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Accepted for/Published in: Journal of Medical Internet Research

Date Submitted: May 3, 2026
Open Peer Review Period: May 3, 2026 - Jun 28, 2026
Date Accepted: Jul 9, 2026
(closed for review but you can still tweet)

The final, peer-reviewed published version of this preprint can be found here:

Prediction of Clinically Meaningful Improvement After Internet-Delivered Cognitive Behavioral Therapy for Depression and Anxiety Disorders: Machine Learning–Based Predictive Model Development and Temporal Validation Study

Kravchenko O, Halvorsen M, Bäckman J, Kaldo V, Crowley JJ, Kuja-Halkola R, Rück C, Wallert J

Prediction of Clinically Meaningful Improvement After Internet-Delivered Cognitive Behavioral Therapy for Depression and Anxiety Disorders: Machine Learning–Based Predictive Model Development and Temporal Validation Study

J Med Internet Res 2026;28:e100162

DOI: 10.2196/100162

PMID: 42567682

Prediction of Clinically Meaningful Improvement after Internet-Delivered Cognitive Behavioral Therapy for Depression and Anxiety Disorders: Machine Learning–Based Predictive Model Development and Temporal Validation Study

  • Olly Kravchenko; 
  • Matthew Halvorsen; 
  • Julia Bäckman; 
  • Viktor Kaldo; 
  • James J Crowley; 
  • Ralf Kuja-Halkola; 
  • Christian Rück; 
  • John Wallert

ABSTRACT

Background:

Up to 50% of patients treated with internet-delivered cognitive behavioral therapy (ICBT) for depression and anxiety disorders do not experience clinically significant symptom reduction. Identifying these patients prior to ICBT initiation can optimize treatment effect.

Objective:

The aim of this study was to enhance baseline prediction of clinically meaningful improvement in patients treated with ICBT for common psychiatric disorders in routine care, which could ultimately inform treatment allocation at intake.

Methods:

We developed multimodal predictive models integrating clinical, sociodemographic, and genetic data to predict clinically meaningful improvement in a sample of n=1790 patients treated with ICBT for major depressive disorder, panic disorder, and social anxiety disorder. Only data available pre-treatment were used to enable baseline prediction. We applied machine learning algorithms of varying complexity (logistic regression, random forest, XGBoost, support vector machines, soft voting, and stacking ensemble), with nested cross-validation, elastic net variable selection, multiple imputation, and temporal validation in a 20% holdout test set (n=356). The primary performance measure was area under the receiver operating characteristic curve (AUC).

Results:

All models showed comparable performance, with random forest achieving the best discrimination (AUCtest 0.749, 95% CI [0.698, 0.797]). Models that included data from national registers outperformed a benchmark model based on self-reported screening data (AUCtest 0.732–0.749 vs 0.695), whereas polygenic scores added no independent predictive value (DeLong test P=.966).

Conclusions:

These promising results provide a foundation for a future prospective trial to ascertain that baseline prediction can effectively guide tailored interventions for at-risk patients.


 Citation

Please cite as:

Kravchenko O, Halvorsen M, Bäckman J, Kaldo V, Crowley JJ, Kuja-Halkola R, Rück C, Wallert J

Prediction of Clinically Meaningful Improvement After Internet-Delivered Cognitive Behavioral Therapy for Depression and Anxiety Disorders: Machine Learning–Based Predictive Model Development and Temporal Validation Study

J Med Internet Res 2026;28:e100162

DOI: 10.2196/100162

PMID: 42567682

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