Rufinamide: a double-blind, placebo-controlled proof of principle trial in patients with epilepsy.

OBJECTIVE: This was the first proof of principle clinical trial assessing the efficacy and safety of rufinamide as adjunctive therapy in epileptic patients. The pharmacokinetic (PK) profile of rufinamide was also determined. METHODS: Fifty patients with diagnoses of partial or primary generalized tonic-clonic seizures were enrolled in this 28-day double-blind, placebo-controlled, weekly rising dose (400-1600 mg/day) trial. PK profiles were obtained after administration of single-dose rufinamide prior to and after the Double-blind phase. RESULTS: In the evaluable patient population, seizure frequency decreased by 41% in the rufinamide group and increased by 52% in the placebo group (P=0.040). Thirty-nine percent (39%) of rufinamide-treated and 16% of placebo-treated patients experienced reduction in seizure frequency of at least 50% relative to baseline (P=0.096). SAFETY: Treatment-emergent adverse events (AEs) consisted mainly of neurologic signs and symptoms commonly associated with antiepileptic drugs (AEDs). PHARMACOKINETICS: At steady state, rufinamide reached a peak plasma concentration with a mean time (Tmax) of 3.4 h and a mean half-life (t1/2) of 7.3 h. No autoinduction of rufinamide metabolism occurred. Rufinamide did not influence the plasma concentration of carbamazepine, phenytoin or valproate when added to these single AED regimens. CONCLUSION: Rufinamide has been shown, in this proof of principle trial, to be safe and effective in reducing seizure frequency in epileptic patients with no relevant influence on the metabolism of other AEDs.

Allergy to carbamazepine: parallel in vivo and in vitro detection.

PURPOSE: Five to 20% of patients discontinue antiepileptic drug (AED) therapy because of adverse reactions. Careful reintroduction, however, may be considered if true drug allergy can be ruled out. Definitive assessment of such immunologically mediated reactions requires demonstration of either specific antibodies or sensitized lymphocytes. METHODS: We investigated whether skin patch tests (PTs) and in vitro lymphocyte proliferation assays (LPAs) were suitable for detection of allergy to carbamazepine (CBZ) and the possibly cross-reactive oxcarbazepine (OCBZ). Data of 65 patients displaying a wide range of possibly allergic side effects to CBZ were available for analysis. Data of CBZ users without any side effects and healthy volunteers served as controls. Both PTs and LPAs were done with CBZ, OCBZ and three metabolites [CBZ-10,11-epoxide (CBZ-E), 10-monohydroxy-CBZ (MHD), and 10,11-dihydroxy-CBZ (DIOL)]. RESULTS: Positive PTs with CBZ were seen in 20% and with OCBZ in 14% of the patients. Positive LPA results with CBZ and OCBZ, respectively, were found in 40 and 19%. Both tests were positive in 14 and 7% of the patients. Cross-reactivity to OCBZ was seen in -40% of CBZ-reactive patients in both PTs and LPAs. CONCLUSION: These data illustrate the additional value of LPAs in the detection of CBZ allergy while showing that a major part of side effects to CBZ and OCBZ is not immunologically mediated, according to PTs and LPAs.

Survey of 260 epileptic patients treated with oxcarbazepine (Trileptal) on a named-patient basis.

We report the clinical findings on all 260 epileptic in- and out-patients of a Dutch epilepsy centre ever treated with oxcarbazepine on a named-patient basis. All but three patients had been previously treated, in vain, with carbamazepine. Of 260 patients, exposed for 935 patient-years, 161 were still treated on reference date, the longest duration of oxcarbazepine treatment being 119 months. Fourteen patients were lost to follow up. Four successfully stopped treatment after full control of their epilepsy for over three years. Seven stopped because they got worse instead of better. Seventy-three did not benefit sufficiently to continue on OCBZ in view of alternative treatment possibilities. In one patient the final diagnosis was pseudo-seizures. The drug is particular useful in patients who require polypharmacy and patients with adverse effects to carbamazepine.

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)

[Disseminated lupus erythematosus induced by carbamazepine (Tegretol)]. / Lupus erythematosus disseminatus geïnduceerd door carbamazepine (Tegretol).

A 20-year-old man is described with drug-induced lupus erythematosus (DILE) induced by carbamazepine prescribed for epilepsy. The symptoms consisted mainly of arthritis and largely disappeared when carbamazepine was replaced by oxcarbazepine. With a simple decision scheme based on serological findings, differentiation between (idiopathic) systemic lupus erythematosus and DILE is possible.

Controlled release carbamazepine: cognitive side effects in patients with epilepsy.

The treatment of epilepsy with carbamazepine (CBZ) may be hampered by cognitive side effects. These side effects are thought to be related to pharmacokinetic properties of the drug. The serum concentration of CBZ is characterized by rapid absorption and a short half-life, which may lead to a considerable fluctuation of the level between doses. Cognitive defects may result from peak levels: short periods with high serum concentration. In a single-blind crossover design, cognitive performance was compared in three conditions. All patients were first tested in the steady state of conventional CBZ. The patients were then assigned randomly to either CBZ-controlled release (CR) or a condition in which conventional CBZ was administered in the same tablet form and dose frequency as CR. Psychological tests were administered four times daily, immediately after the serum samples were taken. A nonmedication control group was tested following the same test scheme to obtain standards for the evaluation of changes in performance during the day. A systematic tendency was found toward higher test performance in the CR condition. This is especially evident for tests of memory and accuracy of visual information processing. The results of the repeated test procedure show that the smoothing effect of the CR condition on serum concentration fluctuations results in a more stable pattern of cognitive functioning during the day.

Duplication in the proximal portion of the long arm of chromosome 15, in a girl without phenotypic features of the Prader-Willi syndrome.

The present report concerns a mentally retarded 14-year-old girl with epilepsy. Her karyotype showed a duplication in the proximal portion of the long arm of chromosome 15. Deficiency as well as excess of chromosome 15 material is sometimes associated with Prader-Willi Syndrome. On clinical investigation no symptoms of this syndrome were found in our patient. The abnormal chromosome appeared to have a duplication for the bands q14 and q15.