Assessing the Efficacy and Safety of a Digital Therapeutic for Symptoms of Depression in Adolescents: Protocol for a Randomized Controlled Trial

Abstract

Background Depression is a serious, prevalent, recurrent, and undertreated disorder in adolescents. Low levels of treatment seeking and treatment adherence in this age group, combined with a growing national crisis in access to mental health care, have increased efforts to identify effective treatment alternatives for this demographic. Digital health interventions for mental illness can provide cost-effective, engaging, and accessible means of delivering psychotherapy to adolescents. Objective This protocol describes a virtual randomized controlled trial designed to evaluate the efficacy and safety of a self-guided, mobile app–based implementation of behavioral activation therapy, SparkRx, for the adjunct treatment of symptoms of depression in adolescents. Methods Participants are recruited directly through web-based and print advertisements. Following eligibility screening and consenting, participants are randomly assigned to a treatment arm (SparkRx) or a control arm (assessment-enhanced usual care) for 5 weeks. The primary efficacy outcome, total score on the 8-item Patient Health Questionnaire (PHQ-8), is assessed at the end of the 5-week intervention period. Additional participant-reported outcomes are assessed at baseline, the postintervention time point, and 1-month follow-up. The safety of the intervention is assessed by participant report (and legal guardian report, if the participant is younger than 18 years) and by patterns of symptom deterioration on the PHQ-8, as part of a larger clinical safety monitoring protocol. The primary efficacy outcome, total PHQ-8 score at the postintervention time point, will be compared between SparkRx and enhanced usual care arms using mixed effect modeling, with baseline PHQ-8 and current antidepressant medication status included as covariates. Secondary efficacy outcomes, including the proportion of participants exhibiting treatment response, remission, and minimal clinically significant improvement (all derived from total PHQ-8 scores), will be compared between groups using chi-square tests. Symptom severity at 1-month follow-up will also be compared between arms. Planned subgroup analyses will examine the robustness of treatment effects to differences in baseline symptom severity (PHQ-8 score <15 or ≥ 15) and age (younger than 18 years and older than 18 years). The primary safety outcome, the number of psychiatric serious adverse events, will be compared between trial arms using the Fisher exact test. All other adverse events will be presented descriptively. Results As of May 2023, enrollment into the study has concluded; 223 participants were randomized. The analysis of the efficacy and safety data is expected to be completed by Fall 2023. Conclusions We hypothesize that the results of this trial will support the efficacy and safety of SparkRx in attenuating symptoms of depression in adolescents. Positive results would more broadly support the prospect of using accessible, scientifically validated, digital therapeutics in the adjunct treatment of mental health disorders in this age range. Trial Registration ClinicalTrials.gov NCT05462652; https://clinicaltrials.gov/study/NCT05462652 International Registered Report Identifier (IRRID) DERR1-10.2196/48740