Abstract
Background The number of patients with epilepsy receiving perampanel or lacosamide as an add-on treatment following levetiracetam treatment has increased. Although levetiracetam causes psychiatric disorders, it is unclear whether they occur with the combined use of these antiepileptic drugs.Objective To determine the frequency of psychiatric disorders in patients using lacosamide or perampanel as an add-on therapy to levetiracetam. Setting A single-center retrospective cohort study. Methods Patients who received levetiracetam, lacosamide, and perampanel between April 1, 2014 and April 30, 2019 in Hachioji Medical Center were selected. They were classified into the levetiracetam+lacosamide or levetiracetam+perampanel group. Medical records from the start of combination therapy contained patient background and the incidence of psychiatric disorders. Main outcome measure Onset of psychiatric disorders. Results Forty-four patients used levetiracetam+lacosamide and 50 used levetiracetam+perampanel. The incidence of psychiatric disorders was significantly lower (p = 0.000047) with levetiracetam+lacosamide (6.8%) than with levetiracetam+perampanel (46%). The time to the onset of psychiatric disorders was within 1 month of dose initiation or increase in one case (33.3%) with levetiracetam+lacosamide and 16 cases (76.2%) with levetiracetam+perampanel. The median time to onset was 56 and 6.5 days with levetiracetam+lacosamide and levetiracetam+perampanel, respectively. There was no significant difference in antiepileptic drug dosages owing to the presence or absence of psychiatric disorders. Conclusion As the frequency of psychiatric disorders was higher with levetiracetam+perampanel therapy, levetiracetam+lacosamide may be preferable. These disorders tended to develop within 1 month of therapy and were not dose-dependent. Antiepileptic drugs should be cautiously prescribed to avoid psychiatric disorders.
Antiepileptic drugs have a dose-dependent association with malformations in offspring of women with epilepsy
