Transforming Psychiatry: The Rise of Prescription Digital Therapeutics

INTRODUCTION

Psychiatric disorders represent a major public health challenge in the United States and contribute to significant morbidity and health care costs. In 2022, mental health conditions affected more than 1 of 5 American adults.^1,2 Moreover, many patients face barriers to effective treatment due to provider shortages, racial and geographic disparities, and social determinants of health (SDOH) that limit access to care.³

Prescription digital therapeutics (PDTs) are FDA-regulated tools that deliver evidence-based interventions via software, and they may help to address these gaps in mental health care for depression, anxiety, schizophrenia, insomnia, substance abuse, and other conditions.⁴ Accessed through smartphones, computers, and wearable devices such as smartwatches, PDTs engage patients directly in their own precision-medicine treatment.⁵ This article reviews unmet psychiatric treatment needs in the US, explores the role and current landscape of PDTs in psychiatric care, and examines managed care considerations for their adoption.

UNMET NEEDS IN PSYCHIATRIC TREATMENT

An increasing demand for psychiatric treatment and a shortage of psychiatric health care providers contribute to several unmet needs in mental health care.^1,6,7

Demand for Psychiatric Treatment

More than 59.3 million US adults are currently living with a mental illness.¹ Disease prevalence depends on several demographic factors but is generally higher among females than males (26.4% vs 19.7%, respectively) and younger adults aged 18 to 25 years compared with those aged 26 to 49 years or at least 50 years (36.2% vs 29.4% vs 13.9%). It also is higher among adults who identify as 2 or more races (35.2%) vs adults who identify as White (24.6%), Hispanic (21.4%), Black or African American (19.7%), American Indian/Alaskan Native (19.6%), and Asian (16.8%).¹

The National Academies of Sciences, Engineering, and Medicine reports that the incidence of mental, emotional, and behavioral (MEB) health conditions appears to be increasing in the US.⁶ In fact, suicide-related deaths in the US are the highest among 10 of its peer nations, including Australia, Canada, and the United Kingdom.⁶ Reports of sadness or hopelessness by youth increased from 2013 to 2021, with more youths seriously considering a suicide attempt. The overdose death rate in youth increased from 1999 to 2022, with the overdose rate in adolescents increasing from 2.4 per 100,000 in 2010 to 5.49 per 100,000 in 2021.⁶ Deaths related to alcohol have also increased over similar time periods.⁶ This increase in mental health conditions also conveys significant economic cost. In the US, the annual cost of mental illness in 2024 was estimated to be $282 billion, and the estimated cost of opioid use and overdose deaths in 2017 was $1.021 trillion.⁶

The magnitude of the mental health crisis highlights the importance of adequate insurance coverage for successful treatment. The federal Mental Health Parity and Addiction Equity Act (MHPAEA) prevents health insurance plans from providing benefits for mental health and substance use disorders that are less favorable than those for surgical or other medical benefits.⁸ This law stipulates that there must be mental health parity—psychiatric disorders must be treated like any other disease and involve equal coverage.⁸

However, the MHPAEA does not ensure good coverage. In the interest of providing better services for people in need, World Mental Health Day (October 10of each year) is set for stakeholders in mental health to discuss current gaps in mental health care and opportunities for improvement.⁹

Shortage of Providers and Access

As the demand for mental health treatment rises, access to mental health services is limited and, in some areas, diminishing.⁷ More than half of US adults live in an area with a shortage of mental health professionals.¹⁰ Moreover, substantially fewer primary care physicians and psychiatrists are expected to be available as the number of retirees exceeds the number of board-certified psychiatrists entering the workforce.⁷ Further, certain patient populations lack broadband internet access to engage physicians who practice telepsychiatry. In 2019, 17% of Americans in rural areas and 21% of Americans in tribal lands lacked access to broadband, whereas this figure was only 1% for those in urban areas.¹¹ Patients in these underserved areas must either access mental health services via telephone or go without care.³

Access to mental health services is often worse for those with low incomes or who are uninsured. In a study of National Ambulatory Medical Care Survey (NAMCS) data from 2007 to 2016, substantially fewer psychiatrists were found to accept any insurance, including public and private insurance plans, compared with their nonpsychiatrist counterparts; for example, the average percentage of psychiatrists accepting public insurance during this time was 28 points lower than that for nonpsychiatrists.¹² Patients with mental illness are disproportionally covered by governmental insurance plans; for example, 70% of patients with schizophrenia are enrolled in Medicaid.¹³ The lower reimbursement rates described in the NAMCS study further restrict access to psychiatric care for this population.

Prisoners and jail inmates constitute another vulnerable population. From 2011 to 2012, 14% of state and federal prisoners and 26% of jail inmates met the threshold of serious psychological distress over the previous 30 days.¹⁴ However, only 74.2% of prisoners and 72.7% of jail inmates who met the threshold for serious psychological distress received mental health treatment in their lifetime, and 54.3% of prisoners and 35% of jail inmates received mental health treatment since admission.¹⁴

Telehealth services represent an opportunity to address some of these provider shortages, especially for residents of rural communities and other vulnerable populations. However, there is still an increased demand for telephone services, as some individuals have no access to videoconferencing platforms. Telehealth reimbursement must be updated to support these services.¹⁵

Impact of SDOH

The impact of mental health varies according to SDOH.³ Compared with urban residents, individuals in rural areas are significantly more likely to not have access to a psychiatrist or broadband psychiatric coverage (OR, 3.05; 95% CI, 2.41-3.85).³ Patients are more likely to be without coverage or have access to a psychiatrist if they are unemployed (OR, 1.12; 95% CI, 1.02-1.24; P = .02) or uninsured (OR, 1.03; 95% CI, 1.00-1.06; P = .05).³ The shortage of psychiatrists and access to broadband psychiatric care compounds this increasing demand for mental health care.

ROLE OF PRESCRIPTION DIGITAL THERAPEUTICS IN PSYCHIATRIC TREATMENT

PDTs are software-based interventions that deliver evidence-based therapeutic programs to prevent, manage, or treat medical conditions.⁵ Regulated by the FDA, PDTs require a prescription from a licensed clinician; they are subject to clinical validation that demonstrates safety and efficacy.⁴ PDTs are designed to be used independently or with traditional medical treatments for specific diseases.⁴ Examples of approved PDTs across nonpsychiatric disease states are listed in Table 1.^16-30

PDTs in mental health services have been developed to confront the high burden of mental health disorders, shortages, and inequities in psychiatric health care and the emergence of technological capabilities of personalized medicine.^4,5 Standalone PDTs provide patients with tools for self-directed mental health management; they can be tailored to patient preferences.⁵ However, a PDT is often a component of a combination therapy plan that integrates with existing pharmacologic and therapeutic interventions.⁵ These therapeutic interventions are delivered digitally via mobile devices such as smartphones and tablets. Their FDA approval through a rigorous process distinguishes them from wellness applications.³¹

The FDA currently regulates PDTs as software as a medical device (SaMD); SaMDs are evaluated for perceived potential risk to patients and are assigned a class rating of class I (low risk), class II (moderate risk), and class III (high risk).³² PDTs are often authorized as class II devices, which require the provision of information to users and clinical data specific to the product to ensure safety and efficacy.³² PDTs may obtain FDA approval via 2 regulatory pathways—de novo and 510(K).⁵ The de novo request pathway classifies a PDT as a safe and efficacious medical device when there is no marketed predecessor.⁵ The 510(K) pathway, on the other hand, involves a submission sent to the FDA before commercialization to ensure safety and efficacy and establishment of substantial equivalence (SE) to a legally marketed device that already exists.⁵ SE is demonstrated by at least 1 device predicate; it supports the claim of the PDT being evaluated, demonstrates the same technological characteristics, and has the same intended use.⁵ The FDA recently released the prescription drug use–related software guidance for PDTs, which gives clear direction on FDA labeling, promotional labeling, categorization, and regulation similar to that required for pharmacotherapeutic treatments.⁴ PDTs must be tested in rigorous clinical trials and meet efficacy and safety standards similar to those for pharmacotherapeutics, which allows for evidence-based decision-making surrounding their use.⁴

Clinical Impact of PDT

The clinical impact of PDTs is still emerging. From May 2021 to December 2024, at least 94 PDTs gained approval globally, including more than a dozen in the US via FDA-regulatory pathways.³³ PDTs may address gaps in patient care arising from unmet needs, shortages of psychiatric providers, and socioeconomic and geographic disparities.³⁴ In a recent report from the Peterson Health Technology Institute (PHTI), PDTs used in combination with usual care produced clinically meaningful improvements in depression and anxiety symptoms compared with usual care alone.³⁵ These findings are evaluated more extensively in the treatment-specific sections below.

Economic Impact of PDT

In the PHTI study,PDTs were estimated to reduce health care costs by $280 per anxiety or depressive episode, which equates to a net savings of $0.72 per member per month, or $8.7 million per million commercial members.³⁵ At these reimbursement rates, PDTs would also reduce total health care spending by $1.3 million for every million Medicare members.³⁵ PDTs may result in additional savings if their use reduces the frequency or duration of patients’ therapy sessions.³⁵

This large economic impact of PDTs has been noted in more conditions than depression and anxiety. The Abilify MyCite PDT (aripiprazole tablets with sensors; Otsuka America Pharmaceutical) is a digital medicine system used to treat schizophrenia. Results of a population modeling study using data from the MONARCH trial (NCT03892889; described below) demonstrated an incremental cost savings of $22,343 over 12 months from a societal perspective and an incremental quality-adjusted life year gain of 0.0298 with use of this technology compared with generic atypical antipsychotic use alone.³⁶ In a separate study, compared with no use of reSET-O (PursueCare), an FDA-authorized PDT that delivers cognitive behavioral therapy (CBT) and contingency management to patients with opioid use disorder, use of reSET-O was associated with a 28% reduced incidence of inpatient stays (incidence rate ratio [IRR], 0.72; 95% CI, 0.55-0.96; P = .026) and a 56% reduced incidence of hospital readmissions (IRR, 0.44; 95% CI, 0.20-0.93; P = .033) and reduction in total costs.³⁷

Overall Impact of PDT on the Broader Health System

PDTs may also have a broader impact on the health system. Velez et al reported that among patients with Medicaid coverage, use of reSET-O was associated with a $4,008,370 (2022 US$) reduction in facility-related costs per 1000 patients per year compared with no use of reSET-O.³⁷ Ongoing efficacy analysis will be needed to ensure enhanced convenience, accessibility, patient outcomes, and potential cost savings to the broader health care system.

CURRENT TREATMENT LANDSCAPE

Within psychiatry, the FDA has approved PDTs to manage attention-deficit/hyperactivity disorder, generalized anxiety disorder, postpartum depression (PPD), major depressive disorder (MDD), schizophrenia, posttraumatic stress disorder, substance use disorder, and opioid use disorder (Table 2).^38-46 As discussed below, several PDTs have been developed or are in development for depression and schizophrenia.

Depression

Postpartum Depression: MamaLift Plus

MamaLift Plus (Curio Digital Therapeutics) is a PDT that has been approved to treat PPD over an 8-week period. The treatment uses cognitive restructuring as the main therapeutic element, and therapy is delivered by text, illustrations, video, and interactive exercises that guide the user through 8 modules.⁴⁷ SuMMER (NCT05958095) was a double-blind, 8-week, placebo-controlled trial that evaluated the clinical efficacy of the MamaLift Plus PDT in improving PPD based on an evaluation of Edinburgh Postnatal Depression Scale (EPDS) scores as an adjunct to clinician-managed outpatient care.⁴⁷ The study included 141 participants.⁴⁷

In the MamaLift Plus arm, 82 of 95 participants (86.3%) achieved an improvement in EPDS score compared with only 11 of 46 patients (23.9%) in the control arm (P <.0001).⁴⁷ Two treatment-emergent adverse events (TEAEs) occurred in the MamaLift Plus group;2 also were noted in the sham control group.⁴⁷ A separate small study surveyed 13 participants to investigate the user experience with the MamaLift Plus application. Results demonstrated that 92.3% of participants agreed or strongly agreed that they were satisfied with the help they received on the app, 69.3% agreed or strongly agreed the app was easy to use, and 76.9% agreed or strongly agreed that the app was well integrated to manage PPD.⁴⁸

Major Depressive Disorder: Rejoyn

Rejoyn (Otsuka Precision Health) is a PDT combination treatment that provides remote access to cognitive emotional training and CBT that includes personalized text messages; it is to be used as an adjunct to antidepressant medication therapy.⁴⁹ Rejoyn was evaluated in MIRAI (NCT04770285), a phase 3, multicenter, randomized, blinded, sham-controlled trial involving 386 adults with MDD based on the Montgomery-Åsberg Depression rating Scale (MADRS) scores.⁴⁹ In the primary efficacy analysis of the modified intent-to-treat (mITT) sample in this trial (n = 354), the mean change in MADRS scores from baseline to 6 weeks was –9.03 in the Rejoyn group and –7.25 in the sham group (between-group difference, –1.78; P = .0568).⁴⁹ In an intent-to-treat analysis involving MADRS scores for 386 participants at 6 weeks, the between-group difference change from baseline was –2.12 (P = .0211), favoring Rejoyn. No TEAEs or discontinuations were considered related to Rejoyn, and no deaths occurred.⁴⁹

Schizophrenia

Abilify MyCite

Abilify MyCite is a PDT indicated to treat schizophrenia. The digital medicine system combines aripiprazole tablets embedded with an ingestible event-marker, a sensor patch worn on the body, and a smartphone mobile application that tracks medication ingestion and helps patients and providers monitor medication adherence.⁵⁰

MONARCH was a phase 3b, mirror-image clinical trial in adults with schizophrenia who were treated with Abilify MyCite after having at least 1 hospitalization over the previous 4 years and receiving an oral standard of care (SOC) for the previous 6 months (retrospective phase). All participants used Abilify MyCite for a prospective 3 months; patients then could continue using the system or resume SOC therapy for another 3 months. The primary end point was the difference in the number of patients with a psychiatric hospitalization in the prospective 3 months vs the number with such hospitalization in the retrospective 3 months in the mITT population.

Within the mITT population (n = 113), no participants were hospitalized during prospective months 1 to 3 (while on Abilify MyCite), whereas 9.7% of participants had been hospitalized during retrospective months 1 to 3 (while on oral SOC), a difference of –9.7% hospitalized individuals (P = .0010).⁵⁰ Positive and Negative Syndrome Scale (PANSS) scores also significantly improved at 3 and 6 months compared with those obtained at baseline (P <.0001).⁵⁰

Separately, a cost-effectiveness study analyzing Abilify MyCite demonstrated incremental cost savings of $22,343 from a societal perspective and an incremental quality-adjusted life year gain of 0.0298 compared with generic atypical antipsychotic use alone.³⁶ As of September 16, 2025, marketing has been discontinued for Abilify MyCite.⁵¹

PEAR-004

PEAR-004 (Pear Therapeutics/Novartis) was an investigational PDT delivered via smartphone for patients with schizophrenia who used antipsychotic therapy; it delivered multimodal neurobehavioral mechanisms of treatment, including cognitive restructuring, illness self-management training, and social skills training.⁵² However, in a study assessing the impact of PEAR-004 on PANSS scores, no statistically significant changes were seen compared with the sham group.⁵²

CT-155

CT-155 (Click Therapeutics/Boehringer Ingelheim) is a PDT that received FDA breakthrough device designation to treat the negative symptoms of schizophrenia. This SaMD is available on smartphones and mobile devices and encourages daily adherence to lessons and activities by providing schizophrenia-specific psychoeducation and therapeutic skills.⁵³ Investigators postulated that a digital working alliance (DWA) between patients and health care providers is needed to establish the efficacy of CT-155.⁵³ Two small studies assessed such DWA using the mobile Agnew Relationship Measure, a questionnaire that uses a 7-point Likert scare to evaluate bonding, partnership, confidence, openness, and initiative as separate therapeutic alliance domains with scores above 4 considered positive; results of both demonstrated positive DWA associated with CT-155 use.⁵³ The efficacy of CT-155 is being explored in CONVOKE (NCT05838625) and will be explored in BI-ENSPIRUS (NCT06791122), which is actively recruiting.^54,55

MANAGED CARE CONSIDERATIONS

The expansion of insurance coverage for PDTs may help establish equitable and affordable access. Legislation resubmitted in May 2025 proposed to provide Medicare and Medicaid coverage of PDTs and called for CMS to establish a Medicare methodology for payments to manufacturers according to certain factors (eg, ongoing use). Under the proposed legislation, manufacturers would be required to report information about PDT transactions (including payment rates and volumes provided) with private payers.⁵⁶

Payer consideration of the shortage of mental health providers and of those providers’ uneven acceptance of insurance may also foster access to PDTs.¹³ Indeed, in a survey- and discussion-based study of 22 pharmacy or medical directors or managers, participants agreed that the highest likelihood of PDT coverage is for mental health conditions, particularly for patients in rural areas.⁵⁷ However, they noted several challenges to broader PDT adoption. For instance, whether PDTs would be better covered under the pharmacy or medical benefit remains under debate.⁵⁷ Questions remain about how updates to a PDT would impact regulatory overview, evidence for efficacy, and, ultimately, health plan coverage, which would impact PDT reimbursement.⁵⁷ Despite these uncertainties, panelists agreed that ongoing economic analysis of PDTs will be important for payer consideration.⁵⁷

CONCLUSIONS

PDTs offer a scalable tool to address a growing need for psychiatric treatment in the US. With several PDTs approved by the FDA and more under development, these digital therapeutics represent an evolving aspect of mental health management. However, PDTs present unique challenges for coverage and reimbursement, and pending legislation mandating CMS coverage for PDTs may change the treatment landscape. As this field evolves and more PDTs gain FDA approval, questions of equitable and affordable access will remain central to coverage decisions.

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