Psychiatric symptoms and quality of life in Saudi individuals with epilepsy receiving perampanel: A cross-sectional comparative study.

BACKGROUND

Perampanel (PER) is a noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist widely used in focal and generalized epilepsies. Although generally well tolerated, psychiatric side effects (PSEs) such as irritability, depression, and behavioral changes have been reported. Given the potential influence of genetic, cultural, and psychosocial factors on psychiatric vulnerability, this study aimed to describe psychiatric symptoms and health‑related quality of life in Saudi individuals with epilepsy treated with PER compared with controls not receiving PER, and to explore clinical factors associated with these outcomes.

METHOD: This cross-sectional observational study included adults and adolescents with epilepsy recruited from two neurology clinics, between February 2023 - 2024, divided into those receiving PER and matched controls not treated with PER. Participants completed standardized psychiatric and quality‑of‑life assessments (GAD‑7, PHQ‑9, NDDI‑E, YMRS, and QOLIE‑31). Clinical variables, including PER dose, titration speed, and concomitant antiseizure medications (ASMs), were examined for associations with psychiatric and QOLIE‑31 outcomes.

RESULTS

Forty‑seven participants were included (23 PER‑treated; 24 controls). There were no statistically significant between‑group differences in anxiety, depressive symptoms, manic symptoms, or quality‑of‑life scores on any scale. Within the PER‑treated group, slower titration was significantly correlated with lower depressive symptom burden on the NDDI‑E and with higher QOLIE‑31 scores for emotional well‑being, social functioning, and overall quality of life. Polytherapy with ASMs other than PER was moderately associated with greater seizure worry on the QOLIE‑31.

CONCLUSION

In this small Saudi cohort, PER treatment was not associated with a demonstrable increase in psychiatric symptom burden compared with controls, whereas titration speed and polytherapy appeared related to mood and quality‑of‑life measures. These findings are exploratory and suggest that cautious, gradual titration and careful use of polytherapy may be important when initiating PER, but larger, adequately powered prospective studies incorporating seizure‑outcome and adverse‑event data are needed to further clarify its psychiatric safety profile.