Seizure disorders and pregnancy.
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Biomedical subjects
Publications and source records attributed to J W Sander.
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The efficacy of allopurinol as an antiepileptic drug has been assessed in a 12 week add-on open uncontrolled study in a small series of 12 patients with intractable epilepsy. Weekly seizure frequencies were observed to be reduced in 4 patients and increased in 5 patients but these changes were not significant and could be attributed to the random variation of seizures.
We report the effects of the addition of nifedipine, a calcium channel antagonist, to the antiepileptic therapy of 20 patients with severe medically refractory epilepsy. Six patients developed side effects and in two the drug had to be discontinued because of these. The commonest side effects were headaches, dizziness and lethargy. Two patients experienced deterioration in seizure control and only 2 patients showed improved seizure control. One of these patients subsequently developed tolerance at 5 months. In 16 patients there was no change.
The pharmacokinetics of midazolam, a water soluble 1,4-benzodiazepine, has been studied in 12 patients (11 male, 1 female; age range 19-57 years) with epilepsy. All patients were taking hepatic enzyme inducing antiepileptic drugs (AEDs) on a regular basis. Midazolam (5 mg) was administered intravenously and 1 week later midazolam was administered intramuscularly, the dose used being dependent on the sedative response to the intravenous dose (10 mg, n = 2; 7 mg, n = 8; 5 mg, n = 2). Serial blood samples were collected at timed intervals for 5-7 h. After intravenous administration initial distribution was rapid with a mean half-life (t 1/2 alpha) of 0.06 +/- 0.03 h followed by a terminal half-life (t 1/2 beta or gamma) of 1.5 +/- 0.3 h. Volume of distribution was 0.62 +/- 0.27 l/kg. After intramuscular administration midazolam was rapidly absorbed with peak serum concentrations achieved at 25 +/- 23 min. Two patients showed delayed absorption. Mean terminal half-life was 2.8 +/- 1.7 h. The absolute bioavailability of intramuscular midazolam was calculated in 11 patients as 87 +/- 18%. Sedation was rapid (less than 1-2 min) but transient (7-75 min) after intravenous and slower (2-30 min) and for a longer period (20-120 min) after intramuscular administration. Since intravenous administration of AEDs including diazepam is not always feasible in status epilepticus there are obvious advantages in having an effective intramuscular formulation. Our data suggest that midazolam may be such a drug.
The traditional view that epilepsy is usually a chronic condition in which the prognosis is consistently poor has been challenged in the last 2 decades. Evidence from population-based studies and from intervention studies in newly diagnosed patients has produced a wealth of information of a much better prognosis. It is now generally accepted that as many as 70-80% of people developing seizures for the first time will eventually achieve terminal remission, whereas the remaining 20-30% will continue to have recurrent seizures despite all treatment. Despite the high recurrence rate after a first epileptic seizure, remission usually occurs early and for most persons, epilepsy is a short-lived condition. The exact role of antiepileptic drugs (AEDs) in this good outcome, however, remains open to debate, because the natural history of the untreated condition is largely unknown. In this article, factors that may influence the prognosis of the epilepsies, including the problems of diagnosis, are reviewed. Special emphasis is given to the issue of spontaneous remission and the question of prognosis of different epileptic syndromes.
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OBJECTIVE: To analyze the cost of monotherapeutic treatment of patients with newly diagnosed epilepsy. PATIENTS AND METHODS: We analysed the cost of treatment with lamotrigine (LTG), carbamazepine (CBZ), phenytoin (PHT) and valproic acid (VPA) using published data regarding the efficacy and tolerability of comparative clinical trials of monotherapy. We established a model of treatment for newly diagnosed patients during the first 12 months after diagnosis. A panel of doctors reached a consensus on the use of resources, costs and model of treatment in Spain. We made a cost minimization analysis for economic assessment of the data based on the fact that randomized trials indicated that CBZ, LTG, PHT and VPA ware of similar efficacy. Analysis was done as 'intention to treat'. Only direct medical costs were considered. RESULTS: In Spain treatment with LTG is twice or three times as expensive as treatment with the other drugs. Sensitivity analysis showed that variations in the interval of use of resources and of costs (defined by the panel of doctors) did not significantly alter the results. CONCLUSIONS: Treatment with LTG is more expensive than treatment with the classical drugs. In view of the methodological limitations of this study, further analysis is necessary, particularly of the methodology of cost-benefit, to evaluate the economic impact of the new antiepileptic drugs and determine whether their use is justified as drugs of first choice.