Risk factors for psychiatric adverse effects associated with perampanel therapy.

Purpose: To identify the risk factors for psychiatric adverse effects associated with perampanel therapy.

Methods: We retrospectively evaluated the adverse effects of perampanel by reviewing clinical records from 895 Japanese patients with epilepsy (aged 1-86 years) who started perampanel therapy at National Epilepsy Center, Shizuoka, Japan, between June 2016 and December 2019. Patients were classified into 3 groups: those without adverse effects (Group I), those with psychiatric adverse effects (Group II), and those with common adverse effects (Group III).

Results: The number of patients assigned to each group was as follows: Group I, n = 641; Group II, n = 93; and Group III, n = 161. The mean follow-up period was 458 ± 265 days (median, 511 days). Kaplan-Meier survival estimates showed that the median time to treatment failure was shorter in Group II than in Group III (294 vs. 392 days, respectively; log-rank test, p < 0.001). According to polytomous logistic regression, younger age (<16 years) was associated with a lower risk of common and psychiatric adverse effects. The risk factors for psychiatric adverse effects (Group II) were intellectual disability (adjusted odds ratio [AOR], 2.6; 95% confidence interval (CI), 1.5-4.5) and psychiatric comorbidity (AOR, 3.8; 95% CI, 2.3-6.3); in patients with intellectual disability, the occurrence of psychiatric adverse effects was concentration dependent. Patients with lamotrigine use had a 0.54-fold lower risk of psychiatric adverse effects. In Group III, concomitant use of inducers was associated with a decreased risk of common adverse effects (AOR, 0.68; 95% CI, 0.46-0.99).

Significance: We found clear differences in the risk factors for psychiatric adverse effects. In patients with intellectual disability, care must be taken when titrating perampanel, and therapeutic drug monitoring should be performed.