After Dust Settles, Digital Therapies Show Some Promise in Treatment of Treatment-Resistant Depression

The first prescription digital treatment for major depressive disorder (MDD) was approved by the FDA this year, but its lukewarm reception by the medical community obscured the broader advances that digital therapeutics have brought to MDD and the subcategory of treatment resistant depression (TRD).

Otsuka Pharmaceutical’s Rejoyn smartphone application, which was authorized by the FDA in April 2024, delivers cognitive behavioral therapy (CBT) in conjunction with ongoing antidepressant medication. CBT focuses on improving individuals’ perception of social encounters, emotional intelligence and mood management skills.

In the pivotal trial, patients in the active arm who scored 28 on average on the Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline saw their scores drop to a healthier 19 after six weeks of using Rejoyn.

In a key analysis, however, patients in the control group who used a sham app saw their MADRS scores drop to 21. The relatively small difference between the treatment and control groups gave physicians and others pause and raised questions about the true reasons for the drop in depression scores across both groups.

But there are other digital tools, and they are demonstrating clear utility in the treatment of MDD and TRD, and physician confidence in them is growing rapidly.

Key advantages of digital technology are its ability to provide monitoring and important information that can help determine a diagnosis. The depression-targeted digital therapeutics can even use the data it collects to predict depressive episodes. The flexibility and additional data these tools provide appear to be changing the treatment paradigm in MDD and TRD.

A study published in July explored the online use of mindfulness-based CBT in individuals with TRD and noted a statistically significant 26% rate of complete remission.

The study duration was 8 weeks and outpatients were enrolled in active (n = 15) and control (n = 13) groups.

A recent literature review of 12 studies found strong evidence favoring the use of digital biomarkers in the management of MDD and TRD. The reviewers said studies revealed it is possible to anticipate and evaluate patients’ depressive episodes based on physical movement patterns, exposure to light, and smartphone usage, as measured by smartphone apps and wearable devices such as Fitbits and Apple Watches.

By analyzing movement patterns alone, investigators were able to achieve “89% accuracy in predicting diagnostic [categories] and monitoring symptom changes,” the reviewers wrote.

Another study included in the review used the AiCure smartphone app to monitor facial, vocal, and head movement characteristics in patients with MDD and found strong correlation between these biomarkers and symptom severity following treatment with selective serotonin reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors.

“The integration of tools and digital markers significantly enhances clinicians’ capabilities in predicting, diagnosing, and providing care and treatment for individuals grappling with MDD and TRD,” lead review author Annarita Vignapiano, of the Department of Mental Health in Salerno, Italy, and her co-authors wrote.

Rebecca B. Price

In an antoher recent study investigators successfully demonstrated that Pavlovian conditioning delivered digitally to improve feelings of self-worth could improve the effects of ketamine treatment in patients with TRD. Patients received a single, 5 milligram (mg) per kilogram dose of ketamine followed by four days (30 to 40 minutes per day) of digital behavioral therapy.

“Our study found that the rapid effects of ketamine can be made more enduring with simple, portable, digital techniques that would be relatively easy to provide to patients in a wide range of settings,” wrote lead author Rebecca B. Price, Ph.D., of the Department of Psychiatry in the University of Pittsburgh School of Medicine.