A Precision Treatment Model for Internet-Delivered Cognitive Behavioral Therapy for Anxiety and Depression Among University Students: A Secondary Analysis of a Randomized Clinical Trial

Abstract

Importance: Guided internet-delivered cognitive behavioral therapy (i-CBT) is a low-cost way to address high unmet need for anxiety and depression treatment. Scalability could be increased if some patients were helped as much by self-guided i-CBT as guided i-CBT.

Objective: To develop an individualized treatment rule using machine learning methods for guided i-CBT vs self-guided i-CBT based on a rich set of baseline predictors.

Design, setting, and participants: This prespecified secondary analysis of an assessor-blinded, multisite randomized clinical trial of guided i-CBT, self-guided i-CBT, and treatment as usual included students in Colombia and Mexico who were seeking treatment for anxiety (defined as a 7-item Generalized Anxiety Disorder [GAD-7] score of ≥10) and/or depression (defined as a 9-item Patient Health Questionnaire [PHQ-9] score of ≥10). Study recruitment was from March 1 to October 26, 2021. Initial data analysis was conducted from May 23 to October 26, 2022.

Interventions: Participants were randomized to a culturally adapted transdiagnostic i-CBT that was guided (n = 445), self-guided (n = 439), or treatment as usual (n = 435).

Main outcomes and measures: Remission of anxiety (GAD-7 scores of ≤4) and depression (PHQ-9 scores of ≤4) 3 months after baseline.

Results: The study included 1319 participants (mean [SD] age, 21.4 [3.2] years; 1038 women [78.7%]; 725 participants [55.0%] came from Mexico). A total of 1210 participants (91.7%) had significantly higher mean (SE) probabilities of joint remission of anxiety and depression with guided i-CBT (51.8% [3.0%]) than with self-guided i-CBT (37.8% [3.0%]; P = .003) or treatment as usual (40.0% [2.7%]; P = .001). The remaining 109 participants (8.3%) had low mean (SE) probabilities of joint remission of anxiety and depression across all groups (guided i-CBT: 24.5% [9.1%]; P = .007; self-guided i-CBT: 25.4% [8.8%]; P = .004; treatment as usual: 31.0% [9.4%]; P = .001). All participants with baseline anxiety had nonsignificantly higher mean (SE) probabilities of anxiety remission with guided i-CBT (62.7% [5.9%]) than the other 2 groups (self-guided i-CBT: 50.2% [6.2%]; P = .14; treatment as usual: 53.0% [6.0%]; P = .25). A total of 841 of 1177 participants (71.5%) with baseline depression had significantly higher mean (SE) probabilities of depression remission with guided i-CBT (61.5% [3.6%]) than the other 2 groups (self-guided i-CBT: 44.3% [3.7%]; P = .001; treatment as usual: 41.8% [3.2%]; P < .001). The other 336 participants (28.5%) with baseline depression had nonsignificantly higher mean (SE) probabilities of depression remission with self-guided i-CBT (54.4% [6.0%]) than guided i-CBT (39.8% [5.4%]; P = .07).

Conclusions and relevance: Guided i-CBT yielded the highest probabilities of remission of anxiety and depression for most participants; however, these differences were nonsignificant for anxiety. Some participants had the highest probabilities of remission of depression with self-guided i-CBT. Information about this variation could be used to optimize allocation of guided and self-guided i-CBT in resource-constrained settings.

Trial registration: ClinicalTrials.gov Identifier: NCT04780542.

Figure 1.. Predictors of Being Optimized by Guided Internet-Delivered Cognitive Behavioral Therapy (i-CBT) or Treatment as Usual vs Self-Guided i-CBT in the Total Sample

PHQ-ADS indicates Patient Health Questionnaire Anxiety and Depression Scale. ^aShapley Additive Explanations (SHAP) values for a specific predictor can differ for participants having the same score on the predictor due to interactions with other predictors, leading to variation in the sign of the association between the predictor and the outcome. The dominant direction of association recorded was based on visual inspection of the beeswarm plot shown to the right of the figure. ^bKey predictors are defined as the up to top 5 predictors in each domain with the highest mean absolute SHAP values of 0.010 or more. ^cSum of 2-week 9-item Patient Health Questionnaire (PHQ-9) score, 2-week 7-item Generalized Anxiety Disorder (GAD-7) score, and 30-day Posttraumatic Stress Disorder (PTSD) Checklist (scale, 0-72). ^dRole impairment overall refers to how much physical health problems interfered with their life overall (scale, 0-10). ^eRole impairment, on average, refers to how much physical health problems led to functional impairment at school or work, in social life or interpersonal relationships, with home management, and life overall (sum of 4 items for a 0-40 scale).

Figure 2.. Predictors of Being Optimized by Guided Internet-Delivered Cognitive Behavioral Therapy (i-CBT) vs All Others Among Participants With Clinically Significant Baseline Depression

SAD indicates social anxiety disorder. ^aShapley Additive Explanations (SHAP) values for a specific predictor can differ for participants having the same score on the predictor due to interactions with other predictors, leading to variation in the sign of the association between the predictor and the outcome. The dominant direction of association recorded was based on visual inspection of the beeswarm plot shown to the right of the figure. ^bKey predictors are defined as the up to top 5 predictors in each domain with the highest mean absolute SHAP values of 0.010 or more. ^cSocial and performance-related anxiety scale (sum of social situation and performance-related anxiety scales). ^dPerformance-related anxiety scale (intensity of anxiety or fear × frequency of avoidance of situations). ^eSocial situation-related anxiety scale (intensity of anxiety or fear × frequency of anxiety). ^fRole impairment overall refers to how much physical health problems interfered with their life overall (scale, 0-10). ^gRole impairment, on average, refers to how much physical health problems led to functional impairment at school or work, in social life or interpersonal relationships, with home management, and life overall (sum of 4 items for a 0-40 scale).