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

Andres M. Kanner, Anna Patten, Alan B. Ettinger, Christoph Helmstaedter, Kimford J. Meador, Manoj Malhotra

Research output: Contribution to journalArticlepeer-review


Objective: 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. Methods: 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. Results: 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. Significance: 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.

Original languageEnglish (US)
Article number108380
JournalEpilepsy and Behavior
StatePublished - Dec 2021


  • Perampanel
  • Psychiatric adverse events
  • Psychiatric history
  • Safety
  • Treatment-resistant focal epilepsy

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Behavioral Neuroscience


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