First-Line Treatment With Carbamazepine in Neonatal Epilepsy

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Low-dose carbamazepine should be considered as first-line treatment in patients with neonatal epilepsy.
Low-dose carbamazepine should be considered as first-line treatment in patients with neonatal epilepsy.

Low-dose carbamazepine (CBZ) should be considered as first-line treatment for benign familial neonatal epilepsy (BNFE), even in cases of status epilepticus, according to data reported recently in Epilepsia. The majority of neonates given CBZ 10 mg/d as needed responded within hours of administration and remained seizure free with continued treatment for up to 16 years.

Tristan Sands, MD, a pediatric neurologist  at the University of California, San Francisco and an epilepsy fellow at Columbia University in New York, and colleagues gathered retrospective data on 19 BNFE patients from 4 epilepsy centers in the US and Italy and followed them for a mean of 7.8 years (ranging 6 months to 16 years). All of the patients began having multiple daily seizures 2 to 5 days after birth and all were given CBZ daily.

Sixteen of the neonates had a family history of neonatal seizures and 1 had a family history of infantile seizures. Seizure types were focal, affecting either hemisphereand included apnea, desaturation, and asymmetric tonic posturing with clonic jerking.

The majority of the patients in the study (12 of 19, or 63%) had been given up to 4 other drugs prior to being switched to low-dose CBZ. The most common of these was intravenous (IV) phenobarbital, to which only 2 out of 14 patients responded initially and 1 of those was switched to CBZ to maintain a complete response. Other drugs that did not arrest the seizures included IV pyridoxine, IV levetiracetam, high-dose IV benzodiazepines (diazepam or midazolam), or oral clonazepam. Some response to loading doses of IV thiopental and IV phenytoin were observed, but seizures recurred and these patients were given CBZ 10 mg.

A total of 89% (17/19) of the BNFE patients responded promptly to low-dose CBZ or oxcarbazepine (OXC) regardless of whether it was the first or last drug administered. The duration of hospitalizations was significantly reduced (P< .01) with earlier administration after seizure onset; those who received CBZ within 3 days of the first seizure were hospitalized for less than a week, compared with those who did not and required longer hospital stays.

Previous research has shown the likelihood of the development of other forms of epilepsy later in life, documented in up to 25% of cases of BNFE2; however Dr Sands and colleagues reported only 1 patient in the current cohort who later developed uncomplicated febrile seizures. Recurrence of seizures occurred in 2 other patients at 8 months upon withdrawal of CBZ therapy.

The most effective duration of therapy appeared to be 12 to 18 months after initiation, as evidenced by the fact that the majority did not have seizure recurrence after this period, with the exception of 1 child who developed Benign Epilepsy with Centrotemporal Spikes (BECTS) at approximately 3 years of age.

The implications of these findings are highly significant in confirming the effectiveness and safety of low-dose CBZ as a first-line agent for the treatment of neonatal seizures. All of the patients showed a complete response to CBZ and the majority continued to develop normally with treatment, including 4 who had initially been diagnosed with status epilepticus.

References

  1. Sands TT, Balestri M, Bellini G, et al. Rapid and safe response to low-dose carbamazepine in neonatal epilepsy. Epilepsia. 2016;(*):1-12. doi:10.111/epi.13596.
  2. Grinton BE, Heron SE, Pelekanos JT, et al. Familial neonatal seizures in 36 families: clinical and genetic features correlate with outcome. Epilepsia. 2015;56:1071–1080.
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