Postmarket Safety Surveillance of FDA-Cleared Prescription Digital Therapeutics Using the Manufacturer and User Facility Device Experience (MAUDE) Database: A Pharmacovigilance Study.

Background and aim Prescription digital therapeutics (PDTs) are software-based medical treatments authorized by the U.S. Food and Drug Administration (FDA) for a range of chronic conditions. As clinical adoption increases, postmarket surveillance becomes essential to ensure safety beyond controlled trial environments. This study aimed to characterize postmarket adverse events and product problems associated with FDA-cleared PDTs using data from the FDA's Manufacturer and User Facility Device Experience (MAUDE) database. This approach supports the generation of hypothesis-forming safety signals in naturalistic care settings, where adherence patterns, off-label use, and user variability are more likely to emerge. Methods We conducted a retrospective, pharmacovigilance study of the MAUDE database through April 30, 2025. Device-specific product codes were used to identify reports related to 13 FDA-cleared PDTs as follows: reSET (Middletown, CT: PursueCare) for substance use disorder, reSET-O (Middletown, CT: PursueCare) for opioid use disorder, Somryst (Alpharetta, GA: Nox Health) and SleepioRx (San Francisco, CA: Big Health) for chronic insomnia, EndeavorRx (Boston, MA: Akili, Inc.) for pediatric attention-deficit/hyperactivity disorder (ADHD), Parallel (San Francisco, CA: Mahana Therapeutics Inc.) and Regulora (Chicago, IL: metaMe Health) for irritable bowel syndrome, Stanza (San Francisco, CA: Swing Therapeutics, Inc.) for fibromyalgia, AspyreRx (New York City, NY: Click Therapeutics, Inc.) for type-2 diabetes, Rejoyn (Princeton, NJ: Otsuka Precision Health, Inc.) for major depressive disorder, DaylightRx (San Francisco, CA: Big Health) for generalized anxiety disorder, MamaLift Plus (Princeton, NJ: Curio Digital Therapeutics) for postpartum depression, and CT-132 (New York City, NY: Click Therapeutics, Inc.) for episodic migraine. Each report was manually reviewed for relevance and data extracted on event type, patient demographics, outcomes, and product details. Results Four reports were initially identified. Two were excluded after verification that they involved non-cleared or over-the-counter digital products. Of the remaining two, one report involved Somryst for insomnia prescribed to a patient with a seizure disorder, a known contraindication listed in its labeling, and resulted in disability. The other involved EndeavorRx, which reported perceived ineffectiveness without clinical harm. No adverse events were identified for the remaining 11 PDTs. Conclusions In this study, only two adverse event reports associated with FDA-cleared PDTs were identified in the MAUDE database. While this may suggest a favorable safety profile, the findings must be interpreted with caution given the limitations of passive surveillance systems, including underreporting, reporting bias, and limited capacity to capture software-specific harms. These preliminary results highlight the need for modernized, active safety monitoring frameworks tailored to the unique risks of digital therapeutics.