepsy-related costs among cases vs. controls (median $7293 vs. $1712, p<0.001), driven by higher inpatient costs. Among cases, costs increased with each subsequent seizure (driven by inpatient costs). Cases had 2.3 times higher adjusted all-cause costs and 8.1 times higher adjusted epilepsy-related costs than controls (both p<0.001). Inpatient/ER-treated breakthrough seizures occurred among 28.4% of our treatment-adherent study sample and were associated with significant incremental health-care utilization and costs, primarily driven by hospitalizations. Our findings suggest the need for better seizure control via optimal patient management and the use of effective AED therapy, which can potentially lower health-care costs. Copyright © 2015 Elsevier Inc. All rights reserved.

Table S1. Complete List of “Narrow” and “Broad” Standardized Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs) for TEAEs Suggestive of Hostility/Aggression.24 Table S2. Concomitant Medications in Double‐Blind Phase III Subjects with TEAEs in the Hostility/Aggression “Narrow‐and‐Broad” SMQ.

Objective: Perampanel, a selective, noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor antagonist, is indicated for adjunctive treatment of partial seizures in patients ≥12 years based on three phase III clinical studies. The perampanel U.S. Prescribing Information includes a boxed warning for serious psychiatric and behavioral adverse reactions. To provide context for this warning, detail on psychiatric and behavioral safety data from perampanel clinical studies is presented. Methods: An analysis of pooled safety data from three phase III studies in patients with partial seizures is presented. Data from phase I and phase II studies in patients with and without epilepsy were also analyzed. Psychiatric and behavioral treatment-emergent adverse events (TEAEs) were evaluated according to Medical Dictionary for Regulatory Activities (MedDRA) terms, using "narrow" and "narrow-and-broad" standardized MedDRA queries (SMQs) for TEAEs suggestive of hostility/aggression. Results: From the three phase III partial-seizure studies, the overall rate of psychiatric TEAEs was higher in the 8 mg (17.2%) and 12 mg (22.4%) perampanel groups versus placebo (12.4%). In the "narrow" SMQ, hostility/aggression TEAEs were observed in 2.8% for 8 mg and 6.3% for 12 mg perampanel groups, versus 0.7% of placebo patients. "Narrow-and-broad" SMQs for hostility/aggression TEAE rates were 12.3% for 8 mg and 20.4% for 12 mg perampanel groups, versus 5.7% for placebo; rates for events resulting in discontinuation were perampanel = 1.6% versus placebo = 0.7%. For events reported as serious AEs (SAEs), rates were perampanel = 0.7% versus placebo = 0.2%. In nonepilepsy patients, psychiatric TEAEs were similar between patients receiving perampanel and placebo. In phase I subjects/volunteers, all psychiatric TEAEs were mild or moderate. These analyses suggest that psychiatric adverse effects are associated with use of perampanel. Significance: Patients and caregivers should be counseled regarding the potential risk of psychiatric and behavioral events with perampanel in patients with partial seizures; patients should be monitored for these events during treatment, especially during titration and at higher doses.