Risk factors for psychiatric adverse effects associated with perampanel therapy

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

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).

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).

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.