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OBJECTIVE: Depression is a relatively common comorbidity in people with epilepsy with a lifetime history identified in 1 in 4 individuals. In this paper, we aimed to provide a systematic review of structural and functional brain region-specific group differences of adults with epilepsy and depression and to discuss existing evidence as compared to that in people with depression. METHODS: We undertook a systematic review of neuroimaging studies of depression in adults with epilepsy through MEDLINE/PubMed, Embase and PsycInfo searches until June 2020. RESULTS: A total of 44 studies were included in the qualitative synthesis: 21 on structural neuroimaging, 9 on functional, and 14 on pharmaco/metabolic neuroimaging. Almost all studies focused on temporal lobe epilepsy (TLE). Patterns of changes in the hippocampi and subcortical structures seem to be different from those reported in depression outside epilepsy. Cortical changes are grossly similar as well as the lack of any laterality effect. Serotonin dysfunction seems to be due to different mechanisms with reduced synaptic availability for depression in epilepsy as compared to reduced 5HT1 receptor density outside epilepsy. Depressive symptoms seem to correlate with a dysfunction in temporolimbic structures contralateral to the epileptogenic zone especially in patients with de novo postsurgical depression. CONCLUSIONS: Depression, at least in TLE, seems to be associated with a different pattern of brain changes as compared to major depression, potentially supporting the notion of phenomenological peculiarities of depression in epilepsy.

Objective\ud We aimed to characterize the demographics of adults with dissociative (nonepileptic) seizures, placing emphasis on distribution of age at onset, male:female ratio, levels of deprivation, and dissociative seizure semiology.\ud \ud Methods\ud We collected demographic and clinical data from 698 adults with dissociative seizures recruited to the screening phase of the CODES (Cognitive Behavioural Therapy vs Standardised Medical Care for Adults With Dissociative Non‐Epileptic Seizures) trial from 27 neurology/specialist epilepsy clinics in the UK. We described the cohort in terms of age, age at onset of dissociative seizures, duration of seizure disorder, level of socioeconomic deprivation, and other social and clinical demographic characteristics and their associations.\ud \ud Results\ud In what is, to date, the largest study of adults with dissociative seizures, the overall modal age at dissociative seizure onset was 19 years; median age at onset was 28 years. Although 74% of the sample was female, importantly the male:female ratio varied with age at onset, with 77% of female but only 59% of male participants developing dissociative seizures by the age of 40 years. The frequency of self‐reported previous epilepsy was 27%; nearly half of these epilepsy diagnoses were retrospectively considered erroneous by clinicians. Patients with predominantly hyperkinetic dissociative seizures had a shorter disorder duration prior to diagnosis in this study than patients with hypokinetic seizures (P < .001); dissociative seizure type was not associated with gender. Predominantly hyperkinetic seizures were most commonly seen in patients with symptom onset in their late teens. Thirty percent of the sample reported taking antiepileptic drugs; this was more common in men. More than 50% of the sample lived in areas characterized by the highest levels of deprivation, and more than two‐thirds were unemployed.\ud \ud Significance\ud Females with dissociative seizures were more common at all ages, whereas the proportion of males increased with age at onset. This disorder was associated with socioeconomic deprivation. Those with hypokinetic dissociative seizures may be at risk for delayed diagnosis and treatment.

This is a case series of 25 patients with drug-resistant epilepsy and psychiatric comorbidities started on Brivaracetam (BRV) at St George’s University Hospitals and Frimley Health in London. Median BRV dose was 125 mg for a median follow period of 8 months. Nineteen had focal epilepsy, four had generalized epilepsies and one had unclassified epilepsy; 76% had mood disorders (either depression or bipolar disorder), 12% intellectual disabilities with autism spectrum disorder and challenging behavior and 12% psychoses. 40% of patients presented at least 50% seizure reduction but none of them became seizure free. A total of 44% patients discontinued BRV, 20% because of adverse events, 20% because of inefficacy and 4% because of both. Depression was reported by 8%, aggressive behavior by 8% while 4% reported both. A total of 91.6% had received Levetiracetam (LEV) before, in whom LEV was discontinued because of psychiatric adverse events (PAEs) in half. 77% of patients who developed PAEs with LEV didn’t do so on BRV suggesting that BRV is better tolerated than LEV in complex patients with psychiatric comorbidities and that the SV2A protein modulation is unlikely to be implicated in LEV-related PAEs.

BACKGROUND: Sexual dysfunction is very common in patients with epilepsy. OBJECTIVE: We sought to review the published literature around sexual dysfunction in epilepsy, and particularly the role played by anti-convulsant drugs. METHOD: We searched all related articles on PubMed using the search terms sexual dysfunction, various AEDs and epilepsy, and restricted the search to English language articles. RESULTS: The most common manifestations of sexual dysfunction in patients with epilepsy are hyposexuality and erectile dysfunction. The cause of this dysfunction is multifactorial and overlapping, and includes changes in the levels of sex hormones, anti-convulsants, the epilepsy itself and psychosocial factors. Traditional anti-convulsants which induce the cytochrome P450 enzyme system have the highest rates of sexual dysfunction, which is primarily mediated by changes in sex hormone levels. Sexual dysfunction associated with newer anti-convulsants is likely to occur through different mechanisms. Some anti-convulsants such as oxcarbazepine and lamotrigine may improve sexual function, but can also rarely be associated with sexual dysfunction. CONCLUSION: Management of sexual dysfunction thought to be caused by anti-convulsants should include the cessation of the offending drug, and consideration of switching to alternative anti-convulsants that have been reported to improve sexual function such as oxcarbazepine, and lamotrigine.

Background and purpose\ud \ud People with epilepsy are at increased risk of accidents and injuries but, despite several studies on this subject, data regarding preventable causes are still contradictory. The aim of this study was to investigate the relationship between injuries, side effects of antiepileptic drugs (AEDs) and depression.\ud Methods\ud \ud Data from a consecutive sample of adult patients with epilepsy attending the outpatient clinics at St George's University Hospital in London were included. All patients were asked if they had had any injury since the last clinic appointment and completed the Liverpool Adverse Event Profile (LAEP) and Neurological Disorders Depression Inventory for Epilepsy.\ud Results\ud \ud Among 407 patients (243 females, mean age 43.1 years), 71 (17.4%) reported injuries since the last appointment. A two-step cluster analysis revealed two clusters with the major cluster (53.5% of the injured group) showing a total score for LAEP ≥45, a positive Neurological Disorders Depression Inventory for Epilepsy screening and presence of AED polytherapy. A total score for LAEP ≥45 was the most important predictor.\ud Conclusions\ud \ud Antiepileptic drug treatment should be reviewed in patients reporting injuries in order to evaluate the potential contribution and burden of AED side effects.

Purpose\ud \ud To examine the prevalence and clinical correlates of fatigue as an adverse event (AE) of antiepileptic drug (AED) treatment in patients with epilepsy.\ud Methods\ud \ud Data from 443 adult outpatients with epilepsy assessed with the Adverse Event Profile (AEP) and the Neurological Disorder Depression Inventory for Epilepsy (NDDIE) were analysed.\ud Results\ud \ud Fatigue is reported by 36.6% of patients as always a problem during AED treatment. Fatigue is more likely to be reported by females (64.8% vs. 35.2%; Chi-Square = 16.762; df = 3; p = 0.001) and during treatment with levetiracetam (42.3% vs. 33.2%; Chi-Square = 11.462; df = 3; p = 0.009). The associations with the female gender and levetiracetam treatment were not mediated by depression, as identified with the NDDIE, and could not be simply explained by the large number of subjects on levetiracetam treatment, as analogous figures resulted from the analysis of a monotherapy subsample (41.7% vs. 30.3%; Chi-Square = 11.547; df = 3; p = 0.009).\ud Conclusions\ud \ud One third of patients with epilepsy reports fatigue as a significant problem during AED treatment. Fatigue is more likely to be reported by females and seems to be specifically associated with LEV treatment. However, fatigue is not mediated by a negative effect of LEV on mood.

Benzodiazepines represent the first-line treatment for the acute management of epileptic seizures and status epilepticus. The emergency use of benzodiazepines must be timely, and because most seizures occur outside of the hospital environment, there is a significant need for delivery methods that are easy for nonclinical caregivers to use and administer quickly and safely. In addition, the ideal route of administration should be reliable in terms of absorption. Rectal diazepam is the only licensed formulation in the USA, whereas rectal diazepam and buccal midazolam are currently licensed in the EU. However, the sometimes unpredictable absorption with rectal and buccal administration means they are not ideal routes. Several alternative routes are currently being explored. This is a narrative review of data about delivery methods for benzodiazepines alternative to the intravenous and oral routes for the acute treatment of seizures. Unconventional delivery options such as direct delivery to the central nervous system or inhalers are reported. Data show that intranasal diazepam or midazolam and the intramuscular auto-injector for midazolam are as effective as rectal or intravenous diazepam. Head-to-head comparisons with buccal midazolam are urgently needed. In addition, the majority of trials focused on children and adolescents, and further trials in adults are warranted.

OBJECTIVES: To investigate clinical correlates of memory complaints (MC) during anti-epileptic drug (AEDs) treatment in adults with epilepsy with special attention to the role of depression, using user-friendly standardized clinical instruments which can be adopted in any outpatient setting. MATERIALS & METHODS: Data from a consecutive sample of adult outpatients with epilepsy assessed with the Neurological Disorder Depression Inventory for Epilepsy (NDDIE), the Adverse Event Profile (AEP) and the Emotional Thermometer (ET) were analysed. RESULTS: From a total sample of 443 patients, 28.4% reported MC as 'always' a problem. These patients were less likely to be seizure free (18.3% vs 34.3%; P < 0.001), had a high number of previous AED trials (4 vs 3; P < 0.001) and high AEP total scores (49 vs 34.2; P < 0.001). There was no correlation with specific AED type or combination. Depression was the major determinant with a 2-fold increased risk (95%CI 1.15-3.86; P = 0.016). When depression was already known and under treatment, patients with MC were less likely to be in remission from depression despite antidepressant treatment (11.9% vs 1.6% P < 0.001). Among patients without depression, those reporting MC presented with significantly high scores for depression (3.3 vs 2; t = 3.07; P = 0.003), anxiety (4.5 vs 2.7; t = 4.43; P < 0.001), anger (3 vs 2; t = 2.623; P = 0.009) and distress (3.8 vs 2.2; t = 4.027; P < 0.001) than those without MC. CONCLUSIONS: Depression has to be appropriately treated and full remission from depression should represent the ultimate goal as subthreshold or residual mood and anxiety symptoms can contribute to MC.

Purpose: A number of studies have suggested that depressed mood is one of the most important predictors of quality of life (QoL) in patients with epilepsy. However, QoL measure used in previous studies was limited to the Quality Of Life in Epilepsy (QOLIE) scales. It could be questioned whether correlation of QOLIE with measures of depression is influenced by the properties of the instruments used rather than being a valid effect. By using visual analogue scales, the current study aims to clarify whether depression and QoL are truly correlated in patients with epilepsy. \ud Methods: Data from a sample of 261 outpatients with epilepsy attending the Epilepsy Clinics of the Atkinson Morley Outpatient Department, St George’s Hospital in London, have been analysed. Patients were screened using the European Quality of Life scale (EQ-5D-3L) which includes an overall visual analogue score (EQ-VAS), the Emotional Thermometer (ET7), Beck Depression Inventory-II (BDI-II), the Hospital Anxiety and Depression Scale (HADS), and the Major Depression Inventory (MDI). \ud Results: Depression was found to significantly correlate with EQ-VAS score with r coefficient ranging from 0.42 to 0.51 and r2 coefficients ranging between 0.18 and 0.26. In addition, we identified patients who were depressed according to DSM-IV criteria (MD) and those with atypical forms of depression (AD). EQ-5D-3L scores in these subjects as compared to those without depression (ND) showed a different impact of AD and MD on QoL. \ud Conclusions: The relationship between depression and quality of life in people with epilepsy has been demonstrated to be a robust and valid effect, not a result of potential bias of the specific measures used. However, the strength of the association is influenced by the individual instrument. Atypical or subsyndromic forms of depression are as relevant as DSM-based depression in terms of impact on QoL.

INTRODUCTION: Drugs marketed during the last few years (i.e. Lacosamide, Ruifinamide, Eslicarbazepine acetate, Brivaracetam and Perampanel) are increasingly regarded as third generation AEDs. This paper presents available data about monotherapy with third generation drugs and on-going clinical trials with special attention to the existing debate about monotherapy license in epilepsy. AREAS COVERED: References were identified by searches of Medline/PubMed. In addition, currently active studies for these AEDs were identified in the ClinicalTrials.gov database. Expert commentary: Results of studies on Eslicarbazepine acetate and Lacosamide clearly suggest good efficacy and tolerability. The selective pharmacological profile, the lack of interactions, the good tolerability with low propensity for cognitive side effects and the availability of different pharmacological formulations represent evident advantages. Although third generation monotherapies are quite promising, long-term safety data is needed in order to understand how these compounds will place in the current armamentarium.

Anxiety disorders are frequent, though probably underdiagnosed, comorbidities in epilepsy. Epilepsy and anxiety may share common neurobiological correlates as shown in animal models and suggested by studies demonstrating anxiety disorders before the manifestation of epilepsy. Comorbid anxiety disorders have a major impact on the affected patients' quality of life and may increase the risk for suicidality. Successful treatment of the epilepsy may alleviate anxiety symptoms. Treatment of anxiety is based on selective serotonin reuptake inhibitors, benzodiazepines (although only as second-line choices), and psychotherapy. Specific AEDs (especially pregabalin) have been shown to have anxiolytic properties. This paper is aimed at reviewing anxiety disorders in patients with epilepsy discussing current scientific evidence about pathophysiology, clinical aspects, and treatment strategies.

PURPOSE: Interpersonal relationships are viewed as important contexts within which psychopathology emerges and persists or desists. Attachment theory describes the dynamics of long-term relationships between humans especially in families and lifelong friendships. The present study was aimed at investigating attachment styles in adult patients with epilepsy as compared to subjects with migraine and their potential correlates with a history of mood disorders. METHODS: A consecutive sample of 219 adult outpatients with epilepsy (117) or migraine (102) was assessed with the Attachment Style Questionnaire (ASQ). RESULTS: Patients with epilepsy and a lifetime history of mood disorders presented elevated scores for Need for approval (p