Perampanel-induced weight gain depends on level of intellectual disability and its serum concentration

Body weight (BW) gain may be induced by perampanel (PER) administration, similar to the well-known adverse effects of valproic acid and gabapentin. Intellectual disability (ID) and serum PER concentration may be risk factors of BW gain.

This study investigated how ID and serum PER concentration are associated with PER-induced BW gain.

Subjects were 76 patients with epilepsy (41 men, aged 16-70 years). All patients were divided by intelligence quotient (IQ) into no ID (IQ ≥ 70, n = 24), mild to moderate ID (70 > IQ ≥35, n = 31), and severe to profound ID (IQ < 35, n = 21) groups. BW was measured before and 2, 4, 6, and 12 months after initiation of PER treatment, and serum PER concentration at 12 months.

BW gains in the mild to moderate ID group at 4, 6, and 12 months were significantly (p <  0.05) higher than in the no ID and in the severe to profound ID groups. At 12 months, BW gain was associated with serum PER concentrations in the no ID (p =  0.034) and the mild to moderate ID (p =  0.001) groups but not in the severe to profound ID group. Multiple linear regression analysis found BW gain at 12 months was positively correlated with the mild to moderate ID group (β = 0.373, p =  0.002) and serum PER concentration (β = 0.241, p =  0.047).

The mild to moderate ID group gained more BW than the no ID group, suggesting that PER-induced food intake was greater due to weaker behavioral control in the mild to moderate ID group. The present study suggests a linear correlation between serum PER concentration and BW change.