Posts tagged antiepileptic drugs
Articles and news from the latest research reports.
Anti-epilepsy drugs can cause inflammations
Glial cells play a crucial role in the nervous system
Hannes Dambach from the Department for Neuroanatomy and Molecular Brain Research, together with a team of colleagues, studied how anti-epilepsy drugs affect the survival of glial cells in cultures. Glial cells are the largest cell group in the brain; they are crucial for supplying neurons with nutrients and affect immune and inflammatory responses. The question of how glial cells are affected by anti-epilepsy drugs had previously not been studied in depth. The RUB work group Clinical Neuroanatomy, headed by Prof Dr Pedro Faustmann, analysed four substances: valproic acid, gabapentin, phenytoin and carbamazepine.
Four anti-epilepsy drugs affect glial cells in different ways
Glial cells treated by the researchers with valproic adic and gabapentin had better survival chances than those treated with phenytoin and carbamazepine. However, carbamazepine had a positive effect, too: it reduced inflammatory responses. Valproic acid, on the other hand, turned out to be pro-inflammatory. In how far the anti-epilepsy drugs affected inflammations was also determined by the applied dose. Consequently, different drugs affected glial cells – and hence indirectly the neurons – in different ways.
Inflammatory responses should be taken under consideration in clinical studies
“Clinical studies should focus not only on the question in how far anti-epilepsy drugs affect the severity and frequency of epileptic seizures,” says Pedro Faustmann. “It is also necessary to test them with regard to the role they play in inflammatory responses in the central nervous system.” Thus, doctors could take the underlying inflammatory condition under consideration when selecting the right anti-epilepsy drug.
Epilepsy may have different causes
In Germany, between 0.5 and 1 percent of the population suffer from epilepsy that requires drug treatment. The disease may have many causes: genetic predisposition, disorders of the central nervous system after meningitis, traumatic brain injury and stroke. Inflammatory responses may also be caused by damage to the brain.
Important breakthrough in identifying the effect of epilepsy treatment
50 years after valproate was first discovered, research published today in the journal Neurobiology of Disease, reports how the drug works to block seizure progression.
Valproate (variously labelled worldwide as Epilim, Depacon, Depakene, Depakote, Orlept, Episenta, Orfiril, and Convulex) is one of the world’s most highly prescribed treatments for epilepsy. It was first discovered to be an effective treatment for epilepsy, by accident, in 1963 by a group of French scientists. In thousands of subsequent experiments, animals have been used to investigate how valproate blocks seizures, without success. Scientists from Royal Holloway and University College London have now identified how valproate blocks seizures in the brain, by using a simple amoeba.
“The discovery of how valproate blocks seizures, initially using the social amoeba Dictyostelium, and then replicated using accepted seizure models, highlights the successful use of non-animal testing in biomedical research,” said Professor Robin Williams from the School of Biological Sciences at Royal Holloway.
“Sodium valproate is one of the most effective antiepileptic drugs in many people with epilepsy, but its use has been limited by side-effects, in particular its effect in pregnant women on the unborn child,” said Professor Matthew Walker from the Institute of Neurology at University College London. “Understanding valproate’s mechanism of action is a first step to developing even more effective drugs that lack many of valproate’s side-effects.
“Our study also found that the decrease of a specific chemical in the brain at the start of the seizure causes even more seizure activity. This holds important implications for identifying underlying causes,” added Professor Williams.
(Source: rhul.ac.uk)
Fetal exposure to antiepileptic drug valproate impairs cognitive development
The effects of antiepileptic drugs during pregnancy have long been a concern of clinicians and women of childbearing age whose seizures can only be controlled by medications. In 1999, a study called the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) began following the children of women who were taking a single antiepileptic agent during pregnancy. The drugs included carbamazepine, lamotrigine, phenytoin or valproate.
Recently released final data from NEAD shows that at age 6, IQ is 7-10 points lower in children exposed in utero to the anti-epileptic drug valproate (Depakote) than those exposed to the other medications. The children exposed to valproate also did poorly on measures of verbal and memory abilities, and non-verbal and executive functions. The results were reported in the January 23, 2013, Lancet Neurology publication on line.
"Data published at ages 3 and 4.5 showed similar results in cognitive impairment," says lead study author Kimford Meador, MD, professor of neurology at Emory University School of Medicine. "Age 6 IQ was our primary outcome goal because it is standardized and predictive of school performance."
The NEAD study is the largest prospective study examining the cognitive effects of fetal antiepileptic drug exposure. The researchers monitored women through pregnancy and followed their children, performing cognitive testing at ages 2,3,4.5 and finally at 6. In addition to the effect on cognitive function, earlier data from NEAD showed an increase in the risk of anatomical birth defects.
Valproate is an anticonvulsant used in the treatment of epilepsy, migraines and bipolar disorder, and is particularly effective in the treatment of primary generalized seizures. Except for a small number of women who only respond to valproate, there are alternative medications.
"These findings consistently show a substantial loss of developmental abilities for these children," says Meador. "Women of childbearing age who have epilepsy should talk with their doctors about their options, and possibly test the safer medications prior to pregnancy to find out if they work."
In order to avoid seizures with potentially serious consequences, Meador emphasizes that women who are already pregnant and taking valproate should not stop without consulting their physicians.
"For a woman who has significant seizures, the risk from the seizure itself is worse than the risk of taking the drugs," he points out. "The number one reason for miscarriage late in pregnancy for women with epilepsy is trauma resulting from a seizure."
Meador will co-lead a follow-up study with Page Pennell, MD, from Harvard. The new study funded by the National Institutes of Health is called Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD), and will investigate the risks of these same drugs to both the mother and the child. The study will be conducted at 19 sites, enrolling 350 women with epilepsy during pregnancy. An additional 100 women with epilepsy who are not pregnant, and 100 healthy pregnant women will serve as controls.
(Source: news.emory.edu)