Negative Effects of Antiepileptic Drugs on Mood in Patients with Epilepsy

Università di Pisa, Pisa, Tuscany, Italy
Drug Safety (Impact Factor: 2.82). 01/2007; 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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    • "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. "

    Annales Médico-psychologiques revue psychiatrique 08/2015; DOI:10.1016/j.amp.2015.07.034 · 0.22 Impact Factor
    • "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 · 3.69 Impact Factor
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    • "Levinson és mtsai kettős vak, placebokontrollált vizsgálatukban azt találták, hogy a vigabatrinnal kezelt személyekben a depresszió előfordulása 12% volt, szemben a placebóval kezelt csoportban tapasztalt 3,5%-kal [14]. A topiramáttal kezelt betegek mintegy 10%-ában alakultak ki dózisfüggően depressziós tünetek, és azon személyek esetében sokkal gyakrabban, akiknek a családjában vagy anamnézisében előfordult már a depresszió vagy más pszichiátriai betegség [9] [15] [16]. "
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    ABSTRACT: Although medications such as anticancer, antimicrobial, immunomodulatory, neurological or hormonal therapies may have a negative impact on mood, adequate attention was not paid until the withdrawal of rimonabant in 2008. In the present study the authors review full spectrum of currently available medications discussing anxiety and depression as possible adverse effects of treatment. A relatively high risk of depression should always be considered when pharmacotherapy applied, especially if current depressive episodes, positive family history, or neurotic personality traits increasing susceptibility to depressogenic effects. Prior to start of medical treatment, the potential effectiveness of the given drug should be precisely evaluated, and alternative medical and non-medical treatment options should also be carefully considered. In addition, monitoring patients during treatment for signs of depressive or anxious symptoms is necessary. Orv. Hetil., 2013, 154, 1327-1336.
    Orvosi Hetilap 08/2013; 154(34):1327-36. DOI:10.1556/OH.2013.29681
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