FDA clears first digital treatment for depression, but experts caution that research is still early

The US Food and Drug Administration is allowing the use of Rejoyn, the first prescription digital treatment for major depressive disorder.

Rejoyn, made by Otsuka Pharmaceutical and Click Therapeutics, is a smartphone app intended for use alongside antidepressant medications for people 22 and older who have a diagnosis of major depressive disorder. It employs a six-week program that combines a new approach called cognitive-emotional training and cognitive behavioral therapy lessons, according to a news release.

Since Rejoyn is classified as a low- to medium-risk medical device, it needed only to prove that it is “substantially equivalent” to another marketed device – meaning it is just as safe and effective – to gain FDA clearance.

“Rejoyn represents a novel and exciting adjunctive treatment option to address major depressive disorder symptoms that complements the current standard of care,” Dr. John Kraus, executive vice president and chief medical officer at Otsuka, said in the release. “While traditional approaches are often effective, many are left with only a partial response to treatment.”

Depression is one of the most common mental health disorders in the US. About 18% of American adults – more than 1 in 6 – say they are depressed or receiving treatment for depression, a 2023 Gallup report found. Research has also found that up to 30% of people who take antidepressant medications are partial responders, meaning they continue to have depressive symptoms while using the drugs.

Rejoyn is designed to serve as an adjunct to antidepressants for these partial responders, according to the news release. The app uses a form of cognitive-emotional training called Emotional Faces Memory Task, in which people are asked to identify and compare emotions displayed on a series of faces. Preliminary research shows that these exercises may stimulate the amygdala and the dorsolateral prefrontal cortex – regions of the brain that are thought to be involved in depression – and have antidepressant effects.

“Rejoyn has a neuromodulatory mechanism designed to act like physical therapy for the brain by delivering personalized, consistent brain-training exercises designed to help improve connections in the brain regions affected by depression,” Dr. Brian Iacoviello, scientific adviser at Click Therapeutics and a co-inventor of Emotional Faces Memory Task, said in the news release.

Dr. John Torous, director of the Division of Digital Psychiatry at Beth Israel Deaconess Medical Center, who was not involved in the development of Rejoyn, said that this cognitive-emotional training approach is not a well-established mechanism and that the research is still exploratory.

The FDA clearance for Rejoyn was granted based on results from a clinical trial involving 386 people ages 22 to 64 who had a diagnosis of major depressive disorder that was not responsive to antidepressants. They were assigned to use either the Rejoyn app or a sham app that gave memory tasks that did not involve cognitive-emotional training or cognitive behavioral therapy.

The study found that while participants using the Rejoyn app showed an improvement in depressive symptoms from baseline, the average change was not significantly different from the change observed with the sham app. There were no side effects reported in the trial.

Torous said that while it is important to note that the trial did not prove that Rejoyn has a statistically significant benefit, the app is also not designed to be a standalone treatment.

“If the benefit is minimal but the risks are minimal, perhaps there’s no harm in trying it,” he said. “Hopefully, we see more evidence come out in the future, because as a clinician psychiatrist, I want to make sure people use something that is going to make them better.”

Otsuka Pharmaceutical said it is evaluating additional areas of research, including other indications and patient populations, but did not outline any specific follow-up studies.

Rejoyn will require a prescription for download and will become available in late 2024, according to the news release. Otsuka said it will make try to make the tool “accessible and affordable” but did not specify the price.

Torous noted that insurance companies may not cover the app because it did not show significant effect in clinical trials. FDA clearance, he said, does not guarantee insurance approval.

“The next frontier is going to be educating everyone on the risks and benefits of these tools. Many clinicians may not be ready or prepared to begin prescribing” them, he said.

There is also the question of how engaged patients will be with the app, Torous said. The Rejoyn study found that 88% of participants completed at least 12 of the 18 treatment sessions.

Thousands of mental health apps geared toward various mental health disorders don’t require a prescription, Torous said. Doctors need to understand the specific needs and preferences of their patients before recommending a digital tool, he said.

“I think that patients and clinicians are curious and excited to learn more, but both want to understand the risks and benefits,” Torous said. “There is an opportunity cost if you do something that is not effective.”