The aim of this study was to determine the tolerability and efficacy of two oral regimens of levetiracetam, 1000 mg and 2000 mg twice daily, as add-on treatment without titration in patients with refractory epilepsy. After a 1- to 4-week baseline, 119 patients were randomized to receive levetiracetam 2000 mg daily, 4000 mg daily, or placebo for a 24-week double-blind period, then levetiracetam 4000 mg daily in a 24-week open-label phase. Somnolence was the most common reason for discontinuation, and along with asthenia, occurred more frequently with levetiracetam than placebo. Responder rates were higher with levetiracetam 2000 mg and 4000 mg daily (48.1% [P < 0.05] and 28.6% [NS], respectively) than placebo (16.1%). In the open-label phase, the overall responder rate was 43.0%. Switching from placebo to levetiracetam increased the overall responder rate from 16.7% to 44.0%. No such increase was observed with patients initiated on levetiracetam 2000 mg daily. Levetiracetam initiated at doses of 2000 mg or 4000 mg daily without titration is well-tolerated and effective as add-on therapy in patients with partial and/or generalized seizures. The higher dose may be related to an increased incidence of somnolence and is not necessarily more effective than the lower dose.
Clinical guidelines for the treatment of epilepsy have been published. A statement on management issues for women with epilepsy has recently been produced by the American Academy of Neurology which has raised awareness of the issues facing women with epilepsy. The communication presented here aims to review current literature on specific issues relating to women with epilepsy, and proposes graded recommendations for its management within a UK health care framework.
The purpose of this paper is to understand the association between antiepileptic drugs (AEDs), patient characteristics, changes in seizure pattern and emergent psychiatric disorder, i.e. psychosis or affective disorder. To this end we carried out a retrospective casenote study on 89 patients who developed psychiatric symptoms during treatment with topiramate, vigabatrin or tiagabine. The psychiatric problem was either an affective or a psychotic disorder (not including affective psychoses). It was discovered that 99% of the patients suffered from complex partial seizures with or without secondary generalization. More than half were on polytherapy with two or more other AEDs. Nearly two-thirds had a previous psychiatric history. There was a strong association between the type of previous psychiatric illness and the type of emerging psychiatric problem, both for psychoses and for affective disorders. Patients on vigabatrin had an earlier onset of epilepsy and more neurological abnormalities than those on topiramate. Those patients on lower doses had a shorter interval between the start of the AED therapy and the onset of the psychiatric problem. A seizure-free period was observed in more than half of the patients before they developed the psychiatric symptoms, and of these more were likely to develop a psychosis rather than an affective disorder. There seemed to be an association of suppression of right-sided seizures and the onset of the psychiatric problem. The conclusions drawn were that patients with a previous history of psychosis or affective disorder tended to develop the same psychiatric problem with new AEDs. Those with a seizure-free period before the onset of the psychiatric problem were more likely to develop a psychosis than an affective disorder.
Visual disturbances are a common side-effect of many antiepileptic drugs. Non-specific retino- and neurotoxic visual abnormalities, that are often reported with over-dosage and prolonged AED use, include diplopia, blurred vision and nystagmus. Some anticonvulsants are associated with specific visual problems that may be related to the mechanistic properties of the drug, and occur even when the drugs are administered within the recommended daily dose. Vigabatrin, a GABA-transaminase inhibitor, has been associated with bilateral concentric visual field loss, electrophysiological changes, central visual function deficits including reduced contrast sensitivity and abnormal colour perception, and morphological alterations of the fundus and retina. Topiramate, a drug that enhances GABAergic transmission, has been associated with cases of acute closed angle glaucoma, while tiagabine, a GABA uptake inhibitor, has been investigated for a potential GABAergic effect on the visual field. Only mild neurotoxic effects have been identified for patients treated with gabapentin, a drug designed as a cyclic analogue of GABA but exhibiting an unknown mechanism while carbamazepine, an inhibitor of voltage-dependent sodium channels, has been linked with abnormal colour perception and reduced contrast sensitivity. The following review outlines the visual disturbances associated with some of the most commonly prescribed anticonvulsants. For each drug, the ocular site of potential damage and the likely mechanism responsible for the adverse visual effects is described.
Summary: Purpose: Symptomatic visual field constriction thought to be associated with vigabatrin has been reported. The current study investigated the visual fields and visual electrophysiology of eight patients with known vigabatrin‐attributed visual field loss, three of whom were reported previously. Six of the patients were no longer receiving vigabatrin.
Methods: The central and peripheral fields were examined with the Humphrey Visual Field Analyzer. Full visual electrophysiology, including flash electroretinography (ERG), pattern electroretinography, multifocal ERG using the VERIS system, electro‐oculography, and flash and pattern visual evoked potentials, was undertaken.
Results: Seven patients showed marked visual field constriction with some sparing of the temporal visual field. The eighth exhibited concentric constriction. Most electrophysiological responses were usually just within normal limits; two patients had subnormal Arden electro‐oculography indices; and one patient showed an abnormally delayed photopic b wave. However, five patients showed delayed 30‐Hz flicker b waves, and seven patients showed delayed oscillatory potentials. Multifocal ERG showed abnormalities that sometimes correlated with the visual field appearance and confirmed that the deficit occurs at the retinal level.
Conclusion: Marked visual field constriction appears to be associated with vigabatrin therapy. The field defects and some electrophysiological abnormalities persist when vigabatrin therapy is withdrawn.
A group of 105 women (54 of whom were, and had only ever been, taking valproate for at least a year, and 51 who had only ever taken either lamotrigine or carbamazepine, for at least a year) were compared with a group of 50 women who did not have epilepsy: any oral contraceptive taken at the time of testing was recorded and blood levels of follicle stimulating hormone (FSH), luteinising hormone (LH), testosterone and prolactin were estimated from days 2 to 6 of the menstrual cycle (day 1 being the first day of bleeding) and an MRI scan made of their pelvis. Women with epilepsy in general were significantly more likely to exhibit evidence on MRI scanning, of polycystic ovaries (PCO): women taking valproate but not an oral contraceptive were significantly more likely to have clinical biochemical evidence of the polycystic ovarian syndrome (PCOS) with raised LH and/or testosterone levels between days 2 and 6 of their menstrual cycle than women who did not have epilepsy: this was not so for women taking lamotrigine or carbamazepine. Since the polycystic ovary syndrome has potentially serious consequences it is suggested that, where possible, valproate is avoided in women of child bearing potential.
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