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The recognition and treatment of psychosis in persons with epilepsy (PWE) is recommended with the apparent dilemma between treating psychosis and opening the possibility of exacerbating seizures. The pooled prevalence estimate of psychosis in PWE is 5.6%. It has been proposed that a 'two hit' model, requiring both aberrant limbic activity and impaired frontal control, may account for the wide range of clinical phenotypes. The role of antiepileptic drugs in psychosis in PWE remains unclear. Alternating psychosis, the clinical phenomenon of a reciprocal relationship between psychosis and seizures, is unlikely to be an exclusively antiepileptic drug-specific phenomenon but rather, linked to the neurobiological mechanisms underlying seizure control. Reevaluation of antiepileptic treatment, including the agent/s being used and degree of epileptic seizure control is recommended. The authors found very few controlled studies to inform evidence-based treatment of psychosis in PWE. However, antipsychotics and benzodiazepines are recommended as the symptomatic clinical treatments of choice for postictal and brief interictal psychoses. The general principle of early symptomatic treatment of psychotic symptoms applies in epilepsy-related psychoses, as for primary psychotic disorders. In the authors' experience, low doses of antipsychotic medications do not significantly increase clinical risk of seizures in PWE being concurrently treated with an efficacious antiepileptic regimen., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Associations between epilepsy and musical or poetic composition have received little attention. We reviewed the literature on links between poetic and musical skills and epilepsy, limiting this to the Western canon. While several composers were said to have had epilepsy, John Hughes concluded that none of the major classical composers thought to have had epilepsy actually had it. The only composer with epilepsy that we could find was the contemporary composer, Hikari Oe, who has autism and developed epilepsy at age 15years. In his childhood years, his mother found that he had an ability to identify bird sound and keys of songs and began teaching him piano. Hikari is able to compose in his head when his seizures are not severe, but when his seizures worsen, his creativity is lost. Music critics have commented on the simplicity of his musical composition and its monotonous sound. Our failure to find evidence of musical composers with epilepsy finds parallels with poetry where there are virtually no established poets with epilepsy. Those with seizures include Lord George Byron in the setting of terminal illness, Algernon Swinburne who had alcohol-related seizures, Charles Lloyd who had seizures and psychosis, Edward Lear who had childhood onset seizures, and Vachel Lindsay. The possibility that Emily Dickinson had epilepsy is also discussed. It has not been possible to identify great talents with epilepsy who excel in poetic or musical composition. There are few published poets with epilepsy and no great composers. Why is this? Similarities between music and poetry include meter, tone, stress, rhythm, and form, and much poetry is sung with music. It is likely that great musical and poetic compositions demand a greater degree of concentration and memory than is possible in epilepsy, resulting in problems retaining a musical and mathematical structure over time. The lack of association between recognizable neuropsychiatric disorders and these skills is a gateway to understanding facets of the relationship between the brain and creativity. This article is part of a Special Issue entitled "Epilepsy, Art, and Creativity"., (Copyright © 2015. Published by Elsevier Inc.)

Epilepsy is a disorder that has been used by dramatists in various ways over the ages and therefore highlights the views of the disorder as people saw it at the time the plays were written and performed. In the 6th century BC, links between tragedy and epilepsy were developed by Greek playwrights, especially Euripides, in Iphigenia among the Taureans and Heracles where epilepsy and madness associated with extreme violence occur together. Both Heracles and Orestes have episodes after a long period of physical exhaustion and nutritional deprivation. During the Renaissance, Shakespeare wrote plays featuring different neurological disorders, including epilepsy. Epilepsy plays a crucial part in the stories of Julius Caesar and Othello. Julius Caesar is a play about politics, and Caesar's epilepsy is used to illustrate his weakness and vulnerability which stigmatizes him and leads to his assassination. Othello is a play about jealousy, and Othello, an outsider, is stigmatized by his color, his weakness, and his 'seizures' as a form of demonic possession. In modern times, Night Mother portrays the hard life of Jessie, who lives with her mother. Jessie has no friends, her father has abandoned the family, and she has no privacy and is ashamed. Stigma and social pressures lead her to commit suicide. Henry James' novella, The Turn of the Screw, portrays a governess with dream-like states, déjà vu, and loss of temporal awareness who has been sent to the country to look after two small children and ends up killing one. This novella was turned into an opera by Benjamin Britten. Most recently, performance art has been portraying epilepsy as the reality of a personally provoked seizure. Both Allan Sutherland and Rita Marcalo have purposely provoked themselves to have a seizure in front of an audience. They do this to show that seizures are just one disability. Whether this provokes stigma in audiences is unknown. Whether the performance artists understand the potential for status epilepticus has not been discussed. This article is part of a Special Issue entitled "Epilepsy, Art, and Creativity"., (Copyright © 2016. Published by Elsevier Inc.)

Epilepsy is both a disease of the brain and the mind. Brain diseases, structural and/or functional, underlie the appearance of epilepsy, but the notion of epilepsy is larger and cannot be reduced exclusively to the brain. We can therefore look at epilepsy from two angles. The first perspective is intrinsic: the etiology and pathophysiology, problems of therapy, impact on the brain networks, and the "mind" aspects of brain functions - cognitive, emotional, and affective. The second perspective is extrinsic: the social interactions of the person with epilepsy, the influence of the surrounding environment, and the influences of epilepsy on society. All these aspects reaching far beyond the pure biological nature of epilepsy have been the topics of two International Congresses of Epilepsy, Brain, and Mind that were held in Prague, Czech Republic, in 2010 and 2012 (the third Congress will be held in Brno, Czech Republic on April 3-5, 2014; www.epilepsy-brain-mind2014.eu). Here, we present the first of two papers with extended summaries of selected presentations of the 2012 Congress that focused on epilepsy, behavior, and art., (Copyright © 2013. Published by Elsevier Inc.)

This article supports a view that certain personality disturbances in epilepsy should be viewed as associated with the cerebral abnormalities that also lead to seizures. Herein I discuss two main variants: that related to temporal lobe epilepsy and that associated with juvenile myoclonic epilepsy. In view of its controversial nature, I also comment on the link between aggression and epilepsy. Recommendations for treatment include psychological and social therapies with further advice about the use of antiepileptic drugs (AEDs) and psychotropic medications in these conditions., (Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.)

Depression is the most frequent psychiatric comorbidity in people with epilepsy (PWE) with lifetime prevalence rates ranging between 30 and 35%. Multifactorial variables play a pathogenic role in the high comorbid occurrence of these two disorders. These variables were critically examined during an international symposium held in Chicago in September 2010, the results of which are presented in two companion manuscripts. The first manuscript summarizes new epidemiologic data highlighting the bidirectional relation between depression and epilepsy and related methodological issues in studying this relationship. An examination of the neurobiologic aspects of primary mood disorders, mood disorders in PWE and pathogenic mechanisms of epilepsy derived from studies in animal models and humans is allowing a better understanding of the complex relation between the two conditions. In the first manuscript, we review data from animal models of epilepsy in which equivalent symptoms of depression and anxiety disorders develop and, conversely, animal models of depression in which the kindling process is facilitated. Data from structural and functional neuroimaging studies in humans provide a further understanding of potential common pathogenic mechanisms operant in depression and epilepsy that may explain their high comorbidity. The negative impact of depression on the control of seizure disorders has been documented in various studies. In this manuscript, these data are reviewed and potential mechanisms explaining this phenomenon are proposed., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The clinical manifestations of depression in people with epilepsy (PWE) are pleomorphic, often associated with anxiety symptoms and anxiety disorders. The ongoing debate of whether the clinical presentation of depression in PWE is unique to this neurologic disorder is reviewed. Comorbid depression can impact the recruitment of PWE for pharmacologic trials with antiepileptic drugs (AEDs). Yet, the impact of depression on the response of the seizure disorder to pharmacotherapy with AEDs and its impact on worse adverse events may bias the interpretation of the trial findings, particularly when depressed patients are included in the AED trials. PWE have a greater suicidal risk than the general population. This risk is mediated by multiple factors, and recent data from the FDA have imputed a potential pathogenic role to all AEDs. The recognition of patients at risk is reviewed. Yet, the validity of the FDA data has been questioned, and the status of this controversial question is analyzed. As in the case of epilepsy, depression and pain syndromes have a relatively high comorbidity. The negative impact of depression on pain is reminiscent of that of depression in PWE; furthermore, the high comorbidity may be also associated with the existence of common pathogenic mechanisms. Neurologists and in particular, epileptologists establish the diagnosis of psychogenic non-epileptic seizures (PNES) in whom a comorbid depressive disorder is very often identified. The role of depression in the course of PNES and its treatment are discussed. Scarce data are available on the treatment of depression in PWE. Thus, clinicians have had to adopt data from patients with primary depressive disorders. We outline a consensus strategy on the identification and treatment of depressive disorders in adult and pediatric patients with epilepsy., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Recent research into mammalian cortical neurophysiology, after 6 decades of Berger's seminal work on electroencephalography, has shifted the older concept of interictal epileptiform activity (IEA) away from that of a mere electrographic graphoelement of relevance to diagnostic implications in epilepsy. Instead, accumulating information has stressed the neuropsychological implications, cognitive and/or behavioral consequence of these electrophysiological events, which are the phenotypic expression of aberrations of actual biophysical cellular function. We feel that this review is germane to neuropsychiatry, however, a rather neglected area of research. There is a great scope for brain-behavior-EEG research in the future that can be complimented by other techniques of "neurobehavioral electrophysiology". This review does not address the "pearls, perils and pitfalls" in the use of EEG in epilepsy, but critically and systematically reappraises the published electroencephalographic correlates of human behavior. We reiterate that epileptiform and other paroxysmal EEG dysrhythmias unrelated to clinical seizures do have neuropsychological, cognitive and/or behavioral implications as seen in the various neuropsychiatric and neurobehavioral disorders discussed in this article. IEA and EEG dysrhythmias should neither be ignored as irrelevant nor automatically attributed to epilepsy. The relevance of these EEG aberrations in the disorders of the brain-mind interface extend beyond epilepsy, and may be an electrophysiological endophenotype of aberrant neuronal behavior indicative of underlying morpho-functional brain abnormalities. Magnetoencephalography (MEG), data fusion models (EEG-fMRI-BOLD), transcranial magnetic stimulation (TMS), evoked potentials (EP); intracranial electrophysiology, and EEG neurofeedback complemented by current functional neuroimaging techniques (fMRI and PET) would certainly help in further understanding the broader relationship between brain and behavior.

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.

This article reviews the relationship between the psychiatry and neurology of epilepsy, especially in the last 100 years. Throughout most of its recorded history of 3 to 4 millennia epilepsy has been viewed as a supernatural or mental disorder. Although first suggested by Hippocrates in the 5th century B.C., the concept of epilepsy as a brain disorder only began to take root in the 17th and 18th centuries. The discipline of neurology emerged from "nervous disorders" or neuropsychiatry in the late 19th century, when vascular theories of epilepsy predominated. By the turn of the 19th century psychiatry and neurology were diverging and epilepsy remained to some extent in both disciplines. It was only in the middle of the 20th century with the development of electromagnetic theories of epilepsy that the concept of epilepsy per se as a neurological disorder was finally adopted in international classifications of disease. This was associated with a refined definition of the ictal, pre-, post-, and interictal psychological disorders of epilepsy, which have contributed to a renaissance of neuropsychiatry. At the beginning of the 21st century and the centenary of the ILAE psychiatry and neurology have been converging again, led in some respects by epilepsy, which has provided several useful models of mental illness and a bridge between the two disciplines.

Objectives: To examine the immediate and sustained effects of volitional sympathetic modulation, using galvanic skin response (GSR) biofeedback training on cortical excitability in patients with drug-resistant epilepsy., Methods: Ten patients undertook 12 sessions of GSR biofeedback training over 1 month, during which they were trained to increase sympathetic arousal, using GSR biofeedback. Contingent negative variation (CNV) (a slow cortical potential reflecting cortical arousal and excitability) and the related post imperative negative variation (PINV) were quantified before and after biofeedback treatment., Results: A significant reduction in CNV amplitude was observed in both the short-term (within the first session, after 10 minutes of GSR biofeedback) and long-term (sustained after 12 training sessions). Specifically, the change in baseline CNV amplitude after the 12 training sessions correlated with a percentage reduction in seizure frequency. Furthermore, changes in baseline amplitude of the PINV also correlated with seizure reduction., Conclusions: Our findings demonstrate that behavioral enhancement of peripheral sympathetic tone (GSR) is associated with modulation of indices of cortical excitability. Moreover, GSR biofeedback training over repeated sessions was associated with a chronic baseline reduction in slow cortical potentials and concurrent therapeutic improvement.

Subclinical electroencephalographic epileptiform discharges in neurobehavioral disorders are not uncommon. The clinical significance and behavioral, diagnostic, and therapeutic implications of this EEG cerebral dysrhythmia have not been fully examined. Currently the only connotation for distinctive epileptiform electroencephalographic patterns is epileptic seizures. Given the prevailing dogma of not treating EEGs, these potential aberrations are either disregarded as irrelevant or are misattributed to indicate epilepsy. This article reappraises the literature on paroxysmal EEG dysrhythmia in normative studies of the "healthy" nonepileptic general populations, neuropsychiatry, and in neurobehavioral disorders. These EEG aberrations may be reflective of underlying morpho-functional brain abnormalities that underpin various neurobehavioral disturbances.

Although mood disorders represent a frequent psychiatric comorbidity in epilepsy, data on bipolar disorder (BD) are still limited, and the role of possible specific confounding variables (seizures and antiepileptic drug therapy) has never been considered. Data for 143 adult outpatients with epilepsy assessed with the Mini International Neuropsychiatric Interview Plus Version 5.0.0 using the Epilepsy Addendum for Psychiatric Assessment, the Mood Disorder Questionnaire, and the Interictal Dysphoric Disorder Inventory revealed that 11.8% had the Diagnostic and Statistical Manual of Mental Disorders-based diagnosis of BD, only 1.4% of whom could be considered as having "pure" BD, because in all other cases BD symptoms were related to phenotype copies of BD such as interictal dysphoric disorder of epilepsy, postictal manic or hypomanic states, and preictal dysphoria.

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.

The role of CNS neuromodulators in cognitive neurorehabilitation can be related to two main issues: 1) the negative impact on cognition of drug categories prescribed for different neurologic symptoms, such as spasticity, extrapyramidal symptoms, or epileptic seizures; 2) their possible role in neuroprotection and amelioration of the cognitive status of the patient, especially attention and memory. This paper reviews different pharmacological aspects of cognitive neurorehabilitation in epilepsy.

This study investigated mismatch negativity (MMN) differences between subjects with non-epileptic seizures (NES), subjects with epilepsy, and healthy controls. Event-related potentials (ERPs) were obtained from 14 patients with NES, 15 patients with epilepsy and 16 healthy control subjects. A conventional MMN procedure was used with a random sequence of 12% deviant tones (922 Hz) and 88% standard tones (1000 Hz). Subjects were instructed to ignore the tones delivered through headphones whilst reading a book. Significant differences in distribution of the mismatch negativity (MMN) in patients with NES compared to controls were obtained (F3, p

Aims: The aims of this project were to evaluate the impact of adjunctive treatment with an anti-epileptic drug (AED) on the health status of people with epilepsy and to investigate how seizure frequency affects their health status., Methods: Adult epilepsy patients, refractory to current treatment, were included in this prospective observational study. Patients commencing adjunctive therapy with one of five AEDs (topiramate, lamotrigine, gabapentin, clobazam, vigabatrin) were eligible for inclusion. The study took place at the outpatient clinics of the National Hospital for Neurology and Neurosurgery, Queen Square, London. Patients completed the EQ-5D, a generic health status measure, at baseline and again after 3 and 6 months. Information was also collected on medications and seizure frequency., Results: In total, 125 patients entered the study and were followed up for 6 months. Patients treated with topiramate had a significant increase (p < 0.05) in EQ-5D score from baseline, indicating an improvement in their health status whereas scores for lamotrigine, clobazam and gabapentin all showed a non-significant decline. When the data were analysed according to seizure frequency, only patients who became seizure-free on adjunctive treatment had a significant increase in their health status. The group who had a 50% reduction in seizure frequency did not have increased health status., Conclusions: In summary, adjunctive treatment with topiramate significantly increased health status as measured by the EQ-5D. These data also suggest that achievement of seizure-freedom is the key to improving health status in this patient group.

We review the literature on the influence of antiepileptic drugs (AEDs) on mood and quality of life in patients with epilepsy. Although many anecdotal reports cover a spectrum of AEDs, most of the controlled data have come from studies of carbamazepine and lamotrigine. Both of these compounds appear to have positive effects on mood, and these data parallel the effects noted in nonepilepsy populations. AEDs that are gamma-aminobutyric acid (GABA)ergic tend to have negative effects on mood, and an affective disorder is often noted as a treatment-emergent effect. It is speculated that the amygdala is an important anatomic structure in the cerebral circuits that regulate mood in affective disorders but also in epilepsy, and an effect of AEDs on such circuits aids mood stability in both populations of patients.

It is now accepted that patients with epilepsy are more prone than the general population to develop psychiatric disorders, being significantly at risk due to psychosocial reasons, the presence of electrophysiologic and anatomopathologic abnormalities mainly in the limbic system, and because they are taking antiepileptic drugs which may have negative psychotropic effects. It is also known that many patients with epilepsy sometimes receive psychotropic medications on account of their psychiatric symptoms. This review focuses on the main problems that a clinician may encompass when treating psychiatric disorders in patients with epilepsy. On one hand, the effects of antiepileptic drugs on mood and behavior for a correct differential diagnosis of psychiatric symptoms. On the other hand, the main factors that may affect choice of therapy, patients' response and compliance, when prescribing antidepressants or antipsychotic drugs, drug interactions and the potential proconvulsive risk are reviewed.

We investigated the effect of galvanic skin response (GSR) biofeedback training on seizure frequency in patients with treatment-resistant epilepsy. Eighteen patients with drug-refractory epilepsy were randomly assigned either to an active GSR biofeedback group (n = 10) or to a sham control biofeedback group (n = 8). Biofeedback training significantly reduced seizure frequency in the active biofeedback group (P = 0.017), but not the control group (P > 0.10). This was manifest as a significant between-group difference in seizure reduction (P 0.01). Furthermore, there was a correlation between degree of improvement in biofeedback performance and reduction of seizure frequency (rho = 0.736, P = 0.001), confirming that the effect of biofeedback treatment was related to physiological change. Our findings highlight the potential therapeutic value of GSR biofeedback in reducing seizure frequency in patients with drug-resistant epilepsy.

Purpose: To investigate the prevalence and psychopathological features of psychiatric adverse events (PAEs) in patients with learning disabilities (LD) in therapy with levetiracetam (LEV)., Method: From a population of 517 consecutively patients with epilepsy started on LEV, we identified 118 patients with epilepsy and LD., Results: Fifteen patients (12.7%) experienced PAEs during LEV therapy. Two (1.7%) developed an affective disorder, nine (7.6%) aggressive behaviour, two (1.7%) emotion lability and two (1.7%) other personality changes such as agitation, anger and hostile behaviour. We observed a significant association with a previous history of status epilepticus and a previous psychiatric history. We did not find a statistically significant association with epilepsy diagnosis, age at onset or duration of the epilepsy, EEG or MRI features. The titration schedule of LEV appeared not to be relevant., Conclusions: LEV therapy was well tolerated in patients with epilepsy and LD and the main problems were related to aggressive behaviour. The titration schedule of LEV was not relevant and a subgroup of patients appeared to be biologically more vulnerable.

The aim of this study was to analyze in detail psychopathology associated with topiramate (TPM) prescription and to analyze the relationship between psychopathology and seizure freedom. We analyzed the data on 103 patients who developed psychiatric disorders during TPM therapy. Forty-six patients developed an affective disorder, 22 aggressive behavior, 16 psychosis, 11 anxiety, and 8 personality changes such as anger, agitation, and hostile behavior. Patients with psychosis were more likely to be seizure-free during psychopathology, to receive psychotropic drug prescription, and to be admitted to hospital. In general, patients seizure-free during psychopathology were more likely to have a diagnosis of idiopathic generalized epilepsy, to be in co-therapy with vigabatrin, and to remit after drug reduction. We observed that psychopathology was related to seizure control in a subgroup of patients. The role of forced normalization, interlinked with interactions with other antiepileptic drugs, could be relevant.

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.

Objective: To evaluate the prevalence of word-finding difficulties as a treatment-emergent adverse event in patients with epilepsy taking topiramate and to identify a clinical phenotype at risk., Methods: The authors investigated the relationship of word-finding difficulties to topiramate titration schedule, seizure frequency and pattern, and EEG and neuroradiologic findings in 431 consecutively and prospectively collected patients taking topiramate., Results: Thirty-one patients (7.2%) developed word-finding difficulties. Presence of simple partial seizures (OR = 6.7 p = 0.007) and a left temporal EEG epileptic focus (OR = 5.2 p = 0.021) were significantly associated with word-finding difficulties., Conclusions: The presence of word-finding difficulties seems to be a titration schedule independent phenomenon that occurs in a subgroup of patients with a specific biologic vulnerability.

The results of volumetric studies of the amygdala and hippocampus in patients with epilepsy who also have psychopathology are described. The main data relate to the increased size of the amygdala in patients with epilepsy and psychosis. The associations between the amygdala and affective disorders, notably dysthymia and euphoria, are also discussed.

This report reviews behavioral adverse events occurring among adults receiving levetiracetam (LEV) or placebo who participated in short-term, placebo-controlled studies in epilepsy (1023), cognitive disorders (719), or anxiety disorders (1510) and epilepsy patients (1393) observed in long-term trials. Behavioral events (affective, psychotic, and suicidal symptoms) were significantly more common among epilepsy patients than cognition or anxiety patients treated with LEV for similar durations (P=0.022). Affective symptoms occurring at 1% or more often in epilepsy placebo-controlled trials included depression (3.8% LEV-2.1% placebo), nervousness (3.8%-1.8%), hostility (2.3%-0.9%), anxiety (1.8%-1.1%), and emotional lability (1.7%-0.2%). Patients with cognitive and anxiety disorders had lower incidences of these symptoms. The incidence of behavioral events in LEV-treated epilepsy patients was lower than rates reported for some other antiepileptic drugs. These data support the hypothesis that some feature related to epilepsy is the cause of many behavioral events rather than the addition of a specific antiepileptic drug.

Purpose: To review transcultural perspectives in the neuropsychiatry of epilepsy., Methods: Systematic literature searches of standard databases, cross-referencing, chapters, and opinion leader articles., Results: Articles from the Indian subcontinent, Africa, and Japan were identified and are reviewed herein. The spectrum of psychopathology in epilepsy is rather similar across cultures. However, psychopathology specific to epilepsy, the interictal behavioural syndrome of Geschwind, for example, has not been well studied outside the Western world., Discussion: There is a need for well-designed epidemiological studies of neuropsychiatric disorders in epilepsy. These should use harmonised protocols and outcome measures. Special attention should be paid to the impact of aetiology on psychiatric co-morbidity and disablement.

We conducted a prospective, long-term audit of lamotrigine and topiramate as add-on treatment for refractory epilepsy. A total of 55 patients participated in the study. Five years after starting the drug 7/20 patients remained on lamotrigine and 13/35 on topiramate. The patients still on the study drugs showed an improvement in seizure frequency, with 5/7 patients being seizure free on lamotrigine and 4/13 on topiramate. Furthermore, we assessed quality of life using the quality of life assessment schedule and found a significant improvement for the patients still on the study drugs. These data suggest that about one third of the patients on lamotrigine or topiramate as add-on therapy stay on the drug in the long term. These patients are likely to benefit with respect to objective and subjective outcome measures.

In this article, the use of benzodiazepines (BZDs) in epilepsy is reviewed. In particular, it concentrates on the use of oral BZDs, and, following a brief discussion as to their value in psychiatric disorders generally, their more specific use in epilepsy is then noted. The main oral drugs are the 1,4BZDs and 1,5-BZDs. The latter is represented only by clobazam (CLB), and the advantages of the 1,5-BZDs over the 1,4-BZDs are reviewed. It is concluded that CLB has a significant value in a number of situations. It is a first-line add-on therapy when standard medications have failed. It is useful in patients that have catamenial seizures, clusters of seizures, and also in the prevention of postictal syndromes. It is used in childhood epilepsy, and is also helpful in the management of febrile seizures.

Abstract: We examined the religious experiences of 28 patients with epilepsy and religiosity, 22 patients with epilepsy and no expressed interest in religion, and 30 volunteer regular churchgoers. We profiled the experiences of the first group, revealing more of their phenomenology, but also their bipolarity, and demonstrated that members of the religious group were significantly more likely to have had past episodes of postictal psychosis, and to have bilateral cerebral dysfunction. We added further data to support the validity of the Bear–Fedio Inventory, and noted that although the experiences of patients with epilepsy are different in content and intensity from the experiences of regular churchgoers, the patients with epilepsy and religiosity conform to those who William James referred to as having, with respect to religion, “an acute fever.” [Copyright &y& Elsevier]

Summary: Objective: Hippocampal sclerosis (HS) has been described as a relevant factor for the development of topiramate-related depression and cognitive deficits. The aim of our study was to clarify whether patients with temporal lobe epilepsy (TLE) and HS were also at risk during therapy with levetiracetam (LEV). Methods: Data of 156 patients was analysed: 78 with TLE and HS and 78 with TLE and normal MRI matched for age, starting dose and titration schedule of LEV. Patients were selected from a population of consecutive patients started on LEV between 2000 and 2002. Results: No differences were observed in prevalence of cognitive adverse events and depression between the two groups. Conclusions: LEV treatment is not associated with cognitive adverse events and depression in patients with hippocampal sclerosis. [Copyright &y& Elsevier]

In this paper, consideration to the present state of anticonvulsant therapy with the new drugs is presented by six international experts. Arguments both for and against poly therapy are given, and a summary of the pharmacokinetic interactions that occur with and among the new drugs is made. The concept of rational combination therapy is discussed. Special consideration is then given to the current place for clobazam, gabapentin, lamotrigine and vigabatrin in the management of epilepsy. and the results of several new trials with these various drugs are given. While it is too early to clarify the exact clinical profiles of these compounds, the place for these drugs, and the patient groups that might most benefit from their prescription are presented. With regards to clobazam, new data on long term efficacy are reported, noting a low frequency of the development of tolerance, and freedom from seizures in up to 10 per cent of patients when given as adjunctive therapy. [ABSTRACT FROM AUTHOR]

The literature on the effects of anticonvulsant drugs on behaviour is reviewed, with particular attention to the new agents. Positive psychotropic effects, and negative influences on behaviour are noted. The latter include depression and psychoses. The drugs most involved seem to be those with GABAergic properties, and the role of forced normalisation is discussed. [ABSTRACT FROM AUTHOR]

Specific inhibitors of 5-HT reuptake are reported to have lower proconvulsive activity than other antidepressants. A patient with post-traumatic epilepsy who had remained fit-free for many years until she was given the 5-HT reuptake inhibitor fluvoxamine is reported. Changes in serotonergic function may play a more widespread role in the pathophysiology of seizure disorders than hitherto thought. [ABSTRACT FROM AUTHOR]

The author comments on the use of terms positive and negative symptoms in psychiatry based on a recent survey conducted by psychiatrists in a market research company. The author found 52 percent of the respondents whose negative symptom is most often associated apathy. First-rank symptoms appear to be more readily identifiable and more clearly defined than the loose descriptive terms positive and negative symptoms.

Several letters to the editor in response to articles in previous issues including "Drug-induced psychosis after long-term treatment with levetiracetam," by K. Bayerlein, H. Frieling, B. Beyer and others in a 2004 issue and recognition of an association between epilepsy and schizophrenia-like psychosis, such as the phenomenon of forced normalization, to make a correct diagnosis are presented.

Explores the interrelation between learning disabilities and epilepsy. Difference between learning disabilities and mental retardation; Epidemiology of epilepsy; Psychosocial management of the disorder.