The US Food and Drug Administration has approved Rejoyn (CT-152), the first prescription digital therapeutic for major depressive disorder, representing a breakthrough in evidence-based digital mental health interventions. Developed through a collaboration between Otsuka Pharmaceutical and Click Therapeutics, the smartphone app received FDA clearance on March 20, 2024, as an adjunctive treatment for adults aged 22 and older with MDD who are already receiving antidepressant medication.
Clinical Evidence and Study Design
The approval was supported by the pivotal Mirai study, a randomized controlled trial conducted in partnership with Verily, Google's healthcare subsidiary. The study enrolled 286 participants aged 22 to 64 with major depressive disorder, randomizing them to receive either Rejoyn or a sham control app in addition to their existing antidepressant therapy.
Rejoyn demonstrated statistically significant efficacy, meeting its primary endpoint with a mean reduction of 8.78 points on the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to week six, compared to 6.66 points for the control group. The therapeutic benefit was further supported by improvements in both patient- and clinician-reported outcome measures.
Therapeutic Mechanism and Design
The digital therapeutic integrates three core components delivered over a six-week treatment period. The app combines cognitive behavioral therapy sessions, emotional faces memory task (EFMT) exercises, and personalized reminders and messaging. This multimodal approach targets brain regions affected by depression through what Click's scientific advisor Brian Iacoviello describes as "physical therapy for the brain."
"When stronger and more balanced connections are created, the regions of the brain responsible for processing and regulating emotions are better able to work together and symptoms of depression can improve," explained Iacoviello, a co-inventor of the EFMT test at Icahn School of Medicine.
The app incorporates mindfulness techniques, deep breathing exercises, and psychoeducation components, requiring a prescription for access rather than being available as a consumer wellness application.
Clinical Implementation Experience
Psychotherapist Saundra Jain, PsyD, co-founder of the WILD 5 Wellness program and clinical affiliate at the University of Texas at Austin School of Nursing, has prescribed Rejoyn in her practice for over six months. "It's the first of its kind," Jain noted. "This is a great augmentation strategy that is now available to us to share with our patients."
Jain emphasizes the distinction between Rejoyn and consumer wellness apps, explaining to patients that it is evidence-backed and different from applications found on standard app platforms. Her clinical experience indicates that patients find the intervention engaging and helpful, with some requesting to repeat the program after completion.
"There is a place for prescription digital therapeutics in our practices when patients are motivated to do more than simply medicines and psychotherapy," Jain observed. "They're very engaged in their treatment, highly motivated, and will oftentimes say something to me like, 'Hey, Saundra, I'm feeling better, but is there something else that I could be doing to feel even better?'"
Market Access and Commercial Considerations
The approval addresses a significant unmet need in depression treatment, where only approximately one-third of patients respond to their first antidepressant medication. Click Therapeutics CEO David Benshoof Klein positioned Rejoyn as providing "hope for those who are looking for new treatment options, especially one that is easily accessible through the device in the palm of your hand."
Patients can obtain prescriptions through their usual healthcare providers or via virtual consultations accessible through the Rejoyn website. Mental health professionals including psychotherapists, psychologists, and social workers can refer patients to this virtual consultation pathway.
The digital therapeutic is scheduled for availability on iOS and Android app stores in the second half of 2024. However, the commercial success of prescription digital therapeutics remains challenging, with uncertain reimbursement pathways contributing to difficulties faced by other companies in the space, including the bankruptcy of Pear Therapeutics and Akili's shift to direct-to-consumer models.
Regulatory and Development Background
Rejoyn emerged from a $300 million collaboration established between Otsuka and Click Therapeutics in 2019, specifically focused on developing digital therapeutics for major depressive disorder. The partnership represents a significant investment in the digital mental health space and demonstrates pharmaceutical industry commitment to evidence-based digital interventions.
The FDA approval establishes a regulatory precedent for prescription digital therapeutics in mental health, potentially paving the way for additional evidence-based digital interventions. The designation as a software-as-a-medical device (SaMD) reflects the therapeutic's classification as a medical intervention rather than a wellness application.
