Negative Effects of Antiepileptic Drugs on Mood in Patients with Epilepsy

Università di Pisa, Pisa, Tuscany, Italy
Drug Safety (Impact Factor: 2.82). 07/2007; 30(7):555-67. DOI: 10.2165/00002018-200730070-00001
Source: PubMed


With the introduction of several new antiepileptic drugs into clinical practice, renewed attention has been focussed on treatment-emergent adverse effects, including mood disorders. There are several possible causes of psychiatric disorders in patients with epilepsy, including antiepileptic drugs, and it is often difficult to determine whether psychopathological manifestations, especially depressive symptoms, are due to drug therapy or to multiple other factors. Assessment of the negative effects of antiepileptic drugs on mood should always consider all potential factors. Case series, audits and open observational studies can identify psychopathological features, case-control studies are useful for identifying the endophenotypes of patients at risk of adverse effects on mood, and controlled clinical trials give good estimates of incidence of such effects, adjusted for the spontaneous occurrence of symptoms.
The barbiturates, vigabatrin and topiramate show greater associations with the occurrence of depressive symptoms than other antiepileptic drugs, presenting in up to 10% of all patients, but even more so in susceptible patients. Data on zonisamide are scarce but it seems that mood disorders may occur in approximately 7% of patients who are receiving high dosages of this drug. In most cases, the use of monotherapy, with slow titration schedules, can significantly reduce the incidence of mood disorders. Tiagabine, levetiracetam and felbamate present an intermediate risk, with prevalence of depression of about 4% or lower. Phenytoin, ethosuximide, carbamazepine, oxcarbazepine, gabapentin, sodium valproate, pregabalin and lamotrigine are all associated with low risks for depression (<1%), and several of these antiepileptic drugs seem to have a positive effect on mood. Antiepileptic drugs can negatively affect mood and behaviour by different mechanisms: potentiation of GABA neurotransmission, folate deficiency, pharmacodynamic interactions with other antiepileptic drugs in polytherapy regimens, forced normalisation.
Individuals with a personal or family history of depression should be carefully followed after initiation of therapy with a new antiepileptic drug, especially if structural brain abnormalities such as hippocampal sclerosis are present.

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Available from: Ley Sander, Jun 28, 2014
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    • "Mood disorders represent a frequently encountered psychiatric comorbidity in patients with epilepsy whose determinants are both biological and psychosocial [1]. They significantly increase morbidity and mortality [2], being an important predictor of low quality of life (QoL) [3], treatment-emergent adverse events of antiepileptic drugs (AEDs) [4], and poor response to AED treatment [5]. Among psychosocial variables, several authors have pointed out the role of stigma, discrimination [6], locus of control, attributional style, adjustment to epilepsy [7], socioeconomic status, social support, and parental overprotection [8]. "
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    ABSTRACT: Purpose: Interpersonal relationships are viewed as important contexts within which psychopathology emerges and persists or desists. Attachment theory describes the dynamics of long-term relationships between humans especially in families and lifelong friendships. The present study was aimed at investigating attachment styles in adult patients with epilepsy as compared to subjects with migraine and their potential correlates with a history of mood disorders. Methods: A consecutive sample of 219 adult outpatients with epilepsy (117) or migraine (102) was assessed with the Attachment Style Questionnaire (ASQ). Results: Patients with epilepsy and a lifetime history of mood disorders presented elevated scores for Need for approval (p<0.001) and Preoccupation with relationships (p<0.001). Age correlated with the Relationships as secondary (r=0.322; p<0.001) and Need for approval (r=0.217; p=0.019) subscales while age at onset correlated only with Relationships as secondary (r=0.225; p=0.015). Seizure-free patients presented lower scores for Need for approval (p=0.003). Patients with migraine and a lifetime history of mood disorders presented lower scores in Confidence (p=0.002) and higher scores in Discomfort with closeness (p=0.026). Conclusions: An anxious-preoccupied attachment correlated with mood disorders in epilepsy while it was an avoidant pattern in migraine. Our results bring further data on the role of psychological variables in mood disorders in epilepsy. Further studies will allow early identification of patients at risk and the development of preventive strategies.
    Full-text · Article · Dec 2015 · Epilepsy & Behavior
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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.
    Full-text · Article · Aug 2015 · Annales Médico-psychologiques revue psychiatrique
    • "The electrical disturbance during a seizure can have several consequences depending on the magnitude of the seizure and the brain region affected. Anti-epileptic drugs are available, but they often worsen other clinical factors (Mula and Sander, 2007; Frye et al., 2013). There is no consensus of optimal treatment strategy when neonates and children are considered (Slaughter et al., 2013) increasing the need of basic neurobiology studies especially during the early development. "
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    ABSTRACT: During brain development, the electrical disturbance promoted by a seizure can have several consequences, because it can disturb a set of steps extremely regulated needed to the correct brain maturation. Animal modeling of seizure is invaluable to contribute to the mechanistic understanding of punctual seizure event, and those that triggered in an immature neural network could alter the mature brain physiology. In the present study we observed that the exposure to kainic acid diluted directly in water of zebrafish decreased the locomotor activity at 7days post-fertilization (dpf) animals and increased at 15 dpf, despite the absence of more specific seizure features. Pre-exposure to kainic acid (500μM) diluted in water at 7 dpf animals reduced the susceptibility to a second exposure 2months later by intraperitoneal injection. The current data suggest that these different responses are associated with neuronal maturation process and open a question about the window of development that are crucial to long lasting effects related to seizure in this animal model.
    No preview · Article · Apr 2014 · Progress in Neuro-Psychopharmacology and Biological Psychiatry
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