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Biomedical subjects

J Overweg

Publications and source records attributed to J Overweg.

41 records · Page 3Linked to original sources

Open dose-ranging trial of flunarizine as add-on therapy in epilepsy.

A double-blind placebo-controlled crossover trial of flunarizine as add-on treatment in therapy-resistant epilepsy offered significant evidence of efficacy, but the plasma levels of flunarizine were lower than anticipated, probably due to induction of liver enzymes by comedication. An open dose-ranging trial was therefore undertaken to investigate the relationships among dose, efficacy, side effects, and blood level. With basal medication held constant, flunarizine was added at 3-month intervals in increasing doses of 0, 10, 15, 20, and 25 mg daily, or until side effects occurred or marked seizure reduction was obtained. Forty-seven patients completed the trial; all were adults with therapy-resistant epilepsy who had at least 3 seizures per month. All had complex partial seizures, with additional types in 20. Sixteen patients showed a 50% and 24 a 25% reduction of seizure incidence on flunarizine; 6 and 7, respectively, showed a corresponding increase. The greatest seizure reduction, when observed, occurred generally at a daily dose of 15-20 mg. Side effects, chiefly drowsiness and weight gain, increased markedly between 15 and 20 mg daily. Flunarizine administration produced no change in serum levels of comedication, but flunarizine levels were lower in patients taking more than one other drug. Seizure reduction was obtained most consistently in patients with secondary generalized epilepsy or neurologic deficits. The findings confirm the antiepileptic action of flunarizine in humans and justify further trials.

Adolescent↗

Acute effects of lamotrigine (BW430C) in persons with epilepsy.

Sixteen epileptic patients took single doses of lamotrigine, 120 mg or 240 mg. Six photosensitive patients showed reduction (with abolition in two) in photosensitivity after lamotrigine administration. Five subjects with frequent interictal spikes showed reduction in spike frequency over 24 h after lamotrigine administration. The half-life (t1/2) of lamotrigine in subjects taking sodium valproate was prolonged, whereas the t1/2 in subjects taking carbamazepine and/or phenytoin was reduced. The area under the curve of co-medication plasma levels was not affected by a single dose of lamotrigine. Five patients reported mild and generally transitory side effects; some of which represented exacerbation of preexisting complaints.

Adolescent↗

Gamma-vinyl GABA (vigabatrin) and mood disturbances.

We explored factors that may predispose patients to adverse mood effects during treatment with vigabatrin (gamma-vinyl GABA; VGB): mood disorders before VGB treatment, type of epilepsy, seizure type and seizure frequency, type and number of comedication, and VGB dose. The clinical relevance of such a study is that it may help identify circumstances in which VGB should be administered with caution. Seventy-three patients (40 males, 33 females), all with refractory epilepsies, who received VGB as add-on therapy, were assessed by the Amsterdamse Stemmingslyst (ASL), a mood-rating scale, before the start of treatment, and demographic and clinical data were recorded. The patients were followed for 6 months after the start of VGB treatment. Treatment with VGB had to be discontinued in 38 patients (52% of the total sample). Mood problems were the main reason for discontinuation in 9 (12.3% of the total sample). In 6 other patients, mood problems were mentioned as the reason for discontinuing treatment, in combination with lack of drug efficacy. Development of adverse mood effects could not be predicted by a specific mood profile on the ASL. Before treatment, the "mood problems discontinuation group" did not show extreme scores for any assessed areas of mood and no significant differences from other patients were noted on the mood scales. Neither did clinical or demographic data show statistically confirmed specific characteristics for the mood problems discontinuation group, though the patients tended to use more antiepileptic drugs (AEDs) as cotherapy, to have a slightly lower daily dose of VGB, to be slightly older, and were mostly female.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Clinical treatment of epilepsy with calcium entry blockers.

In view of the known role of Ca2+ in the paroxysmal depolarisation shifts of epileptic neurons, the possibility arises that certain Ca2+ entry blockers possess antiepileptic activity. The only drug of the class which readily passes blood-brain barrier is flunarizine. This is effective in experimental models of epilepsy and produced significant seizure reduction in two trials in therapy-resistant patients. Efficacy was maintained without development of tolerance. The safety of the drug has already been established in a great number of subjects treated for a long time for other diseases. It has few and mild side effects at therapeutic blood levels.

Epilepsy↗

Aura and post-ictal headache in epileptic patients treated with flunarizine.

Flunarizine is effective for the prophylaxis of both migraine attacks and epileptic seizures. Of 77 patients treated with flunarizine for intractable epilepsy, 28 had an aura preceding their seizures. In 22 this disappeared on flunarizine administration. Of 14 subject to post-ictal headache, 13 reported relief of this symptom on flunarizine.

Epilepsy↗