Overview of psychiatric and behavioral adverse effects of levetiracetam

Levetiracetam (LEV) is a broad-spectrum, second-generation anti-seizure medication and is commonly used as a first-line therapy for both generalized and focal epilepsies. A wide range of adverse effects has been reported with LEV, including neurological, dermatological, muscular, and hematological effects. However, psychobehavioral adverse effects (PBAEs) are the most frequently reported. The aim of this review is to explore different psychobehavioural adverse effect of LEV, the risk factors and specific available interventions. Serious but uncommon psychiatric adverse effects include psychosis and suicidality, whereas behavioral adverse effects, such as irritability, aggression, and agitation, are more common. The mean reported rates of irritability, anger, and aggressiveness are 9.9, 2.5, and 2.6%, respectively, with reported discontinuation rates of 2.4-3.4% attributable to aggression and irritability. Several risk factors have been associated with an increased likelihood of developing PBAEs, including a prior history of psychiatric illness, male sex, age <60 years, poorly controlled epilepsy, secondary generalized epilepsy, and absence seizures. In pediatric populations, the reported prevalence of PBAEs ranges from 12 to 38.7%, with a discontinuation rate of approximately 16% due to these adverse effects. Early recognition of PBAEs is essential when initiating LEV therapy. Patients who develop significant PBAE may require dose reduction or discontinuation of LEV, depending on symptom severity. In severe cases, temporary treatment with antipsychotic medications may be required to control behavioral or psychotic symptoms.