FDA approves first digital treatment for depression, but experts warn research is still early

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

Rejoyn, made by Otsuka Pharmaceutical and Click Therapeutics, is a smartphone app designed to be used in conjunction with antidepressant medications for people over the age of 22 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 only needed to demonstrate 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 complementary treatment option to address the symptoms of major depressive disorder that complements the current standard of care,” Dr. John Kraus, executive vice president and chief medical officer of Otsuka, said in the release. “While traditional approaches are often effective, many only have a partial response to treatment.”

Depression is one of the most common mental health disorders in the U.S. About 18% of American adults (more than 1 in 6) say they are depressed or receive treatment for depression, according to a Gallup report from 2023. Research has also found that up to 30% of people taking antidepressant medications are partial responders, meaning they continue to have depressive symptoms while using the medications.

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 the Emotional Faces Memory Task, in which people are asked to identify and compare the emotions displayed on a series of faces. Preliminary research shows that these exercises can stimulate the amygdala and dorsolateral prefrontal cortex (regions of the brain thought to be involved in depression) and have antidepressant effects.

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

FDA clearance for Rejoyn was granted based on the results of a clinical trial involving 386 people ages 22 to 64 who were diagnosed with major depressive disorder that did not respond to antidepressants. They were assigned to use the Rejoyn app or a simulated app that offered memory tasks that did not involve cognitive-emotional training or cognitive-behavioral therapy.

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

Torous said that while it’s important to note that the trial did not show Rejoyn to have a statistically significant benefit, the app is also not designed to be a stand-alone treatment.

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

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

Torous noted that insurance companies may not cover the app because it didn’t show a significant effect in clinical trials. FDA clearance, he stated, does not guarantee safety approval.

“The next frontier will be educating everyone about the risks and benefits of these tools. Many doctors may not be ready to start prescribing them,” he said.

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

Thousands of mental health apps targeting various mental health disorders do not require a prescription, Torous said. Doctors should understand their patients’ specific needs and preferences before recommending a digital tool, he said.

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