BACKGROUND AND OBJECTIVES:Psychiatric comorbidities are highly prevalent in people with epilepsy, which adversely affect treatment outcomes. The proper choice of antiseizure medication (ASM) is therefore crucial because different ASMs have varying psychiatric safety profiles. This study investigates the psychiatric tolerability of commonly used ASMs in people with newly diagnosed focal epilepsy. METHODS:This post hoc analysis included participants from the Human Epilepsy Project, an international, multicenter prospective cohort. Of 357 participants aged ≥12 years enrolled within 4 months of treatment initiation for focal epilepsy, those receiving levetiracetam, lamotrigine, or sodium channel blockers (SCBs, including carbamazepine, oxcarbazepine, and phenytoin) monotherapy who completed the Mini International Neuropsychiatric Interview at enrollment were included. Median doses at discontinuation for each treatment group were reported. RESULTS:Of 357 patients, 214 (60%) received levetiracetam, 69 (19%) lamotrigine, and 74 (21%) other SCBs. Treatment groups differed significantly by sex (p = 0.028) and education level (p = 0.001). During the 2-year follow-up, levetiracetam and other SCBs had a significantly higher risk of withdrawal because of psychiatric adverse events compared with lamotrigine (p = 0.001 and p = 0.024, respectively). Most withdrawals occurred early. Multivariable Cox regression showed a higher withdrawal risk for levetiracetam vs lamotrigine (adjusted HR 2.76; 95% CI 1.51-5.04; p ≤ 0.001) and for other SCBs vs lamotrigine (adjusted HR 2.25; 95% CI 1.13-4.47; p = 0.021). Discontinuation doses were substantially lower than maintenance doses across all groups (p < 0.001 for levetiracetam and lamotrigine; p = 0.0022 for other SCBs). Among patients without baseline depression or anxiety (n = 232), discontinuation occurred in 40% of those receiving levetiracetam, 40% receiving other SCBs, and 19% receiving lamotrigine. Consistent with the overall cohort, levetiracetam was associated with a higher risk of discontinuation (OR 2.40 [1.18-5.20], p = 0.020) compared with lamotrigine. DISCUSSION:People who were newly diagnosed with focal epilepsy on ASM monotherapy showed that levetiracetam was associated with approximately 2.8-fold risk of treatment withdrawal compared with lamotrigine because of psychiatric adverse events. Our analysis also demonstrated a better psychiatric tolerability profile for lamotrigine compared with other SCBs. Most discontinuations occurred at significantly lower doses than maintenance therapy, suggesting either failure to reach therapeutic dosing or dose tapering before discontinuation.

Area IV of the 2021 Epilepsy Research Benchmarks aims to establish research goals to limit or prevent adverse consequences of seizures and their treatment across the life span. In this commentary, we will highlight key advances in Area IV. We will focus here on the comorbidities of epilepsy with special emphasis on neuropsychiatry, the endocrine system, and sudden unexpected death in epilepsy, which were discussed at the Epilepsy Benchmarks Area IV Symposium during the Annual Meeting of the American Epilepsy Society in December 2025.

Importance Psychiatric disturbances are common in epilepsy and are associated with increased risk of premature mortality, lower quality of life, and poor response to antiseizure medications (ASMs). Objective To evaluate the role of psychiatric disturbances at the time of epilepsy diagnosis in predicting risk of future treatment resistance in focal epilepsy. Design, Setting, and Participants The Human Epilepsy Project (HEP) is a prospective, observational, international, and multicenter cohort study with follow-up for up to 6 years. Participants with newly diagnosed focal epilepsy, enrolled within 4 months of initiating ASM treatment, between the ages 18 and 60 years, and without significant other comorbidities were recruited during the open period of 2012 to 2020. Data analysis was performed from January to September 2025. Exposure Presence of a psychiatric diagnosis. Main Outcomes and Measures Presence of psychiatric diagnosis (mood/anxiety disorders) measured by Mini International Neuropsychiatric Interview (MINI) and/or suicidality measured by Columbia-Suicide Severity Rating Scale (C-SSRS) at enrollment. Treatment response included the following outcomes: treatment resistant (TR), defined as failure of first 2 adequate ASM trials (ongoing seizures at/above therapeutic doses); treatment sensitive (TS), defined by a minimum period of seizure freedom on first 2 adequate ASM trials (12 months/3-fold greatest pretreatment seizure-free interval, whichever is longer); and indeterminate (neither TR/TS). Results Of 376 enrolled adults, 347 (median [IQR] age at seizure onset, 33 [23-44] years; 209 female [60.2%]) completed the MINI and C-SSRS at enrollment. Of these individuals, 191 (55%) were TS, 83 (24%) TR, and 73 (21%) indeterminate. The rate of psychiatric disturbance (mood/anxiety disorder; suicidality) at epilepsy diagnosis was 38% (n = 133). Fifty-seven (16%) had mood/anxiety disorder(s) without suicidality, and 75 (22%) expressed suicidality with or without a psychiatric disorder. Suicidality at epilepsy diagnosis was associated with greater than 2-fold risk of developing TR (relative risk [RR], 2.02; 95% CI, 1.32-3.09; P = .001). There were no significant overall associations between mood/anxiety disorders and TR. Suicidality alone significantly increased TR probability from 16.3% (95% CI, 11.3%-21.3%) in those with no psychiatric disturbance to 47.1% (RR, 2.89; 95% CI, 1.65-5.05; P < .001). Anxiety disorder alone increased TR probability to 32.9% (RR, 2.02; 95% CI, 1.10-3.71; P = .02), although this was not statistically significant after correcting for multiple comparisons. There was no significant change in TR probability when mood disorder alone was present; however, presence of mood disorder with suicidality increased TR probability to 39.6% (RR, 2.43; 95% CI, 1.26-4.68; P = .008). Conclusions and Relevance Results of this cohort study reveal that suicidality at the time of focal epilepsy diagnosis was associated with future drug resistance and may be a marker of more severe neuropathology. Psychiatric screening at time of diagnosis may facilitate early identification of patients at risk for treatment refractory epilepsy syndromes.

BACKGROUND:People with epilepsy (PWE) may experience seizure clusters, broadly defined as ≥2 seizures that occur in close proximity. In epilepsy monitoring units (EMUs), seizure clusters can spontaneously occur during long-term videoelectroencephalogram monitoring (LTVEM) or as a result of antiseizure medication dose adjustments. In this survey, we examined the experiences and practices of expert clinicians with seizure clusters in EMUs. METHODS:A 55-item survey was sent to members of an Epilepsy Education Council who are epilepsy experts. Items described experiences, treatment practices, and negative outcomes with seizure clusters in EMUs. RESULTS:Of the 15 experts (aged 43-77 y), 14 are physicians and 1 is an advanced practice provider; 14 work at level 4 epilepsy centers. The definition of seizure cluster varied across experts, from 2 seizures in 1 hour to 3 seizures over 24 hours. Twelve experts prescribe immediate-use rescue medication (RM) during EMU stay, usually a benzodiazepine. An intranasal route is preferred by 11 if intravenous access is unavailable. Nine experts have had a presurgical evaluation compromised owing to seizure clusters during LTVEM, and 12 have cared for PWE who required transfer to a higher-level care (eg, intensive care unit) owing to seizure clusters. Thirteen experts indicated they would follow expert consensus recommendations for immediate-use RMs in the EMU if available. CONCLUSIONS:In the EMU, seizure clusters may compromise presurgical evaluations and require higher levels of care. Consensus recommendations are needed to guide patient-specific treatment practices before, during, and after EMU admission.

OBJECTIVE:People with focal epilepsy experience one or more seizures prior to diagnosis. The Human Epilepsy Project (HEP) was a prospective study enrolling people with newly diagnosed focal epilepsy. It collected information including cognitive testing at the time of enrollment. This was completed utilizing a computerized test battery called the Cogstate Brief Battery (CBB). A prior analysis found that enrollment CBB test scores were below that of age matched controls and that performance on testing was not independently associated with the longer-term development of treatment resistance over the course of the HEP study. The present study assesses the impact of pretreatment seizures on cognition at time of diagnosis, considering time-to-treatment initiation in relation to seizure onset, pre-treatment seizure frequency, and pretreatment seizure classification. METHODS:Participants with newly diagnosed focal epilepsy and no other major medical comorbidities or intellectual disability (estimated IQ > 70) were enrolled between June 29, 2012, and September 1, 2019. A subset of the 448 enrolled participants (N = 183) were over 18 years old, had complete HEP enrollment data that included pre-treatment seizure histories, and complete enrollment CBB testing for analysis in this study. Performance on enrollment CBB testing was modeled using multiple linear regression with pre-treatment seizure characteristics including seizure type and duration between seizure onset and treatment initiation, controlling for other key baseline participant characteristics. RESULTS:There were no independent associations between cognitive measures on the CBB at the time of enrollment and pre-treatment seizures after correcting for potentially confounding variables. Z-scores for the attention composite on CBB (an average of Identification and Detection tests) were not associated with a global pre-treatment seizure score that quantified time with seizures (days) and seizure count by seizure type (motor, non-motor, bilateral tonic clonic) (p = 0.29). Similarly, z-scores for the memory composite (an average of the One Card Learning test and One Back tests) were not associated with the pre-treatment seizure score (p = 0.1). No additional independent associations were found to be significant between z-scores for attention or memory composites and other potential explanatory variables. SIGNIFICANCE:This study highlights an important finding for people who develop focal epilepsy and otherwise are in good health: pre-treatment time-limited seizures do not have an independent impact on cognition early on, as measured by a brief validated cognitive screening test. This suggests that that cognition at the time of epilepsy diagnosis may be more strongly related to underlying etiology, chronic disease, and comorbidities.

Four to five patients with epilepsy (PWE) can suffer from Major Depressive episodes (MDE). Comorbid anxiety disorders (AD) frequently occur together with MDE. Failure to treat MDE can negatively affect several aspects of their life as well as the management of the epilepsy. Often, suicidal ideation is among its symptoms, which need to be addressed without delay to prevent suicidal attempts or a completed suicide. Unfortunately, access to health care professionals is very limited and, in many communities, non-existent. Accordingly, it falls upon the treating neurologist to begin a pharmacologic trial with psychotropic drugs. The purpose of this manuscript is to provide neurologists with very useful strategies on how to screen and identify MDEs with and without AD in the outpatient clinic and how to select the appropiate psychotropic drugs. Using an illustrative case, we discuss its differential diagnosis, particularly the recognition of iatrogenic episodes, and demonstrate the selection and mode of use of commonly used antidepressant in PWE. Finally, we provide a guide on how the neurologist can assess the suicidal risk of a patient that endorses suicidal ideation and the steps that need to be taken to minimize the risk of suicidal behavior.

BACKGROUND:The prevalence of psychiatric disorders in people with epilepsy is as high as 43% and, among them, psychoses represent a severe comorbidity. AIMS:This is a narrative review discussing the interplay between epilepsy and psychosis and identifying challenges in diagnosing and managing psychotic symptoms in epilepsy, focusing on the past 10 years. METHOD:Articles published between June 2014 and December 2024 were identified through searches in PubMed using the search terms 'psychosis', 'seizure, epilepsy and convulsion', 'epile*', 'seizure*' and 'convuls*'. RESULTS:The association between epilepsy and psychosis was shown to be bidirectional, with people with psychosis being at increased risk of epilepsy. In epilepsy, psychotic symptoms may occur in three clinical scenarios, with clinical presentation and management varying in relationship to these: seizure-related (peri-ictal), treatment-related or independent of the former. CONCLUSIONS:There are no guidelines for the management of psychotic symptoms in epilepsy, but it is possible to apply policies for the treatment of psychoses, taking into account the peculiarities and needs of people with epilepsy.

Background and Objectives Mood, anxiety disorders, and suicidality are more frequent in people with epilepsy than in the general population. Yet, their prevalence and the types of mood and anxiety disorders associated with suicidality at the time of the epilepsy diagnosis are not established. We sought to answer these questions in patients with newly diagnosed focal epilepsy and to assess their association with suicidal ideation and attempts. Methods The data were derived from the Human Epilepsy Project study. A total of 347 consecutive adults aged 18–60 years with newly diagnosed focal epilepsy were enrolled within 4 months of starting treatment. The types of mood and anxiety disorders were identified with the Mini International Neuropsychiatric Interview, whereas suicidal ideation (lifetime, current, active, and passive) and suicidal attempts (lifetime and current) were established with the Columbia Suicidality Severity Rating Scale (CSSRS). Statistical analyses included the t test, χ2 statistics, and logistic regression analyses. Results A total of 151 (43.5%) patients had a psychiatric diagnosis; 134 (38.6%) met the criteria for a mood and/or anxiety disorder, and 75 (21.6%) reported suicidal ideation with or without attempts. Mood (23.6%) and anxiety (27.4%) disorders had comparable prevalence rates, whereas both disorders occurred together in 43 patients (12.4%). Major depressive disorders (MDDs) had a slightly higher prevalence than bipolar disorders (BPDs) (9.5% vs 6.9%, respectively). Explanatory variables of suicidality included MDD, BPD, panic disorders, and agoraphobia, with BPD and panic disorders being the strongest variables, particularly for active suicidal ideation and suicidal attempts. Discussion In patients with newly diagnosed focal epilepsy, the prevalence of mood, anxiety disorders, and suicidality is higher than in the general population and comparable to those of patients with established epilepsy. Their recognition at the time of the initial epilepsy evaluation is of the essence.

BACKGROUND AND OBJECTIVES:Mood, anxiety disorders, and suicidality are more frequent in people with epilepsy than in the general population. Yet, their prevalence and the types of mood and anxiety disorders associated with suicidality at the time of the epilepsy diagnosis are not established. We sought to answer these questions in patients with newly diagnosed focal epilepsy and to assess their association with suicidal ideation and attempts. METHODS:The data were derived from the Human Epilepsy Project study. A total of 347 consecutive adults aged 18-60 years with newly diagnosed focal epilepsy were enrolled within 4 months of starting treatment. The types of mood and anxiety disorders were identified with the Mini International Neuropsychiatric Interview, whereas suicidal ideation (lifetime, current, active, and passive) and suicidal attempts (lifetime and current) were established with the Columbia Suicidality Severity Rating Scale (CSSRS). Statistical analyses included the t test, χ2 statistics, and logistic regression analyses. RESULTS:A total of 151 (43.5%) patients had a psychiatric diagnosis; 134 (38.6%) met the criteria for a mood and/or anxiety disorder, and 75 (21.6%) reported suicidal ideation with or without attempts. Mood (23.6%) and anxiety (27.4%) disorders had comparable prevalence rates, whereas both disorders occurred together in 43 patients (12.4%). Major depressive disorders (MDDs) had a slightly higher prevalence than bipolar disorders (BPDs) (9.5% vs 6.9%, respectively). Explanatory variables of suicidality included MDD, BPD, panic disorders, and agoraphobia, with BPD and panic disorders being the strongest variables, particularly for active suicidal ideation and suicidal attempts. DISCUSSION:In patients with newly diagnosed focal epilepsy, the prevalence of mood, anxiety disorders, and suicidality is higher than in the general population and comparable to those of patients with established epilepsy. Their recognition at the time of the initial epilepsy evaluation is of the essence.

Importance:Epilepsy affects approximately 65 million people worldwide, and 60% have focal seizures. Predicting seizure response and drug resistance to antiseizure medications (ASMs) in people with focal epilepsy remains difficult. Objective:To describe the expected short- and long-term response to treatment with ASMs in people with focal epilepsy using recognized definitions by the International League Against Epilepsy. Design, Setting, and Participants:The Human Epilepsy Project is an international, prospective, observational cohort study that followed up people with newly diagnosed focal epilepsy for up to 6 years between 2012 and 2020. Data were analyzed from 2023 to 2024. The Human Epilepsy Project was conducted at 34 tertiary epilepsy centers across the US, Australia, and Europe. Participants with confirmed diagnosis of focal epilepsy aged 12 to 60 years were enrolled within 4 months of treatment initiation with ASM(s). Data were analyzed from February 2024 to July 2024. Exposure:ASM (variable). Main Outcomes and Measures:The primary outcome was seizure freedom, defined as a period without seizures for 12 months or 3 times the longest pretreatment seizure-free interval, whichever was longer. Treatment response was categorized as sensitive, meaning seizure free receiving 2 or fewer adequate ASM trials; resistant, meaning having 2 or more adequate ASM trials fail; or indeterminate (neither treatment sensitive nor resistant). Results:Among 448 enrolled participants, 267 (59.6%) were female, and median (IQR) participant age was 32 (21-44) years at treatment initiation. Median (IQR) follow-up duration was 3.13 (2.33-3.55) years. Most achieved seizure freedom (267 participants of 448 [59.6%]), largely without relapse (223 [83.5%]). There were 245 treatment-sensitive participants (54.7%), 102 treatment-resistant participants (22.8%), and 101 indeterminate participants (22.5%). Among treatment-sensitive participants, most (217 [89.3%]) responded to monotherapy and half (121 [49.4%], or 27% of total cohort) became seizure free while receiving their first ASM. In the first year of treatment, 251 participants (63%) had ongoing or worsening seizures. Median time to first seizure freedom was 12.1 months (95% CI, 9.7-16.1). This occurred earlier in those who never relapsed (median, 2.2 months; 95% CI, 0.8-3.2) than those who did (median, 7.4 months; 95% CI, 4.0-10.7). Those with infrequent pretreatment seizures were 0.30-fold less likely to be treatment resistant than those with very frequent seizures (hazard ratio, 0.30; 95% CI, 0.14-0.64; P = .002; Holm-Bonferroni-corrected P = .006). Participants with self-reported comorbid psychological disorders were 1.78-fold more likely to be treatment resistant than those without (relative risk, 1.78; 95% CI, 1.26-2.52; P = .001). Conclusions and Relevance:In the Human Epilepsy Project multicenter prospective cohort study, most people with newly diagnosed focal epilepsy took more than a year and more than 1 ASM to become seizure free. Drug resistance can be identified earlier in those with frequent pretreatment seizures, and a history of psychiatric comorbidities at epilepsy diagnosis is an important prognostic factor. Trial Registration:ClinicalTrials.gov Identifier: NCT02126774.

Psychotic disorders are more frequent in people with epilepsy than the general population. They constitute one of the most serious psychiatric comorbidities which require an immediate psychopharmacologic intervention. Yet, access to psychiatrists is often limited or not available and the neurologists taking care of these patients are called-upon to start treatment with antipsychotic medication. The purpose of this manuscript is to provide clinicians with pragmatic psychopharmacologic strategies to treat interictal psychotic disorders in patients with epilepsy. We review the case of a 45 years-old man with a 35-year history of treatment-resistant focal epilepsy of bitemporal origin who developed a de-novo psychotic episode that began with insomnia, mood lability and agitation and evolved into paranoid delusions, auditory hallucinations and a thought disorder. The patient was diagnosed with an interictal psychotic episode and was treated with aripiprazole which resulted in significant improvement after reaching a 20 mg /day dose and allowed for the patient to be discharged home. In summary, interictal psychotic episodes of epilepsy are relatively frequent in patients with epilepsy and require of an early psychopharmacologic treatment to facilitate their remission or stabilization until mental health professionals can take over their long-term care. Compared to primary psychotic disorders, interictal psychotic episodes respond better and at lower doses of antipsychotic drugs.

Psychiatric comorbidities are common and highly impactful among people with epilepsy, yet they are underrecognized and undertreated due to challenges including shortage of specialty mental health providers and lack of neurologist education to enable management by neurologists. The purpose of this special issue is to address these gaps by providing a practical resource for neurologists to safely manage comorbidities via pharmacotherapy for common comorbidities. In this introductory article, we summarize key categories of psychiatric problems in epilepsy and a broad overview of management strategies. These include reactive psychiatric symptoms, interictal psychiatric disorders, peri-ictal psychiatric episodes, and iatrogenic causes of psychiatric symptoms. Reactive psychiatric symptoms can be addressed via epilepsy education and neurologist acknowledgement of the loss of predictability inherent in epilepsy. Interictal psychiatric disorders can be identified via standardized screening instruments and managed using evidence-based pharmacotherapy with a similar approach to the general population. Peri-ictal psychiatric episodes have a consistent temporal relation to seizure occurrence and are primarily managed via prevention through seizure treatment. Patients with personal or family history of psychiatric disorders are at particular risk for iatrogenic psychiatric effects; neurologists should take care in treatment selection among these individuals and be ready to respond to manage iatrogenic effects if they arise. Management of specific psychiatric conditions are addressed in more depth in topic-focused articles throughout the remainder of the special issue.

Despite their high prevalence in epilepsy, neurologists and psychiatrists displayed a limited interest in their psychiatric comorbidities until the decade of the 1980s, when the number of publications started to increase exponentially in leading Neurology (e.g., Neurology, Archives of Neurology, Brain) and Epilepsy (e.g., Epilepsia, Epilepsy Research) scientific journals.

Importance Epilepsy affects approximately 65 million people worldwide. Persistent seizures are associated with a 20% to 40% risk of bodily injuries (eg, fractures, burns, concussions) over 12-month follow-up. The primary goal of epilepsy treatment is to eliminate seizures while minimizing adverse effects of antiseizure drugs (ASDs). Observations An epileptic seizure is defined as a sudden occurrence of transient signs and symptoms caused by abnormal and excessive or synchronous neuronal activity in the brain. Focal and generalized epilepsy are the 2 most frequent types of epilepsy; diagnosis is based on the type of seizures. There are 26 US Food and Drug Administration-approved medications for epilepsy, of which 24 have similar antiseizure efficacy for focal epilepsy and 9 have similar efficacy for generalized epilepsy. The decision to initiate an ASD should be individualized, but should be strongly considered after 2 unprovoked seizures or after 1 unprovoked seizure that occurred during sleep and/or in the presence of epileptiform activity on an electroencephalogram and/or in the presence of a structural lesion on the brain magnetic resonance imaging. The ASDs must be selected based on the seizure and epilepsy types, the epilepsy syndrome, and the adverse effects associated with the drug. For focal epilepsy, oxcarbazepine and lamotrigine are first-line therapy, while levetiracetam can be also considered if there is no history of psychiatric disorder. For generalized epilepsy, the selection of the ASD is based on the type of epilepsy syndrome and the patient's sex, age, and psychiatric history. Seizure freedom is achieved in approximately 60% to 70% of all patients. A total of 25% to 50% of patients also experience neurologic, psychiatric, cognitive, or medical disorders, such as mood, anxiety, and attention deficit disorders and migraines. For these patients, selecting an ASD should consider the presence of these disorders and concomitant use of medications to treat them. ASDs with cytochrome P450 enzyme-inducing properties (eg, carbamazepine, phenytoin) may worsen comorbid coronary and cerebrovascular disease by causing hyperlipidemia and accelerating the metabolism of concomitant drugs used for their treatment. They can also facilitate the development of osteopenia and osteoporosis. Conclusions and Relevance Epilepsy affects approximately 65 million people worldwide and is associated with increased rates of bodily injuries and mortality when not optimally treated. For focal and generalized epilepsy, selection of ASDs should consider the seizure and epilepsy types and epilepsy syndrome, as well as the patient's age and sex, comorbidities, and potential drug interactions.

Suicidality is a relatively common comorbidity in patients with epilepsy (PWE). Population-based studies have revealed lifetime prevalence rates of 25% of suicidal ideation (SI). In addition, PWE without comorbid psychiatric disorders has two to three higher risk of committing suicide and this risk increases by 12- to 32-fold in the presence of various psychiatric disorders. Risk factors are multiple and include socio-demographic, genetic, age and gender, and psychiatric comorbidities. Among the latter, mood, anxiety, and psychotic disorders have been found to be common risk factors for suicidality in PWE, but iatrogenic causes resulting from pharmacotherapy with antiseizure drugs or epilepsy surgery can also cause SI and behavior. Suicidality and epilepsy have a complex bidirectional relation, whereas PWE are at increased risk of suicidality and vice-versa. Common pathogenic mechanisms operant in both conditions may explain this bidirectional relation. SI can be easily identified in outpatient epilepsy clinics with screening instruments and can be treated and thus prevent its escalation to suicidal attempts and completed suicide. The aim of this manuscript is to review these data in detail.

BackgroundPsychiatric safety data from perampanel randomised controlled trials (RCTs; Studies 304/305/306/335) and open-label extensions (OLEx; Studies 307/335 OLEx) in patients with focal epilepsy with/without psychiatric history were analysed.MethodsTreatment-emergent adverse events (TEAEs) were analysed for patients with/without psychi- atric history.ResultsIn RCTs, 352/2187 (16.1%) patients had psychiatric history; psychiatric TEAEs occurred in 73/244 (29.9%) and 21/108 (19.4%) patients with perampanel and placebo, respectively. Psychiatric TEAEs with perampanel 2 and 4 mg/day were 11.1% and 15.4%, respectively, vs placebo (19.4%). In patients without psychiatric history, psychiatric TEAEs were observed in 157/1325 (11.8%) and 47/510 (9.2%) patients with perampanel and placebo, respectively. Psychiatric TEAEs were more frequent in patients with psychiatric history for all combined doses and placebo (both P<0.01). Most common psychiatric TEAEs with peram- panel: anxiety (5.3%)/insomnia and aggression (both 2.0%) with/without psychiatric history.In OLEx, 283/1895 (14.9%) patients had psychiatric history. Psychiatric TEAEs occurred in 151 (53.4%)/521 (32.3%) patients with/without psychiatric history (P<0.01); most common psychiatric TEAE: irritability (16.3%/10.4%, with/without psychiatric history).ConclusionPsychiatric TEAEs were reported by more patients with psychiatric history and were dependent on perampanel dose irrespective of previous psychiatric illness; 2 mg/day and 4 mg/day doses did not increase psychiatric TEAEs.FundingEisai Inc.manoj_malhotra@eisai.com

Summary: Generalized periodic patterns with triphasic wave morphology, long referred to as triphasic waves [TWs], had been associated with metabolic encephalopathies, although other neurologic and systemic causes have since been identified. In a recent classification of periodic patterns, TWs were formally grouped with the generalized periodic discharges, which are often associated with ictal activity. The interpretation of generalized periodic patterns with TWs as nonictal can have significant implications in the management of comatose patients in nonconvulsive status epilepticus. Electrographic characteristics that help distinguish nonictal periodic patterns with TWs from generalized periodic discharge ictal patterns include (1) TWs in long runs of periodic bilaterally synchronous and symmetric discharges, maximal in frontocentral or posterior head regions with and without a frontal-to-occipital lag or posterior-to-anterior lag, respectively; (2) recurrent spontaneous and/or low-dose benzodiazepine-induced attenuation and/or suppression of the periodic pattern and replacement with a diffuse slow wave activity throughout a prolonged EEG recording; and (3) stimulation-induced activation and/or increase in frequency and/or organization of TWs. We coined the term of status triphasicus to describe the electrographic periodic pattern of TWs with these three distinct characteristics. In this article, we discuss the advantages and limitations of keeping the status triphasicus pattern as a distinct electrographic entity different from periodic ictal generalized periodic discharge patterns. We discuss the circumstances in which a status triphasicus pattern can be associated with ictal activity and propose a simple pragmatic classification of status triphasicus that encompasses the different clinical scenarios it can be associated with.