Combining Non-Pharmacological Treatments with Pharmacotherapies for Neurological Disorders: A Unique Interface of the Brain, Drug–Device, and Intellectual Property

Abstract

Mobile medical applications (mHealth), music, and video games are being developed and tested for their ability to improve pharmacotherapy outcomes and medication adherence. Pleiotropic mechanism of music and gamification engages an intrinsic motivation and the brain reward system, supporting therapies in patients with neurological disorders, including neuropathic pain, depression, anxiety, or neurodegenerative disorders. Based on accumulating results from clinical trials, an innovative combination treatment of epilepsy seizures, comorbidities, and the medication non-adherence can be designed, consisting of antiepileptic drugs and disease self-management software delivering clinically beneficial music. Since creative elements and art expressed in games, music, and software are copyrighted, therefore clinical and regulatory challenges in developing copyrighted, drug–device therapies may be offset by a value proposition of the exclusivity due to the patent–independent protection, which can last for over 70 years. Taken together, development of copyrighted non-pharmacological treatments (e-therapies), and their combinations with pharmacotherapies, offer incentives to chronically ill patients and outcome-driven health care industries.

Music-Enhanced Analgesia and Antiseizure Activities in Animal Models of Pain and Epilepsy: Toward Preclinical Studies Supporting Development of Digital Therapeutics and Their Combinations With Pharmaceutical Drugs

“…To innovate treatments for neurological disorders, we have been studying diverse strategies to integrate digital health technologies with CNS drugs (4)(5)(6). Digital health is a branch of healthcare that employs internet, digital, and mobile technologies for improving health and/or treating diseases.…”

“…Music showed clinical benefits of reducing acute and chronic pain (25)(26)(27). For epilepsy, there is clinical and preclinical evidence that specific musical compositions exert anticonvulsant effects (4,(28)(29)(30)(31)(32). Clinical studies showed that exposure to Mozart's K.448 sonata in pediatric epilepsy patients, even those with refractory seizures, caused a significant reduction of seizure frequency and epileptiform discharges (33)(34)(35)(36)(37)(38)(39).…”

Incorporating Natural Products, Pharmaceutical Drugs, Self-Care and Digital/Mobile Health Technologies into Molecular-Behavioral Combination Therapies for Chronic Diseases

“…Rapid progress in wireless and mobile EEG interfaces [198, 199] or the EDA-sensors offers unique opportunities for biofeedback-based streaming of digital content developed specifically for epilepsy patients [3]. Examples of online and mobile technologies and apps for epilepsy patients are studied and reviewed [195, 196, 200].…”

Music therapy as a non-pharmacological treatment for epilepsy

“…Therefore, an alternative method for the prevention and treatment of epilepsy is zurgently needed. Currently, nonpharmacological epilepsy treatments offer alternative treatment options [11,[22][23][24][25][26], of which music therapy has received increasing attention. Studies have suggested that specific auditory stimuli (such as Mozart K.448, i.e., Mozart's Sonata for Two Pianos in D Major, K.448 [27]) can be effective at reducing seizures and may even completely control seizures [28,29].…”