TY - JOUR
T1 - Pharmacodynamic interactions between seletracetam and antiseizure comedications in the human photosensitivity model
AU - Löscher, Wolfgang
AU - Stockis, Armel
AU - Klein, Pavel
AU - Kasteleijn-Nolst Trenité, Dorothee
N1 - Publisher Copyright:
© 2025 The Author(s). Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.
PY - 2025/6
Y1 - 2025/6
N2 - We recently reported that seletracetam (SEL), a highly potent derivative of levetiracetam (LEV), reduces or abolishes the photoparoxysmal electroencephalographic response (PPR) to intermittent photic stimulation (IPS) in patients with epilepsy. Most of the 27 patients in this study were on comedication with different antiseizure medications (ASMs). Here, we reanalyzed the raw data of this clinical trial to determine which, if any, of the ASMs reduced (or increased) the effect of SEL on PPR in individual patients. This was possible because a group of six patients were not taking any ASM, and groups of similar size received different comedications. The effect size of SEL on the standard photosensitivity range (SPR) was calculated by the area under the effect curve from 0 to 8 h (AUEC [0–8]) as SPR change from predose. All patients experienced PPRs in response to IPS during placebo treatment, indicating that the PPR was resistant to treatment with their steady-state ASMs. Oral single-dose treatment with SEL reduced/abolished PPR in most (32/36) exposures, but significant effects of ASM comedication were found. Patients comedicated with LEV + lamotrigine or LEV + valproate exhibited significantly lower AUEC (0–8)s than patients without comedication, whereas no significant effects of lamotrigine or valproate alone were found. Despite the significant reduction of AUEC (0–8) in patients on comedication with LEV, SEL still reduced or abolished PPR in the majority (7/9) of exposures.
AB - We recently reported that seletracetam (SEL), a highly potent derivative of levetiracetam (LEV), reduces or abolishes the photoparoxysmal electroencephalographic response (PPR) to intermittent photic stimulation (IPS) in patients with epilepsy. Most of the 27 patients in this study were on comedication with different antiseizure medications (ASMs). Here, we reanalyzed the raw data of this clinical trial to determine which, if any, of the ASMs reduced (or increased) the effect of SEL on PPR in individual patients. This was possible because a group of six patients were not taking any ASM, and groups of similar size received different comedications. The effect size of SEL on the standard photosensitivity range (SPR) was calculated by the area under the effect curve from 0 to 8 h (AUEC [0–8]) as SPR change from predose. All patients experienced PPRs in response to IPS during placebo treatment, indicating that the PPR was resistant to treatment with their steady-state ASMs. Oral single-dose treatment with SEL reduced/abolished PPR in most (32/36) exposures, but significant effects of ASM comedication were found. Patients comedicated with LEV + lamotrigine or LEV + valproate exhibited significantly lower AUEC (0–8)s than patients without comedication, whereas no significant effects of lamotrigine or valproate alone were found. Despite the significant reduction of AUEC (0–8) in patients on comedication with LEV, SEL still reduced or abolished PPR in the majority (7/9) of exposures.
KW - lamotrigine
KW - levetiracetam
KW - photoparoxysmal response
KW - photosensitive epilepsy
KW - synaptic vesicle glycoprotein 2A
KW - valproate
UR - http://www.scopus.com/inward/record.url?scp=105003303237&partnerID=8YFLogxK
U2 - 10.1111/epi.18420
DO - 10.1111/epi.18420
M3 - Article
AN - SCOPUS:105003303237
SN - 0013-9580
VL - 66
SP - e106-e113
JO - Epilepsia
JF - Epilepsia
IS - 6
ER -