Characterization of Psychiatric Adverse Events Reported with Levetiracetam in the FDA Adverse Event Reporting System (FAERS)

Background: Levetiracetam (LEV) is among the most frequently prescribed antiseizure medications, yet its tolerability is limited in some patients by psychiatric and behavioral adverse events. Because psychiatric comorbidity and psychotropic co-medication are common in epilepsy, attributing such events to LEV rather than to the underlying disease remains difficult. Thus, we sought to characterize LEV-associated psychiatric reporting and to determine whether it differs by age, sex, and concurrent psychotropic use. Methods: Different safety reports submitted to the FDA Adverse Event Reporting System (FAERS) from 2013 through 2022 were extracted and joined by case identifier, restricted to LEV as the primary suspect drug, with co-administered antidepressants and antipsychotics flagged. Reports lacking age or sex were excluded. Groups were compared using the t-test and the chi-square or Fisher exact test, with odds ratios referenced to LEV without a recorded antidepressant or antipsychotic. Results: Among 928 reports (mean age 48.0 ± 20.1 years; 60.9% female), dizziness (30.1%), anxiety (16.5%), agitation (10.3%), insomnia (9.8%), depression (9.6%), and amnesia (8.8%) accounted for more than 85% of adverse events. The profile was age dependent. Agitation was reported more often for adolescents than for adults (adjusted OR 3.22, 95% CI 1.67–6.20). Psychotropic co-medication was recorded in 230 reports (24.8%). Furthermore, anxiety (OR 2.07, 95% CI 1.43–2.99) and depression (OR 1.82, 95% CI 1.15–2.89) were reported more frequently in co-medicated reports, whereas dizziness (OR 0.59, 95% CI 0.42–0.84) and agitation (OR 0.44, 95% CI 0.25–0.83) were reported less frequently. The association with agitation was attenuated and was no longer statistically significant after adjustment (aOR 0.61, 95% CI 0.33–1.14). Conclusions: These findings characterize age- and co-medication-related differences in psychiatric adverse-event reporting with levetiracetam. After correction for multiple comparisons, agitation remained more frequently reported among adolescents, while other apparent age-related differences were not statistically significant. These findings provide descriptive pharmacovigilance evidence regarding psychiatric adverse-event reporting patterns associated with levetiracetam.