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Suicidal behavior and antiepileptic drugs in epilepsy: analysis of the emerging evidence  [cached]
Mula M,Hesdorffer DC
Drug, Healthcare and Patient Safety , 2011,
Abstract: Marco Mula1, Dale C Hesdorffer21Department of Clinical and Experimental Medicine, Amedeo Avogadro University and Division of Neurology, University Hospital Maggiore della Carità, Novara, Italy; 2Gertrude H Sergievsky Center and Department of Epidemiology, Columbia University, New York, NY, USAAbstract: Two years after the warning issued by the Food and Drug Administration on an increased risk of suicide for people taking antiepileptic drugs (AEDs), a number of pharmacoepidemiologic studies have been published but the scientific community is far from definitive answers. The present paper is aimed at reviewing available evidence on the association between AEDs and suicidal behavior, discussing major variables involved such as the relationship between epilepsy, depression, and suicide and the psychotropic potential of AEDs. All studies published so far show a lack of concordance and are constrained by various methodological limitations. What seems to be established is that mood disorders represent a frequent comorbidity in epilepsy and suicide is a serious complication more frequently encountered in epilepsy rather than in the general population. Moreover, a subgroup of patients appears to be at risk of developing treatment-emergent psychiatric adverse effects of AEDs independently of the specific mechanism of action of the drug. The prior history of suicide attempt, especially preceding the onset of the epilepsy, may represent a key element explaining why what is observed is independent of the specific mechanism of the drug. In general terms, risks associated with stopping, or not even starting, AEDs in epilepsy might well be in excess of the risk of suicide in epilepsy, as deaths due to accident and epilepsy itself may predominate. Clinicians need to pay attention not only to seizure patterns when choosing the appropriate AED but also to a number of different parameters (eg, age, gender, working needs, medical comorbidities, history of psychiatric disorders, and suicidality before epilepsy onset) and not the least the mental state of the patient. Missing severe complications such as suicidal behavior or delaying its treatment may worsen the prognosis of epilepsy.Keywords: antiepileptic drugs, suicide, depression, epilepsy, FDA
Suicidal behavior and antiepileptic drugs in epilepsy: analysis of the emerging evidence
Mula M, Hesdorffer DC
Drug, Healthcare and Patient Safety , 2011, DOI: http://dx.doi.org/10.2147/DHPS.S13070
Abstract: icidal behavior and antiepileptic drugs in epilepsy: analysis of the emerging evidence Review (3444) Total Article Views Authors: Mula M, Hesdorffer DC Published Date June 2011 Volume 2011:3 Pages 15 - 20 DOI: http://dx.doi.org/10.2147/DHPS.S13070 Marco Mula1, Dale C Hesdorffer2 1Department of Clinical and Experimental Medicine, Amedeo Avogadro University and Division of Neurology, University Hospital Maggiore della Carità, Novara, Italy; 2Gertrude H Sergievsky Center and Department of Epidemiology, Columbia University, New York, NY, USA Abstract: Two years after the warning issued by the Food and Drug Administration on an increased risk of suicide for people taking antiepileptic drugs (AEDs), a number of pharmacoepidemiologic studies have been published but the scientific community is far from definitive answers. The present paper is aimed at reviewing available evidence on the association between AEDs and suicidal behavior, discussing major variables involved such as the relationship between epilepsy, depression, and suicide and the psychotropic potential of AEDs. All studies published so far show a lack of concordance and are constrained by various methodological limitations. What seems to be established is that mood disorders represent a frequent comorbidity in epilepsy and suicide is a serious complication more frequently encountered in epilepsy rather than in the general population. Moreover, a subgroup of patients appears to be at risk of developing treatment-emergent psychiatric adverse effects of AEDs independently of the specific mechanism of action of the drug. The prior history of suicide attempt, especially preceding the onset of the epilepsy, may represent a key element explaining why what is observed is independent of the specific mechanism of the drug. In general terms, risks associated with stopping, or not even starting, AEDs in epilepsy might well be in excess of the risk of suicide in epilepsy, as deaths due to accident and epilepsy itself may predominate. Clinicians need to pay attention not only to seizure patterns when choosing the appropriate AED but also to a number of different parameters (eg, age, gender, working needs, medical comorbidities, history of psychiatric disorders, and suicidality before epilepsy onset) and not the least the mental state of the patient. Missing severe complications such as suicidal behavior or delaying its treatment may worsen the prognosis of epilepsy.
Neuropsychological effects of antiepileptic drugs (carbamazepine versus valproate) in adult males with epilepsy  [cached]
Ghaydaa A Shehata,Abd El-aziz M Bateh,Sherifa A Hamed,et al
Neuropsychiatric Disease and Treatment , 2009,
Abstract: Ghaydaa A Shehata,1 Abd El-aziz M Bateh,2 Sherifa A Hamed,1 Tarek A Rageh,1 Yaser B Elsorogy11Department of Neurology and Psychiatry, Faculty of Medicine, Assiut University, Egypt; 2Department of Psychology, Faculty of Arts, Banha University, EgyptPurpose: To evaluate the effect of antiepileptic drugs (AEDs) on cognition and behavior in adult epileptic males controlled on treatment with conventional antiepileptic medications. Methods: Cognitive, mood, behavior and personality traits were assessed in 45 epileptic patients treated with carbamazepine and/or valproate and free of seizures for ≥1 year. Thirty-four newly diagnosed or untreated patients with epilepsy and 58 matched healthy subjects were also included for comparison. A battery of psychometric tests was utilized including Stanford-Binet (4th edition), Beck Inventory for Depression, Aggressive Scale and Eysenck Personality Questionnaire.Results: Compared to matched control subjects, treated and untreated epileptic patients had poor performance in different cognitive and behavioral functions testing. Treated patients had worse scores in memory for digits forward and backward, total short-term memory, extroversion and psychosis. The duration of AEDs intake was correlated with memory of objects (r = -0.323; P = 0.030), bead memory (r = -0.314; P = 0.036) and total nonverbal short-term memory (r = -0.346; P = 0.020). Treated and untreated epileptic patients had poor performance of similar extent in behavioral functions testing (depression, aggression and neurosis). The dose of AEDs was correlated with testing scores for neurosis (r = 0.307; P = 0.040), verbal aggression (r = 0.483; P = 0.001) and nonverbal aggression (r = 0.526; P = 0.000), and duration of drug intake was correlated with scores for depression (r = 0.384; P = 0.009), psychosis (r = 0.586; P = 0.0001) and nonverbal aggression (r = 0.300; P = 0.045).Conclusions: This study provides support for the notion that AEDs can impair performance in cognition, mood and behavior. Duration of drug intake and the number of the utilized AEDs are the main confounding variables. This study did not provide clues on how to exclude the effect of epilepsy itself and psychosocial variables as additional important confounding variables.Keywords: cognition, behavior, mood, personality traits, epilepsy, AEDs
Neuropsychological effects of antiepileptic drugs (carbamazepine versus valproate) in adult males with epilepsy
Ghaydaa A Shehata, Abd El-aziz M Bateh, Sherifa A Hamed, et al
Neuropsychiatric Disease and Treatment , 2009, DOI: http://dx.doi.org/10.2147/NDT.S5903
Abstract: ropsychological effects of antiepileptic drugs (carbamazepine versus valproate) in adult males with epilepsy Original Research (6863) Total Article Views Authors: Ghaydaa A Shehata, Abd El-aziz M Bateh, Sherifa A Hamed, et al Published Date October 2009 Volume 2009:5 Pages 527 - 533 DOI: http://dx.doi.org/10.2147/NDT.S5903 Ghaydaa A Shehata,1 Abd El-aziz M Bateh,2 Sherifa A Hamed,1 Tarek A Rageh,1 Yaser B Elsorogy1 1Department of Neurology and Psychiatry, Faculty of Medicine, Assiut University, Egypt; 2Department of Psychology, Faculty of Arts, Banha University, Egypt Purpose: To evaluate the effect of antiepileptic drugs (AEDs) on cognition and behavior in adult epileptic males controlled on treatment with conventional antiepileptic medications. Methods: Cognitive, mood, behavior and personality traits were assessed in 45 epileptic patients treated with carbamazepine and/or valproate and free of seizures for ≥1 year. Thirty-four newly diagnosed or untreated patients with epilepsy and 58 matched healthy subjects were also included for comparison. A battery of psychometric tests was utilized including Stanford-Binet (4th edition), Beck Inventory for Depression, Aggressive Scale and Eysenck Personality Questionnaire. Results: Compared to matched control subjects, treated and untreated epileptic patients had poor performance in different cognitive and behavioral functions testing. Treated patients had worse scores in memory for digits forward and backward, total short-term memory, extroversion and psychosis. The duration of AEDs intake was correlated with memory of objects (r = -0.323; P = 0.030), bead memory (r = -0.314; P = 0.036) and total nonverbal short-term memory (r = -0.346; P = 0.020). Treated and untreated epileptic patients had poor performance of similar extent in behavioral functions testing (depression, aggression and neurosis). The dose of AEDs was correlated with testing scores for neurosis (r = 0.307; P = 0.040), verbal aggression (r = 0.483; P = 0.001) and nonverbal aggression (r = 0.526; P = 0.000), and duration of drug intake was correlated with scores for depression (r = 0.384; P = 0.009), psychosis (r = 0.586; P = 0.0001) and nonverbal aggression (r = 0.300; P = 0.045). Conclusions: This study provides support for the notion that AEDs can impair performance in cognition, mood and behavior. Duration of drug intake and the number of the utilized AEDs are the main confounding variables. This study did not provide clues on how to exclude the effect of epilepsy itself and psychosocial variables as additional important confounding variables.
Effects of Antiepileptic Drugs on Electroencephalographic Findings in Patients with Idiopathic Generalized Epilepsy  [cached]
Ali Akbar ASADI-POOYA,Mehrdad EMAMI
Iranian Journal of Child Neurology , 2011,
Abstract: ObjectiveSeveral antiepileptic drugs (AEDs) such as phenobarbital (Pb), carbamazepine (CBZ), and valproate (VPA) may suppress interictal epileptiform activity. We investigated the effects of AEDs on electroencephalography (EEG) data from patients with idiopathic generalized epilepsy (IGE).Materials & MethodsIn this cross-sectional study, all patients electroclinically diagnosed with IGE were recruited in the outpatient epilepsy clinic at Shiraz University of Medical Sciences from September 2008 through August 2010. A routine EEG was requested at the time of referral for all patients. Statistical analyses were performed using Chi square and Fisher’s exact test.ResultsThis study comprised of 336 patients. For about 20.8% (70 patients) of them, the initial EEG appeared normal. The first EEG was normal in 14.2% of the patients who had newly diagnosed IGE (19 patients). Normal EEG was also detected for 27.6% of the patients who received VPA monotherapy (16 patients), 31% of the patients who received CBZ monotherapy (9 patients), 29.4% of the patients who received Pb monotherapy (5 patients), and 11.1% of the patients who received lamotrigine (LTG) (1 patient).ConclusionThis study shows that compared to LTG, VPA suppresses generalized interictal epileptiform activity in patients with IGE more effectively. Theoretically, if a drug can frequently induce normalization of EEG, then it may be a better drug for treating IGEs.
The role side effects play in the choice of antiepileptic therapy in brain tumor-related epilepsy: a comparative study on traditional antiepileptic drugs versus oxcarbazepine
Marta Maschio, Loredana Dinapoli, Antonello Vidiri, Andrea Pace, Alessandra Fabi, Alfredo Pompili, Maria Carmine Carapella, Bruno Jandolo
Journal of Experimental & Clinical Cancer Research , 2009, DOI: 10.1186/1756-9966-28-60
Abstract: We performed an observational retrospective study on patients with brain tumor-related epilepsy: 35 who had assumed oxcarbazepine monotherapy and 35 patients who had undergone treatment with traditional antiepileptic drugs. Primary variable of efficacy was the mean seizure frequency per month and safety variables were the drop-out for side effects and total incidence of side effects. We applied the Propensity Score technique to minimize selection bias.Our results showed a similar efficacy of oxcarbazepine and traditional antiepileptic drugs over time, but the difference in safety and tolerability between the two groups was significant: traditional AEDs caused more side effects, both serious and non serious.This study highlights the importance of taking into consideration not only seizure control but also the appearance of side effects when choosing antiepileptic drugs in this patients population.Seizures are a common symptom in patients with brain tumors [1]. Literature data on antiepileptic drugs (AEDs) in brain tumor patients indicate that not only complete seizure control is a challenging goal [2] but that reducing unpleasant side effects produced by AEDs is a serious concern as well [3]. Side effects are mostly associated with the administration of traditional, older antiepileptic drugs: carbamazepine (CBZ), phenobarbital (PB), phenytoin (PHT) and valproic acid (VPA) [3-7]. Some limited data in the literature indicate that side effects are less marked when the newer AEDs such as oxcarbazepine, levetiracetam, topiramate, gabapentin and pregabalin are administered [6-13]. However, there have been no comparative studies to date which document the differences in efficacy and tolerability between the newer and older AEDs. The aim of this study was to assess if one of the newer generation AEDs presented significant differences in terms of efficacy as well as safety/tolerability when compared to the traditional AEDs, in patients with brain-tumor related epilepsy.We cho
Transient lesion in the splenium of the corpus callosum and a sudden antiepileptic drugs withdrawal: A case with focal epilepsy in presurgical evaluation  [PDF]
Risti? Aleksandar,Lavrni? Slobodan,Zovi? Ljubica,Vojvodi? Nikola
Vojnosanitetski Pregled , 2010, DOI: 10.2298/vsp1005427r
Abstract: Introduction. A sudden withdrawal of antiepileptic drugs gives higher rate of epileptic seizures in the settings of video electroencephalography (vEEG), monitoring that is a subject to further registration and analysis. A very rare complication of this method is transient lesion of the splenium of corpus callosum (SCC) detected with brain MRI. Case report. We presented a patient with a 5-year history of pharmacoresistant epilepsy admitted to the Institute of Neurology (August, 2008) for vEEG monitoring. Interictal epileptic discharges but none seizure were recorded after the sudden withdrawal of antiepileptic medications, during 5 days of vEEG monitoring Initial brain MRI three days after vEEG monitoring revealed focal lesion in SCC, hyperintense on T2 and FLAIR sequence. A longitudinal radiological follow-up (7 and 49 days after initial acquisition) confirmed transient nature of the lesion without diffusion coefficient changes. Conclusion. SCC lesion, reversible and harmless, may occur after a sudden antiepileptic withdrawal. Its early detection makes further extensive neuroradiological and clinical examinations unnecessary.
The Use of Antiepileptic Drugs (AEDs) for the Treatment of Pediatric Aggression and Mood Disorders  [PDF]
Kaizad R. Munshi,Tanya Oken,Danielle J. Guild,Harsh K. Trivedi,Betty C. Wang,Peter Ducharme,Joseph Gonzalez-Heydrich
Pharmaceuticals , 2010, DOI: 10.3390/ph3092986
Abstract: Aggressive symptomatology presents across multiple psychiatric, developmental, neurological and behavioral disorders, complicating the diagnosis and treatment of the underlying pathology. Anti-Epileptic Drugs (AEDs) have become an appealing alternative in the treatment of aggression, mood lability and impulsivity in adult and pediatric populations, although few controlled trials have explored their efficacy in treating pediatric populations. This review of the literature synthesizes the available data on ten AEDs – valproate, carbamazepine, oxcarbazepine, phenytoin, lamotrigine, topiramate, levetiracetam, zonisamide, gabapentin and tiagabine – in an attempt to assess evidence for the efficacy of AEDs in the treatment of aggression in pediatric populations. Our review revealed modest evidence that some of the AEDs produced improvement in pediatric aggression, but controlled trials in pediatric bipolar disorder have not been promising. Valproate is the best supported AED for aggression and should be considered as a first line of treatment. When monotherapy is insufficient, combining an AED with either lithium or an atypical anti-psychotic can result in better efficacy. Additionally, our review indicates that medications with predominately GABA-ergic mechanisms of action are not effective in treating aggression, and medications which decrease glutaminergic transmission tended to have more cognitive adverse effects. Agents with multiple mechanisms of action may be more effective.
Optimal therapy of epilepsy by measuring serum concentration of antiepileptic drugs with least adverse effects
Jovi?evi? Mirjana,Dikli?-Jeremi? Vera V.,Divjak Ivana,?arkov Marija
Medicinski Pregled , 2003, DOI: 10.2298/mpns0310419j
Abstract: The study comprised 150 epileptic patients treated at the Institute of Neurology of the Clinical Centre Novi Sad. The optimal therapy with least adverse effects and seizures was achieved in patients in whom measurement of serum concentration of antiepileptic drugs was performed. Patients were divided into five groups with respect to the therapy they received: I - carbamazepine; II - valproic acid; III - polytherapy with phenobarbitone and diphenylhydantoin; IV - phenobarbitone and valproic acid; and V - phenobarbitone, valproic acid and carbamazepine. No adverse effects were recorded in over 60% of patients on monotherapy, 35% of patients who received two anticonvulsants, and 30% of patients who received three anticonvulsants. Significant correlation between drug dosage and blood drug concentration (r>0.5) was found in polytherapy with phenobarbitone, carbamazepine and valproic acid (r=0,66); and phenobarbitone and diphenylhydantoin (r=0,53).
Outcomes of Disconnective Surgery in Intractable Pediatric Hemispheric and Subhemispheric Epilepsy  [PDF]
Santhosh George Thomas,Ari George Chacko,Maya Mary Thomas,K. Srinivasa Babu,Paul Swamidhas Sudhakar Russell,Roy Thomas Daniel
International Journal of Pediatrics , 2012, DOI: 10.1155/2012/527891
Abstract: Objectives: To study the outcome of disconnective epilepsy surgery for intractable hemispheric and sub-hemispheric pediatric epilepsy. Methods: A retrospective analysis of the epilepsy surgery database was done in all children (age <18 years) who underwent a peri-insular hemispherotomy (PIH) or a peri-insular posterior quadrantectomy (PIPQ) from April 2000 to March 2011. All patients underwent a detailed pre surgical evaluation. Seizure outcome was assessed by the Engel’s classification and cognitive skills by appropriate measures of intelligence that were repeated annually. Results: There were 34 patients in all. Epilepsy was due to Rasmussen’s encephalitis (RE), Infantile hemiplegia seizure syndrome (IHSS), Hemimegalencephaly (HM), Sturge Weber syndrome (SWS) and due to post encephalitic sequelae (PES). Twenty seven (79.4%) patients underwent PIH and seven (20.6%) underwent PIPQ. The mean follow up was 30.5 months. At the last follow up, 31 (91.1%) were seizure free. The age of seizure onset and etiology of the disease causing epilepsy were predictors of a Class I seizure outcome. Conclusions: There is an excellent seizure outcome following disconnective epilepsy surgery for intractable hemispheric and subhemispheric pediatric epilepsy. An older age of seizure onset, RE, SWS and PES were good predictors of a Class I seizure outcome. 1. Introduction Seizures are the most common neurological events of childhood with approximately 3–5% of children experiencing a seizure at some point in their lives 25% of whom subsequently go on to develop epilepsy [1]. The prevalence of epilepsy in India is 4.9 to 6.2 per 1000 population. Of these patients with epilepsy, 43% comprises of children and adolescents [2]. “Intractable epilepsy” is defined as a failure to respond to at least two antiepileptic drugs (AEDs) given over at least a two-year period [3]. A single definition for “intractable” epilepsy cannot suit all situations as definitions of intractability are individualized to the patient. Of these patients deemed to be intractable, approximately 50% are estimated to have surgically remediable epilepsy [4, 5]. “Hemispheric Epilepsy” (HE) refers to epileptiform activity in all four lobes of one hemisphere, and when it involves more than two lobes of the brain, it is termed “subhemispheric epilepsy” (SHE) [4, 6, 7]. These hemispheric brain lesions are commonly associated with early onset of catastrophic epilepsies and multiple seizure types that inhibit brain development. These respond well to early hemispheric/subhemispheric disconnective/resective surgeries
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