Circadian Rhythm Stabilization App to Prevent Mood Episode Recurrence in Patients With Mood Disorders: A Multicenter, Double-Blind, Sham-Controlled, Randomized Clinical Trial.

Objective

Preventing recurrence is essential for improving the clinical course of major depressive disorder (MDD) and bipolar disorder (BD). The authors developed the Circadian Rhythm for Mood (CRM) smartphone app, which provides individualized 3-day mood forecasts and delivers personalized circadian rhythm feedback using passive sensor data. This study tested the therapeutic efficacy of CRM in preventing mood episode recurrence compared with a sham app.

Methods

In a multicenter, double-blind, randomized clinical trial, 93 adults with MDD or BD were assigned in a 1:1 ratio to active CRM (N=47) or a sham app (N=46) for 12 months. Participants in the active CRM group received personalized circadian rhythm stabilization feedback generated by machine learning. Participants in the sham app group received nonactionable feedback from a dummy algorithm, designed not to influence circadian behavior, with a visually identical interface. The primary outcome was the number of recurrent mood episodes per participant during follow-up.

Results

In the modified intention-to-treat sample (N=80), the sham group (N=42) had a significantly higher recurrence rate than the active CRM group (N=38) (incidence rate ratio=3.39, 95% CI=1.86-6.17). Cumulative recurrent episode-days per person-year were greater in sham group (duration rate ratio=2.76, 95% CI=1.19-6.40), and time to recurrence favored active CRM (hazard ratio=3.03, 95% CI=1.58-5.81). No significant adverse effects were observed.

Conclusions

The circadian rhythm stabilization app significantly reduced recurrence and improved the clinical course in MDD and BD. CRM has potential as an innovative, scalable digital chronotherapeutic adjunct to standard care.