Free Communications: Psychosocial Aspect

Abstract

Abstract Effects of Ethyl Loflazepate for Children with Refractory Epilepsy Accompanied by Severe Motor and Intellectual Disabilities. 1 Hideaki Kanemura, 1 Masao Aihara, and 1 Shinpei Nakazawa ( 1 Department of Pediatrics, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan ). Purpose: Ethyl lofrazepate has been used mainly as an antianxiety agent. Recently, ethyl lofrazepate has been reported to demonstrate good efficacy for acute epilepsy, seizure clusters, and serial seizures. Hypersecretion and hypersalivation are problematic adverse reactions in infants and children treated with benzodiazepine drugs. However, ethyl lofrazepate may have a lower incidence of hypersecretion and hypersalivation compared to other benzodiazepine drugs. We report the efficacy of ethyl lofrazepate in three children with refractory epilepsies accompanied by severe motor and intellectual disabilities. Methods: The subjects comprised three symptomatic localization-related epileptic patients aged 2–8 years with severe motor and intellectual disabilities. All patients had some difficulties in seizure control with standard antiepileptic drugs (AEDs). They had multiple seizure types, including simple partial seizures, complex partial seizures, tonic, myoclonic, and generalized tonic–clonic seizures. Prior to starting ethyl lofrazepate, they had difficulty in breathing due to hypersecretion and hypersalivation induced by benzodiazepine drugs. Parents and caregivers, including nursing staff, were requested to keep seizure diaries for seizure counts. The basic strategy was add-on therapy, in which ethyl lofrazepate was additionally given with standard doses of the AEDs. During the titration phase, concomitant benzodiazepine, if any, was gradually withdrawn and discontinued. Ethyl lofrazepate was started at a dose of 0.015 mg/kg and was increased to 0.05 mg/kg in the second week. Ethyl lofrazepate was taken twice a day in the morning and at night. Clinical laboratory tests including antiepileptic drug levels, blood chemistry, and hematology were performed at baseline, and 2, 4, 8, and 12 weeks after reaching the maximum dose of ethyl lofrazepate. EEGs were obtained from all patients at the same time points. Informed consent was obtained from the parents. Results: Seizures were reduced during the first 12 weeks of treatment with ethyl lofrazepate in all three patients (100%). Two patients became seizure free, and one patient demonstrated at least a 90% reduction. All seizure types were reduced by ethyl lofrazepate. The sample size was too small to determine if any particular seizure type was more affected than any other. The response to ethyl lofrazepate was observed within 6 weeks of initiating treatment. One patient had complete cessation of seizures at 2 weeks and another patient became seizure free at 4 weeks after reaching the maximum dose of ethyl lofrazepate. Epileptic discharges were suppressed in two cases and demonstrated at least 75% reduction in one case. No alteration in blood chemistry or hepatic function was observed in any patient. Blood concentrations of other AEDs were unaffected before and after therapy. No adverse reactions such as hypersecretion or hypersalivation were observed. Respiratory status improved markedly in all patients. There were no other adverse effects that required dose reduction of ethyl lofrazepate in all cases. None had a recurrence of seizures or adverse effects such as hypersecretion or hypersalivation at 6-, 8- and 9-month follow-up of ethyl lofrazepate therapy. Conclusion: The results of our prospective study indicate that ethyl lofrazepate is an effective and safe benzodiazepine for the treatment of refractory epilepsy with severe motor and intellectual disabilities. Dramatic improvement (over 90% reduction in seizure frequency, including complete cessation) was observed in all cases. Unlike other benzodiazepines, adverse effects, such as hypersecretion and hypersalivation, were less noticeable. Based on this study, we conclude that ethyl lofrazepate is an effective adjunctive antiepileptic drug for refractory epileptic children with severe motor and intellectual disabilities complicated by respiratory failure. Further studies are necessary to determine whether these effects are transient or permanent.