We read with interest the article entitled ‘Differential effects of ketamine enantiomers on electroencephalogram (EEG) parameters including the gamma-delta shift phenomenon’ (Koncz et al., 2026). The authors provide valuable electrophysiological data showing that esketamine produced stronger wake-promoting and non-rapid eye movement (NREM) sleep-suppressing effects than arketamine in rats and that only esketamine induced the gamma–delta shift. These findings are of interest in ongoing efforts to identify EEG-based biomarkers of rapid-acting antidepressants. However, we believe that several aspects of the authors' interpretation warrant caution. First, the study was conducted in naïve control rats without depression-like phenotypes (Chang writing—original draft; writing—review and editing. ChatGPT (OpenAI) was used to enhance the readability of the text. Dr. Hashimoto is the inventor on patent applications on ‘The use of R-ketamine in the treatment of psychiatric diseases’, ‘(S)-norketamine and salt thereof as pharmaceutical’, ‘R-ketamine and derivative thereof as prophylactic or therapeutic agent for neurodegeneration disease or recognition function disorder’, ‘Preventive or therapeutic agent and pharmaceutical composition for inflammatory diseases or bone diseases’, ‘R-ketamine and its derivatives as a preventive or therapeutic agent for a neurodevelopmental disorder’ and ‘TGF-β1 in the treatment of depression’ assigned to Chiba University (Chiba, Japan). Dr. Hashimoto has also received research support from Otsuka Pharmaceutical Co., Ltd. (Tokyo, Japan). No new data were generated.
Kenji Hashimoto (Tue,) studied this question.