High-dose diazepam as a long-term treatment strategy for epileptic encephalopathy and developmental epileptic...

To assess the efficacy, safety, developmental and behavioral outcomes associated with 12-month high-dose diazepam (HDD) treatment for epileptic encephalopathy (EE) and developmental epileptic encephalopathy (DEE) spike-and-wave activation in sleep (SWAS).

A single-center prospective study involving twenty patients (mean age 6.1 years, 60 % males) who received two equal doses of oral HDD 1 mg/kg/day (maximum 40 mg), once daily, with a 24-hour interval between doses. Treatment was evaluated by EEG at regular intervals. Patients who exhibited positive responses were subjected to a carefully managed tapering schedule adjusted based on their tolerability. Cognitive changes and adverse events (AEs) were recorded.

The average duration of SWAS before HDD treatment was 2.5 years (range: three months to eight years). Ten patients (50 %) showed EEG improvement after one month, with decreasing response rates over time: 25 % at three months and 20 % at 12 months. Additionally, all patients who remained in remission at 12 months were diagnosed with EE-SWAS. AEs occurred in 60 % of patients, including drowsiness (30 %) and behavioral issues (25 %). Four patients (20 %) discontinued treatment due to intolerable AEs.

HDD demonstrated promising short-term efficacy in reducing epileptiform activity in children with SWAS, though its long-term effectiveness was modest, with responses declining over time. The treatment was generally well-tolerated. However, the occurrence of AEs underscores the importance of vigilant monitoring and tailored management to maximize its therapeutic potential.