BACKGROUND University students experience disproportionately high rates of anxiety and depression, which threatens their academic success. Digital mental health interventions (DMHIs) offer a scalable, cost-effective approach to universal prevention. StriveWeekly is a skills-based DMHI designed to prevent anxiety and depression among university students. A prior randomized controlled trial (RCT) demonstrated its effectiveness and acceptability. OBJECTIVE This study aimed to test replication of StriveWeekly’s effectiveness in reducing or preventing anxiety, depression, and stress symptoms, when delivered in a next context: with a different student population (undergraduate students at midsized private college), during a global pandemic, and with new engagement strategies. Secondary aims included examining mediators of symptom change, and user engagement and acceptability. METHODS We conducted a cluster-randomized pragmatic RCT with 519 full-time undergraduates (7.2% of student body). Participants were randomized to the intervention (n = 244) or waitlist control (n = 275). StriveWeekly consisted of seven weekly modules teaching cognitive and behavioral skills. Surveys were administered online at baseline, posttest, 2-month follow-up, and 4-month follow-up. RESULTS Intervention effects replicated prior findings. The group × time interaction was significant (t = −2.62, p = .009, power = 81%) for Depression Anxiety Stress Scale (DASS-21) scores, favoring StriveWeekly with a small between-group effect over the waitlist (d = 0.24). Waitlist participants worsened (d = 0.19), while intervention participants remained stable (d = −0.04). Among asymptomatic students at baseline (n = 202), symptom onset was lower in the intervention group (15.7%) versus waitlist (28.7%; χ² = 4.26, p = .047). Effects were maintained at 2-month follow-up and converged for students who received delayed access to the intervention. Mediation analyses showed direct effects of higher module completion and specific modules (behavioral activation, cognitive reappraisal) on symptom improvement, but no indirect effects via self-reported habit change. Engagement was high: 93% of immediate intervention participants initiated StriveWeekly, and average completion was 41% of modules. Acceptability ratings indicated most participants found the program easy to use and satisfactory overall. CONCLUSIONS StriveWeekly demonstrated small but significant preventive effects on anxiety and depression symptoms, even during pandemic-related stressors. We successfully replicated prior trial results. Findings support the generalizability of StriveWeekly as a scalable, effective DMHI for campus-wide mental health promotion. We discuss considerations for guiding ethical and evidence-based implementation of DMHIs on campuses, especially given the dearth of commercially available DMHIs and the rise of student artificial intelligence (AI) tool use. CLINICALTRIAL ClinicalTrials.gov: NCT049278450
Rith‐Najarian et al. (Thu,) studied this question.