Does a psychiatric history play a role in the development of psychiatric adverse events to perampanel… and to placebo?

The purpose of this study was to establish whether a past psychiatric history could play a role in the development of psychiatric treatment-emergent adverse events (PTEAEs) in patients randomized to perampanel (PER) or placebo. The development of PTEAEs was compared between patients with/without a psychiatric history in a post hoc analysis from four randomized placebo-controlled trials (RPCTs) of PER (304/305/306/335) in patients with treatment-resistant focal epilepsy. Among the 2,187 patients enrolled in the RPCTs, 352 (16.1%) had a psychiatric history (PER n = 244; placebo n = 108), while 1835 patients (83.9%) did not (PER n = 1325; placebo n = 510). Compared to patients without a psychiatric history, those with a positive history reported more PTEAEs for both patients randomized to PER (11.8% vs. 29.9%, p < 0.01) or to placebo (9.2% vs. 19.4%, p < 0.01). The prevalence of PTEAEs was not higher among patients randomized to 2 mg and 4 mg/day doses than placebo in both those with and without psychiatric history. Rather, the higher prevalence rates were among subjects randomized to 8 mg (29.8%) and 12 mg (36.4%) PER doses in patients with a past psychiatric history. A psychiatric history appears to increase the risk of PTEAEs in patients randomized to placebo and to PER at doses of 8 and 12 mg/day. It should be identified in all patients considered for treatment with PER, particularly when prescribed at doses above 4 mg/day.

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Copyright © 2021. Published by Elsevier Inc.

Déclaration de conflit d'intérêts

Declaration of Competing Interest Dr. Kanner has received honoraria from Eisai (for serving as chair and member of advisory boards and as support for lectures at an international epilepsy meeting on psychiatric aspects of epilepsy), Sunovion (as support for local lecture on psychiatric aspects of epilepsy) and Greenwich Biosciences (as support for lectures on psychiatric aspects of epilepsy at a national meeting). Dr. Meador has received research support from the National Institutes of Health and Sunovion Pharmaceuticals, and travel support from Eisai. The Epilepsy Study Consortium pays Dr Meador’s university for his research consultant time related to Eisai, GW Pharmaceuticals, NeuroPace, Novartis, Supernus, Upsher-Smith Laboratories, and UCB Pharma. Dr. Helmstaedter reports grants from EU Grant E-Epilepsy, personal fees and non-financial support from UCB, personal fees from EISAI, non-financial support from Desitin Pharma, personal fees from GW-Pharma, grants from EpiCare European Network (ERN), personal fees from Precisis AG, outside the submitted work; In addition, Dr. Helmstaedter has a patent Trade Mark EpiTrack® with royalties paid. Dr. Ettinger has received compensation for participation on the Eisai Speaker's Bureau and an Eisai advisory board. Dr. Patten is employed at Eisai Inc. Dr. Malhotra is employed at Eisai Inc.