Personalized digital intervention for depression based on social rhythm principles adds significantly to outpatient treatment

Ellen Frank, Meredith L Wallace, Mark L Matthews, Jeremy Kendrick, Jeremy Leach, Tara Moore, Gabriel Aranovich, Tanzeem Choudhury, Nirav R Shah, Zeenia Framroze, Greg Posey, Samuel Burgess, David J Kupfer, Ellen Frank, Meredith L Wallace, Mark L Matthews, Jeremy Kendrick, Jeremy Leach, Tara Moore, Gabriel Aranovich, Tanzeem Choudhury, Nirav R Shah, Zeenia Framroze, Greg Posey, Samuel Burgess, David J Kupfer

Abstract

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 software solution based on social rhythm regulation principles. The full intent-to-treat (ITT) sample consisted of 133 individuals, aged 18-65. An exploratory sub-sample of interest was those individuals who presented with moderately severe to severe depression at study entry (baseline PHQ-8 score ≥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 precision digital intervention of which we are aware. Participants were randomly allocated to receive Cue plus care-as-usual or digital monitoring only plus care as usual. Within the full study and depressed-at-entry 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 non-linear 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 full sample, the group difference in the slope of PHQ-8 was negligible (Cohen's d = -0.10); however, the Cue group demonstrated significantly greater improvement from baseline to 16 weeks (p = 0.040). In the depressed-at-entry sample, we found evidence for benefit of Cue. The 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). 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 (https://ichgcp.net/clinical-trials-registry/NCT03152864?term=ellen+frank&draw=2&rank=3).

Keywords: depression; depressive symtpoms; digital intervention platform; passive monitoring; social rhythm disruption; social rhythm regularity; treatment.

Conflict of 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. Frank, Matthews, Leach, and Aranovich, Moore, Posey and Burgess are employees of and hold equity in HealthRhythms, Inc. Choudhury, Shah and Kupfer are advisors to and hold equity in HealthRhythms, Inc. 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. Framroze declares that she has no commercial or financial relationships that could be construed as a potential conflict of interest.

© 2022 Frank, Wallace, Matthews, Kendrick, Leach, Moore, Aranovich, Choudhury, Shah, Framroze, Posey, Burgess and Kupfer.

Figures

Figure 1
Figure 1
Design of RCT comparing a digital intervention platform with monitoring only.
Figure 2
Figure 2
Sample learning module screens.
Figure 3
Figure 3
Sample micro-intervention/behavior change suggestion.
Figure 4
Figure 4
CONSORT diagram.
Figure 5
Figure 5
Loess trajectories of PHQ-8 for Cue and measure (control) conditions in full study sample.
Figure 6
Figure 6
Means and standard errors of PHQ scores by study week-full sample.
Figure 7
Figure 7
Loess trajectories of PHQ-8 for Cue and measure (control) conditions in depressed-at entry participants (initial PHQ-8 ≥ 15).
Figure 8
Figure 8
Means and standard errors of PHQ scores by study week – depressed-at-entry sample.

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