You Can Now Treat Depression With an App

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Until recently, clinical depression treatments have fallen into just two categories: psychotherapy and antidepressant medications. But this year, the U.S. Food and Drug Administration cleared the first app-based treatment for major depressive disorder, which just became available for use this summer.

The app, called Rejoyn, is cleared as a supplement to currently approved therapies and works by using specifically designed tasks on a smartphone app to rewire neural signals. The idea is to tap into the brain’s circuits so depressive signals and pathways don’t spiral into the debilitating emotional episodes typical of clinical depression.

The evolution of a depression app

Dr. Dennis Charney, now dean of the Icahn School of Medicine at Mount Sinai, first got the idea for Rejoyn when studying prisoners of war years ago. He and his colleagues were focused on learning about resilience and what makes certain people better than others at coping with tragedy. The researchers interviewed about 30 Vietnam veterans, most of whom had survived years of torture and solitary confinement. “A number of them started telling us that when they were in solitary and all they could do was think, that their cognitive capacities increased dramatically,” says Charney.

That’s a well-known phenomenon in brain science called neuroplasticity: the ability of the brain to improve and reinforce certain circuits with practice. Some of the prisoners developed an ability to multiply 12 numbers at a time, while others wrote books in their mind that they eventually published. Another designed an entire house that he built after his release. These "exercises" allowed the prisoners to refocus their intellectual, emotional, and cognitive energy on something other than their challenging conditions, and essentially move beyond them.

If these men were able to strengthen cognitive circuits in their brain under such horribly limited circumstances, Charney says he and his team wondered whether it would also be possible to “correct the abnormal circuits involved in depression” using similar tasks.

Years of research—which eventually led to Rejoyn—fine-tuned the tasks that people could easily do on their phone. What seems to work is a task that “does not remind people of past personal experiences, and is not related specifically to what is causing someone’s depression,” says Charney. It focuses more broadly on the depression circuit in the brain that links the prefrontal cortex, which is involved in memory, and the subcortical regions including the amygdala and hippocampus, which are tied to emotions associated with depression. In people with depression, imaging studies have shown that the memory and intellectual circuits are less active while the emotional signals are overactive, and that imbalance likely contributes to the negativity and hopelessness that are hallmarks of depression.

Inspired by a paper in 2008 that described how a computerized brain training program could improve working memory, Charney challenged one his mentees at the time, Brian Iacoviello, to develop a training exercise that might target key nodes in the brain’s neural networks that would have antidepressant effects.“We thought about targeting that imbalance and came up with a relatively straightforward, elegant, simple approach to activate both regions simultaneously through a computerized brain exercise,” says Iacoviello, now an adjunct assistant professor in the psychiatry department at Mount Sinai and a co-developer of Rejoyn. By doing so, they hoped to restore the balance between the circuits and return them to equal footing. “And maybe that would drive some antidepressant effect.”

The (shockingly simple) digital treatment

The task itself displays real faces showing different emotions—sad, happy, disgusted, angry, surprised—that users are asked to remember. The first level asks them to remember the emotion depicted in the previous face, and to answer yes or no about whether the current face they see on their screen matches that emotion. The next level asks people to remember the emotion they saw that was two faces prior to the current one. Because the faces depict emotions, the amygdala is activated—and asking people to remember these emotions stimulates the prefrontal cortex at the same time.

People doing the treatment repeat the same task three times a week for six weeks.

The researchers tested the task in two small trials in which they randomly assigned people with depression to do the task or a similar one in which people were asked to remember shapes rather than emotional faces. “We showed, to my surprise, that their depression got better,” Charney says of the group asked to remember the emotional faces. “In our studies, the patients did not receive psychotherapy and were not on other medications for their depression.”

Brain-imaging studies confirmed that a change was occurring in the brains of the patients who did the exercise. “The amygdala was still activated the way it should be, but now the dorsolateral prefrontal cortex was also able to come online and exert influence, quieting down the amygdala signal, so it looks more like a balanced, normalized connectivity pattern,” says Iacoviello.

“Neurons that fire together, wire together,” says Iman Ahmed, director of digital therapeutics at Otsuka Precision Health, a Japanese pharmaceutical and health company that licensed the technology in 2019 and conducted a large trial on Rejoyn involving several hundred patients. “It’s a matter of bringing the theoretical mechanisms of disease that people understood, reverse engineering them, and getting to the point of using computation to present a task in a way someone is able to do at home.”

Rethinking mental-health treatment

While the idea of using an app to treat depression is still new, mental-health professionals are beginning to see the power of such a digital therapeutic. “I would say 90% to 95% of people who are taking antidepressants aren’t quite where they want to be,” says Dr. Rakesh Jain, a psychiatrist in Austin. “That’s where Rejoyn has a potential role as an add-on therapy for those individuals who have suboptimal responses to their antidepressants.”

The fact that Rejoyn works on rewiring specific brain signals is also appealing, Jain says, since it has the potential to address more of the root causes of depression. “I’m beginning to realize that I don’t just want to control the symptoms of my patients, but I want to leverage the brain’s neuroplasticity—because if I don’t improve the neuroplasticity, then the patient is vulnerable to relapse.”

Digital therapeutics are still too new to fully understand what effect they will have long-term, and not all have been reviewed by the FDA, says Dr. Darlene King, chair of the American Psychiatric Association's Mental Health IT Committee. While Rejoyn is approved for depression, "it is not designed as a standalone treatment," says King; the approval is as a supplement to existing treatments or therapy to improve their effectiveness. "It's great to have another treatment. But we also don't know how engaged patients will be."

Charney says people in the trial were remarkably adherent to completing the exercises daily, mainly because the task was relatively easy to do. He believes that the task-based approach could be used to retrain abnormal brain circuits in other mental illnesses as well. “I think the concept of brain exercises that tap into circuits is going to be applicable to other conditions—PTSD for example,” he says. The strategy likely won’t be as effective in psychiatric conditions where neurons in the brain have been damaged or lost, such as as in schizophrenia, but could be useful in conditions where brain circuits can still be accessed and modified.

Otsuka is initially making Rejoyn available to patients for $50 out of pocket, and insurers will be charged $200 once they cover the therapy. Currently no insurers reimburse for Rejoyn—another hurdle digital-based approaches face in gaining wider acceptance among patients and providers. While the company would not say how many people have prescribed or used the app since it was cleared, a spokesperson said it was "pleased with the response from patients and providers. We have seen steady adoption since the launch in August."

Ultimately, different brain exercises may be developed to address different circuits involved in other psychiatric disorders. Having a completely new way to address these conditions, in addition to psychotherapy and medications, could eventually help more people to find interventions that work for them, and could even help more people experience more durable success in managing their mental illness. As more patients utilize digital therapies like Rejoyn, health care providers will have a better idea of how to optimize their effectiveness and what role they can play in improving mental health.

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