The Effect of Predicted Compliance With a Web-Based Intervention for Anxiety and Depression Among Latin American University Students: Randomized Controlled Trial
Authors: Benjet Corina , Zainal Nur Hani , Albor Yesica , Alvis-Barranco Libia , Carrasco Tapia Nayib , Contreras-Ibáñez Carlos C , Cortés-Morelos Jacqueline , Cudris-Torres Lorena , de la Peña Francisco R , González Noé , Gutierrez-Garcia Raúl A , Vargas-Contreras Eunice , Medina-Mora Maria Elena , Patiño Pamela , Gildea Sarah M , Kennedy Chris J , Luedtke Alex , Sampson Nancy A , Petukhova Maria V , Zubizarreta Jose R , Cuijpers Pim , Kazdin Alan E , Kessler Ronald C 
Published: February 2025

Background
Web-based cognitive behavioral therapy (wb-CBT) is a scalable way to reach distressed university students. Guided wb-CBT is typically superior to self-guided wb-CBT over short follow-up periods, but evidence is less clear over longer periods.

Objective
This study aimed to compare short-term (3 months) and longer-term (12 months) aggregate effects of guided and self-guided wb-CBT versus treatment as usual (TAU) in a randomized controlled trial of Colombian and Mexican university students and carry out an initially unplanned secondary analysis of the role of differential predicted compliance in explaining these differences.

Methods
The 1319 participants, recruited either through email and social media outreach invitations or from waiting lists of campus mental health clinics, were undergraduates (1038/1319, 78.7% female) with clinically significant baseline anxiety (Generalized Anxiety Disorder–7 score≥10) or depression (Patient Health Questionnaire–9 score≥10). The intervention arms comprised guided wb-CBT with weekly asynchronous written human feedback, self-guided wb-CBT with the same content as the guided modality, and TAU as provided at each university. The prespecified primary outcome was joint remission (Generalized Anxiety Disorder–7 score=0-4 and Patient Health Questionnaire–9 score=0-4). The secondary outcome was joint symptom reduction (mean scores on the Patient Health Questionnaire Anxiety and Depression Scale) at 3 and 12 months after randomization.

Results
As reported previously, 3-month outcomes were significantly better with guided wb-CBT than self-guided wb-CBT (P=.02) or TAU (P=.02). However, subsequent follow-up showed that 12-month joint remission (adjusted risk differences=6.0-6.5, SE 0.4-0.5, and P<.001 to P=.007; adjusted mean differences=2.70-2.69, SE 0.7-0.8, and P<.001 to P=.001) was significantly better with self-guided wb-CBT than with the other interventions. Participants randomly assigned to the guided wb-CBT arm spent twice as many minutes logged on as those in the self-guided wb-CBT arm in the first 12 weeks (mean 12.5, SD 36.9 vs 5.9, SD 27.7; χ21=107.1, P<.001), whereas participants in the self-guided wb-CBT arm spent twice as many minutes logged on as those in the guided wb-CBT arm in weeks 13 to 52 (mean 0.4, SD 7.5 vs 0.2, SD 4.4; χ21=10.5, P=.001). Subgroup analysis showed that this longer-term superiority of self-guided wb-CBT was confined to the 40% (528/1319) of participants with high predicted self-guided wb-CBT compliance beyond 3 months based on a counterfactual nested cross-validated machine learning model. The 12-month outcome differences were nonsignificant across arms among other participants (all P>.05).

Conclusions
The results have important practical implications for precision intervention targeting to maximize longer-term wb-CBT benefits. Future research needs to investigate strategies to increase sustained guided wb-CBT use once guidance ends.

Trial Registration
ClinicalTrials.gov NCT04780542; https://www.clinicaltrials.gov/study/NCT04780542

International Registered Report Identifier (IRRID)
RR2-10.1186/s13063-022-06255-3