Treatment of Comorbid Anxiety and Epilepsy.

Objective: Anxiety is among the most common psychiatric illnesses, and it commonly co-occurs with epilepsy. This review of the existing literature on anxiety comorbid with epilepsy aims to generate new insights into strategies for assessment and treatment. Methods: The authors conducted a narrative literature review to select key publications that help clarify the phenomenology and management of comorbid anxiety and epilepsy. Results: Anxiety symptoms may be relevant even if the criteria for a diagnosis of an anxiety disorder are not met. Associating specific seizure types or seizure localization with anxiety symptoms remains difficult; however, the amygdala is a brain region commonly associated with seizure foci and panic or fear sensations. The hypothalamic-pituitary-adrenal axis may also be relevant for anxiety symptoms, particularly for the selection of treatments. Nonpharmacological treatment is appropriate for anxiety comorbid with epilepsy, particularly because relaxation techniques may reduce hypersympathetic states, which improve symptoms. Medication options include antidepressants and anticonvulsants that may have efficacy for anxiety symptoms. Benzodiazepines are a good choice to address this comorbid condition, although side effects may limit utility. Conclusions: Ultimately, there are numerous treatment options, and although there is a limited evidence base, quality of life may be improved with appropriate treatment for individuals experiencing comorbid anxiety and epilepsy.

Cross-sectional and longitudinal evaluation of cannabidiol (CBD) product use and health among people with epilepsy.

Recent approval of Epidiolex® (pharmaceutical cannabidiol/CBD) for the treatment of Lennox Gastaut syndrome (LGS) and Dravet syndrome highlights a therapeutic efficacy of CBD in the treatment of epilepsy. However, a large number of patients with epilepsy elect to use alternative artisanal CBD products due to cost or access constraints. Despite widespread availability and variety of these artisanal CBD products, studies evaluating their safety or efficacy are rare, making conclusions about clinical utility uncertain. The purpose of the present study was to evaluate cross-sectional and longitudinal associations of artisanal CBD product use with quality of life, mental health, healthcare utilization, and epilepsy-specific outcomes within a large, observational cohort of people with epilepsy. Participants who reported using artisanal CBD products at baseline (Artisanal CBD Users; n = 280) and participants who used no cannabis-based products (Controls; n = 138) completed web-based assessments evaluating psychiatric symptoms, healthcare utilization, and epilepsy-specific factors. Follow-up surveys were collected in a subset of participants (n = 190) following baseline assessment for longitudinal comparison. Cross-sectionally, higher quality of life, lower psychiatric symptom severity, and improved sleep were observed among Artisanal CBD Users at baseline compared with Controls. Initiation of artisanal CBD product use was also related to improved health outcomes longitudinally. No group differences were observed for seizure control, but both groups included a high number of individuals with no past month seizures. Artisanal CBD Users reported significantly better epilepsy medication tolerability, use of fewer prescription medications overall, and reduced healthcare utilization compared with Controls. These findings are consistent with research indicating that practitioners recommending CBD in clinical care for epilepsy report integrating the use of CBD both as a means to improve patient quality of life as well as for seizure control.

Common psychiatric comorbidities in epilepsy: How big of a problem is it?

Psychiatric illness and epilepsy commonly co-occur in adults and in children and adolescents. Theories of comorbidity are complex, but recurring associations between the conditions suggest overlap that is more than simple co-occurrence. Common underlying pathophysiology may imply that epilepsy itself may constituently include psychiatric symptoms. Conditions such as depression or cognitive difficulties commonly occur and in some cases, are considered to be associated with specific epilepsy characteristics such as localization or seizure type. Regardless of etiologic attributions to psychiatric comorbidity, it is clear today that treatment for epilepsy needs to target psychiatric illness. In many cases, quality-of-life improvements depend more upon addressing psychiatric symptoms than seizures themselves. This article is part of the Special Issue "Obstacles of Treatment of Psychiatric Comorbidities in Epilepsy".

Should adult neurologists play a role in the management of the most common psychiatric comorbidities? Practical considerations.

Despite the high prevalence and negative impact of psychiatric comorbidities on the life of adults with epilepsy, significant unmet mental health care need exists because of a variety of factors, including poor access to mental health care providers. A potential solution to address access barriers is neurologist-driven diagnosis and management of common psychiatric conditions in epilepsy, of which mood and anxiety disorders are the most common. In this manuscript, patient selection criteria and practical treatment strategies are outlined for common mood and anxiety disorders that can be safely managed by neurologists. This article is part of the Special Issue "Obstacles of Treatment of Psychiatric Comorbidities in Epilepsy".

Key issues in addressing the comorbidity of depression and pediatric epilepsy.

Depression is a common comorbidity associated with epilepsy. However, the etiology of depression is difficult to establish given the heterogeneity in both epilepsy and depression. Nevertheless, the co-occurrence is so common that a bidirectional relationship between depression and epilepsy has been theorized. Persons with temporal lobe seizure foci and partial-onset epilepsy may be more vulnerable to the development of depression. In pediatrics, depression differs but may be readily identified by understanding nuances of mood states and variability of neurovegetative symptom presentation. Although no clear treatment guidance exists in the context of epilepsy, antidepressants have been relatively well studied in pediatrics and are effective and well tolerated. Anticonvulsant drugs may also improve depressive symptoms though clinical research is lacking in pediatrics. Treatment of depression may independently improve outcome for epilepsy and for quality of life. Future studies will clarify etiologies of depression in the context of epilepsy and improve the evidence base for treatment outcomes.

Key issues in addressing the comorbidity of attention deficit hyperactivity disorder and pediatric epilepsy.

Attention deficit hyperactivity disorder (ADHD) is a common comorbidity of epilepsy encountered by clinicians. However, relatively little information is available to guide optimal diagnostic and treatment strategies. Differentiating ADHD from effects of epilepsy requires careful history taking and emphasis upon characteristic symptoms and course of illness. Rating scales for ADHD are well validated and may aid clinical management. Use of antiepileptic drugs may cause cognitive or behavioral side effects yet may improve behavior in some cases. Historically, clinicians have been hesitant to treat ADHD comorbidity for fear of lowering the seizure threshold. However, an aggregate of recent evidence now suggests that stimulants may be well tolerated and effective for ADHD comorbid with epilepsy. Studies that further clarify pathophysiology and treatment outcomes are needed in order to enhance clinical efficacy and quality of life for this population.

Psychopharmacology Management in Autism Spectrum Disorder.

Persons with autism spectrum disorder (ASD) may have other psychiatric conditions that warrant treatment. Symptoms may not be easy to discern from rigidity or irritability that are sometimes considered to be constituent parts of ASD. Pathophysiology that involves hyperexcitable neurons and anomalous connectivity may provide justification for using psychopharmacologic agents, although nonmedical strategies may also be effective. Hyperactivity, irritability, and tantrums with or without aggression may be rational targets for psychopharmacological intervention. The best-studied drug class to date has been the second-generation antipsychotics targeting irritability.

Navigating Neurogenetics for Child and Adolescent Psychiatry Practice.

Neurodevelopmental disorders (NDDs) are a group of conditions characterized by impairments of brain processes that impact cognition, communication, motor abilities, and/or behavior during development. These conditions typically have significant effects across the life span and impact personal, social, academic, or occupational functioning. The US Centers for Disease Control and report that 1 in 6 children has a developmental disability, making it highly likely for child and adolescent psychiatrists to encounter children with NDDs in daily practice.1 While the etiologies of NDDs are broad, genetic syndromes are a common cause of NDDs. The diagnostic yield of thorough genetic testing for NDDs as a group is about 40% based on meta-analysis, including 30% to 50% yield in patients with global developmental delay (GDD) or intellectual disability (ID) and 15% to 20% yield in patients with in autism spectrum disorder.1-3 The findings are extremely heterogeneous, including chromosomal copy number variants (CNVs) and more than 2,000 known monogenic disorders associated with NDDs.3 Diagnostic yields will increase over time with advances in technology and disease gene discovery.3.

Guidelines for Specialized Epilepsy Centers: Executive Summary of the Report of the National Association of Epilepsy Centers Guideline Panel.

The National Association of Epilepsy Centers first published the guidelines for epilepsy centers in 1990, which were last updated in 2010. Since that update, epilepsy care and the science of guideline development have advanced significantly, including the importance of incorporating a diversity of stakeholder perspectives such as those of patients and their caregivers. Currently, despite extensive published data examining the efficacy of treatments and diagnostic testing for epilepsy, there remain significant gaps in data identifying the essential services needed for a comprehensive epilepsy center and the optimal manner for their delivery. The trustworthy consensus-based statements (TCBS) process produces unbiased, scientifically valid guidelines through a transparent process that incorporates available evidence and expert opinion. A systematic literature search returned 5937 relevant studies from which 197 articles were retained for data extraction. A panel of 41 stakeholders with diverse expertise evaluated this evidence and drafted recommendations following the TCBS process. The panel reached consensus on 52 recommendations covering services provided by specialized epilepsy centers in both the inpatient and outpatient settings in major topic areas including epilepsy monitoring unit care, surgery, neuroimaging, neuropsychology, genetics, and outpatient care. Recommendations were informed by the evidence review and reflect the consensus of a broad panel of expert opinions.

Psychiatric symptoms in children prior to epilepsy surgery differ according to suspected seizure focus.

PURPOSE: Children and adolescents with epilepsy have an overrepresentation of psychiatric illness. However, few studies in pediatrics have characterized specific psychiatric conditions associated with seizure localization. In addition, degree to which psychiatric illness may be more prominent in children refractory to standard medical treatment for epilepsy is not known. The aim of this study was to assess psychiatric symptoms in children with medically refractory epilepsy and ascertain whether symptoms were associated with specific localization. METHODS: Case records were reviewed for 40 children with medically refractory epilepsy at the time of their referral for presurgical evaluation. Patients received a clinical psychiatric evaluation and parents completed the Child Behavioral Checklist (CBCL). Seizure localization was verified by pediatric epileptologists, and suitability for surgical procedures was verified by neurosurgical specialists. Groups were compared based on localization of seizure foci, either in the temporal lobe or predominantly extratemporal. KEY FINDINGS: The majority of the sample had psychiatric diagnoses and behavior problems, well beyond the level reported in chronic epilepsy populations. In addition, children with temporal lobe seizure foci had more CBCL behavioral problem categories rated in the clinically significant range, and also were more likely to have clinical diagnoses of depression. SIGNIFICANCE: Routine psychiatric evaluation prior to epilepsy surgery may be important for pediatric patients with medically refractory epilepsy. Psychiatric illness, particularly depression, may be especially prominent for those with temporal lobe seizure foci.

Stress, seizures, and hypothalamic-pituitary-adrenal axis targets for the treatment of epilepsy.

Epilepsy is a heterogeneous condition with varying etiologies including genetics, infection, trauma, vascular, neoplasms, and toxic exposures. The overlap of psychiatric comorbidity adds to the challenge of optimal treatment for people with epilepsy. Seizure episodes themselves may have varying triggers; however, for decades, stress has been commonly and consistently suspected to be a trigger for seizure events. This paper explores the relationship between stress and seizures and reviews clinical data as well as animal studies that increasingly corroborate the impact of stress hormones on neuronal excitability and seizure susceptibility. The basis for enthusiasm for targeting glucocorticoid receptors for the treatment of epilepsy and the mixed results of such treatment efforts are reviewed. In addition, this paper will highlight recent findings identifying a regulatory pathway controlling the body's physiological response to stress which represents a novel therapeutic target for modulation of the hypothalamic-pituitary-adrenal (HPA) axis. Thus, the HPA axis may have important clinical implications for seizure control and imply use of anticonvulsants that influence this neuronal pathway.

Healthcare utilisation in the United Arab Emirates for children with attention-deficit hyperactivity disorder and comorbidities.

The prevalence of attention-deficit hyperactivity disorder is consistent worldwide. Psychiatric comorbidities are common, although less is known about how those comorbidities affect utilisation of healthcare services. Access to paediatric mental healthcare is a challenge in many regions. However, access to care in the United Arab Emirates (UAE) is supported by a well-established healthcare infrastructure with widely available primary care physicians. A review of diagnosis codes suggests that a clear correlation exists between the number of comorbidities and increased utilisation of available mental health services. Infrastructure in the UAE may represent a successful model for paediatric mental healthcare.

Cannabidiol Treatment for Neurological, Cognitive, and Psychiatric Symptoms in Sturge-Weber Syndrome.

BACKGROUND: A prior drug trial of cannabidiol for treatment-resistant epilepsy in patients with Sturge-Weber syndrome (SWS), a rare neurovascular condition, implicated improvements in neurological, quality of life (QOL), neuropsychologic, psychiatric, and motor outcomes. METHODS: Ten subjects with SWS brain involvement, controlled seizures, and cognitive impairments received study drug in this Johns Hopkins institutional review board-approved, open-label, prospective drug trial. Oral cannabidiol was taken for six months (dose ranged from 5 to 20 mg/kg/day). SWS neuroscore, port-wine birthmark score, QOL, and adverse events were recorded every four to 12 weeks. Neuropsychologic, psychiatric, and motor assessments were administered at baseline and six months' follow-up. Most evaluations were conducted virtually due to the coronavirus disease 2019 pandemic. RESULTS: Cannabidiol was generally well tolerated. Six subjects reported mild to moderate side effects related to study drug and continued on drug; one subject withdrew early due to moderate side effects. No seizures were reported. Significant improvements in SWS neuroscore, patient-reported QOL, anxiety and emotional regulation, and report of bimanual ability use were noted. Migraine QOL scores were high at baseline in these subjects, and remained high. Neuropsychologic and other QOL and motor outcomes remained stable, with some within-subject improvements noted. CONCLUSIONS: Further studies are needed to determine whether Epidiolex can improve quality of life and be beneficial for neurological, anxiety, and motor impairments in SWS independent of seizure control. Large multicentered studies are needed to extend these preliminary findings.

Hypothalamic-pituitary-adrenal axis targets for the treatment of epilepsy.

Stress is a common seizure trigger in persons with epilepsy. The body's physiological response to stress is mediated by the hypothalamic-pituitary-adrenal (HPA) axis and involves a hormonal cascade that includes corticotropin releasing hormone (CRH), adrenocorticotropin releasing hormone (ACTH) and the release of cortisol (in humans and primates) or corticosterone (in rodents). The prolonged exposure to stress hormones may not only exacerbate pre-existing medical conditions including epilepsy, but may also increase the predisposition to psychiatric comorbidities. Hyperactivity of the HPA axis negatively impacts the structure and function of the temporal lobe of the brain, a region that is heavily involved in epilepsy and mood disorders like anxiety and depression. Seizures themselves damage temporal lobe structures, further disinhibiting the HPA axis, setting off a vicious cycle of neuronal damage and increasing susceptibility for subsequent seizures and psychiatric comorbidity. Treatments targeting the HPA axis may be beneficial both for epilepsy and for associated stress-related comorbidities such as anxiety or depression. This paper will highlight the evidence demonstrating dysfunction in the HPA axis associated with epilepsy which may contribute to the comorbidity of psychiatric disorders and epilepsy, and propose treatment strategies that may dually improve seizure control as well as alleviate stress related psychiatric comorbidities.

Pediatric psychogenic nonepileptic seizures: a study of assessment tools.

The goal of this study was to identify assessment tools and associated behavioral domains that differentiate children with psychogenic nonepileptic seizures (PNES) from those with epilepsy. A sample of 24 children with PNES (mean age 14.0 years, 14 female), 24 children with epilepsy (mean age 13.6 years, 13 female), and their parents were recruited from five epilepsy centers in the United States. Participants completed a battery of behavioral questionnaires including somatization, anxiety, and functional disability symptoms. Children with PNES had significantly higher scores on the Childhood Somatization and Functional Disability Inventories, and their parents reported more somatic problems on the Child Behavior Checklist (CBCL). Depression, anxiety, and alexithymia instruments did not differentiate the groups. Measures of somatization and functional disability may be promising tools for differentiating the behavioral profile of PNES from that of epilepsy. Increased somatic awareness and perceived disability emphasize the similarity of PNES to other pediatric somatoform disorders.

The intersections of stress, anxiety and epilepsy.

Stress is ubiquitous in chronic medical conditions; however, the connections to psychiatric and neurologic conditions are not always clearly established. Epilepsy is a unique illness that is intimately intertwined with stress and anxiety not only as a result of the disease process but also as a cause of disease exacerbation. Anxiety and depression also involve stress management and often overlap with epilepsy. Anxiety symptoms themselves may be present as intrinsic aspects of seizure phenomena, either during the events or closely related to them. The pathways of stress and anxiety involve the hypothalamic pituitary adrenal (HPA) axis and explain at least in part how stress may lead to worsening seizure control. Ultimately, the study of stress, anxiety, and epilepsy offers insight into mind and body connections, and furthers understanding of neuropsychiatric illness.