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Psychiatric and behavioral adverse events in randomized clinical studies of the noncompetitive AMPA receptor antagonist perampanel
Author(s) -
Ettinger Alan B.,
LoPresti Antonia,
Yang Haichen,
Williams Betsy,
Zhou Sharon,
Fain Randi,
Laurenza Antonio
Publication year - 2015
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.13054
Subject(s) - perampanel , placebo , hostility , adverse effect , ampa receptor , aggression , medicine , psychiatry , epilepsy , psychology , clinical psychology , glutamate receptor , receptor , alternative medicine , pathology
Summary Objective Perampanel, a selective, noncompetitive α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) glutamate receptor antagonist, is indicated for adjunctive treatment of partial seizures in patients ≥12 years based on three phase III clinical studies. The perampanel U.S. Prescribing Information includes a boxed warning for serious psychiatric and behavioral adverse reactions. To provide context for this warning, detail on psychiatric and behavioral safety data from perampanel clinical studies is presented. Methods An analysis of pooled safety data from three phase III studies in patients with partial seizures is presented. Data from phase I and phase II studies in patients with and without epilepsy were also analyzed. Psychiatric and behavioral treatment‐emergent adverse events ( TEAE s) were evaluated according to Medical Dictionary for Regulatory Activities (Med DRA ) terms, using “narrow” and “narrow‐and‐broad” standardized Med DRA queries ( SMQ s) for TEAE s suggestive of hostility/aggression. Results From the three phase III partial‐seizure studies, the overall rate of psychiatric TEAE s was higher in the 8 mg (17.2%) and 12 mg (22.4%) perampanel groups versus placebo (12.4%). In the “narrow” SMQ , hostility/aggression TEAE s were observed in 2.8% for 8 mg and 6.3% for 12 mg perampanel groups, versus 0.7% of placebo patients. “Narrow‐and‐broad” SMQ s for hostility/aggression TEAE rates were 12.3% for 8 mg and 20.4% for 12 mg perampanel groups, versus 5.7% for placebo; rates for events resulting in discontinuation were perampanel = 1.6% versus placebo = 0.7%. For events reported as serious AE s ( SAE s), rates were perampanel = 0.7% versus placebo = 0.2%. In nonepilepsy patients, psychiatric TEAE s were similar between patients receiving perampanel and placebo. In phase I subjects/volunteers, all psychiatric TEAE s were mild or moderate. These analyses suggest that psychiatric adverse effects are associated with use of perampanel. Significance Patients and caregivers should be counseled regarding the potential risk of psychiatric and behavioral events with perampanel in patients with partial seizures; patients should be monitored for these events during treatment, especially during titration and at higher doses.