A case of forced normalization due to perampanel

Background

Forced normalization (FN) refers to the onset of psychiatric symptoms following an electroencephalogram (EEG) documented reduction in epileptic activity, cessation of clinical seizures, or both in patients with epilepsy. FN is mainly triggered by anti-seizure medication (ASM). Many ASMs have been implicated in the development of FN. However, few studies have reported perampanel (PER) induced FN.

Case report: A 10-year-old boy with a history of brain tumor resection was diagnosed with focal epilepsy based on the seizure type and EEG findings. Levetiracetam was irritable and ineffective. Lacosamide provided only partial effectiveness, leading us to prescribe PER as an add-on therapy. Approximately a week after initiating PER, the seizures resolved. However, the patient experienced concomitant emotional and cognitive instability, loss of appetite, and depression. The epileptic discharges ceased a month after starting PER, and we concluded that the FN was attributable to PER. Psychiatric symptoms gradually improved over a few months after the PER dose reduction.

Discussion

Patients with structural etiology and focal epilepsy are vulnerable to FN, putting our patients at a high risk for FN. Administration of a new ASM is the most common trigger for FN. This report is the first to describe FN induced by PER. Like other ASMs, psychiatric symptoms, seizure frequency, and EEG changes should be assessed when administering PER. Clinicians should be aware that discontinuing or reducing the dosage of the triggering medication can improve FN symptoms.