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The Psychiatric Pediatric Issues Task Force of the International League Against Epilepsy (ILAE) aimed to develop recommendations for the diagnosis and treatment of anxiety and depression in children and adolescents with epilepsy. The Task Force conducted a systematic review and identified two studies that assessed the accuracy of four screening measures for depression and anxiety symptoms compared with a psychiatric interview. Nine studies met the eligibility criteria for treatment of anxiety and depressive disorders or symptoms. The risk of bias and certainty of evidence were assessed. The evidence generated by this review followed by consensus where evidence was missing generated 47 recommendations. Those with a high level of agreement (≥80%) are summarized. Diagnosis: (1) Universal screening for anxiety and depression is recommended. Closer surveillance is recommended for children after 12 years, at higher risk (e.g., suicide-related behavior), with subthreshold symptoms, and experiencing seizure worsening or therapeutic modifications. (2) Multiple sources of ascertainment and a formal screening are recommended. Clinical interviews are recommended whenever possible. The healthcare provider must always explain that symptom recognition is essential to optimize treatment outcomes and reduce morbidity. (3) Questioning about the relationship between symptoms of anxiety or depression with seizure worsening/control and behavioral adverse effects of antiseizure medications is recommended. Treatment: (1) An individualized treatment plan is recommended. (2) For mild depression, active monitoring must be considered. (3) Referral to a mental health care provider must be considered for moderate to severe depression and anxiety. (4) Clinical care pathways must be developed. (5) Psychosocial interventions must be tailored and age-appropriate. (6) Healthcare providers must monitor children with epilepsy who are prescribed antidepressants, considering symptoms and functioning that may not improve simultaneously. (7) Caregiver education is essential to ensure treatment adherence. (8) A shared-care model involving all healthcare providers is recommended for children and adolescents with epilepsy and mental health disorders. We identified clinical decisions in the management of depression and anxiety that lack solid evidence and provide consensus-based guidance to address the care of children and adolescents with epilepsy., (© 2024 International League Against Epilepsy.)

Objective: To investigate changes in depressive and suicidality status and their relationship with seizure outcomes after the addition or substitution of another antiseizure medication (ASM) in adults with drug-resistant focal epilepsy., Methods: Seven hundred seventy consecutively enrolled patients were assessed and followed prospectively for seizure outcome and depressive status over a 6-month period after starting treatment with a newly introduced ASM. The Neurological Disorders Depression Inventory for Epilepsy (NDDIE) was used to screen for depression and suicidality. Correlations of NDDIE results with clinical and treatment-related variables were assessed by using a stepwise logistic regression model., Results: At baseline, 50% of patients had a positive screening test result for depression and 13% had a positive screening test result for suicidal ideation. A psychiatric comorbidity at baseline was associated with a 2.3 times increased risk of an initially negative NDDIE screening result becoming positive at re-assessment after 6 months. In addition, the number of ASMs taken at baseline correlated with an increased risk of a change in depression screening test results from negative to positive during follow-up, whereas no association was identified with sociodemographic and epilepsy-related variables, including seizure outcomes. Approximately 6% of patients who were initially negative at screening for suicidal ideation became positive at the 6-month re-assessment. The risk of switch from a negative to a positive screening test result for suicidal ideation was increased more than two-fold in individuals who screened positive for depression at baseline, and was unrelated to the type of ASM introduced, sociodemographic variables, or seizure outcomes., Significance: Almost 1 in 5 adults with drug-resistant focal epilepsy who screen negative for depression become positive when re-assessed 6 months after a treatment change. At re-assessment 6 months later, 6.1% who screen initially negative for passive suicidal ideation become positive. These changes in screening status are independent of type of ASM introduced or seizure outcomes but correlate with psychiatric status at baseline., (© 2023 International League Against Epilepsy.)

Limited guidance exists regarding the assessment and management of psychogenic non-epileptic seizures (PNES) in children. Our aim was to develop consensus-based recommendations to fill this gap. The members of the International League Against Epilepsy (ILAE) Task Force on Pediatric Psychiatric Issues conducted a scoping review adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-SR) standards. This was supplemented with a Delphi process sent to pediatric PNES experts. Consensus was defined as ≥80% agreement. The systematic search identified 77 studies, the majority (55%) of which were retrospective (only one randomized clinical trial). The primary means of PNES identification was video electroencephalography (vEEG) in 84% of studies. Better outcome was associated with access to counseling/psychological intervention. Children with PNES have more frequent psychiatric disorders than controls. The Delphi resulted in 22 recommendations: Assessment-There was consensus on the importance of (1) taking a comprehensive developmental history; (2) obtaining a description of the events; (3) asking about potential stressors; (4) the need to use vEEG if available parent, self, and school reports and video recordings can contribute to a "probable" diagnosis; and (5) that invasive provocation techniques or deceit should not be employed. Management-There was consensus about the (1) need for a professional with expertise in epilepsy to remain involved for a period after PNES diagnosis; (2) provision of appropriate educational materials to the child and caregivers; and (3) that the decision on treatment modality for PNES in children should consider the child's age, cognitive ability, and family factors. Comorbidities-There was consensus that all children with PNES should be screened for mental health and neurodevelopmental difficulties. Recommendations to facilitate the assessment and management of PNES in children were developed. Future directions to fill knowledge gaps were proposed., (© 2023 International League Against 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., (© 2021 International League Against Epilepsy.)

Objective: Dissociative traits represent a disturbance in selfhood that may predispose to, and trigger, functional seizures (FSs). The predictive representation and control of the internal physiological state of the body (interoception) are proposed to underpin the integrity of the sense of self ("minimal selfhood"). Therefore, discrepancies between objective and subjective aspects of interoception may relate to symptom expression in patients with FSs. Here, we tested whether individual differences in trait measures of interoception relate to dissociative symptoms, and whether state interoceptive deficits predict FS occurrence., Methods: Forty-one participants with FSs and 30 controls completed questionnaire ratings of dissociation, and measures of (1) interoceptive accuracy (IA)-objective performance on heartbeat detection tasks; (2) trait interoceptive sensibility-subjective sensitivity to internal sensations (using the Porges Body Perception Questionnaire); and (3) state interoceptive sensibility-subjective trial-by-trial measures of confidence in heartbeat detection. Interoceptive trait prediction error (ITPE) was calculated from the discrepancy between IA and trait sensibility, and interoceptive state prediction error (ISPE) from the discrepancy between IA and state sensibility., Results: Patients with FSs had significantly lower IA and greater trait interoceptive sensibility than healthy controls. ITPE was the strongest predictor of dissociation after controlling for trait anxiety and depression in a regression model. ISPE correlated significantly with FS frequency after controlling for state anxiety., Significance: Patients with FSs have disturbances in interoceptive processing that predict both dissociative traits reflecting the disrupted integrity of self-representation, and the expression of FSs. These findings provide insight into the pathophysiology of functional neurological disorder, and could lead to novel diagnostic and therapeutic approaches., (© 2020 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objective: Although many studies have attempted to describe treatment outcomes in patients with drug-resistant epilepsy, results are often limited by the adoption of nonhomogeneous criteria and different definitions of seizure freedom. We sought to evaluate treatment outcomes with a newly administered antiepileptic drug (AED) in a large population of adults with drug-resistant focal epilepsy according to the International League Against Epilepsy (ILAE) outcome criteria., Methods: This is a multicenter, observational, prospective study of 1053 patients with focal epilepsy diagnosed as drug-resistant by the investigators. Patients were assessed at baseline and 6, 12, and 18 months, for up to a maximum of 34 months after introducing another AED into their treatment regimen. Drug resistance status and treatment outcomes were rated according to ILAE criteria by the investigators and by at least two independent members of an external expert panel (EP)., Results: A seizure-free outcome after a newly administered AED according to ILAE criteria ranged from 11.8% after two failed drugs to 2.6% for more than six failures. Significantly fewer patients were rated by the EP as having a "treatment failure" as compared to the judgment of the investigator (46.7% vs 62.9%, P < 0.001), because many more patients were rated as "undetermined outcome" (45.6% vs 27.7%, P < 0.001); 19.3% of the recruited patients were not considered drug-resistant by the EP., Significance: This study validates the use of ILAE treatment outcome criteria in a real-life setting, providing validated estimates of seizure freedom in patients with drug-resistant focal epilepsy in relation to the number of previously failed AEDs. Fewer than one in 10 patients achieved seizure freedom on a newly introduced AED over the study period. Pseudo drug resistance could be identified in one of five cases., (© 2019 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.)

Objective: To evaluate interrater agreement in categorizing treatment outcomes and drug responsiveness status according to the International League Against Epilepsy (ILAE) definition of drug-resistant epilepsy., Methods: A total of 1053 adults with focal epilepsy considered by the investigators to meet ILAE criteria for drug resistance were enrolled consecutively at 43 centers and followed up prospectively for 18-34 months. Treatment outcomes for all antiepileptic drugs (AEDs) used up to enrollment (retrospective assessment), and on an AED newly introduced at enrollment, were categorized by individual investigators and by 2 rotating members of a 16-member expert panel (EP) that reviewed the patient records independently. Interrater agreement was tested by Cohen's kappa (k) statistics and rated according to Landis and Koch's criteria., Results: Agreement between EP members in categorizing outcomes on the newly introduced AED was almost perfect (90.1%, k = 0.84, 95% confidence interval [CI] 0.80-0.87), whereas agreement between the EP and individual investigators was moderate (70.4%, k = 0.57, 95% CI 0.53-0.61). Similarly, categorization of outcomes on previously used AEDs was almost perfect between EP members (91.7%, k = 0.83, 95% CI 0.81-0.84) and moderate between the EP and investigators (68.2%, k = 0.50, 95% CI 0.48-0.52). Disagreement was related predominantly to outcomes considered to be treatment failures by the investigators but categorized as undetermined by the EP. Overall, 19% of patients classified as having drug-resistant epilepsy by the investigators were considered by the EP to have "undefined responsiveness.", Significance: Interrater agreement in categorizing treatment outcomes according to ILAE criteria ranges from moderate to almost perfect. Nearly 1 in 5 patients considered by enrolling neurologists to be "drug-resistant" were classified by the EP as having "undefined responsiveness.", (© 2018 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.)

Objective: Standard mortality ratio for suicide in patients with epilepsy is three times higher than in the general population, and such a risk remains high even after adjusting for clinical and socioeconomic factors. It is thus important to have suitable screening instruments and to implement care pathways for suicide prevention in every epilepsy center. The aim of this study is to validate the use of the Neurological Disorder Depression Inventory for Epilepsy (NDDIE) as a suicidality-screening instrument., Methods: The study sample included adult patients with epilepsy assessed with the Mini International Neuropsychiatric Interview (MINI) and the NDDIE. A high suicidality risk according to the Suicidality Module of the MINI was considered the gold standard. Receiver operating characteristic analyses for NDDIE total and individual item scores were computed and subsequently compared using a nonparametric approach. The best possible cutoff was identified with the highest Youden index (J). Likelihood ratios were then computed, and specificity, sensitivity, positive, and negative predictive values calculated., Results: The study sample consisted of 380 adult patients with epilepsy: 46.3% male; mean age was 39.4 ± 14.6; 76.7% had a diagnosis of focal epilepsy; mean age at onset of the epilepsy was 23.3 ± 17.5. According to the MINI, 74 patients (19.5%) fulfilled criteria for a major depressive episode and 19 (5%) presented a high suicidality risk. A score >2 (J = 0.751) for item 4 "I'd be better off dead" of the NDDIE displayed excellent psychometric properties with a good to excellent validity (area under the curve [AUC] 0.906; 95% confidence interval [CI] 0.820-0.992; p < 0.001), sensitivity 84.21% (95% CI 60.4-96.6), specificity 90.86% (95% CI 87.4-93.6), likelihood ratio+ 9.21 (95% CI 6.3-13.5), likelihood ratio- 0.17 (95% CI 0.06-0.50)., Significance: Item 4 of the NDDIE has shown to be an excellent suicidality screening instrument allowing the development of further care pathways for suicide prevention in epilepsy centers., (Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.)

This White Paper builds on the publication of the International League Against Epilepsy (ILAE) and International Bureau for Epilepsy (IBE) report "Listening for a change-medical and social needs of people with intellectual disability who have epilepsy" (Listening for a change the medical and social needs of people with epilepsy and intellectual disability, ILAE, 2013). The Paper presents an overview of the recommendations of the report, which aim to improve the health and social care of this important population of people with epilepsy worldwide. Actions in four domains are indicated: (1) the development of standards and initiatives that would enhance diagnosis, pathways to investigation, and treatment; (2) the development of guidelines for treatment, specifically best practice in the management of antiepileptic drugs including rescue medication; (3) the development of standards for primary care, multidisciplinary teamwork, and clinical consultations, with emphasis on the need to enhance communication and improve access to information; and (4) the enhancement of links among different stakeholders including medical services, educational establishments, employment services, organizations providing opportunities for social engagement, and family members. The breadth of needs of this population is a challenge to the epilepsy world, spanning all the professional groupings, care providers, and the research modalities in epilepsy., (Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.)

Behavioral disorders are common in people with epilepsy and intellectual disability. Although in some genetic disorders behavioral problems are part of the established phenotype, they may also be a manifestation of underlying physical or mental illness, or may be unrecognized seizure activity. In light of this, assessment of behavioral disorders should take into account person factors such as the physical health and mental state of the person and environmental factors such as the quality of their interactions with carers and their living conditions. Video-electroencephalography ( EEG) is recommended where possible. We review potential pharmacologic and behavioral management strategies for behavioral disorders in people with intellectual disability., (Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.)

During recent years growing attention has been paid to psychiatric comorbidities in epilepsy. However, anxiety disorders still remain underrecognized and undertreated. This is largely related to the lack of specific screening instruments and the frequent co-occurrence with mood disorders. Data on treatment are insufficient and clinical practice still relies heavily on individual experience. In this article we review evidence-based treatment strategies for primary major anxiety disorders and adapt them to the specific needs of patients with epilepsy. In panic disorder, a combined approach, namely serotonin-reuptake inhibitors (SSRIs) and cognitive behavioral therapy (CBT) is always indicated during the acute phase. Long-term maintenance treatment may include combined therapy or CBT alone depending on individual cases. For generalized anxiety disorders pregabalin has to be considered first choice for short-term and long-term treatment. In social anxiety disorder and posttraumatic stress disorder SSRIs, in particular sertraline and paroxetine, can be safely used. Obsessive-compulsive disorder represents a serious condition that needs to be approached in a psychiatric setting. CBT should be considered as the first choice in patients with epilepsy. If drug treatment is needed, epileptologists have to be aware that high-dose antidepressants are appropriate and that SSRIs, in particular sertraline, should be considered first choice. In these patients, careful clinical monitoring is indicated, in selected cases, for potential seizure precipitation and side effects due to pharmacodynamics interactions., (Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.)

In 2008, the U.S. Food and Drug Administration (FDA) issued an alert to health care professionals about an increased risk of suicide ideation and suicide behavior in people treated with antiepileptic drugs (AEDs). Since then, a number of retrospective cohort and case-control studies have been published that are trying to address this issue, but gathered results are contradictory. This report represents an expert consensus statement developed by an ad hoc task force of the Commission on Neuropsychobiology of the International League Against Epilepsy (ILAE). Although some (but not all) AEDs can be associated with treatment-emergent psychiatric problems that can lead to suicidal ideation and behavior, the actual suicidal risk is yet to be established, but it seems to be very low. The risk of stopping AEDs or refusing to start AEDs is significantly worse and can actually result in serious harm including death to the patient. Suicidality in epilepsy is multifactorial, and different variables are operant. Clinicians should investigate the existence of such risk factors and adopt appropriate screening instruments. If necessary, patients should be referred for a psychiatric evaluation, but AED treatment should not be withheld, even in patients with positive suicidal risks. When starting an AED or switching from one to other AEDs, patients should be advised to report to their treating physician any change in mood and suicidal ideation. Data on treatment-emergent psychiatric adverse events need to be collected, in addition to general safety information, during controlled studies in order to have meaningful information for patients and their relatives when a new drug is marketed., (Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.)

Purpose: Psychogenic nonepileptic seizures (PNES) are among the most common clinical manifestations of conversion disorder and consist of paroxysmal behavior that resembles epileptic seizures. Preliminary data from functional neuroimaging studies gave plausible evidence that limbic circuits and sensorimotor cortex might be engaged in conversion disorder. Nonetheless, no advanced magnetic resonance imaging (MRI) studies have focused on patients with PNES., Methods: We enrolled 20 consecutive patients in whom the diagnosis of PNES was based on ictal video-electroencephalography (EEG) of the habitual episodes and 40 healthy subjects matched for age and sex All patients underwent a formal neuropsychological investigation and a neuropsychiatric assessment. All of the patients also underwent two distinct morphologic whole-brain MR measurements, voxel-based morphometry (VBM), and cortical thickness analysis, in a multimethod approach., Key Findings: None of the patients had serious medical or neurologic illness, substance abuse, or psychotic disorder, or were taking antipsychotic drugs. VBM and cortical thickness analyses in the patients with PNES revealed abnormal cortical atrophy of the motor and premotor regions in the right hemisphere and the cerebellum bilaterally. We also observed a significant association between increasing depression scores and atrophy involving the premotor regions., Significance: The results of this study illustrate that motor and premotor regions in the right hemisphere and the cerebellum bilaterally play an important role in the pathogenesis of PNES and that these structures are correlated with depressive symptoms. Our findings suggest a multistep model in the pathogenesis of PNES, in which the phenomenology is driven by psychological factors interacting with specific biologic abnormalities., (Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.)

In order to address the major impact on quality of life and epilepsy management caused by associated neuropsychiatric conditions, an international consensus group of epileptologists met with the aim of developing clear evidence-based and practice-based statements to provide guidance on the management of these conditions. Using a Delphi process, this group prioritized a list of key management areas. These included: depression, anxiety, psychotic disorders, nonepileptic seizures, cognitive dysfunction, antiepileptic drug (AED)-related neurobehavioral disorders, suicidality, disorders in children and adolescents, disorders in children with intellectual disability, and epilepsy surgery. Clinical practice statements were developed for each area and consensus reached among members of the group. The assessment and management of these conditions needs to combine knowledge of psychiatric disorders, knowledge of the impact of epilepsy and its treatment on psychopathology, and an ability to deliver care within epilepsy services. The aim of these statements is to provide guidance on quality care for people with epilepsy that have a range of neuropsychiatric disorders., (Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.)

Cesare Lombroso (1835-1909) still represents one of the most famous and, at the same time, controversial figures of neuropsychiatry. His idea of the "atavist" criminal, prisoner of his/her biologic inheritance, became extremely popular in Western countries. Unfortunately, Lombroso's theory of a strict connection between epilepsy and the criminal personality exerted a long-lasting negative influence on both medical and public opinion, and strongly contributed to the stigmatization of patients with epilepsy. In this report, we aim to present the complete and unabridged series of passages of Cesare Lombroso's works, published only in the Italian language, discussing the issue of epilepsy and crime. All original Italian quotations are offered and an English translation is provided. Although we believe that the medical profession must be well aware of the "evil" distortions generated by Lombrosian theories, which clearly emerge from his original transactions, any comment is deliberately avoided because, in our opinion, people and their ideas must be judged in accordance with the historical period to which they belonged., (Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.)

Purpose: The issue of phenomenology of mood disorders in epilepsy still remains controversial. It has been suggested that a subgroup of patients may develop an affective syndrome also known as interictal dysphoric disorder (IDD). However, the number of behavioral changes that may occur around the ictus needs to be taken into account for an accurate distinction between "true" psychiatric phenomenology and periictal phenomena. This study aimed at identifying clinical correlates of the IDD, with special attention to the relationship between symptoms and seizures., Methods: A sample of 142 consecutive adult outpatients with epilepsy were assessed using the Interictal Dysphoric Disorder Inventory (IDDI), a 38-item, self-report questionnaire specifically developed to evaluate presence and severity of IDD symptoms as well as their habitual association with seizures (coded as before, after, during, or when seizure-free) and their duration., Results: IDD was diagnosed in 31 subjects but symptoms showed a clear-cut relationship with epileptic seizures in 54.8% of cases, leading to an operative distinction between true IDD and periictal dysphoric symptoms (PDS). There was no significant difference among patients with IDD, PDS, or those without psychopathology. In the IDD group, symptoms were chronic and unremitting in one-third of cases, with labile affective symptoms being correlated with age at onset of seizures (rho = -0.612, p = 0.020) and duration of the epilepsy (rho = 0.833, p < 0.001)., Discussion: An operative distinction between IDD and PDS bears the opportunity to identify different clinical endophenotypes that may have different prognoses and require different treatment strategies.

Purpose: To determine whether a fast titration schedule of topiramate (TPM) has different effects on the occurrence of depression, in relation to other risk factors for TPM-induced depression, including history of depression (HxDEP), febrile seizures (FS), and hippocampal sclerosis (HS)., Methods: Using data from a large case registry of patients prescribed TPM, two models were constructed: Model 1 examined the independent effect of rapid TPM titration after separate adjustment for FS, HxDEP, and HS. Model 2 examined effect of the cooccurrence of rapid titration on the development of depression with each of these risk factors., Results: A total of 423 patients were included (51.8% females), mean age (SD) 35.5 (11.8) years, mean duration of epilepsy of 22.2 (11.5) years. Forty-four patients (10.4%) developed depression during TPM therapy. A rapid TPM titration was associated with 5-fold increased risk of depression that increased to 12.7-fold in the presence of both FS and rapid TPM titration, 23.3-fold in the presence of both HxDEP and rapid TPM titration, and 7.6-fold in the presence of both HS and rapid TPM titration schedule., Conclusions: Our study suggests that a rapid titration schedule is associated with an increased risk of developing depression during TPM therapy. HxDEP and FS are major contraindications to the use of a rapid titration, with a 23.3-fold and 12.7 fold increased risk, respectively.

Pathological gambling symptoms (PGS), that is, the subjective urge to gamble and the actual gambling behaviors, are currently acknowledged as relatively common symptoms among Western countries, with an estimated point prevalence of 0.6-1.1% in the general population. Converging evidence suggests that PGS are overrepresented in patients with neurological conditions affecting dopaminergic reward pathways, and can be expressed in both impulse control disorders and obsessive-compulsive spectrum disorders. This study explored the clinical correlates of PGS in patients with epilepsy. Eighty-eight consecutive adult outpatients recruited at three epilepsy clinics in northern Italy were assessed using the Gambling-Symptom Assessment Scale (G-SAS), along with a battery of psychometric instruments to index depression (Beck Depression Inventory [BDI]), anxiety (Spielberger State-Trait Anxiety Inventory [STAI]), and obsessionality (Yale-Brown Obsessive Compulsive Scale [YBOCS]) symptoms. On the G-SAS, patients with a diagnosis of temporal lobe epilepsy (TLE) reported a mean [sd] G-SAS score of 2.0 [5.7], significantly higher than patients with frontal lobe epilepsy (FLE) (0.6 [1.7]) and idiopathic generalized epilepsy (IGE) (0.4 [1.4]). Moreover, multiple regression analysis showed that G-SAS scores were selectively predicted by YBOCS scores, thus suggesting an association between the expression of obsessional spectrum symptoms and PGS in patients with TLE. Alterations in the mesolimbic reward system could represent the putative neuropathological substrate for this multifaceted clinical picture.

Purpose: Different authors suggested the occurrence of a pleomorphic affective syndrome in patients with epilepsy named interictal dysphoric disorder (IDD). We sought to investigate whether IDD occurs only in patients with epilepsy and to validate IDD features against DSM-IV criteria., Methods: Consecutive patients with a diagnosis of epilepsy (E) or migraine (M) have been assessed using the BDI, MDQ, and the Interictal Dysphoric Disorder Inventory (IDDI), a questionnaire specifically created to evaluate IDD symptoms. Diagnosis of current and lifetime DSM-IV Axis I disorders was established using the MINI Plus version 5.0.0., Results: A total of 229 patients (E = 117; M = 112) were evaluated. Females were significantly more represented in the migraine group (E = 46.5% vs. M = 73.3% p = 0.009), but there was no difference in age, duration of the disease, or education level. Patients with epilepsy were more likely to screen positively at MDQ (E = 17% vs. M = 5.3% p = 0.006) and to have a diagnosis of bipolar disorder (E = 14.5% vs. M = 4.5% p = 0.013) as compared to migraine patients. There was no between-groups difference in IDD prevalence (E = 17%; M = 18.7%) and IDDI total scores (E = 4.1 +/- 2.0 vs. M = 3.8 +/- 2.0). Validation of IDD against DSM-IV categories showed current major depression being the foremost diagnostic category correlated with IDD in both epilepsy (OR = 0.32-0.12-0.88, p = 0.028) and migraine (OR = 0.10, 95% CI = 0.02-0.49, p = 0.004) samples. Current anxiety disorder correlated with IDD only in migraine patients (OR = 0.19, 95% CI = 0.05-0.77, p = 0.02)., Conclusion: IDD represents a homogenous construct that can be diagnosed in a relevant proportion of patients but it is not typical only of epilepsy, occurring in other central nervous system disorders such as migraine.

Purpose: To investigate the hypothesis that some patients with epilepsy are generally prone to develop psychiatric adverse events (PAEs) during antiepileptic drug (AED) therapy irrespective of the mechanism of action of the drugs., Methods: From a large case registry of patients prescribed topiramate (TPM) and levetiracetam (LEV), data of patients who had a trial with both drugs were analyzed. Demographic and clinical variables of those who developed PAEs with both drugs (group 1) were compared with those who did not (group 2). Subsequently, from the whole case registry, psychopathological features, demographic, and clinical variables of patients developing PAEs with TPM were compared with those of patients developing PAEs with LEV., Results: The case registry included over 800 patients. Among 108 patients having a trial with both drugs, we identified 9 patients in group 1 and 71 in group 2. Previous psychiatric history, family psychiatric history and history of febrile convulsions showed to be significant clinical correlates. Comparing patients who developed PAEs with LEV with those who developed PAEs with TPM, there were no differences in epilepsy related variables. Well-defined DSM-IV disorders were more frequent with TPM than with LEV. Seizure freedom was associated with psychosis., Conclusions: This study suggests that a subgroup of patients is generally prone to develop PAEs during AED therapy, despite different pharmacological properties of the AEDs. A particular clinical profile and relevant variables have been identified.

Purpose: To clarify the role of hippocampal sclerosis (HS) in developing psychiatric and cognitive adverse events during therapy with topiramate (TPM) in patients with temporal lobe epilepsy (TLE)., Methods: We analyzed the data of 70 patients with TLE and HS and 128 patients with cryptogenic TLE matched for age, sex, starting dose, and titration schedule of TPM. They were selected from the first consecutive 431 patients started on TPM between 1995 and 1999., Results: Patients with HS were more likely to develop cognitive adverse events (CAEs; p = 0.002) and depression (p = 0.018) and to be receiving a polytherapy regimen (p = 0.007). However, regression analysis demonstrated that only HS was a predictive factor for the occurrence of CAEs (OR = 2.4; p < 0.001) and depression (OR = 2.3; p = 0.02)., Conclusions: Patients with TLE and HS were more prone to develop CAEs and depression than were patients with cryptogenic TLE, during TPM therapy, despite the same titration schedule. The presence of HS and not duration of epilepsy or polytherapy regimen represented the main risk factor.

Purpose: The aim of this study was to determine the prevalence of psychiatric adverse events (PAEs) in patients with epilepsy treated with topiramate (TPM). Classification, relation to TPM dosing, and outcome were evaluated to identify a patient profile at risk of developing PAEs., Methods: We evaluated the data of the first consecutive and prospectively collected patients in therapy with TPM., Results: Follow-up information was available for 431 patients. PAEs occurred in 103 (23.9%) patients; M/F ratio, 55:48; mean age (+/-SD), 36.5 +/- 11.2. In 46 (10.7%) patients, an affective disorder developed; in 16 (3.7%), a psychotic disorder; in 24 (5.6%), aggressive behavior with or without irritability; in 17 (3.9%), other behavior abnormalities such as agitated behavior, anger/hostility behavior, or anxiety. High starting dose and rapid titration schedule were relevant for the development of PAEs. Family psychiatric history and family history of epilepsy, personal history of febrile convulsions, psychiatric history, and presence of tonic-atonic seizures were found to be significant risk factors. Low seizure frequency before starting TPM and TPM/lamotrigine coadministration had a protective effect for PAEs., Conclusions: We found that PAEs associated with TPM were related to the titration schedule of the drug and that a unique patient profile is suggested by the clinical history.