perampanel and Weight-Gain

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.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Epilepsy; Female; Follow-Up Studies; Humans; Intellectual Disability; Male; Middle Aged; Nitriles; Pyridones; Regression Analysis; Time Factors; Weight Gain; Young Adult

Perampanel (PER) was first licensed in the United Kingdom in 2012 for the adjunctive treatment of focal seizures with or without secondary generalization in adults and children over 12years of age. It has recently also been approved for use as add-on therapy for patients with primary generalized tonic-clonic seizures. This prospective audit reports preliminary outcomes with adjunctive PER in patients with focal-onset seizures in everyday clinical practice using a standard design.. To date, 54 patients (38 males, 16 females; 21-65years, median: 48years) have completed the study. The median monthly seizure frequency was 4 (range: 1-60). At baseline, patients were taking a median of 2 other antiepileptic drugs (range: 1-4 drugs), with their seizures having previously failed to improve on a median of 3 schedules (range: 1-15 schedules). After 12weeks of stable dosing, PER was added, aiming at a target range of 6-12mg/daily. Review took place every 6-8weeks until one of 4 endpoints was reached: seizure freedom for ≥6months on a given PER dose, ≥50% (responder) or <50% (marginal effect) seizure reduction over 6months, compared with the prospective baseline, on the highest tolerated PER dose, or withdrawal of PER due to a lack of efficacy or side effects.. Three (5.6%) patients have remained seizure-free, with 8 (14.8%) demonstrating a ≥50% response and a further 17 (31.5%) reporting a marginal effect. Of the 26 (48.1%) dropping out of PER treatment, 21 (38.9%) did so because of side effects. The commonest problems were nausea, vomiting, ataxia, dizziness, and sedation. Overall, 6 (11%) patients developed neuropsychiatric problems, with 3 reporting irritability and/or aggression. Two patients had substantial weight gain, and another patient suffered recurrent falls. Treatment with enzyme-inducing AEDs had no effect on PER dosing in patients responding to PER or withdrawing due to side effects.. These data support the value of adjunctive PER in some patients with pharmacoresistant epilepsy in everyday clinical practice.

Topics: Adult; Aged; Aggression; Anticonvulsants; Ataxia; Drug Therapy, Combination; Epilepsies, Partial; Female; Humans; Male; Middle Aged; Nitriles; Prospective Studies; Pyridones; Treatment Outcome; United Kingdom; Vomiting; Weight Gain; Young Adult