Resident Physician Duke University Hospital Durham, North Carolina
Rationale: Perampanel (PER) is a noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor antagonist, currently indicated for the treatment of focal and primarily generalized tonic-clonic seizures. Neuropsychiatric side effects (NPSE) appear to be among the most common limiting factors with the use of PER. The objective of this study is to assess the tolerability of PER, with emphasis on NPSE. Methods: We performed a retrospective chart review of 66 consecutive patients treated with PER. The neuropsychiatric parameters were classified in four categories: irritability/anger/hostility (IAH), aggression (physical or verbal), mood (depression, anxiety, suicidality), and psychosis. Results: Ages ranged from eight to 76 years (29 men, 37 women). Forty-seven patients (71.2%) reported at least one adverse effect. Thirty-two patients (48.5%) reported NPSE in at least one of the four categories: IAH: 23 (34.8%); Aggression: 17 (25.8%); Mood: 10 (15.2%); Psychosis: 2 (3%). Of the 23 patients with IAH, 13 experienced the side effects at doses ≤4mg/d. IAH were seen at doses as low as 0.5 mg/d. Of 64 patients on PER, only 11 were able to maintain a dose ≥8 mg/d. PER was discontinued in 47 patients (71.2%), with lack of efficacy as the sole reason for discontinuation in six, and non-NPSE side effects in two. Of the 23 patients with IAH, 18 eventually discontinued the medication, with only one solely due to lack of efficacy. Conclusions: NPSE appear to be the most common limiting factor in the use of PER, observed in almost half of our patients. NPSE were dose-dependent and seen at very low doses, with a peak threshold for emergence at 4 mg/d. A very cautious titration is recommended when starting PER. Funding: Please list any funding that was received in support of this abstract.: None
