When Software Becomes Medicine: Ignoring It May Soon Be Malpractice.

The convergence of mobile software, artificial intelligence, and biomedical science is ushering in a new era of precision medicine, defined not only by personalization but by real-time adaptability. This shift is exemplified by the evolution of Prescription Digital Therapeutics (PDTs): smartphone-based applications that treat a disease or condition and are regulated in the US by the FDA. Early PDTs (PDT 1.0) such as reSET for substance use disorder, reSET-O for opioid use disorder, and Somryst for chronic insomnia digitized cognitive behavioral therapy (CBT) into a smartphone app and laid the foundation for regulated digital interventions. Now in the era of PDT 2.0, we see greater personalization, multimodal approaches beyond CBT, robust clinical validation, and targeting drug-like endpoints with Rejoyn for major depressive disorder, CT-132 for episodic migraine prevention, Luminopia for amblyopia, and CT-155 in development for negative symptoms of schizophrenia. Despite promising results, widespread adoption remains limited by reimbursement, clinician and patient awareness, and integration into clinical workflows. On the horizon is smart medicine: a convergence of traditional pharmacotherapy with PDTs that work together to enhance overall effectiveness, safety and tolerability, and engagement, adherence, and personalization. These medicines optimize outcomes in ways conventional therapies cannot and, in true closed-loop principles, assess for disease and symptoms and modulate both the digital and drug interventions. Drawing from my work experience on multiple PDTs, this paper highlights how PDTs are transforming care. The FDA's Prescription Drug Use-Related Software (PDURS) guidance affirms the regulatory foundation for integrating PDTs and drugs. Meaningful therapeutic advancements now depend not only on the molecular design but also on the mechanisms, digital or otherwise, that support its success. I postulate that within the next five years, omitting digital interventions when indicated will not just be outdated, it may be malpractice.