(762) Long-term Evaluation of Adjunctive Perampanel on Mental Health in Pediatric Patients with Partial-Onset Seizures (POS) or Primary Generalized Tonic-Clonic Seizures (PGTCS) in Study 311
Consultant Adult Developmental Neuropsychiatrist, Associate Professor (Hon.) Cornwall Partnership NHS Foundation Trust, Truro, UK
Rationale: In the U.S., perampanel is approved for POS (adjunctive and monotherapy) in patients aged ≥ 4 years, and adjunctive treatment of PGTCS in patients aged ≥ 12 years. Study 311 (NCT02849626) was a multicenter, open-label, single-arm study of adjunctive perampanel in patients (aged 4–< 12 years) with POS (with/without secondarily generalized seizures [SGS]) or PGTCS. We assessed long-term (1 year) incidence of psychiatric treatment-emergent adverse events (TEAEs) and suicidal ideation/behavior during Study 311 since both have been associated with anti-seizure medications (ASMs). Methods: Patients completing the 27-week Core Study (4-week Pretreatment; 23-week Treatment) could enter Extension A (29-week Maintenance; 4-week Follow-up). Psychiatric TEAEs were assessed. Suicidal ideation/behavior were monitored for all patients (aged 4–< 12 years) and clinically significant observations were recorded as TEAEs. Suicidality was also assessed via the Columbia-Suicide Severity Rating Scale (C-SSRS) in patients aged ≥ 6 years at consent/assent. Results: Overall, 136/180 patients enrolled in the Core Study entered Extension A. During Core Study baseline, 64/180 (35.6%) patients had a history of psychiatric disorders. Psychiatric TEAEs occurred in 66/180 (36.7%) patients during the Core Study; a further five patients reported psychiatric TEAEs during Extension A (total: n=71/180 [39.4%]). Of the 71 patients, 32 (45.1%) had a history of psychiatric symptoms. Most common psychiatric TEAEs were irritability (n=24 [13.3%]) and aggression (n=18 [10.0%]; one was a serious TEAE) (Table 1). Other serious psychiatric TEAEs were disruptive mood dysregulation disorder and visual hallucination (n=1 each). Eleven (6.1%) patients had psychiatric TEAEs leading to discontinuation (most common: aggression and irritability [n=3 each]). Four (2.7%) patients with no reported lifetime history of suicidality had a positive score on the C-SSRS during perampanel treatment (Table 2). Based on investigator assessment, 1/4 of these patients (aged 10 years; PGTCS; no lifetime history of suicidality) was reported to have two adverse events of suicidal ideation, while on perampanel 10 mg/day (maintenance dose) in the Core Study. The events were deemed clinically relevant and recorded as TEAEs though both resolved. No additional TEAEs of suicidality were recorded during Extension A. Three patients had a lifetime history of suicidality but none experienced suicidality with perampanel. Conclusions: The proportion of patients reporting psychiatric TEAEs was similar during the Core Study and Extension A, suggesting long-term perampanel treatment does not increase the frequency of these events. The rare incidence of suicidality during long-term perampanel treatment suggests adjunctive perampanel is safe and well tolerated in terms of mental health in pediatric patients with POS or PGTCS. Similar to other ASMs, patients receiving perampanel should be monitored for psychiatric TEAEs, as recommended in the prescribing information. Funding: Please list any funding that was received in support of this abstract.:
