Fetal malformations associated with the use of methylphenobarbital and carbamazepine during pregnancy. Two case reports and review of the literature.

The use of antiepileptic drugs (AEDs) during pregnancy has been associated with an increased risk of major and minor fetal malformations. This paper describes 2 infants with malformations born to epileptic mothers who used AEDs throughout pregnancy. In the first case, the AED used for seizure control was methylphenobarbital, while in the second case the patient had been prescribed carbamazepine. We noted major and minor congenital malformations in both infants exposed in utero to these anticonvulsant drugs. Pregnant women still experience poor obstetrical care because they report to tertiary centers at the end of their pregnancy or when in labor, making it difficult to provide proper medical care for both the infant and the mother.

Barbiturate anticonvulsants: a neuropsychological and quantitative electroencephalographic study.

We studied 11 epileptic children aged 7 to 14 years with quantitative electroencephalographic (EEG) and neuropsychological tests, both on and off the barbiturate anticonvulsants phenobarbital and mephobarbital, comparing them to 13 controls matched for age and IQ who received testing at similar intervals. Neuropsychological tests employed were the Wechsler Intelligence Scale for Children-Revised (WISC-R), Bender-Gestalt, controlled oral word association test (COWAT), selected subtests of the Wechsler Memory Scale-Revised, Purdue Peg Board, Stroop Test, Trail Making Test, Wide Range Achievement Test-Revised, and Achenbach Behavior Rating Scale. There was no difference between on- and off-drug quantitative EEG in percentage power of any frequency band between 0.6 and 32 Hz. Neuropsychological data from all 11 subjects were analyzed with a two-factor analysis of variance with repeated measures on the time factor. The only difference from controls was on the Stroop Test. Parents reported clear behavioral changes in 6 of 11 subjects, but in 4 of these children the behavioral changes were sufficiently mild that parents chose to continue the barbiturate anticonvulsants: irritability, oppositional attitude, and overactivity were described. Mephobarbital was reported by parents to cause less severe problems than phenobarbital in subjects who had taken both barbiturate anticonvulsants. Barbiturate anticonvulsants have no effect on quantitative EEG and limited effects on neuropsychological tests in school-aged children.

Barbiturate anticonvulsants in refractory affective disorders.

Despite an increasing literature demonstrating both acute and long-term positive psychopharmacological effects of both valproate and carbamazepine, phenytoin has remained a controversial intervention, and barbiturate anticonvulsants have generally received poor press with regard to psychotropic effects. In the present investigation, 27 seizure-free, affectively ill patients who received therapeutic trials of primidone and/or mephobarbital after failing on antidepressants, lithium, carbamazepine, valproate, and phenytoin were analyzed with regard to effects on illness severity and affective cycle rate over a period of as long as four years. Nine (33%) of the patients had a sustained positive therapeutic effect on affective state and/or psychotic symptoms to primidone and three (11%) had positive effects on mephobarbital after primidone failure. Four (15%) had brief positive effects that were not sustained, and the remaining 11 (41%) had no effects or negative effects to these agents. The theoretical and practical implications of this new and unexpected finding are discussed.

Tratamiemto de los icteros del recién nacido con un inductor enzimático, el metilfenobarbital / Management of icterus in neonates with an enzymatic inductor, methylphenobarbital

Se realiza un estudio doble ciego. se utilizó un inductor enzimático, el metilfenobarbital y un placebo para evaluar los efectos del primero sobre los icteros del recién nacido. Los pacientes se dividieron en 2 grupos: uno que comprendia a niños con peso entre 2 500 y 3 499 g y otro, con peso entre 3 500 y 4 000 g. Para el primer grupo se utilizó una dosis de 30 mg del producto y para el segundo 40 mg. Las cifras de bilirrubina disminuyeron significativamente en el primer grupo, no así en el segundo. Se especuló que el no resultado significativo en el segundo grupo pudo haber sido por una dosis insuficiente del metilfenobarbital

Tratamiemto de los icteros del recién nacido con un inductor enzimático, el metilfenobarbital / Management of icterus in neonates with an enzymatic inductor, methylphenobarbital

Se realiza un estudio doble ciego. se utilizó un inductor enzimático, el metilfenobarbital y un placebo para evaluar los efectos del primero sobre los icteros del recién nacido. Los pacientes se dividieron en 2 grupos: uno que comprendia a niños con peso entre 2 500 y 3 499 g y otro, con peso entre 3 500 y 4 000 g. Para el primer grupo se utilizó una dosis de 30 mg del producto y para el segundo 40 mg. Las cifras de bilirrubina disminuyeron significativamente en el primer grupo, no así en el segundo. Se especuló que el no resultado significativo en el segundo grupo pudo haber sido por una dosis insuficiente del metilfenobarbital

[A barbiturate derivative-induced depressive syndrome in a 9-year-old boy with complex focal seizures and secondary generalization--a case report]. / Ein durch Barbituratabkömmlinge induziertes depressives Syndrom bei einem 9jährigen Jungen mit komplexen fokalen Anfällen und sekundärer Generalisierung - ein Fallbericht.

The mental side-effects of long-term anticonvulsant medication are still not widely enough known. The paper describes the case of a depressive syndrome induced in a nine-year-old boy, with complex localised attacks and secondary generalisation, which completely receded on treatment with Convulsofin.

Induction of bilirubin-eliminating processes by methylphenobarbital in mature newborn babies.

In order to find a drug for the prevention of metabolic hyperbilirubinemia of the newborn, which has less sedative effects than phenobarbital (PB) the effect of methylphenobarbital (MPB) on the plasma bilirubin concentration of newborns was studied in a double blind trial. MPB (3 x 10 mg/kg on the first day) reduced the plasma bilirubin level in mature newborns on day four by 33% in comparison to those on placebo. The results justify further investigations in premature babies, who frequently suffer from disturbances which may facilitate the development of bilirubin encephalopathy.

A randomized, double-blind, crossover study of phenobarbital and mephobarbital.

Some pediatric neurologists maintain that mephobarbital (Mebaral) causes fewer behavioral side effects than phenobarbital. Because this hypothesis has not been previously tested, we conducted a prospective, double-blind, randomized, crossover study of these two anticonvulsants. Both drugs were equally effective in reducing the frequency of seizure, although serum phenobarbital levels were significantly higher when the patients were taking phenobarbital compared to mephobarbital. As measured by the Abbott Parent Questionnaire, there was no significant deterioration of behavior with either phenobarbital or mephobarbital, regardless of which drug was administered first.

Mephobarbital and phenobarbital plasma concentrations in epileptic patients treated with mephobarbital.

Plasma mephobarbital and phenobarbital concentrations were determined in 11 epileptic patients receiving mephobarbital alone or in combination with other antiepileptic drugs. The analysis was carried out by a selective ion monitoring (SIM) mass fragmentography technique following formation of N-propyl derivatives of both drugs. The plasma concentrations of phenobarbital ranged from 4 to 32 micrograms/ml and those of mephobarbital from 0.2 to 1.7 micrograms/ml. Differences in the metabolism rates of the drugs accounted for the plasma concentration differences; mephobarbital is metabolized more rapidly than phenobarbital. Phenobarbital concentrations obtained by SIM mass fragmentography were similar to those obtained by gas-liquid chromatographic on-column methylation, which quantitates only "total phenobarbital" (mephobarbital plus phenobarbital).

Behavior disturbance, phenobarbital, and febrile seizures.

Of 109 children treated daily with phenobarbital following the first fibrile convulsion, 42% developed a behavior disorder, usually hyperactivity. Daily phenobarbital therapy was prematurely discontinued in 54% of the children with behavior abnormality (20% of those treated). The behavior disturbance usually appeared within several months, was no correlated with high blood barbiturate levels, disappeared in 73%, and improved in all children when barbiturate therapy was discontinued. No characteristics of the child, the initial febrile seizure, or recurrence of febrile seizures were significantly correlated with the occurrence of the behavior disorder except for behavioral abnormality preceding the initial febrile convulsion. Eighteen percent of the children who received no phenobarbital developed behavior disorder, most often hyperactivity. The behavior disturbance spontaneously disappeared in 52%. Among these children not given phenobarbital, the group with normal behavior had a greater frequency of family history of seizures, especially febrile convulsions, and a lower frequency of preseizure behavior disturbance; abnormalities of pregnancy, labor, delivery, and neonatal period; delayed milestones; long seizures; abnormal results of neurological examination; abnormal EEG; and recurrent febrile seizures.

Acetazolamide-accelerated anticonvulsant osteomalacia.

Severe osteomalacia was present in two epileptic patients who were under long-term treatment with congeners of phenytoin, phenobarbital, and acetazolamide. These patients showed slightly low serum calcium, normal or low serum phosphate, and normal parathyroid hormone concentrations. Discontinuation of acetazolamide produced an immediate threefold drop in the level of urinary calcium excretion and a slight rise in tubular reabsorption of phosphate, with no dectectable change in serum calcium or phosphate concentrations. Acetazolamide may have accelerated the development of osteomalacia by several mechanisms, including increased renal calcium excretion.