Concentration of valproate during pregnancy, in the newborn and in breast milk.

The serum-valproate level of four patients with epilepsy was followed during pregnancy. A decrease in serum level occurred late in pregnancy and was followed by a pronounced increase in the first week after delivery. The maternal serum concentration of valproate was compared to that of the umbilical cord. The level in cord blood was 145-219% higher than that in maternal blood. The concentration of valproate in breast milk was found to be 5-10% of the maternal serum concentration. The serum concentration was measured in one breastfed child. The level was 7.6% of the maternal serum concentration. All children were healthy without any signs of intoxication or malformation. Based on our experience, pregnant patients treated with valproate must be carefully controlled especially during the last month of pregnancy and in the first two weeks after delivery. The amount of valproate excreted into the breast milk was negligible and should not prevent breast feeding.

The effect of L-Deprenyl on on-off phenomena in Parkinson's disease.

L-Deprenyl, a specific monoamine oxidase subtype B inhibitor, has been reported a valuable adjunct to conventional treatment of Parkinsonism. A double-blind cross-over controlled study was performed in 19 parkinsonian patients with on-off type problems. Five mg L-Deprenyl per day reduced the number of on-off episodes. Side effects such as hyperkinesias, vivid dreams, dizziness with diaphoresis were frequent. Severe side effects such as nightmares, postural hypotension, confusion, and dizziness with headaches necessitated discontinuation of the drug in 4 patients. L-Deprenyl was of limited value in this group of patients with longstanding Parkinsonism.

[The epileptic mother and her child]. / Die epilepsiekranke Mutter und ihr Kind.

This study is a review of the literature on the influence of epilepsy and antiepileptic medication on the course of pregnancy and the foetus, as well as of the effect of pregnancy on the disease. Antiepileptic treatment is supposedly responsible for the increased rate of abnormal bleeding after delivery. Data on the perinatal mortality of epileptics are conflicting. The offspring of epileptic women are often smaller than normal neonates, indicating retarded growth, and the incidence of malformations is 1.25 times higher. Until now there has been no direct evidence of a teratogenic effect of the commonly used antiepileptic drugs, and the risk of malformations may possibly be correlated with the severity of the epilepsy. The effect of pregnancy on seizure frequency seems to be quite variable. Higher seizure frequency is seen during pregnancy, but this is not a universal phenomenon. The incidence of seizures in gestational epilepsy has no predictive value with respect to the course of later pregnancy. A positive correlation seems to exist between the development of eclampsia and later epilepsy, a family history of epilepsy and cerebral dysrhythmias. Status epilepticus is uncommon in pregnancy. The requirement of several antiepileptic drugs is increased during pregnancy. The metabolism of carbamazepine, primidone, and clorazepate is probably accelerated in the gestational period, but data on other antiepileptic drugs are inconclusive or lacking. The intestinal absorption of antiepileptic drugs may be impaired during pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Progabide: a controlled trial in partial epilepsy.

Progabide (SL 76002) was studied in a randomized double-blind crossover trial using 20 outpatients suffering from partial complex seizures. Progabide was added to the concomitant antiepileptic treatment in a fixed dosage schedule. The design included an open therapy control unit. No significant difference was established between the number of partial seizures during treatment with progabide and placebo. A trend was observed for lower seizure frequency of secondary generalized seizures during treatment with progabide. Only mild and transient side effects were observed. There was no difference between the side effects of progabide and placebo.

Carbamazepine monotherapy in epileptic out-patients.

The effect and side-effects of carbamazepine monotherapy have been studied retrospectively in 280 epileptic out-patients. The majority of these patients suffered from grand mal epilepsy, partial complex seizures or a combination of both seizure types. Side-effects, in 63% exanthema, led to withdrawal in 10% of the patients. Satisfactory effect of treatment, defined as reduction of seizure frequency by at least 75% or unchanged satisfactory seizure control, was seen in 76% of patients, most commonly those with grand mal. Deterioration was observed in 9% of patients. These results were independent of whether or not carbamazepine monotherapy was drug of first choice. Serum concentrations of carbamazepine, measured in 236 patients, were found to be within the therapeutic range in 72% and above the range in 22%. Our results, which we consider to represent 'normal daily life in an epilepsy out-patient clinic', are comparable with those of controlled prospective studies, but there was a considerably higher frequency of withdrawal due to side-effects.

Treatment of epilepsy in women of child-bearing age: patients' opinion of teratogenic potential of valproate.

83 epileptic women of child-bearing age in treatment with valproate were informed of the potential teratogenic effect of valproate and the precautions available to avoid the suspected risk of malformation i.e. neural tube defect. 66% of the women wished and were able to be pregnant. Out of these 51% at present preferred to continue with valproate. 9% of the patients were immediately switched to other antiepileptic drugs and the remaining part had not yet made up their minds. The study demonstrates that following the statement from the Danish Health Authorities it is difficult also to pay attention to the individual wishes of the women.

[The epileptic mother and her child (author's transl)]. / La mère épileptique et son enfant.

Antiepileptic drugs are thought to be responsible for an abnormally high incidence of post-partum haemorrhages. Data on perinatal mortality of epileptic patients are discordant. Children of epileptic mothers are frequently undersized. Although they have an incidence of malformations 1.25 times higher than average, these may be associated with the severity of seizures and with the disease itself, since there is no evidence that anticonvulsants are teratogenic. The influence of pregnancy on epileptic attacks is extremely variable. Seizures occurring during a pregnancy need not necessarily occur during subsequent pregnancies. There seems to be a positive correlation between eclampsy, late epilepsy, familial epilepsy and abnormal EEGs. Status epilepticus is unusual in child-bearing women. The dosage of several antiepileptic drugs needs to be increased during pregnancy, probably because of accelerated metabolism and reduced intestinal absorption. Decrease in plasma protein levels seems to be of little significance. Antiepileptic drugs which cross the placenta are usually excreted by the newborn within a week, but children of mothers who are given diazepam during delivery may be intoxicated. Drug concentrations in milk are low, but the child must be supervised if the mother takes phenobarbitone or diazepam. However, in most cases breast-feeding is safe. Pregnant epileptic women should be carefully examined throughout pregnancy and post-partum for obstetrical reasons and because the drugs they absorb may give abnormal blood levels.