Are Psychiatric Adverse Events of Antiepileptic Drugs a Unique Entity? A Study on Topiramate and Levetiracetam

Department of Clinical & Experimental Medicine, Section of Neurology, Amedeo Avogadro University, Novara, Italy.
Epilepsia (Impact Factor: 4.57). 01/2008; 48(12):2322-6. DOI: 10.1111/j.1528-1167.2007.01262.x
Source: PubMed


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.
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.
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.

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Available from: Ley Sander, Nov 16, 2014
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    • "La première question que doivent se poser les psychiatres qui prennent en charge des troubles de l'humeur chez des patients souffrant d'épilepsie est de savoir si le syndrome dépressif n'est pas secondaire à des antiépileptiques. Ces derniers peuvent être à l'origine ou majorer les symptômes dépressifs et/ou anxieux [23] [30] [31]. La seconde question est d'interroger le lien entre épilepsie et syndrome dépressif. "
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    ABSTRACT: La prévalence des pathologies psychiatriques est plus élevée chez les patients présentant une épilepsie que dans la population générale. Chez plus de la moitié des patients présentant une épilepsie, les épisodes dépressifs caractérisés ont tendance à avoir des manifestations cliniques inhabituelles (notamment sur la durée et le type de symptômes) comparativement aux critères stricts des classifications nosographiques internationales psychiatriques. Un certain nombre de données humaines et animales tendent à mettre en évidence un lien physiopathologique spécifique entre épilepsie et syndrome dépressif. Cette physiopathologie pourrait expliquer la spécificité de la sémiologie du syndrome dépressif chez les patients souffrant d’épilepsie. Cette spécificité clinique conduit à distinguer différentes formes cliniques de syndrome dépressif en fonction de leurs apparitions par rapport aux phénomènes ictaux : péri-ictaux (pré-ictale, ictale, post-ictale) et inter-ictaux. Les épilepsies du lobe temporal sont particulièrement associées à des syndromes dépressifs péri-ictaux. Parmi ces syndromes : (i) la dysphorie péri-ictale est caractérisée par des symptômes apparaissant dans les 24 heures précédant la crise, (ii) le syndrome dépressif ictal par des symptômes apparaissant au moment de la crise, (iii) le syndrome dépressif post-ictal par des symptômes apparaissant dans les 72 heures après la crise. Les syndromes inter-ictaux sont indépendants des crises. Le plus caractéristique est le syndrome dysphorique inter-ictal et regroupe des symptômes dépressifs labiles (humeur dépressive, anhédonie, douleurs et insomnie), des symptômes affectifs labiles (anxiété et attaque de panique) et des symptômes spécifiques dysphoriques (irritabilité paroxystique et euphorie). L’ensemble de ces syndromes dépressifs sont fréquents chez les patients présentant une épilepsie et, bien que les critères des classifications nosographiques internationales psychiatriques ne soient pas forcément retrouvés, altèrent le fonctionnement du patient. Il s’agit donc : (i) de dépister systématiquement un syndrome dépressif chez les patients souffrant d’épilepsie par la Neurological Disorders Depression Inventory for Epilepsy NDDI-E qui est une échelle de dépistage validée en langue française diffusé par l’International League Against Epilepsy ILAE et (ii) de savoir diagnostiquer les syndromes dépressifs péri-ictaux et inter-ictaux.
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    • "Therefore, along with the observed difference in total AEP scores, this finding may also suggest that a subgroup of patients is at an increased risk of treatment-emergent adverse events of AEDs, especially when they are in polytherapy. This point has already been raised by another study comparing patients who developed a similar pattern of psychiatric reactions with two completely different AEDs, namely LEV and topiramate [30]. It is, thus, becoming evident that intrinsic variables (related to the disease or the individual patient) are probably more relevant than drug-related variables such as the mechanism of action. "
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    ABSTRACT: The purpose of this study was to identify clinical correlates of self-reported aggressiveness (SRA) in patients with epilepsy treated with levetiracetam (LEV) with special reference to the role of depression. A consecutive sample of adult outpatients with epilepsy was assessed with the Neurological Disorder Depression Inventory for Epilepsy, the Adverse Event Profile (AEP), and the Emotional Thermometer. From a total sample of 163 consecutive patients treated with LEV, SRA at any level (from rarely a problem to always) was associated with a 7-fold increased risk of being depressed (95% CI: 3.0-17.5; p<0.001). Self-reported aggressiveness was reported as "always" a problem by 9.8% of the patients. In these patients, apart from depression, SRA was associated with high AEP total scores (55.1 vs. 39.3; p<0.001) and polytherapy (43.8% vs. 19.8%; p=0.034). Anxiety scores were not elevated (4.9 vs. 3.6; p=0.183). Self-reported aggressiveness during treatment with LEV is not an isolated symptom but is associated with depressed mood. Anxiety-mediated mechanisms do not seem to be involved. Copyright © 2015 Elsevier Inc. All rights reserved.
    Full-text · Article · Apr 2015 · Epilepsy & Behavior
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    • "The emergence of new anticonvulsant drugs in the past decade and the increased reporting of behavioral disturbances with several of these drugs, associated with an improvement in seizure status, however, have brought FN again into the focus of scientific attention and curiosity. Patients taking ethosuximide, vigabatrin, levetiracetam (LEV), and topiramate (TPM) with multiple daily seizures (mostly if focal and originating from the limbic lobe), sleep disturbances, and previous psychiatric disorders seem to be more vulnerable.15 FN has only been rarely reported in children and adolescents.16 "
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