Precision Digital Intervention for Depression Based on Social Rhythm Principles Adds Significantly to Outpatient Treatment

We conducted a 16-week randomized controlled trial in psychiatric outpatients with a lifetime diagnosis of a mood and/or anxiety disorder to measure the impact of a first of its kind precision digital intervention based on social rhythm regulation principles (Cue). The full intent to treat (ITT) sample consisted of 133 individuals, aged 18 to 65. The primary sample of interest were individuals with moderately severe to severe depression at study entry (baseline PHQ-8 score greater than or equal to 15; N=28). Cue is a novel digital intervention platform that capitalizes on the smartphone’s ability to continuously monitor depression relevant behavior patterns and use each patient’s behavioral data to provide timely, personalized micro interventions, making this the first example of a digital precision intervention that we are aware of. Participants were randomly allocated to receive Cue plus care as usual or digital monitoring only plus care as usual. Within the depressed and full ITT samples, we fit a mixed effects model to test for group differences in the slope of depressive symptoms over 16 weeks. To account for the nonlinear trajectory with more flexibility, we also fit a mixed effects model considering week as a categorical variable and used the resulting estimates to test the group difference in PHQ change from baseline to 16 weeks. In the depressed at entry sample, we found evidence for benefit of Cue. The large group difference in the slope of PHQ-8 (Cohen’s d = -0.72) indicated a meaningfully more rapid rate of improvement in the intervention group than in the control group. The Cue group also demonstrated significantly greater improvement in PHQ-8 from baseline to 16 weeks (p=0.009). In the full sample, the group difference in the slope of PHQ-8 was negligible (Cohen’s d =-0.10); however, the Cue group again demonstrated significantly greater improvement from baseline to 16 weeks (p=0.040). We are encouraged by the size of the intervention effect in those who were acutely ill at baseline and by the finding that across all participants, 80% of whom were receiving pharmacotherapy, we observed significant benefit of Cue at 16 weeks of treatment. These findings suggest that a social rhythm focused digital intervention platform may represent a useful and accessible adjunct to antidepressant treatment. () ### Competing Interest Statement The authors declare the following commercial and/or financial relationships with HealthRhythms, Inc, the developer of the digital intervention platform that is the focus of this report. Drs. Frank, Matthews, Leach, and Aranovich, Ms. Moore, Mr. Posey and Mr. Burgess and are employees of and hold equity in HealthRhythms, Inc. Drs. Choudhury, Shah and Kupfer are advisors to and hold equity in HealthRhythms, Inc. Dr. Wallace is employed as a part-time consultant to HealthRhythms, Inc and is also a statistical consultant for Noctem Health and Sleep Number Bed Corporation. Ms. Framroze declares that she has no commercial or financial relationships that could be construed as a potential conflict of interest. ### Clinical Trial NCT03152864 ### Funding Statement Research reported in this publication was supported by a Small Business Innovation Research (SBIR) award from the National Institute of Mental Health Award Number R44MH113520. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the University of Utah Institutional Review Board which provided ethical oversight throughout the conduct of the trial and continues to provide ethical oversight of the use of the study data. All participants in the protocol described in this paper provided informed consent according to procedures approved by the University of Utah Institutional Review Board. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data contained in the present report are available upon reasonable request to the authors