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Infectious disorders. Part 5

Chapter by: Datta, N; Ettinger, Alan B
in: Synopsis of neurology, psychiatry and related systemic disorders by Ettinger, Alan B; Weisbrot, Deborah M; Gallimore, Casey [Eds]
Cambridge, United Kingdom ; New York, NY : Cambridge University Press, 2019
pp. ?-
ISBN: 9781107069565
CID: 5363522

Heredofamilial disorders. Part 2

Chapter by: Datta, N; Ettinger, Alan B; Weisbrot, DM
in: Synopsis of neurology, psychiatry and related systemic disorders by Ettinger, Alan B; Weisbrot, Deborah M; Gallimore, Casey [Eds]
Cambridge, United Kingdom ; New York, NY : Cambridge University Press, 2019
pp. ?-
ISBN: 9781107069565
CID: 5363462

Patient versus neurologist preferences: A discrete choice experiment for antiepileptic drug therapies

Ettinger, Alan B; Carter, John A; Rajagopalan, Krithika
OBJECTIVE:This assessment was conducted to quantify and compare patient and neurologist preferences regarding antiepileptic drug (AED) attributes for treating epilepsy. METHODS:Patients with epilepsy (≥18years, treated with AEDs) and neurologists were recruited from nationally representative US panels to complete an online survey that included a discrete choice experiment (DCE). Participants chose between two hypothetical AEDs, characterized by six attributes in the DCE, which included 1) level of seizure control/reduction; 2) dosing frequency, 3) diminished coordination and balance, 4) psychiatric issues, 5) diminished energy level, and 6) dietary restrictions. The Sawtooth Software Choice-Based Conjoint (CBC) System for CBC Analysis was used to estimate treatment attribute ranking and weighting. RESULTS:Of the 720 respondents (518 patients and 202 neurologists), both patients and neurologists ranked seizure control as the most important attribute (rank 1) and dietary restrictions as the least important attribute (rank 6). However, seizure control had a significantly greater weighting in neurologists' decision-making than among patients (45% vs 32%, p<0.005). On the other hand, patients considered the risks of psychiatric adverse effects (19% vs 15%), diminished coordination and balance (16% vs 10%), and fatigue or diminished energy (13% vs 11%) as significantly more important (p<0.05) than did neurologists. CONCLUSION:Patients and neurologists had similar preference ranking order, with seizure reduction being ranked the most important attribute. However, neurologist treatment preferences were significantly more influenced by seizure reduction while patient preferences were significantly more influenced by adverse effects that may impact their quality of life. Understanding how patient and neurologist perspectives differ should encourage dialog to communicate the potential risks and benefits of AED therapy and assist in the shared decision-making process.
PMID: 29433949
ISSN: 1525-5069
CID: 5327472

Epilepsy, Antiepileptic Drugs, and Aggression: An Evidence-Based Review

Brodie, Martin J; Besag, Frank; Ettinger, Alan B; Mula, Marco; Gobbi, Gabriella; Comai, Stefano; Aldenkamp, Albert P; Steinhoff, Bernhard J
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, and we 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.
PMCID:4931873
PMID: 27255267
ISSN: 1521-0081
CID: 5327462

Comparing Anti-Epileptic Drug Preferences Between Neurologists and Patients: Results from a National Survey and Discrete Choice Experiment [Meeting Abstract]

Ettinger, Alan; Velez, Fulton; Carter, John
ISI:000411279000004
ISSN: 0028-3878
CID: 5356482

Clinical and economic burden of breakthrough seizures

Divino, Victoria; Petrilla, Allison A; Bollu, Vamsi; Velez, Fulton; Ettinger, Alan; Makin, Charles
PURPOSE/OBJECTIVE: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. METHODS: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. PRINCIPAL RESULTS/RESULTS: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). CONCLUSION/CONCLUSIONS: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.
PMID: 26255884
ISSN: 1525-5069
CID: 5327452

Psychiatric and behavioral adverse events in randomized clinical studies of the noncompetitive AMPA receptor antagonist perampanel

Ettinger, Alan B; LoPresti, Antonia; Yang, Haichen; Williams, Betsy; Zhou, Sharon; Fain, Randi; Laurenza, Antonio
OBJECTIVE: Perampanel, a selective, noncompetitive alpha-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.
PMCID:4758397
PMID: 26140524
ISSN: 1528-1167
CID: 1650812

Attention-deficit/hyperactivity disorder symptoms in adults with self-reported epilepsy: Results from a national epidemiologic survey of epilepsy

Ettinger, Alan B; Ottman, Ruth; Lipton, Richard B; Cramer, Joyce A; Fanning, Kristina M; Reed, Michael L
OBJECTIVE:To assess symptoms of attention-deficit/hyperactivity disorder (ADHD) and their impact among adults with epilepsy from a large community-based survey. METHODS:Adults who self-reported epilepsy were sent a postal survey including the Adult ADHD Self-Report Scale version 6 (ASRS-6), Physicians Health Questionnaire (PHQ-9), Generalized Anxiety Disorder Assessment 7 (GAD-7), and questions about seizure frequency and number of antiepileptic drugs (AEDs) during the preceding 3 months. Individuals with ASRS-6 scores >14 were classified as ASRS+, and those with lower scores as ASRS-. Outcome measures included the Quality of Life in Epilepsy Inventory 10 (QOLIE-10), Quality of Life and Enjoyment and Satisfaction Questionnaire (Q-LES-Q), and the Sheehan Disability Scale (SDS). The relationship of ADHD symptoms to quality of life outcomes was modeled hierarchically, with linear regression controlling for sociodemographic covariates, comorbid depression and anxiety, seizure frequency, and number of AEDs. RESULTS:Among 1,361 of respondents with active epilepsy, 18.4% (n = 251) were classified as ASRS+ and at risk for ADHD. Compared to ASRS- cases, ASRS+ individuals were more likely to have elevated depression and anxiety scores as well as greater seizure frequency and more AED use (p < 0.05 for all). Modeling results comparing ASRS+ and ASRS- cases, controlling for all covariates, indicated that ASRS+ cases had lower quality of life (Beta [β] = -3.07, 95% confidence interval [CI] -4.19 to -1.96) and worse physical (β = -0.048 95% CI -0.076 to -0.020) and social functioning (β = -0.058, 95% CI -0.081 to -0.035) on the Q-LES-Q, and increases in family (β = 1.57, 95% CI 1.09-2.05), social (β = 1.68, 95% CI 1.20-2.16), and work-related disability (β-1.86, 95% CI 1.27-2.46). SIGNIFICANCE/CONCLUSIONS:ADHD symptoms occur in nearly one of five adults with epilepsy, and are associated with increased psychosocial morbidity and lowered QOL. Future studies should clarify the nature and causes of ADHD symptoms in adults with epilepsy.
PMID: 25594106
ISSN: 1528-1167
CID: 5327442

Anxiety in epilepsy

Chapter by: Harden, C; Goldstein, MA; Ettinger, Alan B
in: Psychiatric Issues in Epilepsy : a Practical Guide to Diagnosis and Treatment by Ettinger, Alan B [Ed]
Philadelphia : Wolters Kluwer, 2015
pp. ?-
ISBN: 9781469877495
CID: 5363342

Psychiatric aspects of pediatric epilepsy

Chapter by: Weisbrot, DM; Ettinger, Alan B
in: Psychiatric Issues in Epilepsy : a Practical Guide to Diagnosis and Treatment by Ettinger, Alan B [Ed]
Philadelphia : Wolters Kluwer, 2015
pp. ?-
ISBN: 9781469877495
CID: 5363332