Oxcarbazepine (GP 47.680): a possible alternative to carbamazepine?

A double-blind randomized crossover design trial of carbamazepine (CBZ) and oxcarbazepine (OCBZ) was performed with 48 in-patients with epilepsy. All were stabilized on polytherapy including CBZ and had at least two seizures per week. CBZ was replaced by the trial medication. Each trial period started with a titration, followed by a 12-week steady state. Concomitant medications were kept constant during the trial. The criteria for assessment were seizure fit frequency and severity; tolerability; hematology and blood chemistry; plasma levels of antiepileptic drugs; EEG; cardiovascular parameters; and treatment preference. The following differences regarding OCBZ were detected: 9% reduction of the total number of seizures, with a significant reduction of tonic-clonic (20%) and tonic (31%) seizures; increased alertness and concentration ability in five patients; an allergic skin reaction with CBZ that completely disappeared in two patients while receiving OCBZ; an increase of valproate and phenytoin plasma levels in a number of patients, probably caused by reduced enzyme induction; a slight but significant reduction of serum Na, not causing clinical symptoms; less seizures than in the CBZ period in 25 patients (52%); and a preference for OCBZ in 23 patients (48%). We consider OCBZ at least as effective as CBZ with a slightly better tolerability. In severe cases, the wider therapeutic window might improve seizure control.

Double-blind study of milacemide in hospitalized therapy-resistant patients with epilepsy.

Milacemide, 2-N-pentylaminoacetamide, a glycine prodrug, which readily crosses the blood-brain barrier, has been tested for antiepileptic efficacy and tolerability in 30 patients compared in a double-blind design with 30 patients treated with placebo. All patients continued to receive, without alteration, their previous partly effective medication. All patients presented an average of at least 10 seizures a month during the 6 months preceding the trial with no more than 50% fluctuation. The ratio of seizure frequency in the trial period over the seizure frequency in the baseline period (RSF) was calculated. In the milacemide group, 9 of 29 patients had an RSF less than 0.7 as opposed to 2 of 29 in the placebo group. Although no firm proof of therapeutic efficacy, this and the dramatic improvement of a patient with myoclonus epilepsy indicates that further studies are warranted. This opinion is strengthened if one considers the subgroup of patients aged less than or equal to 25 years in which a statistically significant reduction in seizure frequency was observed with milacemide treatment. The drug was well tolerated.

Temporal characteristics of seizures and epileptiform discharges.

The time relations of epileptic events have been studied in 3 sets of data: (I) counts of individual epileptiform discharges in twelve 48 h EEG recordings, (IIa) seizure calendars of 30 therapy-resistant outpatients participating in a drug trial, (IIb) seizure calendars of 10 mentally subnormal epileptic patients resident in a long-stay unit. The EEG data I were characterized most often by a Poisson distribution of intervals between discharges and the occurrence of marked periodicities, particularly at night. The periods of rhythmic nocturnal events ranged from 13 to 142 min and did not appear to correspond to the REM/non-REM cycle. In the seizure data IIa and b a Poisson distribution of intervals between events was found in half the patients. Periodicities occurred only in group IIa and did not correspond to weekly or monthly cycles. A stochastic process is considered to be the model which best fits these data.

Carbamazepine and serum sodium levels.

Serum sodium levels of 674 epileptic patients were tabulated according to the following categories: less than 135 mmol/L, hyponatremia (28 patients); 135-145 mmol/L, normonatremia (530 patients); greater than 145 mmol/L, hypernatremia (116 patients). One hundred one patients were treated with antiepileptics without carbamazepine (CBZ), 113 with CBZ monotherapy, and 460 with CBZ plus other antiepileptic drugs. Twenty-three patients could be followed up after the first detection of a serum sodium level of less than 135 mg/L. Ten patients were consistently hyponatremic (greater than 50% of the follow-up measurements were less than 135 mg/L), whereas the remaining 13 were occasionally hyponatremic. The following facts could be derived from the study: (1) The hyponatremic group was significantly older compared with the other groups. (2) In patients not treated with CBZ, no hyponatremia was seen. Only two patients on CBZ monotherapy showed hyponatremia. (3) The combination of CBZ, valproic acid, especially in high dosages, and barbiturates seemed to lead to hyponatremia. (4) The excretion of antidiuretic hormone, measured in 12 patients, was subnormal (less than 25 ng/24 h) in seven hyponatremic patients and in three normonatremic patients and normal (25-250 ng/24 h) in two other normonatremic patients. (5) Cyclic AMP, measured in five hyponatremic patients, was normal. (6) In all patients the hyponatremia was slight and did not cause any clinical symptoms. Special treatment was not required.