Limited data: levetiracetam, ketogenic diet, and modified Atkins diet decrease seizure frequency in children younger than 3 years with epilepsy

Reference

Treadwell JR, Kessler SK, Wu M, Abend NS, Massey SL, Tsou AY. Pharmacologic and dietary treatments for epilepsies in children aged 1-36 months: a systematic review. Neurology 2023;100(1):e16-e27.

Synopsis

This team searched several databases for any study published since 1999 that included children aged 1 month to 36 months of age with epilepsy and reported changes in seizure frequency for pharmacologic and dietary interventions. The authors included randomized trials as well as observational studies. The authors used validated tools to assess the risk of bias and ultimately included 23 studies, only 6 of which were randomized. None of the studies were at low risk of bias. The authors wisely chose not to pool the data. Fifteen studies (n = 1533 children) assessed pharmacologic agents and 8 assessed dietary interventions (n = 411 children). Based on 4 studies, levetiracetam appears to be more effective than valproate, phenobarbital, or no therapy in decreasing seizures or stopping them altogether. The authors report they could draw no conclusions about the effectiveness of the other agents (topiramate, lamotrigine, phenytoin, vigabatrin, rufinamide, or stiripentol. Three medications had low rates of discontinuation (levetiracetam, topiramate, and lamotrigine). Although serious adverse events were rare, the attribution of harm to specific agents in low-quality studies is dicey. For example, one study of levetiracetam reported 32% of children had severe adverse events, but the authors reported that only 2% were due to the drug. The dietary interventions of some form of ketogenic diet were associated with reductions in seizure frequency that ranged from 12% to 37%. Four studies also included a modified Atkins diet; it was also associated with fewer seizures but to a lesser degree than the ketogenic diets. Withdrawal from the dietary studies because of intolerance or excessive weight loss ranged from 2% to 20%. Adverse gastrointestinal effects (constipation, nausea, vomiting, and so forth) were the most common reported (one-quarter to one-third of children).