Brett Michael Colbert ¹ Derek Michael Dykxhoorn ² Shaheen Lakhan ^1*

• ¹ Click Therapeutics, Inc., New York, United States
• ² Leonard M. Miller School of Medicine, University of Miami, Miami, Florida, United States

The five ar cles included in this Research Topic explore key aspects of PDTs, from clinical efficacy and engagement to regulatory frameworks and implementa on science, offering a comprehensive overview of the current digital therapeu c landscape.Thorndike et al. showcase the real-world efficacy of Somryst®, a PDT delivering digital Cogni ve Behavioral Therapy for Insomnia (CBT-I). Results from the DREAM study revealed significant reduc ons in insomnia severity, depression, and anxiety symptoms over a one-year follow-up, highligh ng the scalability and durability of PDTs in addressing sleep disorders, par cularly for individuals with limited access to in-person care. Blanc et al. explore the promise of virtual reality-based PDTs through NurtureVR™, emphasizing its capacity to reduce stress among perinatal Black and La na women. Their qualita ve study iden fies barriers such as accessibility and cultural relevance, advoca ng for equity-focused innova ons to address mental health dispari es in underserved popula ons. Similarly, Carrasco et al. present a protocol for evalua NurtureVR™ in expectant and postpartum Black and La na mothers, integra ng mindfulness, relaxa on, and guided imagery techniques to tackle significant dispari es in maternal mental health outcomes. This study emphasizes the importance of culturally tailored digital interven ons in perinatal care.Expanding on the founda onal elements of PDTs, Ferrante et al. discuss the NIH's role in suppor ng PDT development for condi ons like depression, substance use, and cogni ve disorders. They highlight regulatory hurdles and the necessity for sustained research funding to ensure widespread adop on and equitable implementa on. Docherty et al. provide a historical perspec ve, tracing the evolu on of psychotherapy from Freudian analysis to the emergence of PDTs. By situa ng PDTs within this broader context, they argue that digital therapeu cs represent a natural progression of evidence-based care, bridging gaps in accessibility while retaining fidelity to therapeu c principles. Together, these ar cles illuminate the dynamic intersec ons of clinical efficacy, equity, innova on, and historical evolu on, showcasing how PDTs are reshaping mental health care and laying a founda on for future advancements. The ar cles in this special issue provide important insights into the development, implementa on, and outcomes of PDTs. It is clear that the field has now entered a pivotal phase in its development. The recent release of the FDA's Prescrip on Drug Use-Related So ware (PDURS) guidance is a watershed moment for PDTs. This guidance provides a clear regulatory pathway for so ware and prescrip on drug combina ons-whether the so ware enhances drug delivery efficacy, monitors adherence, or supports clinical decision-making.The PDURS guidance directly addresses two cri cal challenges that have limited PDT integra on into rou ne care -regulatory ambiguity and clinical valida on. First, it clarifies how end-user outputs from are categorized as either FDA-required labeling or promo onal labeling. For instance, if so ware func ons provide a clinically meaningful benefit, such outputs can be included in the prescribing informa on (PI) and are subject to FDA review as part of the drug's approval process. This offers an unprecedented opportunity for PDT developers to align their so ware with the same eviden ary standards as pharmacological treatments. This guidance opens the door for so ware-enhanced drugs tailored to both new drugs in development, as well as older drugs that are facing adop on or patent lifecycle challenges.Second, the PDURS guidance underscores the importance of demonstra ng clinically meaningful outcomes. For PDTs to be included in FDA-required labeling, sponsors must conduct rigorous, wellcontrolled studies showing that the so ware provides measurable improvements in pa ent outcomes. This creates a framework for high-quality evidence genera on, ensuring that PDTs meet the same safety and efficacy standards as tradi onal therapeu cs.The implica ons of these new guidelines for psychiatry are profound. PDTs are uniquely suited to address mental health disorders, where outcomes o en depend on complex interac ons between behavioral, neurobiological, and environmental factors. With the PDURS framework in place, PDTs can now be developed, validated, and prescribed alongside pharmacological treatments, enabling a truly integrated approach to psychiatric care. This will not only enhance pa ent outcomes but also provide clinicians with new tools to deliver precision medicine at scale. The ar cles in this Research Topic, including the historical perspec ve provided by Docherty et al., combined with the regulatory clarity offered by the PDURS guidance, signal that PDTs have reached an inflec on point. By grounding the evolu on of PDTs within a historical trajectory, Docherty et al. remind us that the field builds on a strong founda on of evidence-based care, even as it moves toward innova ve digital solu ons for delivery of this care. Moving forward, several key priori es will shape the trajectory of PDTs in psychiatry: Prescrip on Digital Therapeu cs represent a transforma ve innova on in psychiatric care, offering scalable, evidence-based solu to some of the most pressing challenges in mental health. The ar cles in this special issue illustrate the remarkable progress being made in PDT development, regula on, and implementa on. Yet it is the FDA's PDURS guidance that heralds the next big step in the integra on of PDTs into clinical medicine. PDTs are poised to be integrated into clinical prac ce alongside pharmacological treatments, validated by rigorous evidence, and recognized as essen al components of pa ent care.As we stand at this turning point, it is clear that the future of PDTs in psychiatry is brighter than ever. By embracing this new paradigm, clinicians, researchers, and regulators can work together to ensure that PDTs fulfill their poten al to improve mental health outcomes for all.