Pharmacodynamic interactions between seletracetam and antiseizure comedications in the human photosensitivity model

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.