title: Effects of marketed antiepileptic drugs and placebo in the human photosensitivity screening protocol.
abstract: A study of epilepsy patients with a reproducible range of photoparoxysmal responses (PPR) (epileptiform discharges evoked by flashing lights) has been used as a "proof-of-concept" trial to determine if novel potential antiepileptic drugs (AEDs) should proceed in development. The standard design for this trial requires a 3-day inpatient stay and is single-blind. We evaluated two marketed and effective AEDs-one narrow-spectrum [carbamazepine (CBZ)], and one broad-spectrum [levetiracetam (LEV)]-using a novel double-blinded, cross-over outpatient version of the trial to detect acute drug effects of the two marketed AEDs on photosensitivity. We tested 6 patients with a known stable photosensitivity response, using single oral doses of CBZ 400 mg and LEV 1000 mg, compared to 2 test days with single placebo doses. Patients who received LEV had the lowest mean PPR (compared with placebo and CBZ). The mixed effect model showed a significant effect of LEV in all eye closure conditions (p < 0.001). There was no evidence of a significant change in PPR after CBZ or placebo treatment. In conclusion, LEV 1000 mg, but not CBZ 400 mg, was effective in suppressing photosensitivity within a 6-h period compared with placebo showing the ability of our novel photosensitivity trial design to demonstrate effects of broad-spectrum AEDs. We cannot confirm the ability of the photosensitivity trial to detect the narrow-spectrum AED CBZ in our design. The novel outpatient study design is feasible and is expected to reduce costs compared with previous methodology.
authors.affiliation: Department of Neurology, NYU Langone Medical Center, 223 E. 34th Street, New York, NY, 10016, USA, Jacqueline.French@nyumc.org.
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: French
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Krauss
authors.forename: Dorothee
authors.initials: D
authors.lastname: Kasteleijn
authors.forename: Bree D
authors.initials: BD
authors.lastname: DiVentura
authors.forename: Emilia
authors.initials: E
authors.lastname: Bagiella
mesh_terms: D000927:Anticonvulsants / Q000627:therapeutic use*; D002220:Carbamazepine / Q000627:therapeutic use*; D004311:Double-Blind Method; D020195:Epilepsy, Reflex / Q000188:drug therapy*; D005260:Female; D006801:Humans; D000077287:Levetiracetam; D008027:Light / Q000009:adverse effects*; D008297:Male; D010889:Piracetam / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015990:Placebo Effect
chemical_list: D000927:Anticonvulsants; D002220:Carbamazepine; D000077287:Levetiracetam; D010889:Piracetam