Long‐term music adjuvant therapy enhances the efficacy of sub‐dose antiepileptic drugs in temporal lobe epilepsy

Aims Noninvasive music adjuvant therapy shows great potential in improving seizure control when combined with routine antiepileptic drugs. However, the diversity of previous music protocols has resulted in disparate outcomes. The optimized protocol and features for music adjuvant therapy are still not fully understood which limits its feasibility. Methods By applying different regimens of music therapy in various temporal lobe epilepsy models, we evaluated the effect of music in combination with sub‐dose drugs on epileptic seizures to determine the optimized protocol. Results A subgroup of kindled mice that were responsive to music adjuvant therapy was screened. In those mice, sub‐dose drugs which were noneffective on kindled seizures, alleviated seizure severity after 12 h/day Mozart K.448 for 14 days. Shorter durations of music therapy (2 and 6 h/day) were ineffective. Furthermore, only full‐length Mozart K.448, not its episodes or other music varieties, was capable of enhancing the efficacy of sub‐dose drugs. This music therapeutic effect was not due to increasing cerebral drug concentration, but instead was related with the modulation of seizure electroencephalogram (EEG) spectral powers in the hippocampus. Conclusion These results indicate that long‐term full‐length Mozart K.448 could enhance the anti‐seizure efficacy of sub‐dose drugs and may be a promising noninvasive adjuvant therapy for temporal lobe epilepsy. Music adjuvant therapy promotes the efficacy of sub‐dose antiepileptic drugs in both hippocampal and amygdaloid kindled temporal lobe epileptic mice. Listening to full‐length Mozart K.448 for 12 h/day is the optimal protocol for music adjuvant therapy.