Behavioral Adverse Events Research Articles

Aggravation of Behavioural Side Effects of Antiseizure Medications during COVID-19

Epilepsy affects more than 50 million people worldwide, 80% of whom reside in developing countries. The ongoing COVID-19 pandemic has impacted the physical, emotional and psychological well-being of people across the world including patients with epilepsy, who have a higher prevalence of psychological distress during public health emergencies. Long-term adherence to therapy is crucial for the successful management of epilepsy. Anti-Seizure Medications (ASMs) are however, known to be associated with Behavioural Adverse Events (BAEs) and psychiatric adverse events. Adverse events not only are a common cause of ASM discontinuation, they also negatively impact Quality of Life (QoL) in majority of Persons with Epilepsy (PWE). Many of the proposed COVID-19 treatments also have the potential for neuropsychiatric side effects as well as drug-drug interactions. Hence, it is important to carefully consider the riskbenefit of each agent before initiating therapy in a PWE.

Postmarketing experience with brivaracetam in the treatment of epilepsies: A multicenter cohort study from Germany.

To evaluate factors predicting efficacy, retention, and tolerability of add-on brivaracetam (BRV) in clinical practice. A multicenter, retrospective cohort study recruiting all patients who started BRV between February and November 2016 with observation time between 3 and 12 months. Of a total of 262 patients (mean age 40, range 5-81 years, 129 male) treated with BRV, 227 (87%) were diagnosed to have focal, 19 (7%) idiopathic generalized and 8 (3%) symptomatic generalized epilepsy, whereas 8 (3%) were unclassified. The length of exposure to BRV ranged from 1 day to 12 months, with a median retention time of 6.1 months, resulting in a total exposure time to BRV of 1,504 months. The retention rate was 79.4% at 3 months and 75.8% at 6 months. Efficacy at 3 months was 41.2% (50% responder rate) with 14.9% seizure-free for 3 months and, at 6 months, 40.5% with 15.3% seizure-free. Treatment-emergent adverse events were observed in 37.8% of the patients, with the most common being somnolence, dizziness, and behavioral adverse events (BAEs). BAE that presented under previous levetiracetam (LEV) treatment improved upon switch to BRV in 57.1% (20/35) and LEV-induced somnolence improved in 70.8% (17/24). Patients with BAE on LEV were more likely to develop BAE on BRV (odds ratio [OR] 3.48, 95% confidence interval [CI] 1.53-7.95). BRV in broad clinical postmarketing use is a well-tolerated anticonvulsant drug with 50% responder rates, similar to those observed in the regulatory trials, even though 90% of the patients included had previously been exposed to LEV. An immediate switch from LEV to BRV at a ratio of 10:1 to 15:1 is feasible. The only independent significant predictor of efficacy was the start of BRV in patients not currently taking LEV. The occurrence of BAE during previous LEV exposure predicted poor psychobehavioral tolerability of BRV treatment. A switch to BRV can be considered in patients with LEV-induced BAE.

SAFETY AND EFFICACY OF ESLICARBAZEPINE ACETATE (ZEBINIX) IN EVERYDAY CLINICAL PRACTICE USING A RETROSPECTIVE MULTICENTRE AUDIT

Purpose We report on the safety and efficacy of eslicarbazepine acetate (ESL) in routine clinical practice. Method Retrospective multicentre audit of outcomes following ESL treatment for localisation-related epilepsy across 7 UK sites (2009–2013). Results 201 patients with median values for age 43.0 (18–83) years; duration of epilepsy 17.0 (0–65) years; 2 (0–4) concomitant AEDs, 12 months (2 days-53 months) duration of ESL treatment and 0–12 (87.1% ≥2) previous AED exposures. ESL dosage ranged from 400–1600 mg/day. Baseline seizure types comprised secondarily generalised tonic-clonic seizures (78.1%), complex partial seizures (74.1%) and simple partial seizures (23.4%). Psychiatric comorbidity was reported in 29.9% of patients, most commonly mood disorders. 101 patients (50.2%) experienced ≥50% seizure frequency reduction. 39 subjects (19.4%) became seizure free, of whom 11 (28.2%) had 0–1 previous AED exposures. ESL was discontinued in 70 patients (34.8%) for reasons related to tolerability (n=43), efficacy (n=7), both (n=4) or other (n=16). Adverse events (AEs) were fatigue (18.9%), dizziness (10.0%) and disturbance in attention/concentration (9.0%); most were observed with AED polytherapy. Psychiatric and behavioural AEs (n=6, 3.0%) included suicidal ideation (n=1) and led to ESL withdrawal in 2 patients (1.0%). Hyponatraemia was reported (n=14, 7.0%) and led to discontinuation in 4 patients (2.0%). Conclusion ESL has comparable efficacy to other AEDs for partial-onset seizures with or without secondary generalisation. Discontinuation due to tolerability was mainly related to AED polytherapy. Reported AEs were consistent with ESL9s known safety profile. The benign neuropsychiatric profile with once-daily dosing may convey some advantage in AED selection.

Rasagiline-associated motor improvement in PD occurs without worsening of cognitive and behavioral symptoms

Background Cognitive and behavioral adverse events (AEs) such as hallucinations, confusion, depression, somnolence and other sleep disorders commonly limit effective management of motor symptoms in PD. Rasagiline ( N-propargyl-1( R)-aminoindan) mesylate is a novel, second-generation, selective, irreversible monoamine oxidase type B inhibitor, demonstrated in monotherapy and adjunctive trials to be effective for PD with excellent tolerability. Methods The occurrence of cognitive and behavioral AEs and the change from baseline in the Unified Parkinson's Disease Rating Scale (UPDRS) part I mental subscores were reviewed in two multicenter, randomized, placebo-controlled, 26-week trials of rasagiline for early and moderate-to-advanced patients with PD. The UPDRS is a multi-item rating scale specific to PD; part I rates the patient's intellectual impairment, thought disorders, depression and motivation/initiative. Results The TEMPO study evaluated rasagiline monotherapy in early PD patients ( n = 404). The PRESTO study evaluated rasagiline as adjunctive therapy in moderate-to-advanced PD patients with motor complications who were receiving optimized levodopa/carbidopa ( n = 472). In the analysis of adverse event reporting for both studies, no cognitive and behavioral AE in either the rasagiline 1 mg or placebo groups exceeded 10% of the study population and the frequency differences between rasagiline 1 mg and placebo never exceeded 3%. There was no adverse effect on the UPDRS mental subscore relative to placebo in either of the two studies. Conclusion Rasagiline 1 mg once daily improves PD symptoms and motor fluctuations in early and moderate-to-advanced PD patients without causing significant cognitive and behavioral AE or adverse changes in mentation, behavior and mood.

Treatment of Gunshot Fractures of Limbs

Treatment of Gunshot Fractures of Limbs