Resting-State EEG Signature of Early Consciousness Recovery in Comatose Patients with Traumatic Brain Injury.

BACKGROUND: Resting-state electroencephalography (rsEEG) is usually obtained to assess seizures in comatose patients with traumatic brain injury (TBI). We aim to investigate rsEEG measures and their prediction of early recovery of consciousness in patients with TBI. METHODS: This is a retrospective study of comatose patients with TBI who were admitted to a trauma center (October 2013 to January 2022). Demographics, basic clinical data, imaging characteristics, and EEGs were collected. We calculated the following using 10-min rsEEGs: power spectral density, permutation entropy (complexity measure), weighted symbolic mutual information (wSMI, global information sharing measure), Kolmogorov complexity (Kolcom, complexity measure), and heart-evoked potentials (the averaged EEG signal relative to the corresponding QRS complex on electrocardiography). We evaluated the prediction of consciousness recovery before hospital discharge using clinical, imaging, and rsEEG data via a support vector machine. RESULTS: We studied 113 of 134 (84%) patients with rsEEGs. A total of 73 (65%) patients recovered consciousness before discharge. Patients who recovered consciousness were younger (40 vs. 50 years, p = 0.01). Patients who recovered also had higher Kolcom (U = 1688, p = 0.01), increased beta power (U = 1,652 p = 0.003) with higher variability across channels (U = 1534, p = 0.034) and epochs (U = 1711, p = 0.004), lower delta power (U = 981, p = 0.04), and higher connectivity across time and channels as measured by wSMI in the theta band (U = 1636, p = 0.026; U = 1639, p = 0.024) than those who did not recover. The area under the receiver operating characteristic curve for rsEEG was higher than that for clinical data (using age, motor response, pupil reactivity) and higher than that for the Marshall computed tomography classification (0.69 vs. 0.66 vs. 0.56, respectively; p < 0.001). CONCLUSIONS: We describe the rsEEG signature in recovery of consciousness prior to discharge in comatose patients with TBI. rsEEG measures performed modestly better than the clinical and imaging data in predicting recovery.

Mood disorders in adults with epilepsy: a review of unrecognized facts and common misconceptions.

Epilepsy is one of the most common neurologic conditions. Its clinical manifestations are not restricted to seizures but often include cognitive disturbances and psychiatric disorders. Prospective population-based studies have shown that people with epilepsy have an increased risk of developing mood disorders, and people with a primary mood disorder have an increased risk of developing epilepsy. The existence of common pathogenic mechanisms in epilepsy and mood disorders may explain the bidirectional relation between these two conditions. Recognition of a personal and family psychiatric history at the time of evaluation of people for a seizure disorder is critical in the selection of antiseizure medications: those with mood-stabilizing properties (e.g., lamotrigine, oxcarbazepine) should be favoured as a first option in those with a positive history while those with negative psychotropic properties (e.g., levetiracetam, topiramate) avoided. While mood disorders may be clinically identical in people with epilepsy, they often present with atypical manifestations that do not meet ICD or DSM diagnostic criteria. Failure to treat mood disorders in epilepsy may have a negative impact, increasing suicide risk and iatrogenic effects of antiseizure medications and worsening quality of life. Treating mood disorders in epilepsy is identical to those with primary mood disorders. Yet, there is a common misconception that antidepressants have proconvulsant properties. Most antidepressants are safe when prescribed at therapeutic doses. The incidence of seizures is lower in people randomized to antidepressants than placebo in multicenter randomized placebo-controlled trials of people treated for a primary mood disorder. Thus, there is no excuse not to prescribe antidepressant medications to people with epilepsy.

ILAE clinical practice recommendations for the medical treatment of depression in adults with epilepsy.

The aim of this document is to provide evidence-based recommendations for the medical treatment of depression in adults with epilepsy. The working group consisted of members of an ad hoc Task Force of the International League Against Epilepsy (ILAE) Commission on Psychiatry, ILAE Executive and the International Bureau for Epilepsy (IBE) representatives. The development of these recommendations is based on a systematic review of studies on the treatment of depression in adults with epilepsy, and a formal adaptation process of existing guidelines and recommendations of treatment of depression outside epilepsy using the ADAPTE process. The systematic review identified 11 studies on drug treatments (788 participants, class of evidence III and IV); 13 studies on psychological treatments (998 participants, class of evidence II, III and IV); and 2 studies comparing sertraline with cognitive behavioral therapy (CBT; 155 participants, class of evidence I and IV). The ADAPTE process identified the World Federation of Societies of Biological Psychiatry guidelines for the biological treatment of unipolar depression as the starting point for the adaptation process. This document focuses on first-line drug treatment, inadequate response to first-line antidepressant treatment, and duration of such treatment and augmentation strategies within the broader context of electroconvulsive therapy, psychological, and other treatments. For mild depressive episodes, psychological interventions are first-line treatments, and where medication is used, selective serotonin reuptake inhibitors (SSRIs) are first-choice medications (Level B). SSRIs remain the first-choice medications (Level B) for moderate to severe depressive episodes; however, in patients who are partially or non-responding to first-line treatment, switching to venlafaxine appears legitimate (Level C). Antidepressant treatment should be maintained for at least 6 months following remission from a first depressive episode but it should be prolonged to 9 months in patients with a history of previous episodes and should continue even longer in severe depression or in cases of residual symptomatology until such symptoms have subsided.

Long-term seizure and psychiatric outcomes following laser ablation of mesial temporal structures.

OBJECTIVE: Postsurgical seizure outcome following laser interstitial thermal therapy (LiTT) for the management of drug-resistant mesial temporal lobe epilepsy (MTLE) has been limited to 2 years. Furthermore, its impact on presurgical mood and anxiety disorders has not been investigated. The objectives of this study were (1) to identify seizure outcome changes over a period ranging from 18 to 81 months; (2) to investigate the seizure-free rate in the last follow-up year; (3) to identify the variables associated with seizure freedom; and (4) to identify the impact of LiTT on presurgical mood and anxiety disorders. METHODS: Medical records of all patients who underwent LiTT for MTLE from 2013 to 2019 at the University of Miami Comprehensive Epilepsy Center were retrospectively reviewed. Demographic, epilepsy-related, cognitive, psychiatric, and LiTT-related data were compared between seizure-free (Engel Class I) and non-seizure-free (Engel Class II + III + IV) patients. Statistical analyses included univariate and multivariate stepwise logistic regression analyses. RESULTS: Forty-eight patients (mean age = 43 ± 14.2 years, range = 21-78) were followed for a mean period of 50 ± 20.7 months (range = 18-81); 29 (60.4%) achieved an Engel Class I outcome, whereas 11 (22.9%) had one to three seizures/year. Seizure-freedom rate decreased from 77.8% to 50% among patients with 24- and >61-month follow-up periods, respectively. In the last follow-up year, 83% of all patients were seizure-free. Seizure freedom was associated with having mesial temporal sclerosis (MTS), no presurgical focal to bilateral tonic-clonic seizures, and no psychopathology in the last follow-up year. Presurgical mood and/or anxiety disorder were identified in 30 patients (62.5%) and remitted after LiTT in 19 (62%). SIGNIFICANCE: LiTT appears to be a safe and effective surgical option for treatment-resistant MTLE, particularly among patients with MTS. Remission of presurgical mood and anxiety disorders can also result from LiTT.

Neuropsychiatric Treatments for Epilepsy: Nonpharmacological Approaches.

Neuropsychiatric conditions are frequently found in patients with epilepsy (PWE). These entities can be as disabling as epilepsy resulting in a significant negative impact on the quality of life of this population if not addressed and treated appropriately. In this article, we provide an overview of non-pharmacological treatments currently available to these patients-and review their effect on mood and anxiety disorders as well as epilepsy. These treatment strategies will allow the practitioner to optimize clinical care during the initial evaluation, which begins with the recognition of the neuropsychiatric condition followed by the appropriate individualized psychotherapeutic approach and/or neuromodulation therapy. To plan a comprehensive treatment for PWE, practitioners must be familiar with these therapeutic tools. Additional clinical research is needed to further create a multidisciplinary team in the assessment and management of neuropsychiatric disorders in PWE.

Antiseizure Medications for Adults With Epilepsy: A Review.

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.

Does a psychiatric history play a role in the development of psychiatric adverse events to perampanel and to placebo?

OBJECTIVE: The purpose of this study was to establish whether a past psychiatric history could play a role in the development of psychiatric treatment-emergent adverse events (PTEAEs) in patients randomized to perampanel (PER) or placebo. METHODS: The development of PTEAEs was compared between patients with/without a psychiatric history in a post hoc analysis from four randomized placebo-controlled trials (RPCTs) of PER (304/305/306/335) in patients with treatment-resistant focal epilepsy. RESULTS: Among the 2,187 patients enrolled in the RPCTs, 352 (16.1%) had a psychiatric history (PER n = 244; placebo n = 108), while 1835 patients (83.9%) did not (PER n = 1325; placebo n = 510). Compared to patients without a psychiatric history, those with a positive history reported more PTEAEs for both patients randomized to PER (11.8% vs. 29.9%, p < 0.01) or to placebo (9.2% vs. 19.4%, p < 0.01). The prevalence of PTEAEs was not higher among patients randomized to 2 mg and 4 mg/day doses than placebo in both those with and without psychiatric history. Rather, the higher prevalence rates were among subjects randomized to 8 mg (29.8%) and 12 mg (36.4%) PER doses in patients with a past psychiatric history. SIGNIFICANCE: A psychiatric history appears to increase the risk of PTEAEs in patients randomized to placebo and to PER at doses of 8 and 12 mg/day. It should be identified in all patients considered for treatment with PER, particularly when prescribed at doses above 4 mg/day.

Mood and quality of life in patients treated with brain-responsive neurostimulation: The value of earlier intervention.

OBJECTIVE: To establish whether earlier treatment using direct brain-responsive neurostimulation for medically intractable focal-onset seizures is associated with better mood and Quality of Life (QoL) compared to later treatment intervention. METHODS: Data were retrospectively analyzed from prospective clinical trials of a direct brain-responsive neurostimulator (RNS® System) for treatment of adults with medically intractable focal-onset epilepsy. Participants completed the Quality of Life in Epilepsy Inventory (QOLIE-31) yearly through 9 years of follow-up and the Beck Depression Inventory-II (BDI-II) through 2 years of follow-up. Changes in each assessment after treatment with responsive neurostimulation were calculated for patients who began treatment within 10 years of seizure onset (early) and those who began treatment 20 years or more after seizure onset (late). RESULTS: The median duration of epilepsy was 18.3 years at enrollment. At 9 years, both the early (N = 51) and late (N = 109) treatment groups experienced similar and significant reductions in the frequency of disabling seizures (73.4% and 77.8%, respectively). The early treatment patients had significant improvements in QoL and mood. However, the late treatment patients not only failed to show these improvements but also declined in the emotional QoL subscale. CONCLUSIONS: Patients treated with brain-responsive neurostimulation earlier in the course of their epilepsy show significant improvements in multiple domains of QoL and mood that are not observed in patients treated later in the course of their epilepsy despite similar efficacy in seizure reduction. Even with similar and substantial reductions in seizure frequency, the comorbidities of uncontrolled epilepsy may be less responsive to treatment when too many years have passed. The results of this study suggest that, as with resective and ablative surgery, treatment with brain-responsive neurostimulation should be delivered as early as possible in the course of medically resistant epilepsy to maximize the opportunity for improvements in mood and QoL.

Disconnection of hippocampal networks contributes to memory dysfunction in individuals with temporal lobe epilepsy.

A deficit in declarative memory function is common among individuals with temporal lobe epilepsy. The purpose of this study is to evaluate the relationship between the volume of the hippocampus, entorhinal cortex along with the surrounding parahippocampal white matter and memory performance in those with temporal lobe epilepsy. T1 weighted MRI scans were acquired using a 3-D pulse sequence in 50 individuals with temporal lobe epilepsy. Hippocampal and entorhinal cortex volumes were derived by manually tracing consecutive coronal slices aligned perpendicular to the long axis of the hippocampus. In addition, parahippocampal white matter volumes were determined using voxel based morphometry. Finally, declarative memory was assessed using immediate and delayed verbal and visual memory tests from the Wechsler Memory Scale third edition. Significant correlations were seen between right and left hippocampal volumes and delayed verbal memory test scores. In addition, left parahippocampal white matter showed positive correlations with immediate and delayed verbal and visual recall. Furthermore, regression models found that the right hippocampus and left parahippocampal white matter were the best predictors of immediate and delayed verbal and visual memory performance. These results show that a decrease in white matter fibers projecting to the hippocampus may cause a disruption of incoming multi-modal sensory information, contributing to the memory decline seen in individuals with temporal lobe epilepsy.

Obstacles in the treatment of common psychiatric comorbidities in patients with epilepsy: What is wrong with this picture?

The aim of this special issue is to highlight a major problem that plagues the management of patients with epilepsy (PWE): the failure to identify and treat relatively frequent psychiatric comorbidities, in particular, depression and anxiety disorders. The causes are multiple, starting from the neurologists' failure to investigate the existence of these common comorbidities during the initial evaluation or even throughout the course of treatment of these patients. Does this phenomenon reflect a lack of curiosity, ignorance, or both? The problem is compounded by the limited or lack of access to treatment once the psychiatric comorbidity has been identified. This special issue tries to analyze the causes of this very serious problem that not only has serious implications in the comprehensive management of PWE but also raises serious questions on the lack of communication between neurologists and psychiatrists… truly a "bizarre phenomenon". This article is part of the Special Issue "Obstacles of Treatment of Psychiatric Comorbidities in Epilepsy".

Neurobiologic properties of mood disorders may have an impact on epilepsy: Should this motivate neurologists to screen for this psychiatric comorbidity in these patients?

Epilepsy and psychiatric comorbidities have a complex relation, which can be manifested by their relatively high comorbid occurrence and the existence of a bidirectional relation, whereby not only are people with epilepsy (PWE) at greater risk of developing psychiatric disorders, but patients with primary psychiatric disorders are at higher risk of developing epilepsy. The existence of common pathogenic mechanisms operant in primary psychiatric disorders and epilepsy has been postulated as one of the leading hypothesis to explain their close and very complex relation. The neurobiologic characteristics of mood disorders can be used as a model to test this hypothesis. In this manuscript, we highlight data that suggest how several neurobiologic aspects of mood disorders can facilitate the epileptogenic process in animal models and explain the increased risk of patients with primary mood disorders to develop epilepsy in general and treatment-resistant epilepsy in particular. It is our hope that the inclusion of these data in this Special Issue will motivate neurologists to screen common psychiatric comorbidities in PWE. This article is part of the Special Issue "Obstacles of Treatment of Psychiatric Comorbidities in Epilepsy".

Psychiatric complications after epilepsy surgery but where are the psychiatrists?

In patients with refractory epilepsy, there is a significant risk of postoperative psychiatric complications after epilepsy surgery. The main risk factors for this phenomenon include a lifetime or family history of psychiatric illness; these risk factors can be easily identified through a preoperative evaluation performed by a psychiatrist. Despite this, very few comprehensive epilepsy centers include a psychiatrist on the treatment team. Preoperative evaluations often fail to identify patients at risk of postoperative psychiatric complications, thus missing the opportunity to counsel and prophylactically treat patients at risk. In this article, we review the risk factors for the development of postoperative psychiatric complications and discuss the reasons why epilepsy centers continue to perform presurgical evaluations without psychiatrists. Additionally, we provide practical solutions for neurologists in the identification and management of postoperative psychiatric disorders. This article is part of the Special Issue "Obstacles of Treatment of Psychiatric Comorbidities in Epilepsy".

Psychiatric comorbidities go unrecognized in patients with epilepsy: "You see what you know".

Patients with epilepsy (PWE) have a significantly higher prevalence of psychiatric comorbid disorders involving depression, anxiety, psychotic, and attention-deficit disorders compared with the general population or patients with other chronic medical conditions. Currently, there is no systematic approach in the evaluation and management of psychiatric comorbidities in these patients. In addition, neurologists are not trained to recognize these disorders, and consequently, they remain undertreated. Despite the high prevalence of psychiatric comorbidities in patients evaluated for epilepsy surgery, most epilepsy centers in North America do not include a psychiatric evaluation as part of the presurgical work-up. Despite the intimate relationship between psychiatric comorbidities and epilepsy, collaboration between epileptologists and psychiatrists is sparse at best and nonexistent at worse. The purpose of this paper was to highlight and try to understand the causes behind the persistent lack in communication between neurologists and psychiatrists, the gap in the training of neurologists on psychiatric aspects of neurologic disorders and vice versa and to propose new initiatives to fix the problem. This article is part of the Special Issue "Obstacles of Treatment of Psychiatric Comorbidities in Epilepsy".

Epilepsy as a Network Disorder (2): What can we learn from other network disorders such as dementia and schizophrenia, and what are the implications for translational research?

There is common agreement that many disorders of the central nervous system are 'complex', that is, there are many potential factors that influence the development of the disease, underlying mechanisms, and successful treatment. Most of these disorders, unfortunately, have no cure at the present time, and therapeutic strategies often have debilitating side effects. Interestingly, some of the 'complexities' of one disorder are found in another, and the similarities are often network defects. It seems likely that more discussions of these commonalities could advance our understanding and, therefore, have clinical implications or translational impact. With this in mind, the Fourth International Halifax Epilepsy Conference and Retreat was held as described in the prior paper, and this companion paper focuses on the second half of the meeting. Leaders in various subspecialties of epilepsy research were asked to address aging and dementia or psychosis in people with epilepsy (PWE). Commonalities between autism, depression, aging and dementia, psychosis, and epilepsy were the focus of the presentations and discussion. In the last session, additional experts commented on new conceptualization of translational epilepsy research efforts. Here, the presentations are reviewed, and salient points are highlighted.

Concurrent mood and anxiety disorders are associated with pharmacoresistant seizures in patients with MTLE.

OBJECTIVE: To investigate whether mood disorders (MD) and anxiety disorders (AD) are associated with seizure control in patients with mesial temporal lobe epilepsy (MTLE). We compared patients without any current psychiatric disorder, patients with current MD and/or AD, patients with subsyndromic depression episodes (SSDE) and anxiety episodes (SSAE), and patients with family psychiatric history. METHODS: In a cross-sectional study, we included 144 consecutive patients with MTLE (82 pharmacoresistant and 62 treatment-responsive patients). Every patient underwent a psychiatric evaluation including the Structured Clinical Interview for DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) Axis I (SCID-I), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Neurological Disorders Depression Inventory for Epilepsy (NDDI-E), and Interictal Dysphoric Disorder Inventory (IDDI). Patients were divided into four groups: PsychNeg (G1, n = 61), current SSDE and SSAE (G2, n = 26), Current MD or AD (G3, n = 25), and current mixed MD/AD (G4, n = 32). RESULTS: Among patients with pharmacoresistant MTLE, 68.3% (56/82) experienced symptoms of depression and/or anxiety (G2, G3, and G4) (odds ratio [OR] 2.8, 95% confidence interval [CI] 1.41-5.53, p < 0.01). Patients with mixed MD/AD (G4, n = 24/32) were more likely to have pharmacoresistant MTLE (OR 4.04, 95% CI 1.57-10.42, p < 0.01) than psychiatric asymptomatic patients (G1, n = 26/61), and their seizure frequency was significantly higher (p < 0.01). Positive family psychiatric history was more frequent in pharmacoresistant patients (n = 27/82, OR 2.28, 95% CI 1.02-5.05, p = 0.04). Finally, 31.6% of patients with MD and or AD were not receiving psychiatric treatment. SIGNIFICANCE: Identification of comorbid MD/AD and of family psychiatric history is of the essence in patients with MTLE, as they appear to be associated with worse seizure control.

Laser thermal ablation for mesiotemporal epilepsy: Analysis of ablation volumes and trajectories.

OBJECTIVE: To identify features of ablations and trajectories that correlate with optimal seizure control and minimize the risk of neurocognitive deficits in patients undergoing laser interstitial thermal therapy (LiTT) for mesiotemporal epilepsy (mTLE). METHODS: Clinical and radiographic data were reviewed from a prospectively maintained database of all patients undergoing LiTT for the treatment of mTLE at the University of Miami Hospital. Standard preoperative and postoperative evaluations, including contrast-enhanced magnetic resonance imaging (MRI) and neuropsychological testing, were performed in all patients. Laser trajectory and ablation volumes were computed both by manual tracing of mesiotemporal structures and by nonrigid registration of ablation cavities to a common reference system based on 7T MRI data. RESULTS: Among 23 patients with at least 1-year follow-up, 15 (65%) were free of disabling seizures since the time of their surgery. Sparing of the mesial hippocampal head was significantly correlated with persistent disabling seizures (p = 0.01). A lateral trajectory through the hippocampus showed a trend for poor seizure outcome (p = 0.08). A comparison of baseline and postoperative neurocognitive testing revealed areas of both improvement and worsening, which were not associated with ablation volume or trajectory. SIGNIFICANCE: At 1-year follow-up, LiTT appears to be a safe and effective tool for the treatment of mTLE, although a longer follow-up period is necessary to confirm these observations. Better understanding of the impact of ablation volume and location could potentially fine-tune this technique to improve seizure-freedom rates and associated neurologic and cognitive changes.

Can Neurochemical Changes of Mood Disorders Explain the Increase Risk of Epilepsy or its Worse Seizure Control?

The existence of a bidirectional relation between mood disorders and epilepsy has been suggested by six population-based studies. Furthermore, three studies have associated a higher risk of treatment-resistant epilepsy with a history of depression preceding the onset of epilepsy. Common pathogenic mechanisms operant in depression and epilepsy may provide a possible explanation of these observations. This article reviews some of the leading pathogenic mechanisms of depression with respect to potential proconvulsant properties that may provide explanations for these phenomena.

The impact of antidepressants on seizure frequency and depressive and anxiety disorders of patients with epilepsy: Is it worth investigating?

PURPOSE: Depression and anxiety disorders in patients with epilepsy (PWE) remain under-recognized and under-treated, despite being the most common psychiatric co-morbidities. Selective serotonin re-uptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are considered first-line treatment for primary depression and anxiety disorders. We performed this study to investigate if SSRIs and SNRIs could affect the seizure frequency of PWE and to assess whether such effect is independent of the response of the mood and anxiety disorders to these drugs. METHODS: This was a retrospective study of 100 consecutive PWE who were started on an SSRI or SNRI for the treatment of a depressive and/or anxiety disorder. Every patient underwent a psychiatric evaluation by one of the investigators using a semi-structured interview who also managed the pharmacologic treatment in all the patients. Patients were excluded if they had a diagnosis of psychogenic non-epileptic seizures or if they had undergone epilepsy surgery or the implant of the vagal nerve stimulator six months before and after the start of the antidepressant therapy. The final analysis was conducted in 84 patients. For each type of seizure, an average and maximal monthly seizure frequency during the six months preceding and following the start of psychotropic drugs was extracted from the medical records. We identified the number of patients whose seizure frequency during treatment with antidepressants: (i) shifted from a <1/month to a ≥1 seizure/month and vice-versa, (ii) increased beyond maximal/monthly baseline frequency, and (iii) patients who developed de-novo generalized tonic-clonic (GTC) seizures. RESULTS: None of the patients with a baseline seizure frequency <1seizure/month went on to have ≥1seizure/month after initiating treatment with antidepressants, had an increase in frequency beyond baseline maximal counts or developed de-novo-GTC seizures. Furthermore, there was no seizure recurrence among patients that had been seizure-free. Among the patients with a baseline seizure frequency ≥1/month, 27.5% had a reduction in seizure frequency to <1/month, which suggested a positive effect of SSRI/SNRI on seizure frequency (p=0.001, McNemar test). Among the patients with a baseline seizure frequency ≥1seizure/month, 48% exhibited a >50% reduction in seizure frequency after the start of treatment with SSRIs or SNRIs. A therapeutic response to SSRIs and SNRIs was found in 73% of patients. The change in seizure frequency was independent of the improvement in psychiatric symptomatology. CONCLUSION: In this retrospective observational study, SSRIs or SNRIs did not appear to worsen seizure frequency. Also, in patients with frequent seizures, SSRIs and SNRIs may be associated with a possible decrease in seizure frequency. Furthermore, these drugs appear to yield good therapeutic response of psychiatric symptoms independently of seizure frequency. It is pivotal to replicate these data in prospective, double-blind, placebo-controlled trials.

Antiseizure, antidepressant, and antipsychotic medication prescribing in elderly nursing home residents.

OBJECTIVE: The incidence of epilepsy is highest in the elderly and the prevalence of epilepsy is higher in nursing home residents than in other cohorts. Co-medications that act in the central nervous system (CNS) are frequently prescribed in this population. The objective was to identify the most commonly prescribed antiseizure drugs (ASDs) and determine the frequency of use of antipsychotic and antidepressant medications in elderly nursing home residents receiving ASDs. METHODS: Data were obtained from a pharmacy database serving 18,752 patients in Minnesota and Wisconsin nursing homes. Prescribing information was available on ASD, antidepressant, and antipsychotic drugs on one day in October 2013. The frequency distribution by age, formulation, trademarked/generic drugs, route of administration, and multiple drug combinations were determined. RESULTS: Overall, 66.8% of 18,752 residents received at least one CNS-active drug as classified by the Generic Product Identifier classification system. For those 65years and older, ASDs were prescribed for 14.3% residents. Gabapentin comprised 7.3%; valproate 3.0%; levetiracetam 1.8%; and phenytoin 0.9%. An antidepressant was used in 64.2% of persons prescribed an ASD. Antidepressant use varied for specific ASDs and ranged from 50 to 75%. An antipsychotic medication was used in 30% of persons prescribed an ASD and ranged from 16.8 to 54.2% for specific ASDs. Both antidepressant and antipsychotic use occurred in 22.2% of persons prescribed an ASD, respectively. SIGNIFICANCE: The pattern of CNS-active drug use has changed from previous years in this geographic region. Use of phenytoin has declined markedly, but antidepressant use has increased substantially. The CNS side effect profile of these medications and the possible long-term consequences in this population can greatly complicate their therapy.