Negative Effects of Antiepileptic Drugs on Mood in Patients with Epilepsy

Università di Pisa, Pisa, Tuscany, Italy
Drug Safety (Impact Factor: 2.62). 01/2007; 30(7):555-67. DOI: 10.2165/00002018-200730070-00001
Source: PubMed

ABSTRACT 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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    • "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.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 04/2014; 55. DOI:10.1016/j.pnpbp.2014.04.004 · 4.03 Impact Factor
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    • "The primary application is in mood stabilization [11], but interesting data are also emerging regarding anxiety disorders [12] and withdrawal syndromes [13]. As for the old generation of AEDs, both carbamazepine and valproate demonstrated positive psychotropic properties upon their introduction for the treatment of epilepsy [14]. Over time, a number of controlled studies have been carried out in patients with acute mania evaluating the effects of these two AEDs against placebo, lithium, or antipsychotic drugs and demonstrating positive effects, especially in subjects with unstable forms of bipolar disorder such as those who rapidly cycle [15]. "
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    ABSTRACT: Epilepsy is, of course, not one disease but rather a huge number of disorders that can present with seizures. In common, they all reflect brain dysfunction. Moreover, they can affect the mind and, of course, behavior. While animals too may suffer from epilepsy, as far as we know, the electrical discharges are less likely to affect the mind and behavior, which is not surprising. While the epileptic seizures themselves are episodic, the mental and behavioral changes continue, in many cases, interictally. The episodic mental and behavioral manifestations are more dramatic, while the interictal ones are easier to study with anatomical and functional studies. The following extended summaries complement those presented in Part 1.
    Epilepsy & Behavior 06/2013; 28(2). DOI:10.1016/j.yebeh.2013.03.012 · 2.06 Impact Factor
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    • "Such adverse events were usually mild to moderate and generally related to the central nervous system (ie, somnolence, dizziness, depression, anorexia). Cognitive and psychiatric adverse events during treatment with zonisamide have been considered to be of concern.36,37 However, they seem to develop in predisposed subjects36 and careful patient selection reduces this problem.38 "
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    ABSTRACT: Epilepsy is one of the most common neurologic disorders, affecting about 50 million people around the world. It is recognized that around 50% of patients with newly diagnosed epilepsy become seizure-free with the first drug treatment, so the choice of first antiepileptic drug is crucial. This paper provides a comprehensive overview of zonisamide as monotherapy for partial seizures, with special attention to the possibility of a once-daily regimen. The available data suggest that zonisamide is an effective and well tolerated option as monotherapy. Once-daily dosing is indicated, considering the long plasma half-life and linear pharmacokinetics of the drug. Zonisamide 300 mg was shown to be noninferior to carbamazepine 600 mg in terms of efficacy and safety, but even lower doses may be effective. Finally, the broad spectrum of efficacy in different seizure types, the low drug interaction potential, and the possibility of weight loss make zonisamide a preferred option in many epilepsy practices. Further data on monotherapy, especially in special populations, such as women of childbearing potential, are needed.
    Drug Design, Development and Therapy 05/2013; 7:397-402. DOI:10.2147/DDDT.S43612 · 3.03 Impact Factor
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