• Electroencephalography
• Epilepsy
• Psychiatric disorders

Forced normalization (FN) is a unique phenomenon that is often seen in the treatment of epilepsy. FN is characterized by abnormal mental behavior and disordered emotions in epilepsy patients despite a significantly improved electroencephalogram and successful seizure control; the occurrence of FN seriously affects patients’ quality of life. The causes of FN include antiseizure medications (ASMs), epilepsy surgery and vagus nerve stimulation, with ASMs being the most common cause. However, with the timely reduction or discontinuation of ASMs and the use of antipsychotic drugs, the overall prognosis is good. Here, we perform an extensive review of the literature pertaining to FN, including its epidemiology, possible mechanisms, clinical features, treatment and prognosis.

• Forced normalization
• Antiseizure medications
• Neurotransmitter
• Antipsychotic drugs
• Electroshock

Treatment-resistant schizophrenia is a severe form of schizophrenia characterized by poor response to at least two antipsychotic drugs and is typically treated with clozapine. However, clozapine lowers the epileptic threshold, leading to seizures, which are severe side effects of antipsychotics that result in multiple complications. Clozapine-related seizures are generally considered to be dose-dependent and especially rare in the low-dose (150-300 mg/d) clozapine treated population. Due to clinical rarity, little is known about its clinical characteristics and treatment.

A 62-year-old Chinese man with a 40-year history of treatment-resistant schizophrenia presented to the Emergency Department with symptoms of myoclonus, consciousness disturbance and vomiting after taking 125 mg clozapine. Upon admission, the patient had a suddenly generalized tonic-clonic seizure lasting for about half a minute with persistent disturbance of consciousness, fever, cough and bloody sputum, which was considered to be low-dose clozapine-related seizure. After antiepileptic and multiple anti-infection treatments, the patient was discharged without epileptic or psychotic symptoms.

Our aim is to highlight the early prevention and optimal treatment of clozapine-related seizure through case analysis and literature review.

• Seizure
• Treatment-resistant schizophrenia
• Antipsychotic
• Antiepileptic
• Electroconvulsive therapy
• Case report

Irritability has been described as a frequent adverse event in patients affected by epilepsy and treated with perampanel (PER), levetiracetam (LEV), and less frequently with valproic acid (VPA). Since the questionnaire for irritability (I‐EPI) is a validated instrument to measure this psychiatric manifestation in patients affected by epilepsy, in this study we aimed at investigating the effect of PER as first add‐on therapy on I‐EPI. Moreover, we compared the effectiveness and I‐EPI scores obtained at 12‐month follow‐up visits in patients treated by PER, LEV, or VPA in order to measure irritability as a consequence of these treatments.

We collected data from 17 patients treated by PER, 16 patients treated by LEV, and 16 patients under VPA treatment followed for 12 months.

We did not document significant changes of I‐EPI questionnaire between baseline and follow‐up in the PER group. As concerning the comparison of I‐EPI among PER, LEV, and VPA groups, we documented lower global scores in PER than both LEV (P < 0.05) and VPA (P < 0.05) groups. Moreover, patients under PER treatment showed lower scores than LEV and VPA (P < 0.05) in I‐EPI items measuring the gentle personality, anxiety of having epileptic seizures in front of others, and irritability in thinking that they can have an epileptic seizure.

This retrospective study described a stable and possibly lower degree of irritability in patients starting PER than LEV and VPA treatments, although we documented the comparable effectiveness of PER, LEV, and VPA as first add‐on treatments in patients affected by uncontrolled epileptic seizures. However, the small sample of patients included in this study and the absence of I‐EPI scores obtained at baseline visits in LEV and VPA groups require further investigations to confirm this preliminary evidence.

• 12-month follow-up
• I-EPI
• effectiveness
• epilepsy
• irritability
• levetiracetam
• perampanel
• valproic acid

• anticonvulsant
• antiepileptic (aed)-induced psychotic disorder (aipd)
• epilepsy seizures
• forced normalization
• kindling
• levetiracetam
• phenytoin
• psychoses
• seizure control convulsions.
• seizure disorder

• Adverse events
• Efficacy
• Levetiracetam
• Perampanel
• Tolerability

• alternative psychosis
• dopamine
• electroencephalogram
• epilepsy
• forced normalization
• kindling

• Epilepsy
• Forced normalization
• Normal EEG
• Psychosis

• depression
• epilepsy
• medication
• risk factors
• seizures
• side effects