levetiracetam and perampanel

To compare the efficacy and safety of antiseizure medications (ASMs), both as monotherapies and adjunctive therapies, for idiopathic generalized epilepsies (IGEs) and related entities.. Two reviewers independently searched PubMed, Embase, and the Cochrane Library for relevant randomized controlled trials from December 2022 to February 2023. Studies on the efficacy and safety of ASM monotherapies or adjunctive therapies for IGEs and related entities-including juvenile myoclonic epilepsy, childhood absence epilepsy (CAE), juvenile absence epilepsy, or generalized tonic-clonic seizures alone (GTCA)-were included. Efficacy outcomes were the proportions of patients remaining seizure free for 1, 3, 6, and 12 months; safety outcomes were the proportions of any treatment-emergent adverse event (TEAE) and TEAEs leading to discontinuation. Network meta-analyses were performed in a random-effects model to obtain odds ratios and 95% confidence intervals. Rankings of ASMs were based on the surface under the cumulative ranking curve (SUCRA). This study is registered with PROSPERO (No. CRD42022372358).. Twenty-eight randomized controlled trials containing 4282 patients were included. As monotherapies, all ASMs were more effective than placebo, and valproate and ethosuximide were significantly better than lamotrigine. According to the SUCRA for efficacy, ethosuximide ranked first for CAE, whereas valproate ranked first for other types of IGEs. As adjunctive therapies, topiramate ranked best for GTCA as well as overall for IGEs, while levetiracetam ranked best for myoclonic seizures. For safety, perampanel ranked best (measured by any TEAE).. All of the studied ASMs were more effective than placebo. Valproate monotherapy ranked best overall for IGEs, whereas ethosuximide ranked best for CAE. Adjunctive topiramate and levetiracetam were most effective for GTCA and myoclonic seizures, respectively. Furthermore, perampanel had the best tolerability.

Topics: Anticonvulsants; Child; Epilepsy, Generalized; Ethosuximide; Humans; Levetiracetam; Network Meta-Analysis; Randomized Controlled Trials as Topic; Seizures; Topiramate; Valproic Acid

Epileptic myoclonus or myoclonic seizures can occur in idiopathic generalized epilepsy (IGE) and progressive myoclonus epilepsy (PME). However, symptomatic myoclonus which is stimulus-sensitive and provoked by movement is typically seen in PME and Lance-Adams syndrome. Symptomatic myoclonus is not always associated with epileptiform discharges on the electroencephalogram. Therapeutic interventions such as anti-seizure medications (ASMs), the ketogenic diet and vagus nerve stimulation are not always effective. There is emerging evidence that perampanel (PER), an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, may be effective for the treatment of myoclonic seizures and symptomatic myoclonus. We performed a systematic review of the literature to assess the efficacy of PER as treatment for myoclonic seizures and symptomatic myoclonus. Twenty-seven studies with a total sample size of 260 patients were included. The efficacy of PER was analysed separately for myoclonic seizures and symptomatic myoclonus. In the group with myoclonic seizures, 50% responder, 75% responder and seizure freedom rates were reported as 74.3% (101/ 136), 60.3% (82/136) and 57.4% (78/136), respectively, with a follow-up duration of 6-12 months. However, in one post-hoc analysis of data from patients with IGE, the efficacy of PER as treatment for myoclonic seizures during the double-blind phase showed no significant difference compared to placebo. The efficacy of PER for symptomatic myoclonus was reported in a total of 119 patients. Four studies (n=88 patients) reported the efficacy of PER as a decrease in myoclonus score/scale. In the remaining 31 patients, symptomatic myoclonus resolved in three patients, decreased in 21 patients and seven patients showed no improvement. We also analysed the number of patients who were already on levetiracetam (LEV) or valproic acid (VPA) at the time of PER initiation; these data were available for 153 patients. Of these, 56.8% were on LEV and 75.1% were on VPA when PER was initiated. This systematic review suggests that PER maybe effective as treatment for drug-resistant myoclonic seizures and symptomatic myoclonus. It may also be effective in patients who have already failed to respond to LEV and VPA. These findings are preliminary yet encouraging. This study has several limitations, particularly given the scarcity of high-quality randomized controlled trials and marked heterogeneity regarding the type and results of

Topics: Anticonvulsants; Epilepsies, Myoclonic; Epilepsy, Generalized; Humans; Immunoglobulin E; Levetiracetam; Myoclonic Epilepsies, Progressive; Myoclonus; Nitriles; Pyridones; Randomized Controlled Trials as Topic; Seizures; Treatment Outcome; Valproic Acid

To understand the currently available post-marketing real-world evidence of the incidences of and discontinuations due to the BAEs of irritability, anger, and aggression in people with epilepsy (PWE) treated with the anti-seizure medications (ASMs) brivaracetam (BRV), levetiracetam (LEV), perampanel (PER), and topiramate (TPM), as well as behavioral adverse events (BAEs) in PWE switching from LEV to BRV.. A systematic review of published literature using the Cochrane Library, PubMed/MEDLINE, and Embase was performed to identify retrospective and prospective observational studies reporting the incidence of irritability, anger, or aggression with BRV, LEV, PER, or TPM in PWE. The incidences of these BAEs and the rates of discontinuation due to each were categorized by ASM, and where possible, weighted means were calculated but not statistically assessed. Behavioral and psychiatric adverse events in PWE switching from LEV to BRV were summarized descriptively.. A total of 1500 records were identified in the searches. Of these, 44 published articles reporting 42 studies met the study criteria and were included in the data synthesis, 7 studies were identified in the clinical trial database, and 5 studies included PWE switching from LEV to BRV. Studies included a variety of methods, study populations, and definitions of BAEs. While a wide range of results was reported across studies, weighted mean incidences were 5.6% for BRV, 9.9% for LEV, 12.3% for PER, and 3.1% for TPM for irritability; 3.3%* for BRV, 2.5% for LEV, 2.0% for PER, and 0.2%* for TPM for anger; and 2.5% for BRV, 2.6% for LEV, 4.4% for PER, and 0.5%* for TPM for aggression. Weighted mean discontinuation rates were 0.8%* for BRV, 3.4% for LEV, 3.0% for PER, and 2.2% for TPM for irritability and 0.8%* for BRV, 2.4% for LEV, 9.2% for PER, and 1.2%* for TPM for aggression. There were no discontinuations for anger. Switching from LEV to BRV led to improvement in BAEs in 33.3% to 83.0% of patients (weighted mean, 66.6%). *Denotes only 1 study.. This systematic review characterizes the incidences of irritability, anger, and aggression with BRV, LEV, PER, and TPM, and it provides robust real-world evidence demonstrating that switching from LEV to BRV may improve BAEs. While additional data remain valuable due to differences in methodology (which make comparisons difficult), these results improve understanding of the real-world incidences of discontinuations due to these BAEs in clinical practice and can aid in discussions and treatment decision-making with PWE.

Topics: Anticonvulsants; Humans; Levetiracetam; Nitriles; Observational Studies as Topic; Pyridones; Pyrrolidinones; Retrospective Studies; Topiramate; Treatment Outcome

To date, there has not been a single randomized controlled trial (RCT) conducted to directly compare the efficacy and safety of perampanel to brivaracetam in the adjunctive treatment of focal-onset seizures. This study makes these comparisons through the use of indirect treatment comparison (ITC) methods.. A systematic review was conducted to identify RCTs that evaluated either one of perampanel or brivaracetam in the treatment of patients with focal-onset seizures. The Bucher ITC method was then used to compare efficacy and safety outcomes between perampanel and brivaracetam. Additional subgroup analyses, by levetiracetam usage (prior or concomitant), were conducted.. Eight RCTs (four comparing perampanel to placebo, four comparing brivaracetam to placebo) were included in the ITC. For patients taking concomitant levetiracetam, perampanel showed a significantly better responder rate compared to brivaracetam [relative risk (RR) and 95 % confidence interval (CI): 2.62 (1.15, 5.99)]. For patients who had previously, or never, taken levetiracetam, there was no difference in the responder rate. In the overall population, both perampanel and brivaracetam were more effective than placebo in terms of responder rate, seizure freedom, and secondarily generalized tonic-clonic seizure responder rate; however, for these outcomes, no evidence of a difference between perampanel and brivaracetam was found. Patients taking brivaracetam showed significantly less dizziness compared to patients taking perampanel. No differences for any other safety outcome were found.. Perampanel and brivaracetam are effective for the adjunctive treatment of focal-onset seizures and display similar adverse event profiles. Perampanel demonstrated an improved focal-onset seizure responder rate compared to brivaracetam in patients taking concomitant levetiracetam. This may be due to the similarity in the mechanism of action between brivaracetam and levetiracetam.

Topics: Anticonvulsants; Drug Therapy, Combination; Humans; Levetiracetam; Nitriles; Pyridones; Pyrrolidinones; Randomized Controlled Trials as Topic; Seizures; Treatment Outcome

Perampanel como terapia añadida precoz en el tratamiento de la epilepsia.

Topics: Adolescent; Adult; Anticonvulsants; Drug Synergism; Drug Therapy, Combination; Epilepsy; Gastrointestinal Diseases; Humans; Levetiracetam; Nitriles; Pyridones; Randomized Controlled Trials as Topic; Sleepiness; Treatment Outcome; Young Adult

To estimate the comparative efficacy among antiepileptic drugs in the pediatric population (0-18 years).. Using the Embase and MEDLINE databases, we updated to February 2017 the search strategy of the National Institute for Health and Care Excellence guidelines for epilepsy. We only included randomized clinical trials conducted in children and mixed-age populations. According to the PRISMA network meta-analysis guideline, the study-level quality assessment was made with the Cochrane risk-of-bias tool. Three investigators independently selected articles. The efficacy outcome was considered to be seizure freedom or ≥50% seizure reduction.. We selected 46 randomized clinical trials. A total of 5652 individuals were randomized to 22 antiepileptic drugs and placebo. The point estimates of carbamazepine and lamotrigine efficacy showed their superiority with respect to all comparator antiepileptic drugs for the treatment of newly diagnosed focal epilepsy. In refractory focal epilepsy, levetiracetam (odds ratio [OR] = 3.3, 95% credible interval [CrI] = 1.3-7.6) and perampanel (OR = 2.5, 95% CrI = 1.1-5.8) were more effective compared to placebo. Ethosuximide and valproic acid were both superior to lamotrigine against absence seizures. The OR point estimate showed the superiority of adrenocorticotropic hormone over all comparators in infantile spasms. A wide heterogeneity in the length of follow-up was observed among the studies.. This network meta-analysis suggests that the quality of studies should be improved through the use of comparative designs, relevant outcomes, appropriate follow-up length, and more reliable inclusion criteria.

Topics: Adolescent; Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Anticonvulsants; Carbamazepine; Child; Child, Preschool; Drug Resistant Epilepsy; Epilepsies, Partial; Epilepsy; Epilepsy, Absence; Ethosuximide; Hormones; Humans; Infant; Lamotrigine; Levetiracetam; Network Meta-Analysis; Nitriles; Odds Ratio; Piracetam; Pyridones; Spasms, Infantile; Treatment Outcome; Triazines; Valproic Acid

A generalized tonic-clonic seizure (GTCS) is the most severe form of common epileptic seizure and carries the greatest risk of harm. The aim of this review is to provide an evidence-based guide for the selection of antiepileptic drugs (AEDs) for patients with GTCSs. Eight AEDs are approved in Europe and the USA for the treatment of both primarily GTCSs (PGTCSs) and secondarily GTCSs (SGTCSs) and are considered in this paper.. Each AED is evaluated using five criteria: (1) efficacy, by seizure type (a: PGTCSs and b: SGTCSs); (2) adverse effects; (3) interactions; (4) adherence and dosing; and (5) mechanism of action (MOA). To ensure the inclusions of robust data, only efficacy data accepted by regulatory authorities were considered, and data related to adverse effects, interactions, adherence, and MOA were all extracted from UK Summaries of Product Characteristics (SPCs).. (1a) There is class 1 evidence of the efficacy of only four AEDs in controlling PGTCSs (lamotrigine, levetiracetam, perampanel, and topiramate). (1b) There is no class 1 evidence of the efficacy of any AED in SGTCSs although some evidence from pooled/subgroup analyses or meta-analyses supports the use of the four AEDs (levetiracetam, perampanel, topiramate, and with less robust data for lamotrigine). (2) AEDs are associated with different, but to some extent overlapping, common adverse effect profiles but have differing idiosyncratic adverse effects. (3) Pharmacokinetic interactions are seen with most, but not all, AEDs and are most common with carbamazepine and phenytoin. (4) Good adherence is important for seizure control and is influenced by frequency of dosing, among other factors. (5) Mechanism of action is also a consideration in rationalising AED selection when switching or combining AEDs.. Ultimately, the choice of AED depends on all these factors but particularly on efficacy and adverse effects. Different patients will weigh the various factors differently, and the role of the treating physician is to provide accurate information to allow patients to make informed choices.

Topics: Anticonvulsants; Benzodiazepines; Carbamazepine; Drug and Narcotic Control; Drug-Related Side Effects and Adverse Reactions; Humans; Lamotrigine; Levetiracetam; Nitriles; Phenytoin; Pyridones; Seizures; Topiramate; Treatment Outcome

Antiepileptic drugs (AEDs) are effective against seizures, but their use is often limited by adverse effects, among them psychiatric and behavioral ones including aggressive behavior (AB). Knowledge of the incidence, risk factors, and the underlying mechanisms of AB induced by AEDs may help to facilitate management and reduce the risk of such side effects. The exact incidence of AB as an adverse effect of AEDs is difficult to estimate, but frequencies up to 16% have been reported. Primarily, levetiracetam (LEV), perampanel (PER), and topiramate (TPM), which have diverse mechanisms of action, have been associated with AB. Currently, there is no evidence for a specific pharmacological mechanism solely explaining the increased incidence of AB with LEV, PER, and TPM. Serotonin (5-HT) and GABA, and particularly glutamate (via the AMPA receptor), seem to play key roles. Other mechanisms involve hormones, epigenetics, and "alternative psychosis" and related phenomena. Increased individual susceptibility due to an underlying neurological and/or a mental health disorder may further explain why people with epilepsy are at an increased risk of AB when using AEDs. Remarkably, AB may occur with a delay of weeks or months after start of treatment. Information to patients, relatives, and caregivers, as well as sufficient clinical follow-up, is crucial, and there is a need for further research to understand the complex relationship between AED mechanisms of action and the induction/worsening of AB.

Topics: Aggression; Anticonvulsants; Epilepsy; Humans; Levetiracetam; Nitriles; Pyridones; Topiramate

Primary generalized tonic clonic seizures (pGTCS) are still linked to major concerns for the clinic and hazards for patients suffering from idiopathic generalized epilepsy (IGE), so a quick search of the most effective and appropriate therapy is needed to control them. The key criteria for proper treatment are syndromic diagnosis and distinction between newly diagnosed and refractory patients. Other criteria include age, gender and comorbidities. Areas covered: Treatment for pGTCS has expanded in the last two years, with new antiepileptic drugs like perampanel joining valproic acid, lamotrigine, levetiracetam, topiramate, while further evidence-based data are required for zonisamide and lacosamide. Expert opinion: Currently, valproic acid can be considered as a first choice in male or menopausal women, and in the absence of weight issue, both in adults and in children, and in the absence of side effects such as insomnia and headache. Today, valproic acid is not recommended in child-bearing age and in relation to possible cognitive problems, especially in children. Lamotrigine and levetiracetam can be a viable alternative as a first choice. Topiramate is also effective as a first choice, but concerns may arise from its potential cognitive and memory adverse side effects. Additionally, perampanel and lacosamide are promising treatments.

Topics: Acetamides; Anticonvulsants; Epilepsy, Generalized; Epilepsy, Tonic-Clonic; Female; Fructose; Humans; Isoxazoles; Lacosamide; Lamotrigine; Levetiracetam; Male; Nitriles; Piracetam; Pyridones; Randomized Controlled Trials as Topic; Topiramate; Treatment Outcome; Triazines; Valproic Acid; Zonisamide

This study was proposed to compare the relative efficacy and tolerability of the second and third generation AEDs for refractory epilepsy. The 50% responder rate (RR) was selected as the efficacy outcome whereas the incidence of dizziness and somnolence were considered to evaluate the tolerability of AEDs. Odds ratio (OR) and their 95% credible interval (CrI) were obtained using a consistency model and surface under the cumulative ranking curve (SUCRA) value was calculated to rank AEDs. Topiramate appeared to be significantly more effective than placebo, eslicarbazepine acetate, perampanel, pregabalin, zonisamide, gabapentin and lamotrigine with respect to the 50% RR (all OR > 1). Patients who were managed by eslicarbazepine acetate, perampanel, oxcarbazepine, topiramate and pregabalin were more likely to suffer from dizziness compared to those who receive placebo (all OR > 1). Perampanel, topiramate and pregabalin were related to elevated risks of somnolence compared to placebo (all OR > 1). Moreover, topiramate ranked highest with respect to 50% RR (SUCRA = 0.968) whereas levetiracetam appeared to have balanced efficacy and tolerability (SUCRA = 0.769, 0.743, 0.604 and 0.659). In conclusion, topiramate was the most efficacious AED, while levetiracetam was able to provide patients with balanced efficacy and tolerability.

Topics: Anticonvulsants; Dibenzazepines; Drug Resistant Epilepsy; Humans; Levetiracetam; Network Meta-Analysis; Nitriles; Pyridones; Topiramate

In 4 Phase III registration trials (3 in patients with partial seizures, N=1480; 1 in patients with PGTCS, N=163), perampanel administered to patients already receiving 1-3 concomitant antiepileptic drugs (AEDs) demonstrated statistically superior efficacy compared to placebo in reducing seizure frequency. However, use of perampanel in these studies was associated with a risk of psychiatric and behavioral adverse reactions, including aggression, hostility, irritability, anger, and homicidal ideation and threats. The present study is a post hoc analysis of pooled data from these 4 trials to determine if concomitant treatment with levetiracetam and/or topiramate increased the risk of hostility- and aggression-related AEs. Treatment-emergent AEs (TEAEs) were determined using a "Narrow & Broad" search based on the Medical Dictionary for Regulatory Activities (MedDRA) standard MedDRA query (SMQ) for hostility- and aggression-related events. The rate of hostility- and aggression-related TEAEs was observed to be similar among perampanel-treated patients: a) receiving levetiracetam (N=340) compared to those not receiving levetiracetam (N=779); b) receiving topiramate (N=223) compared to those not receiving topiramate (N=896); and c) receiving both levetiracetam and topiramate (N=47) compared to those not receiving levetiracetam and topiramate (N=1072). Severe and serious TEAEs related to hostility and aggression were rare and occurred at a similar rate regardless of concomitant levetiracetam and/or topiramate therapy. Taken together, these results suggest that concomitant treatment with levetiracetam and/or topiramate has no appreciable effect on the occurrence of hostility- or aggression-related TEAEs in patients receiving perampanel.

Topics: Adolescent; Adult; Aged; Aggression; Anticonvulsants; Child; Drug Therapy, Combination; Epilepsies, Partial; Fructose; Hostility; Humans; Levetiracetam; Middle Aged; Nitriles; Piracetam; Pyridones; Topiramate; Treatment Outcome; Young Adult

Mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS) is a syndrome that is often refractory to drug treatment. The effects on specific syndromes are not currently available from the pre-marketing clinical development of new AEDs; this does not allow the prediction of whether new drugs will be more effective in the treatment of some patients.. We have reviewed all the existing literature relevant to the understanding of a potential effectiveness in MTLE-HS patients for the latest AEDs, namely brivaracetam, eslicarbazepine, lacosamide, perampanel and retigabine also including the most relevant clinical data and a brief description of their pharmacological profile. Records were identified using predefined search criteria using electronic databases (e.g., PubMed, Cochrane Library Database of Systematic Reviews). Primary peer-reviewed articles published up to the 15 June 2015 were included.. All the drugs considered have the potential to be effective in the treatment of MTLE-HS; in fact, they possess proven efficacy in animal models; currently considered valuable tools for predicting drug efficacy in TLE. Furthermore, for some of these (e.g., lacosamide and eslicarbazepine) data are already available from post-marketing studies while brivaracetam acting on SV2A like levetiracetam might have the same potential effectiveness with the possibility to be more efficacious considering its ability to inhibit voltage gated sodium channels; finally, perampanel and retigabine are very effective drugs in animal models of TLE.

Topics: Acetamides; Anticonvulsants; Carbamates; Clinical Trials as Topic; Dibenzazepines; Epilepsy, Temporal Lobe; Hippocampus; Humans; Lacosamide; Levetiracetam; Nitriles; Phenylenediamines; Piracetam; Pyridones; Sclerosis; Syndrome

The purpose was to evaluate the efficacy of treatment and the occurrence of aggression-related adverse events among children receiving perampanel (PER) with concomitant levetiracetam (LEV).. Patients were selected according to the following criteria: 1) between 12 and 18 years old; 2) seizures refractory to at least 2 first-line drugs; 3) at least 4 seizures a month before PER administration; and 4) at least 12 months of follow-up. Patients were subdivided into groups with and without LEV as concomitant treatment. PER was administered at a dose of 2 mg/day, increasing by 2 mg/day every 2 weeks up to 12 mg/day if seizures appeared. In comparison with the baseline seizure frequency, response to PER treatment was classified as follows: complete cessation (100% seizure control); response (≥50% reduction in seizures); and exacerbation (≥50% increase in seizures). Responders were identified as patients showing complete cessation or response.. The study group comprised 39 outpatients with a mean age of 13.7 years at enrollment. Responder status was seen in 13 of the 19 patients with LEV and 4 of the 20 patients without LEV. PER appeared significantly more effective in patients with LEV than in those without LEV (p = 0.0076). Seizure-free status was significantly more frequent among patients with LEV (47.4%) than among those without LEV (15.0% (p = 0.0407)). Aggression was present in 2 patients without LEV, but none with LEV.. The present study suggests the utility of PER with concomitant LEV for children with drug-resistant epilepsy.

Topics: Adolescent; Aggression; Anticonvulsants; Child; Child, Preschool; Drug Resistant Epilepsy; Drug Therapy, Combination; Female; Humans; Levetiracetam; Male; Mental Disorders; Nitriles; Pyridones; Treatment Outcome

Assess cognitive effects of adjunctive perampanel in adolescents.. In this double-blind study (ClinicalTrials.gov identifier: NCT01161524), patients aged 12 to <18 years with partial-onset seizures despite receiving 1-3 antiepileptic drugs were randomized (2:1) to perampanel or placebo. Perampanel was increased weekly in 2-mg increments to 8-12 mg/day (6-week titration; 13-week maintenance). Changes in neuropsychological outcomes were assessed at end of maintenance: Cognitive Drug Research (CDR) System Global Cognition Score (primary end point), five CDR System domain T-scores (secondary end points), letter fluency, category fluency, and Lafayette Grooved Pegboard Test (LGPT).. One hundred thirty-three patients were randomized. In the full analysis set, there were no differences of perampanel (n = 79) vs. placebo (n = 44) in CDR System Global Cognition Score (least squares mean change, -0.6 vs. 1.6; p = 0.145), Quality of Working Memory (1.1 vs. 2.0; p = 0.579), or Power of Attention (-6.9 vs. -2.7; p = 0.219). There were small differences with perampanel vs. placebo in other CDR System domains: improvements in Quality of Episodic Memory (3.0 vs. -1.2; p = 0.012), and worsening in Continuity of Attention (-3.3 vs. 1.6; p = 0.013) and Speed of Memory (0.3 vs. 7.0; p = 0.032). Letter fluency, category fluency, and LGPT were not significantly different between groups. The most frequent adverse events with perampanel were dizziness (30.6%) and somnolence (15.3%).. Perampanel did not differ from placebo in the global cognitive score, two of five subdomains, and four other cognitive measures. Perampanel was worse on two and better on one subdomain.

Topics: Acetamides; Adolescent; Anticonvulsants; Attention; Carbamazepine; Child; Cognition; Double-Blind Method; Drug Therapy, Combination; Epilepsies, Partial; Female; Fructose; Humans; Lacosamide; Lamotrigine; Levetiracetam; Male; Memory, Short-Term; Neuropsychological Tests; Nitriles; Oxcarbazepine; Piracetam; Pyridones; Topiramate; Treatment Outcome; Triazines; Valproic Acid

Neuroelectric disruptions such as seizures and cortical spreading depolarization may contribute to the development of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH). However, effects of antiepileptic drug prophylaxis on outcomes remain controversial in SAH. The authors investigated if prophylactic administration of new-generation antiepileptic drugs levetiracetam and perampanel was beneficial against delayed neurovascular events after SAH. This was a retrospective single-center cohort study of 121 consecutive SAH patients including 56 patients of admission World Federation of Neurological Surgeons grades IV - V who underwent aneurysmal obliteration within 72 h post-SAH from 2013 to 2021. Prophylactic antiepileptic drugs differed depending on the study terms: none (2013 - 2015), levetiracetam for patients at high risks of seizures (2016 - 2019), and perampanel for all patients (2020 - 2021). The 3rd term had the lowest occurrence of delayed cerebral microinfarction on diffusion-weighted magnetic resonance imaging, which was related to less development of DCI. Other outcome measures were similar among the 3 terms including incidences of angiographic vasospasm, computed tomography-detectable delayed cerebral infarction, seizures, and 3-month good outcomes (modified Rankin Scale 0 - 2). The present study suggests that prophylactic administration of levetiracetam and perampanel was not associated with worse outcomes and that perampanel may have the potential to reduce DCI by preventing microcirculatory disturbances after SAH. Further studies are warranted to investigate anti-DCI effects of a selective α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor antagonist perampanel in SAH patients in a large-scale prospective study.

Topics: Anticonvulsants; Brain Ischemia; Cerebral Infarction; Cohort Studies; Humans; Levetiracetam; Microcirculation; Prospective Studies; Retrospective Studies; Seizures; Subarachnoid Hemorrhage

Patients with epilepsy often show treatment-related psychiatric symptoms. Among the novel antiseizure medications (ASM), Perampanel (PER), Levetiracetam (LEV), and Topiramate (TPM) have been reported to have a relatively high frequency of psychiatric adverse events. However, these psychiatric symptoms are not identical; PER and LEV show adverse events of irritability and aggression, while TPM shows typical symptoms of depression and schizophrenia. It is important to understand the characteristics of these psychiatric adverse events to design appropriate treatment regimens for epileptic patients. (Received August 1, 2022; Accepted December 24, 2022; Published April 1, 2023).

Topics: Anticonvulsants; Epilepsy; Humans; Levetiracetam; Mental Disorders; Topiramate

Antiseizure medication (ASM) as monotherapy or in combination is the treatment of choice for most patients with epilepsy. Therefore, knowledge about the typical adverse events (AEs) for ASMs and other coadministered drugs (CDs) is essential for practitioners and patients. Due to frequent polypharmacy, it is often difficult to clinically assess the AE profiles of ASMs and differentiate the influence of CDs.. This retrospective analysis aimed to determine typical AE profiles for ASMs and assess the impact of CDs on AEs in clinical practice.. The Liverpool AE Profile (LAEP) and its domains were used to identify the AE profiles of ASMs based on data from a large German multicenter study (Epi2020). Following established classifications, drugs were grouped according to their mode of action (ASMs) or clinical indication (CDs). Bivariate correlation, multivariate ordinal regression (MORA), and artificial neural network (ANNA) analyses were performed. Bivariate correlation with Fisher's z-transformation was used to compare the correlation strength of LAEP with the Hospital Anxiety and Depression Scale (HADS) and Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) to avoid LAEP bias in the context of antidepressant therapy.. Data from 486 patients were analyzed. The AE profiles of ASM categories and single ASMs matched those reported in the literature. Synaptic vesicle glycoprotein 2A (SV2A) and voltage-gated sodium channel (VGSC) modulators had favorable AE profiles, while brivaracetam was superior to levetiracetam regarding psychobehavioral AEs. MORA revealed that, in addition to seizure frequency, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) modulators and antidepressants were the only independent predictors of high LAEP values. After Fisher's z-transformation, correlations were significantly lower between LAEP and antidepressants than between LAEP and HADS or NDDI-E. Therefore, a bias in the results toward over interpreting the impact of antidepressants on LAEP was presumed. In the ANNA, perampanel, zonisamide, topiramate, and valproic acid were important nodes in the network, while VGSC and SV2A modulators had low relevance for predicting relevant AEs. Similarly, cardiovascular agents, analgesics, and antipsychotics were important CDs in the ANNA model.. ASMs have characteristic AE profiles that are highly reproducible and must be considered in therapeutic decision-making. Therapy using perampanel as an AMPA modulator should be considered cautiously due to its relatively high AE profile. Drugs acting via VGSCs and SV2A receptors are significantly better tolerated than other ASM categories or substances (e.g., topiramate, zonisamide, and valproate). Switching to brivaracetam is advisable in patients with psychobehavioral AEs who take levetiracetam. Because CDs frequently pharmacokinetically interact with ASMs, the cumulative AE profile must be considered.. DRKS00022024, U1111-1252-5331.

Topics: Adult; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Anticonvulsants; Epilepsy; Humans; Levetiracetam; Retrospective Studies; Topiramate; Valproic Acid; Zonisamide

Aggression is the most commonly encountered antiepileptic-drug (AED)-induced psychiatric adverse effects. Levetiracetam (LEV) is well known to be associated with increased rates of aggression, while perampanel (PER) is also recognized as a potentially aggression-promoting agent, though opinions vary. However, few studies have addressed questions regarding whether the nature of irritability-aggression differs between those drugs. The present study used a standardized rating scale to examine aggression among patient with epilepsy who received LEV or PER using specific measures to confirm the effects of the drugs.. We enrolled 144 consecutive outpatients receiving treatment for epilepsy with LEV (n = 103) or PER (n = 41), and determined their effects regarding aggression using the Buss-Perry Aggression Questionnaire (BAQ). For analysis, total BAQ scores for the LEV and PER subjects were compared to determine whether the aggression-promoting effects of the agents differed, and which BAQ subdomains (physical aggression, verbal aggression, anger, hostility) were related to production of aggression in patients taking either LEV or PER. As a subsidiary analysis, clinical variables inclusive of administered AED type that showed a significant impact on BAQ scores were determined.. The LEV group had a significantly higher hostility score (19.4 ± 5.8) as compared to the PER group (17.2 ± 6.3) in subscale analysis (p < 0.05). In multiple regression analysis, LEV had a significant association with higher hostility score (P = 0.006).. Our results indicate that while easily visible outward-directed aggression tends to be dominant in patients given PER, aggression provoked by LEV may be felt more subjectively or in an inward-directed manner, which can lead to more diverse expression and misrecognition.

Topics: Aggression; Anticonvulsants; Epilepsy; Humans; Levetiracetam; Nitriles; Pyridones

Patients with glioblastoma frequently suffer epileptic seizures and often require anticonvulsant therapy during the treatment course. The present study investigated four common antiepileptic drugs, perampanel, carbamazepine (CBZ), sodium valproate (VPA) and levetiracetam (LEV), which are expected to have antitumor effects, and determined the most beneficial drug for the treatment of malignant glioma by comparing antitumor effects such as inhibition of cell proliferation and suppression of migration and invasion (using Transwell assays). The inhibition of cell growth was investigated using six malignant glioma cell lines (A‑172, AM‑38, T98G, U‑138MG, U‑251MG and YH‑13). Significant inhibition of cell proliferation was observed in all six cell lines treated with perampanel, three cell lines treated with CBZ, four cell lines treated with VPA and two cell lines treated with LEV at the therapeutic blood concentration levels for the drugs to be used as antiepileptics. Further antitumor effects in combination with temozolomide were investigated using T98G and U‑251MG cell lines, and were confirmed in both cell lines with perampanel and in T98G cells with LEV, but not observed with CBZ and VPA. Cell migration was significantly suppressed in both T98G and U‑251MG cell lines with perampanel, but not with CBZ, VPA or LEV. To investigate the mechanisms by which perampanel suppresses the migration of malignant glioma cells, the expression of mRNA related to epithelial‑mesenchymal transition following perampanel treatment was analyzed using reverse transcription‑quantitative PCR in the T98G and U‑251MG cell lines. The expression of

Topics: Anticonvulsants; Cadherins; Carbamazepine; Glioma; Humans; Levetiracetam; Matrix Metalloproteinase 2; RNA, Messenger; Temozolomide; Valproic Acid

We report our clinical experience of the effectiveness and tolerability of adjunctive perampanel treatment in a Chinese paediatric population with refractory epilepsy. We also compare the effectiveness and tolerability of perampanel with or without concomitant oxcarbazepine or levetiracetam. This retrospective observational study was conducted from September 2019 to September 2020 in the paediatric neurology clinics of two tertiary hospitals in the Chinese mainland. We reviewed the data obtained from 96 paediatric patients aged 2-14 years whose seizures were pharmacoresistant and who could be followed up for a minimum of six months. The effectiveness was estimated by the perampanel response rate at 6- and 12-month follow-up evaluations. Adverse events were also recorded. Patients were stratified by age (2-7 and 7-14 years), and with/without concomitant oxcarbazepine or levetiracetam. The population comprised 96 patients with refractory epilepsy. The retention rate was 84.4% and 81.0% at 6 and 12 months, respectively. The most common dose used was 4 mg (48.5%). Corresponding 50% responder and seizure freedom rates were as follows: 46.9% and 20.8% at six months, and 51.2% and 27.4% at 12 months, respectively. Adverse effects were reported in 22 patients (22.9%). The most common adverse effects were irritability, somnolence, and dizziness. The 50% and 100% responder rates and adverse effects were greater in patients aged 7-14 years than in those aged 2-7 years. The proportion of responder and seizure-free rates and adverse effects were similar with or without oxcarbazepine. Perampanel was more effective in patients concomitantly treated with levetiracetam, however, this did not result in significantly more adverse events, including aggression. The present study suggests that perampanel, with or without concomitant oxcarbazepine or levetiracetam, is generally safe, well-tolerated, and efficacious in paediatric patients with uncontrolled epilepsy in a clinical setting.

Topics: Adolescent; Child; Child, Preschool; China; Drug Resistant Epilepsy; Humans; Levetiracetam; Nitriles; Oxcarbazepine; Pyridones; Retrospective Studies

The present study evaluated whether patients with epilepsy who received both levetiracetam (LEV) and perampanel (PER) therapy showed side effects of irritability. The study also examined the relationship between patient characteristics and irritability when it occurred as a side effect.. We retrospectively examined medical records of 98 patients with epilepsy who were treated with both LEV and PER at the Department of Psychiatry in the Epilepsy Center of Nishiniigata Chuo National Hospital in Japan. We performed multiple regression analyses with the presence/absence of irritability due to LEV or PER as the dependent variables and clinical characteristics of the patients as independent variables.. LEV and PER caused irritability in 7 and 17 of 98 patients, respectively. LEV- and PER-related irritability did not occur in the same patients. A logistic multiple regression analysis revealed that EEG findings of temporal focal epileptic discharge were significantly associated with increased incidence of irritability due to LEV. LEV-related irritability decreased significantly with higher dosages of LEV. Another logistic multiple regression analysis revealed that a psychiatric comorbidity of irritability and EEG findings of nontemporal focal epileptic discharge were significantly associated with increased incidence of irritability due to PER.. LEV and PER cause irritability in different patient groups. Additionally, irritability as a side effect was present only at low dosages of LEV, but PER tended to cause irritability even at high dosages.

Topics: Anticonvulsants; Epilepsy; Humans; Japan; Levetiracetam; Nitriles; Piracetam; Pyridones; Retrospective Studies

This study investigated to which degree levetiracetam (LEV) and perampanel (PER), antiseizure medications (ASM) that are both known to cause aggression and irritability, share the same or different, behavioral side-effect profiles. In this self-report study, 68 participants with epilepsy treated with LEV (n = 35) or PER (n = 33) as part of their medication were asked to rate their behavioral experience with the respective drug as positive, neutral, or negative. Results of a German adaptation of the Adverse Events Profile (AEP) and of the "FPZ", a German personality questionnaire, were analyzed as a function of drug and rating. Thirty-eight percent of the LEV group and 36% of the PER group experienced negative change after the evaluated drug was introduced. By subdividing participants in the LEV sample into those who attributed the negative effects to LEV and those with neutral or positive experience with LEV, a negative evaluation of LEV was associated with significantly worse scores in cognition, mood, and physical domains (80% versus 20-40%). Subdividing participants in the PER sample into those who attributed negative the side effects to PER, and those with a neutral or positive experience with PER, significance could be shown for mood domains only (100% versus 50%), and within this domain only for increased aggression and irritability. Comparing features of the behavioral negative side effects of LEV and PER revealed that LEV appears to have a negative impact on a much broader range of behaviors than PER, which specifically seems to induce aggression and irritability and no other psychiatric side effects. Further research should aim at different expression and different mechanisms of aggression and irritability underlying the superficially similar effects of the two drugs.

Topics: Aggression; Anticonvulsants; Humans; Levetiracetam; Nitriles; Piracetam; Pyridones; Self Report

Background The number of patients with epilepsy receiving perampanel or lacosamide as an add-on treatment following levetiracetam treatment has increased. Although levetiracetam causes psychiatric disorders, it is unclear whether they occur with the combined use of these antiepileptic drugs. Objective To determine the frequency of psychiatric disorders in patients received lacosamide or perampanel in combination with levetiracetam. Setting A single-center retrospective cohort study. Method Patients who received levetiracetam + lacosamide or levetiracetam + perampanel were selected. Medical records from the start of combination therapy contained characteristics of patients and the incidence of psychiatric disorders. Main outcome measure The frequency of psychiatric disorders, the time to onset, dose reduction or discontinuation following psychiatric disorders, and the clinical course following disorder onset. Results Forty-four patients used levetiracetam + lacosamide and 50 used levetiracetam + perampanel. The incidence of psychiatric disorders was significantly lower (p < 0.001) with levetiracetam + lacosamide (6.8%) than with levetiracetam + perampanel (44%). The incidence of affect lability was significantly higher with levetiracetam + perampanel than with levetiracetam + lacosamide (p = 0.018). The time to the onset of psychiatric disorders was within 1 month of dose initiation or increase in one case (33.3%) with levetiracetam + lacosamide and 16 cases (72.7%) with levetiracetam + perampanel. There was no significant difference in clinical characteristics and antiepileptic drug dosages owing to the presence or absence of psychiatric disorders. Conclusion As the frequency of psychiatric disorders was higher with levetiracetam + perampanel therapy, levetiracetam + lacosamide may be preferable. These disorders tended to develop within 1 month of therapy and were not dose-dependent. Antiepileptic drugs should be cautiously prescribed to avoid psychiatric disorders.

Topics: Anticonvulsants; Drug Therapy, Combination; Humans; Lacosamide; Levetiracetam; Mental Disorders; Nitriles; Pyridones; Retrospective Studies; Treatment Outcome

Chronic post-hypoxic myoclonus is a condition in which the predominant clinical picture is myoclonus following hypoxic brain damage, usually due to cardiorespiratory arrest. It is a condition that is usually treated with antiepileptic drugs, in most cases with a modest clinical response.. We report the case of a patient who started with jerking movements, compatible with myoclonus in the four limbs and the face the day after recovering from a cardiorespiratory arrest. An electroencephalogram was performed during which the myoclonias were recorded with no electrical correlates. During admission, and in successive visits after discharge, different antiepileptic treatments were tried for the myoclonias, which were refractory and affected the patient's quality of life. Two years after onset, treatment with perampanel up to a dose of 4 mg was initiated and the patient reported a significant clinical improvement, as evidenced in the visits.. Perampanel may be an effective alternative for the treatment of myoclonias in patients with chronic post-hypoxic myoclonus.. Respuesta a perampanel en un paciente con mioclono posthipóxico crónico.. Introducción. El mioclono posthipóxico crónico es un cuadro cuya clínica predominante son las mioclonías que acontecen tras un daño cerebral hipóxico, generalmente por parada cardiorrespiratoria. Es una entidad que se trata generalmente con fármacos antiepilépticos, con una modesta respuesta clínica en la mayoría de los casos. Caso clínico. Paciente que comienza con movimientos de sacudidas, compatibles con mioclonías de las cuatro extremidades y faciales al día siguiente de una parada cardiorrespiratoria recuperada. Se realizó un electroencefalograma durante el cual se registraron las mioclonías sin presentar correlato eléctrico. Durante el ingreso, y en sucesivas visitas tras el alta, se probaron diferentes tratamientos antiepilépticos para las mioclonías, que fueron refractarias y comportaron una afectación de la calidad de vida del paciente. Tras dos años de evolución, se inició tratamiento con perampanel hasta una dosis de 4 mg y el paciente refirió una mejoría clínica importante, evidenciada en consultas. Conclusiones. El perampanel puede suponer una alternativa eficaz para el tratamiento de las mioclonías en pacientes con mioclono posthipóxico crónico.

Topics: Anticonvulsants; Carcinoma, Papillary; Clonazepam; Drug Therapy, Combination; Electroencephalography; Heart Arrest; Humans; Hypoxia, Brain; Levetiracetam; Male; Middle Aged; Myoclonus; Nitriles; Postoperative Complications; Pyridones; Seizures; Thyroid Neoplasms; Thyroidectomy; Valproic Acid

After introduction of levetiracetam (LEV), treatment of seizures in patients with malignant brain tumors has prominently improved. On the other hand, we still experience some cases with LEV-uncontrollable epilepsy. Perampanel (PER) is a noncompetitive α-amino-3-hydroxy-5-methyl-4-isoaxazolepropionate acid receptor antagonist that has recently been approved for treating focal epilepsy as a secondary drug of choice. Available literature reporting PER medication in patients with gliomas is still sparse. Here, we report our initial experience with glioma patients and report efficacy of adding low dose 2-4 mg PER to LEV in patients whose seizure were uncontrollable with LEV monotherapy. Clinical outcome data of 18 consecutive patients were reviewed. This included nine males and nine females aged 24-76 years (median, 48.5 years), treated for glioma between June 2009 to December 2018. We added PER to patients with LEV-uncontrollable epilepsy. Adverse effects, irritability occurred in two patients, but continuous administration was possible in all cases. Though epileptic seizures occurred in four cases receiving 2 mg PER, 17 cases achieved seizure freedom by dose increments; final dose, 2-4 mg PER added to LEV 500-3000 mg. Our study revealed anti-epileptic efficacy of low dose PER 2-4 mg as first add-on therapy to LEV in glioma patients who have failed or intolerable to LEV monotherapy. Low dose PER added on to LEV may have favorable efficacy with tolerable adverse effects in glioma patients with LEV-uncontrollable epilepsy.

Topics: Adult; Aged; Anticonvulsants; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Brain Neoplasms; Combined Modality Therapy; Drug Resistance; Drug Resistant Epilepsy; Female; Follow-Up Studies; Glioma; Humans; Levetiracetam; Magnetic Resonance Imaging; Male; Middle Aged; Neuroimaging; Neurosurgical Procedures; Nimustine; Nitriles; Pyridones; Radiotherapy, Adjuvant; Receptors, AMPA; Retrospective Studies; Temozolomide; Young Adult

The purpose of this study was to determine the efficacy of perampanel (PER) on secondary bilateral synchrony (SBS) and behavioral problems in adolescents with epilepsy who showed insufficient response to levetiracetam (LEV).. The primary criterion for patient selection was the presence of SBS. The criteria such as age between 12 and 18 years, seizures refractory to antiseizure medications including LEV, at least four seizures a month, neuropsychological impairments, and at least 12 months of follow-up also had to be fulfilled. Patients were given PER at an initial dose of 2 mg/day, followed by increments of +2 mg/day every 2 weeks. Concomitant medications remained unchanged during evaluation period. Responders for electroencephalogram (EEG) and seizures were identified as showing a ≥50 % reduction from the baseline SBS on EEG and seizure frequency, respectively. Neuropsychological impairments as per the Japanese manuals for the Aberrant Behavior Checklist (ABC-J) were evaluated before and after PER administration.. Eight of 14 patients were considered responders for seizures. Among these 8 responders, 6 patients were considered responders for EEG and behavioral problems. Mean ABC-J scores in both EEG non-responders and responders were decreased significantly at 12 months (p < 0.05 and p < 0.05, respectively). ABC-J scores were significantly lower in EEG responders than in EEG non-responders at 12 months (p < 0.01). Moreover, among patients with decreased ABC-J scores, the degree of decrease was larger in EEG responders than in EEG non-responders (p < 0.01).. PER may be useful in reducing SBS on EEG, seizure frequency, and behavioral problems.

Topics: Adolescent; Anticonvulsants; Epilepsy; Humans; Infant; Levetiracetam; Nitriles; Piracetam; Problem Behavior; Pyridones; Treatment Outcome

Irritability has been described as a frequent adverse event in patients affected by epilepsy and treated with perampanel (PER), levetiracetam (LEV), and less frequently with valproic acid (VPA). Since the questionnaire for irritability (I-EPI) is a validated instrument to measure this psychiatric manifestation in patients affected by epilepsy, in this study we aimed at investigating the effect of PER as first add-on therapy on I-EPI. Moreover, we compared the effectiveness and I-EPI scores obtained at 12-month follow-up visits in patients treated by PER, LEV, or VPA in order to measure irritability as a consequence of these treatments.. We collected data from 17 patients treated by PER, 16 patients treated by LEV, and 16 patients under VPA treatment followed for 12 months.. We did not document significant changes of I-EPI questionnaire between baseline and follow-up in the PER group. As concerning the comparison of I-EPI among PER, LEV, and VPA groups, we documented lower global scores in PER than both LEV (P < 0.05) and VPA (P < 0.05) groups. Moreover, patients under PER treatment showed lower scores than LEV and VPA (P < 0.05) in I-EPI items measuring the gentle personality, anxiety of having epileptic seizures in front of others, and irritability in thinking that they can have an epileptic seizure.. This retrospective study described a stable and possibly lower degree of irritability in patients starting PER than LEV and VPA treatments, although we documented the comparable effectiveness of PER, LEV, and VPA as first add-on treatments in patients affected by uncontrolled epileptic seizures. However, the small sample of patients included in this study and the absence of I-EPI scores obtained at baseline visits in LEV and VPA groups require further investigations to confirm this preliminary evidence.

Topics: Adult; Anticonvulsants; Anxiety; Drug Therapy, Combination; Epilepsy; Female; Humans; Irritable Mood; Levetiracetam; Male; Nitriles; Personality; Preliminary Data; Pyridones; Retrospective Studies; Treatment Outcome; Valproic Acid

Perampanel (PER) is a third generation antiepileptic drug (AED), recently approved as add-on therapy in both focal and generalized seizures. Levetiracetam (LEV) is a second generation AED, widely used in patients with epilepsy because of its favorable safety and efficacy profiles. Perampanel and LEV treatments have been associated with the occurrence of similar adverse events (AEs) (sleepiness, irritability, depression, anxiety, aggressiveness). The aim of the present retrospective single center study was to verify the efficacy and tolerability of PER and LEV used as first add-on therapy in patients with epilepsy affected by secondarily generalized seizures. We collected data from 15 patients treated with PER and 26 patients treated with LEV and followed at our site with follow-up visits at 3, 6, and 12months. This retrospective study documented the comparable efficacy of PER and LEV as first add-on treatments in patients affected by uncontrolled secondarily generalized seizures. However, more patients withdrawn LEV because of AEs compared with PER at the 3- and 12-month follow-up visits. The better tolerability of PER observed in this study could be related to the low therapeutic dose of PER prescribed when it is used as first adjunctive treatment for better controlling secondarily generalized seizures.

Topics: Adult; Aggression; Anticonvulsants; Anxiety; Depression; Dizziness; Drug-Related Side Effects and Adverse Reactions; Epilepsy; Female; Humans; Irritable Mood; Levetiracetam; Male; Middle Aged; Nitriles; Pyridones; Retrospective Studies; Seizures; Treatment Outcome; Wakefulness

Psychiatric comorbidities are common in people with epilepsy. A retrospective study of characteristics associated with withdrawal due to psychiatric side effects was undertaken in patients with treated epilepsy participating in prospective audits with new antiepileptic drugs (AEDs). A total of 1058 treated patients with uncontrolled seizures (942 focal-onset seizures, 116 generalized genetic epilepsies [GGEs]) participated in eight prospective, observational audits from 1996 to 2014. These patients were prescribed adjunctive topiramate (n=170), levetiracetam (n=220), pregabalin (n=135), zonisamide (n=203), lacosamide (n=160), eslicarbazepine acetate (n=52), retigabine (n=64), or perampanel (n=54). Doses were titrated according to efficacy and tolerability to optimize zeizure outcomes and reduce side effects. Psychiatric comorbidities were recorded prior to and after the addition of each AED. At baseline, patients with focal-onset seizures (189 of 942; 20.1%) were statistically more likely to have psychiatric diagnoses compared to patients with GGEs (14 of 116, 12.1%; p=0.039). Following adjunctive AED treatment, neuropsychiatric adverse effects led to AED withdrawal in 1.9-16.7% of patients. Patients with a pre-treatment psychiatric history (22 of 209; 10.5%) were statistically more likely to discontinue their new AED due to psychiatric issues compared to patients with no previous psychiatric diagnosis (50 of 849; 5.9%; p=0.017). Patients receiving sodium channel blocking AEDs (4 of 212, 1.9%) were statistically less likely to develop intolerable psychiatric problems, compared to those on AEDs possessing other mechanisms of action (68 of 846, 8.0%; p=0.012). Depression was the commonest problem, leading to discontinuation of AEDs in 2.8% (n=30) patients. Aggression was statistically more common in men (11 of 527, 2.1%) compared to women (1 of 531, 0.2%; p=0.004). Patients with learning disability (12 of 122, 9.8%; p=0.0015) were statistically less likely to have psychiatric issues prior to adjunctive AED treatment compared to other patients (208 of 936, 22.2%), but there were no statistically significant differences once the new AEDs were added (8 of 122 patients with learning disability, 6.6%; 64 of 936 other patients, 6.8%). Awareness of these issues may assist clinicians in avoiding, identifying and treating psychiatric comorbidities in people with epilepsy.

Topics: Acetamides; Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Dibenzazepines; Drug-Related Side Effects and Adverse Reactions; Epilepsy; Female; Fructose; Humans; Lacosamide; Levetiracetam; Male; Medical Audit; Mental Disorders; Middle Aged; Nitriles; Piracetam; Pregabalin; Prospective Studies; Pyridones; Retrospective Studies; Seizures; Sodium Channel Blockers; Topiramate; Young Adult

Topics: Adult; Anticonvulsants; Drug Resistant Epilepsy; Electroencephalography; Female; Glutamic Acid; Humans; Levetiracetam; Nitriles; Psychoses, Substance-Induced; Pyridones; Synaptic Transmission; Topiramate; Zonisamide