A 29-year-old female patient suffers from idiopathic generalized epilepsy with myoclonic jerks in her upper extremities since her 13th year of life. In addition, she had experienced a total of five generalized tonic clonic seizures after awakening since her 14th year of life. These grand mal seizures commonly are triggered by sleep deprivation the night before. Age at epilepsy onset and both seizure types indicate juvenile myoclonic epilepsy.
Initially, the patient was treated with lamotrigine, but this resulted in an increase of early morning myoclonia. Unfortunately, this is a typical adverse effect of sodium channel blockers. After that, the patient was treated with valproic acid which – in a dose of 1,200 mg daily – resulted in complete seizure freedom for the last 10 years.
The patient now presents with the perspective of becoming pregnant in the forthcoming months. We explained to the patient that pregnancies while treated with valproic acid on the one hand are associated with an increased risk for gross malformations and on the other hand may result in impaired intellectual capabilities of the offspings. Occurrence of both complications is a function of the antiepileptic drug dose.
A recent warning by the European Medicines Agency pointed to the teratogenic effects of valproic acid. It stated that in women who can become pregnant valproic acid may only be administered if other suitable drugs had not been efficacious or had been associated with harmful adverse effects.
We switched the patient from valproic acid to levetiracetam. In idiopathic generalized epilepsy, this antiepileptic drug is not licensed for monotherapy but only for add-on treatment (“off lable use”, i.e. treatment beyond license). Nevertheless, levetiracetam exhibits excellent efficacy in juvenile myoclonic epilepsy. Unfortunately, yet 3 weeks after levetiracetam treatment onset, the patient developed psychiatric adverse effects including anxiety and depressive symptoms. The next antiepileptic drug was topiramate but some weeks later the patient had a generalized tonic clonic seizure – after prior 10 years of seizure freedom. The patient denied further dose increase. In that situation, we recommended to the patient returning to valproic acid. We aimed at a significantly lower dose of 600 mg daily and distributed the dose to four times daily 150 mg. In addition, we administered 5 mg folic acid.
In summary, pregnancies with valproic acid treatment – at best – should be avoided at all. In idiopathic generalized epilepsy, this antiepileptic drug is the most efficacious substance, other drugs are not able to prevent seizure recurrences that reliably. Thus, sometimes it seems impossible to refrain from valproic acid in pregnancies. In these cases, a low maximal daily dose should be sought for in order to prevent damaging – teratogenic – effects on the child.
Cases of the months before