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
χ 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.