Seven years have passed since the FDA cleared its first prescription digital therapeutic. The regulatory landscape has filled in considerably since then, though perhaps not in the tidy pattern early evangelists imagined. More than twenty apps and VR programs now carry federal authorization for conditions as varied as opioid use disorder and lazy eye, chronic pain and episodic migraine. Some belong to pharmaceutical giants. Others were plucked from bankruptcy auctions. A handful have secured the holy grail—unique Medicare billing codes. Many more are still fighting payer policies designed for pills and procedures, not software.
What's emerged isn't quite the frictionless future the first wave of founders promised investors. But it's real, it's accumulating users, and it's beginning to reshape how clinicians approach treatment gaps that pharmacology alone can't close.
Mental Health Takes the Lead
Mental health conditions have drawn the heaviest regulatory traffic—and for good reason. The category combines enormous unmet need with relatively straightforward digital delivery models.
Big Health now holds two recent clearances in hand. DaylightRx for generalized anxiety disorder cleared via 510(k) K233872 on August 30, 2024. SleepioRx for chronic insomnia followed shortly before, its FDA letter dated August 5, 2024 (510(k) K233577). Both require prescriptions.
Rejoyn represents something different: a collaboration between Otsuka Pharmaceutical and Click Therapeutics that secured 510(k) clearance on March 30, 2024, for adjunctive treatment of major depressive disorder in adults 22 and older. Otsuka announced the U.S. launch that August, giving the drugmaker its first digital therapeutic play in the MDD market—a space where branded pharmaceuticals have faced patent cliffs and generic competition for years.
For the narrower slice of postpartum depression, Curio Digital Therapeutics won clearance for MamaLift Plus (510(k) K223515, decision dated April 22, 2024). It targets mild-to-moderate PPD in the same age bracket—adults 22 and up—as an adjunct to standard care.
The insomnia category now sports two FDA-cleared options, which may be one more than the market can comfortably support. Before SleepioRx arrived, there was Somryst. Originally developed by Pear Therapeutics and cleared in March 2020, Somryst's journey illustrates just how volatile this sector remains. When Pear filed for bankruptcy in May 2023, Somryst went on the auction block. Nox Health picked it up for $3.9 million the following month—a bargain-basement price for a product that had already cleared the regulatory hurdles.
The Pear Assets Find Second Lives
Pear's flagship products were, in fact, the sector's regulatory pioneers. The company's reSET app for substance use disorder earned De Novo authorization on September 14, 2017 (DEN160018)—the first prescription digital therapeutic to do so. Its sibling, reSET-O for opioid use disorder, gained clearance in December 2018. Both carried the prescription-only designation that would become standard for the category.
After Pear's collapse, the apps sat largely dormant through most of 2023 and into 2024. Then PursueCare, a telehealth company focused on addiction treatment, acquired them in December 2023. PursueCare relaunched patient access that September, wagering it could crack the distribution and reimbursement puzzles that had ultimately undone Pear. Whether that bet pays off remains an open question; the company is working with a much leaner operational model than Pear's venture-backed apparatus, but the fundamental payer friction hasn't disappeared.
Beyond Talk Therapy: Sensors and Haptics
Not every mental health intervention relies on cognitive behavioral therapy modules. NightWare takes a hardware-first approach—it's a smartwatch-based system that monitors sleep disruption in real time and delivers haptic alerts (vibrations, essentially) designed to reduce nightmare severity without fully waking the wearer. The FDA granted De Novo authorization (DEN200033) on November 6, 2020, for use in PTSD and nightmare disorder. Prescription required.
Freespira offers something different again: sensor-based respiratory training for panic disorder, panic attacks, and PTSD. The company secured initial 510(k) clearances between 2013 and 2018 for adult populations. This year it added an adolescent indication (ages 13-17) via 510(k) K233337, pointing to clinical data showing a 54% reduction in panic disorder symptom severity and 44% reduction in PTSD symptoms in that younger cohort. The device works by retraining breathing patterns—hardly the sexiest pitch, but effective in trials.
Pain Management Moves Into Virtual Reality
AppliedVR's RelieVRx (formerly marketed as EaseVRx) represents one of the sector's more tangible success stories, at least on the reimbursement front. It's a skills-based VR therapy for chronic low back pain—patients wear a headset, complete modules on pain psychology and relaxation techniques, and log their progress. The FDA authorized it through De Novo classification (DEN210014) on November 16, 2021.
More importantly, CMS established a unique HCPCS Level II billing code for RelieVRx effective in 2023. That's a rare victory in a sector where reimbursement has been the graveyard of clinical promise. The code doesn't guarantee payment from every insurer, but it provides a standardized mechanism for providers to bill—a step most digital therapeutics haven't achieved.
For fibromyalgia, Swing Therapeutics received De Novo clearance (product code QMY) on May 16, 2023, for Stanza, a prescription digital therapeutic targeting fibromyalgia symptoms in adults. Fibromyalgia has proven notoriously difficult to treat with conventional drugs, which may give Stanza an opening—though the company will face the same payer skepticism that has dogged other software-based therapies.
When the Prescription Is a Video Game
Akili's EndeavorRx occupies the most conceptually unusual corner of this market. It's a video game, full stop—aliens, obstacles, points, the works. But it's also an FDA-authorized medical device for pediatric ADHD. The agency granted De Novo authorization (DEN200026) on June 15, 2020, for children. Akili later expanded the label via 510(k) K231337 on December 13, 2023, stretching eligibility to ages 8-17.
It remains prescription-only, though Akili has hedged its bets. The company released EndeavorOTC in 2024, a non-prescription version aimed at adults—effectively creating two product lines from the same core technology, one navigating the prescription reimbursement maze, the other going direct to consumer. Whether that's strategic diversification or a sign of frustration with the prescription model is open to interpretation.
Luminopia One treats amblyopia—lazy eye—in children through VR-delivered therapeutic content. It modifies cartoons and other video to stimulate the weaker eye while suppressing input from the stronger one. The FDA granted De Novo authorization (DEN210005) in October 2021. A 510(k) clearance secured in early 2025 expanded the eligible age range to 8-12 years. Prescription required.
The Migraine Frontier
Click Therapeutics, already a player through its Otsuka partnership on Rejoyn, notched another authorization earlier this year. The company received FDA marketing authorization for CT-132 on April 15, 2025—the first prescription digital therapeutic explicitly cleared for preventive treatment of episodic migraine in adults. The De Novo clearance positions Click in a category historically dominated by pharmaceuticals (topiramate, beta blockers) and Botox injections.
Whether neurologists will prescribe an app instead of writing for generic topiramate remains to be seen. Migraine prevention is a notoriously frustrating treatment area—many patients cycle through multiple drugs before finding something that works—which could create an opening for a non-pharmaceutical option. Then again, most insurers won't pay for software they've been covering in pill form for pennies per dose.
Gut Conditions Meet Cognitive Therapy
Two distinct apps target irritable bowel syndrome through psychological routes, reflecting growing clinical acceptance that IBS has significant brain-gut interaction components.
Mahana IBS (originally developed by Parallel, now under Mahana Therapeutics) delivers cognitive behavioral therapy for IBS in adults. The FDA cleared the web-based version via De Novo (DEN200029) on November 25, 2020, then cleared the mobile app through 510(k) K211372 on June 2, 2021. Both versions are prescription-only.
Regulora, from metaMe Health, takes a different therapeutic tack: gut-directed hypnotherapy for IBS-associated abdominal pain in adults. It received 510(k) clearance (K211463) on November 30, 2021. Also prescription-only. The clinical rationale rests on decades of research showing hypnotherapy can reduce visceral pain sensitivity—a mechanism entirely separate from standard IBS drugs like antispasmodics.
The Diabetes Management Cluster
Type 2 diabetes has attracted multiple entrants, perhaps because continuous monitoring and behavior change fit naturally into app-based delivery.
Better Therapeutics received De Novo authorization (DEN220058) on July 7, 2023, for AspyreRx (also known as BT-001), a CBT-based prescription digital therapeutic positioned as adjunct therapy for type 2 diabetes. The company went public via SPAC in 2021, giving it capital to navigate the commercialization phase—though its stock price has since cratered, reflecting broader market skepticism about digital therapeutics as investment vehicles.
Insulia, developed by Voluntis (now part of Aptar Digital Health), functions as a basal insulin titration companion for adults with T2D. It received initial 510(k) clearance on December 6, 2016, and has been updated through subsequent clearances running from 2017 to 2021. Prescription-only.
Welldoc's BlueStar Rx may be the longest-running FDA-cleared platform in this entire space, with initial clearance stretching back to 2010. The system includes prescription-only features such as insulin dosing support and a bolus calculator. Welldoc has filed multiple subsequent 510(k)s over the years, including clearances for Type 1 diabetes support in 2019 and insulin-related features from 2020 through 2023. Longevity counts for something—Welldoc has outlasted numerous better-funded competitors—but the company has never quite broken through to mainstream adoption.
Sensors for Breathing and Pelvic Health
Propeller Health's platform represents a hybrid model: sensors that attach to prescription inhalers, paired with an app that tracks usage patterns for asthma and COPD management. The FDA cleared the Propeller system with GSK's Ellipta inhaler in November 2016, then cleared a sensor designed for Symbicort in May 2020. Deployment happens by prescription or formal enrollment through health plans.
Renovia's leva Pelvic Health System addresses an entirely different set of conditions. It combines an intravaginal motion sensor with an app for pelvic floor muscle rehabilitation—essentially providing real-time biofeedback during Kegel exercises. The system received 510(k) clearances (K192270 on November 22, 2019, and K212495 on September 8, 2021) for indications including urinary incontinence and, as of the 2021 clearance, chronic fecal incontinence. Prescription-only.
What the Accumulated Evidence Suggests
The companies that have navigated FDA clearance span a wide range of business models. Some, like the Otsuka-Click collaboration and the Propeller-GSK partnership, embed digital therapeutics inside existing pharmaceutical distribution networks. Others operate as standalone digital health startups, fighting for attention in crowded specialty markets. A few exist only because they were scooped up at bankruptcy auctions—distressed assets that new owners believe they can monetize where the original builders failed.
The technical approaches vary just as widely: cognitive behavioral therapy modules, VR experiences, sensor-based feedback loops, even prescription video games. What unites them all is regulatory validation and the requirement that a licensed healthcare provider prescribe or formally order the intervention.
That prescription requirement hasn't guaranteed commercial viability—Pear Therapeutics' collapse drives the point home—but it has established a regulatory foundation that didn't exist a decade ago. CMS's decision to create a dedicated billing code for RelieVRx suggests at least some institutional appetite to integrate these tools into standard care pathways. Coverage policies remain inconsistent, though, varying wildly by insurer and by region.
The regulatory pipeline hasn't stopped filling. Click Therapeutics' migraine authorization earlier this year demonstrates that new therapeutic categories continue to open up. Whether prescription digital therapeutics ultimately become routine interventions—the software equivalent of a statin prescription—or remain niche offerings for specific patient populations will depend less on clinical evidence, which most of these products have published, and more on whether the healthcare system can figure out how to pay for software the way it pays for surgery. That's the puzzle Pear couldn't solve. It's the puzzle two dozen other companies are working on now.
