A depression app got FDA authorisation after missing its main trial endpoint

Rejoyn, a smartphone app that delivers a course of cognitive-emotional and behavioural exercises, is the first prescription digital therapeutic the US Food and Drug Administration has authorised as an add-on treatment for major depression [s1][s2]. In its pivotal phase 3 trial it did beat a sham app — but on the trial's own pre-specified primary measure the difference fell just short of statistical significance, and the clearance rests instead on a supportive analysis [s1].

That is not a disqualifying result, but it is the fact anyone weighing the app should have first.

What was tested

The MIRAI trial was a phase 3, multicentre, randomised, blinded, sham-controlled study run remotely [s1]. It enrolled adults aged 22 to 64 with major depressive disorder who had responded inadequately to their current antidepressant taken on its own [s1]. Participants kept taking that medication and were randomised either to CT-152 — the trial name for Rejoyn — which delivered the therapeutic intervention through smartphone apps over a six-week course, or to a control group given a sham app containing a working-memory task [s1]. Both groups also received supportive text messages [s1]. In total 386 people were randomised, 194 to CT-152 and 192 to sham [s1].

The pre-specified primary outcome was the change in the Montgomery-Åsberg Depression Rating Scale, or MADRS, a clinician-rated measure of depression severity, from baseline to week six [s1].

The result the trial was designed to test

In the primary efficacy population — the 354 participants who completed at least one session and one post-baseline assessment — MADRS scores fell by 9.03 points in the Rejoyn group and 7.25 points in the sham group [s1]. The difference of 1.78 points favoured the app, but with a P value of 0.0568 it did not cross the conventional 0.05 threshold for statistical significance [s1].

A trial that misses its primary endpoint has, by its own pre-registered standard, not demonstrated its effect. The honest way to read MIRAI is that the study set itself a test and came up narrowly short of passing it.

The analysis the authorisation rests on

The trial also ran a supportive analysis on the full randomised sample of all 386 participants — the intent-to-treat population [s1]. In that analysis the between-group difference in six-week MADRS change was 2.12 points, favouring CT-152, with a P value of 0.0211 [s1]. On safety, no treatment-emergent adverse events or discontinuations were judged related to CT-152, and no deaths occurred [s1]. On the strength of these data, the paper states, CT-152 became the first FDA-authorised prescription digital therapeutic for the adjunctive treatment of major depression [s1]. The FDA cleared Rejoyn, marketed by Otsuka, through its 510(k) pathway on 30 March 2024 [s2].

Two things are worth keeping straight. A supportive secondary analysis is not the primary endpoint, and regulators and journals generally treat it as hypothesis-supporting rather than confirmatory. And even taken at face value, the effect is small: a difference of about two points on a MADRS scale that runs from 0 to 60, where a clinically meaningful response is usually defined as a halving of the score. Whether a two-point separation from a sham app is something a patient would notice is a fair question the trial does not answer.

What "adjunctive" and "sham-controlled" are doing here

Two design features shape how to read the number. Rejoyn is an add-on: everyone in the trial stayed on an antidepressant, so the comparison is between medication-plus-app and medication-plus-sham, not app-versus-nothing [s1]. And the control was an active sham — a working-memory game with supportive texts — rather than a blank. A sham that itself provides some engagement and attention sets a harder, and more honest, bar than a no-treatment control, which is a point in the trial's favour even as it makes a significant result harder to reach [s1].

What to watch

Whether real-world data show a benefit that holds outside a trial, since a six-week app course depends heavily on people actually using it. Whether the modest effect seen here is durable beyond the study window. And, more broadly, whether prescription digital therapeutics can convert regulatory clearance into routine use — a category that has repeatedly cleared the FDA bar only to struggle with payment and uptake. Clearance establishes that a product met a standard; it does not establish how much it helps.

Sources

1. [s1] A digital therapeutic (CT-152) as adjunct to antidepressant medication: A phase 3 randomized controlled trial. Journal of Affective Disorders, 14 May 2025. https://doi.org/10.1016/j.jad.2025.119409
2. [s2] FDA 510(k) clearance record K231209 (Rejoyn). U.S. Food and Drug Administration, decision 30 March 2024. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm?ID=K231209