Digital Therapeutic Shows Promise in Depression Care

Digital therapeutics (DTx) are digital health tools that the FDA and other regulatory agencies have reviewed and authorized to deliver validated medical interventions.¹ In 2025, the Journal of Affective Disorders published study findings suggesting that adjunct use of DTx CT-152 (Rejoyn; Otsuka Precision Health) improves major depressive disorder (MDD) symptoms.¹ Based on the study results, the FDA authorized CT-152 as a prescription DTx.

Digital therapeutics are digital health tools | Image credit: tadamichi | stock.adobe.com

CT-152 is a smartphone app delivering self-paced remote cognitive-emotional training with 18 emotional faces memory task (EFMT) sessions, 18 cognitive-behavioral therapy (CBT) sessions, and personalized text messages.¹ Evidence suggests that EFMT and CBT may adjust the connectivity between areas of the brain involved in interpreting and processing emotions.²

A phase 3 multicenter, randomized, double-blind, sham-controlled trial assessed the efficacy and safety of CT-152 as an adjunct to antidepressant therapy (ADT) in adults with MDD.¹ The study included participants 22 to 64 years old with a score of 18 or greater on the 17-item Hamilton Rating Scale for Depression. Participants had to be on a stable monotherapy dose of ADT for at least 4 weeks, with less than 50% reduction in depression symptoms.¹

Investigators randomly assigned 386 participants 1:1 to the CT-152 or sham app group for 6 weeks, with all continuing their pre-study ADT dose.¹ The sham app delivered shape memory task (SMT) plus messaging. In the 4-week follow-up, CT-152 participants could access completed CBT lessons, and both groups received supportive texts, but the sham group lacked SMT access.¹

The primary outcome was change in Montgomery-Asberg Depression Rating Scale (MADRS) score from baseline to week 6.¹ Secondary outcomes included response rate and change in MADRS and other scale scores from baseline to week 6.

Baseline characteristics were similar between groups, with a mean age of 42.6 years and a baseline MADRS score of 28.4 ± 6.0, consistent with moderate depression.^1,3 Most participants were women (86.0%). In the modified intention-to-treat (mITT) analysis (n = 354), the primary outcome was not significantly different between groups.¹ However, more participants in the CT-152 group achieved a partial or full response rate (30%-49% or >50% reduction, respectively). In contrast, the ITT analysis (N = 386) showed a statistically significant improvement in MADRS score with CT-152 compared to the sham group. None of the participants experienced severe adverse effects or discontinued the trial due to adverse events.¹

This study suggests that CT-152 is safe and effective as an adjunct to ADT monotherapy in adults with MDD. At least 60% of participants reported satisfaction with the app and found notifications and messaging helpful, while 68.6% of providers rated it convenient for delivering treatment.¹ Otsuka offers 6-week CBT-based lessons with EFMT exercises and supportive text messages, with CBT lessons available for an additional 4 weeks.⁴ The platform offers the advantage of avoiding adverse effects associated with additional pharmacologic therapy.⁵ Although some insurance companies may not cover the DTx, it is eligible for payment with a health savings account (HSA) and flexible spending account (FSA).

Implications by Practice Area

Consultant pharmacists may consider DTx as a nonpharmacologic option for participants with MDD who have an inadequate response to ADT, particularly when medication-related adverse effects are a concern. Additionally, nurse practitioners should educate participants about the HSA/FSA reimbursement option when insurance does not cover CT-152.

REFERENCES

1. Rothman B, Slomkowski M, Speier A, et al. A digital therapeutic (CT-152) as adjunct to antidepressant medication: a phase 3 randomized controlled trial (the Mirai study). J Affect Disord. 2025;388:119409. doi:10.1016/j.jad.2025.119409

2. Hoch MM, Doucet GE, Moser DA, et al. Initial evidence for brain plasticity following a digital therapeutic intervention for depression. Chronic Stress (Thousand Oaks). 2019;3:2470547019877880. doi:10.1177/2470547019877880

3. Aripiprazole (Abilify): Depression, Major Depressive Disorder (MDD) [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2016 Nov. Accessed August 26, 2025. https://www.ncbi.nlm.nih.gov/books/NBK409740/

4. Rejoyn Clinician Brief Summary. Otsuka Precision Health, Inc. Updated July 2024. Accessed August 26, 2025. https://www.rejoynhcp.com/Clinician-Brief-Summary.pdf

5. Rejoyn FAQs. Accessed August 26, 2025. https://www.rejoyn.com/faqs ‌