<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE article PUBLIC "-//NLM//DTD Journal Publishing DTD v2.0 20040830//EN" "journalpublishing.dtd"><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" dtd-version="2.0" xml:lang="en" article-type="review-article"><front><journal-meta><journal-id journal-id-type="nlm-ta">J Med Internet Res</journal-id><journal-id journal-id-type="publisher-id">jmir</journal-id><journal-id journal-id-type="index">1</journal-id><journal-title>Journal of Medical Internet Research</journal-title><abbrev-journal-title>J Med Internet Res</abbrev-journal-title><issn pub-type="epub">1438-8871</issn><publisher><publisher-name>JMIR Publications</publisher-name><publisher-loc>Toronto, Canada</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">v28i1e86079</article-id><article-id pub-id-type="doi">10.2196/86079</article-id><article-categories><subj-group subj-group-type="heading"><subject>Review</subject></subj-group></article-categories><title-group><article-title>Artificial Intelligence for Predicting Treatment Response in Patients With Anxiety Disorders After Cognitive Behavioral Therapy: Systematic Review and Meta-Analysis</article-title></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name name-style="western"><surname>Liu</surname><given-names>Jiawen</given-names></name><degrees>MA</degrees><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name name-style="western"><surname>Wang</surname><given-names>Junhui</given-names></name><degrees>MEng</degrees><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author"><name name-style="western"><surname>Wu</surname><given-names>Zhaobin</given-names></name><degrees>MEng</degrees><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author"><name name-style="western"><surname>Adam Assim</surname><given-names>Mohamad Ibrani Shahrimin Bin</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="aff2">2</xref></contrib></contrib-group><aff id="aff1"><institution>Youth League Committee, Liuzhou Railway Vocational Technical College</institution><addr-line>No. 2 Wenyuan Road, Yufeng District</addr-line><addr-line>Liuzhou</addr-line><addr-line>Guangxi Zhuang Autonomous Region</addr-line><country>China</country></aff><aff id="aff2"><institution>Faculty of Humanities, Management and Science, Universiti Putra Malaysia</institution><addr-line>Bintulu</addr-line><addr-line>Sarawak</addr-line><country>Malaysia</country></aff><aff id="aff3"><institution>School of Automation, Guangxi University of Science and Technology</institution><addr-line>Liuzhou</addr-line><addr-line>Guangxi</addr-line><country>China</country></aff><contrib-group><contrib contrib-type="editor"><name name-style="western"><surname>Brini</surname><given-names>Stefano</given-names></name></contrib></contrib-group><contrib-group><contrib contrib-type="reviewer"><name name-style="western"><surname>Ahmadu</surname><given-names>Charlotte</given-names></name></contrib><contrib contrib-type="reviewer"><name name-style="western"><surname>Ghosh</surname><given-names>Dhrubajyoti</given-names></name></contrib><contrib contrib-type="reviewer"><name name-style="western"><surname>Mohanadas</surname><given-names>Sadhasivam</given-names></name></contrib><contrib contrib-type="reviewer"><name name-style="western"><surname>Virupaksha</surname><given-names>Sandesh Gubbi</given-names></name></contrib><contrib contrib-type="reviewer"><name name-style="western"><surname>Zhang</surname><given-names>Yonggang</given-names></name></contrib></contrib-group><author-notes><corresp>Correspondence to Jiawen Liu, MA, Youth League Committee, Liuzhou Railway Vocational Technical College, No. 2 Wenyuan Road, Yufeng District, Liuzhou, Guangxi Zhuang Autonomous Region, 545000, China, 60 1116670058; <email>liujiawen@ltzy.edu.cn</email></corresp></author-notes><pub-date pub-type="collection"><year>2026</year></pub-date><pub-date pub-type="epub"><day>18</day><month>3</month><year>2026</year></pub-date><volume>28</volume><elocation-id>e86079</elocation-id><history><date date-type="received"><day>17</day><month>10</month><year>2025</year></date><date date-type="rev-recd"><day>12</day><month>02</month><year>2026</year></date><date date-type="accepted"><day>24</day><month>02</month><year>2026</year></date></history><copyright-statement>&#x00A9; Jiawen Liu, Junhui Wang, Zhaobin Wu, Mohamad Ibrani Shahrimin Bin Adam Assim. Originally published in the Journal of Medical Internet Research (<ext-link ext-link-type="uri" xlink:href="https://www.jmir.org">https://www.jmir.org</ext-link>), 18.3.2026. </copyright-statement><copyright-year>2026</copyright-year><license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/"><p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (<ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">https://creativecommons.org/licenses/by/4.0/</ext-link>), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in the Journal of Medical Internet Research (ISSN 1438-8871), is properly cited. The complete bibliographic information, a link to the original publication on <ext-link ext-link-type="uri" xlink:href="https://www.jmir.org/">https://www.jmir.org/</ext-link>, as well as this copyright and license information must be included.</p></license><self-uri xlink:type="simple" xlink:href="https://www.jmir.org/2026/1/e86079"/><abstract><sec><title>Background</title><p>Artificial intelligence (AI) models have been increasingly explored for predicting treatment response to cognitive behavioral therapy (CBT) in patients with anxiety disorders. Identifying potential responders in advance may help inform treatment planning and support clinical decision-making. Although a growing number of studies have applied AI techniques in this context, reported performance estimates vary across studies, and the overall predictive accuracy has not been comprehensively quantified.</p></sec><sec><title>Objective</title><p>This systematic review and meta-analysis aims to quantify the overall performance of AI models in predicting treatment response following CBT for anxiety disorders and to examine how data sources, algorithmic approaches, and diagnostic subtypes influence predictive performance.</p></sec><sec sec-type="methods"><title>Methods</title><p>A systematic literature search was conducted in PubMed, Embase, Web of Science, Cochrane Library, and PsycINFO up to August 2025. We included studies that validated AI models for predicting CBT treatment response (remission or response) in patients diagnosed with an anxiety disorder. The risk of bias was assessed using the PROBAST+AI (Prediction Model Risk of Bias Assessment Tool for Artificial Intelligence) tool. Predictive performance metrics, including sensitivity, specificity, accuracy, and area under the curve (AUC), were extracted and pooled. Pooled estimates for sensitivity, specificity, and diagnostic accuracy were derived using the Restricted Maximum Likelihood estimator, with CIs adjusted via the Hartung-Knapp-Sidik-Jonkman method. Prediction intervals were calculated and reported alongside these pooled estimates to illustrate the expected distribution of effects in real-world settings.</p></sec><sec sec-type="results"><title>Results</title><p>Eleven studies were included in the meta-analysis. The pooled sensitivity of AI-based models for predicting treatment response was 0.73 (95% CI 0.58&#x2010;0.85; <italic>I</italic>&#x00B2;=82.8%), and the pooled specificity was 0.75 (95% CI 0.59&#x2010;0.89; <italic>I</italic>&#x00B2;=96.7%). The overall pooled accuracy was 0.74 (95% CI 0.62&#x2010;0.84; <italic>I</italic>&#x00B2;=94.6%). The summary AUC was 0.81 (95% CI 0.78&#x2010;0.85), indicating moderate discriminative performance. Subgroup analyses showed that models incorporating multimodal data achieved superior predictive performance, with a pooled sensitivity of 0.84 and an accuracy of 0.82. In addition, predictive performance was the highest in patients with social anxiety disorder compared with other anxiety disorder subtypes.</p></sec><sec sec-type="conclusions"><title>Conclusions</title><p>This meta-analysis quantitatively synthesized AI performance in predicting CBT response for anxiety disorders, moving beyond narrative reviews to provide pooled evidence. In contrast to existing reviews that encompass broader diagnostic groups, our focused approach establishes a precise benchmark for this clinical domain, highlighting the current moderate overall performance. Furthermore, we extend beyond previous work by demonstrating the superior predictive utility of multimodal data, identifying social anxiety disorder as the most predictable subtype, and systematically evaluating the impact of data modalities and algorithm types. Future efforts should prioritize robustly validated multimodal models, laying essential groundwork for the potential development of AI-assisted tools to personalize treatment planning in anxiety disorders.</p></sec><sec><title>Trial Registration</title><p>PROSPERO CRD420251137096; https://www.crd.york.ac.uk/PROSPERO/view/CRD420251137096</p></sec></abstract><kwd-group><kwd>artificial intelligence</kwd><kwd>treatment response</kwd><kwd>anxiety disorders</kwd><kwd>cognitive behavioral therapy</kwd><kwd>meta-analysis</kwd></kwd-group></article-meta></front><body><sec id="s1" sec-type="intro"><title>Introduction</title><p>Anxiety disorders constitute a group of mental disorders characterized by intense, excessive, and persistent worry and fear, exhibiting high prevalence rates. They not only cause significant functional impairment in patients&#x2019; social, academic, and occupational functioning but also impose substantial socioeconomic burdens at the societal level, including considerable health care resource consumption and productivity losses [<xref ref-type="bibr" rid="ref1">1</xref>,<xref ref-type="bibr" rid="ref2">2</xref>]. Cognitive behavioral therapy (CBT) is a first-line evidence-based intervention for anxiety disorders [<xref ref-type="bibr" rid="ref3">3</xref>,<xref ref-type="bibr" rid="ref4">4</xref>]. However, treatment response varies considerably, with a notable subset of patients showing suboptimal or inadequate improvement [<xref ref-type="bibr" rid="ref5">5</xref>]. This heterogeneity underscores a critical clinical need: the ability to preemptively identify likely responders and, more importantly, those at high risk of nonresponse who may benefit from treatment augmentation or alternative interventions from the outset [<xref ref-type="bibr" rid="ref6">6</xref>]. Early and accurate prediction of treatment response can optimize care pathways, improve resource allocation, and reduce delays, aligning with the goals of precision mental health [<xref ref-type="bibr" rid="ref7">7</xref>].</p><p>Clinical assessment of anxiety disorders typically relies on structured or semistructured interviews and standardized scales [<xref ref-type="bibr" rid="ref8">8</xref>], such as the Hamilton Anxiety Rating Scale (HAM-A) [<xref ref-type="bibr" rid="ref9">9</xref>], Clinical Global Impressions&#x2013;Improvement (CGI-I) [<xref ref-type="bibr" rid="ref10">10</xref>], and Liebowitz Social Anxiety Scale (LSAS) [<xref ref-type="bibr" rid="ref7">7</xref>], which are fundamental for symptom identification, outcome evaluation, and longitudinal monitoring. However, they possess inherent limitations for predictive purposes. First, they depend heavily on self-report and subjective ratings, making them vulnerable to recall bias and social desirability effects, thereby compromising objectivity [<xref ref-type="bibr" rid="ref11">11</xref>]. Second, heterogeneity in measured constructs, scoring procedures, and cutoff thresholds across instruments constrains comparability and diagnostic consistency across studies and clinical settings [<xref ref-type="bibr" rid="ref12">12</xref>]. Consequently, there is growing recognition that these traditional metrics alone may be insufficient for reliably forecasting an individual&#x2019;s unique response trajectory to a specific therapy such as CBT [<xref ref-type="bibr" rid="ref13">13</xref>].</p><p>Against this background, artificial intelligence (AI), particularly machine learning (ML) and deep learning (DL), has attracted increasing attention as a methodological framework for advancing outcome prediction in mental health research. AI-based models can integrate large-scale, high-dimensional, and multimodal data and capture complex, nonlinear relationships that are difficult to model with conventional statistical techniques [<xref ref-type="bibr" rid="ref14">14</xref>]. In recent years, a growing number of studies have applied ML and DL methods to predict treatment response across a range of psychiatric interventions, including CBT for anxiety disorders [<xref ref-type="bibr" rid="ref15">15</xref>,<xref ref-type="bibr" rid="ref16">16</xref>]. These studies have incorporated diverse data sources, including baseline clinical characteristics, symptom trajectories, neuroimaging markers, psychophysiological measures, and digital behavioral indicators, and have reported varying levels of predictive accuracy [<xref ref-type="bibr" rid="ref17">17</xref>,<xref ref-type="bibr" rid="ref18">18</xref>]. However, the anxiety disorders comprise clinically distinct subtypes, such as social anxiety disorder (SAD), generalized anxiety disorder (GAD), and panic disorder (PD), which differ in symptom profiles and underlying mechanisms [<xref ref-type="bibr" rid="ref19">19</xref>]. This diagnostic heterogeneity may further influence model generalizability and predictive stability across populations [<xref ref-type="bibr" rid="ref7">7</xref>,<xref ref-type="bibr" rid="ref20">20</xref>]. To date, however, quantitative evidence synthesizing the predictive performance of AI models for CBT response in different anxiety disorder subtypes remains limited, and potential sources of heterogeneity across studies remain insufficiently explored and require systematic investigation [<xref ref-type="bibr" rid="ref21">21</xref>].</p><p>This systematic review and meta-analysis aims to quantitatively synthesize the overall performance of AI models in predicting treatment response following CBT for anxiety disorders. We also seek to explore the influence of key factors, such as data sources, algorithmic approaches, and diagnostic subtypes, on predictive performance and to preliminarily investigate potential sources of the observed heterogeneity.</p></sec><sec id="s2" sec-type="methods"><title>Methods</title><sec id="s2-1"><title>Ethical Considerations</title><p>As this is a systematic review and meta-analysis, ethics approval and consent to participate are not applicable. The manuscript does not include the identification images or other personal or clinical details of participants.</p><p>The meta-analysis adhered rigorously to the PRISMA-DTA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy) reporting guidelines [<xref ref-type="bibr" rid="ref22">22</xref>] and the PRISMA-S extension for reporting literature searches [<xref ref-type="bibr" rid="ref23">23</xref>]. We have provided the completed PRISMA-DTA (<xref ref-type="supplementary-material" rid="app3">Checklist 1</xref>), PRISMA 2020 Abstract (<xref ref-type="supplementary-material" rid="app4">Checklist 2</xref>), and PRISMA-S (<xref ref-type="supplementary-material" rid="app5">Checklist 3</xref>) checklists. The research protocol was registered in the PROSPERO registry (registration ID: CRD420251137096).</p></sec><sec id="s2-2"><title>Feasibility Assessment for Meta-Analysis</title><p>Prior to initiating the full systematic review, a preliminary scoping search was conducted to assess the feasibility of quantitative synthesis. This step aimed to determine whether sufficient studies reported the extractable predictive performance metrics necessary for a meta-analysis. In the scoping search, although the field is nascent, several published studies met the core data requirements, supporting the rationale for proceeding with a formal systematic review and meta-analysis.</p></sec><sec id="s2-3"><title>Search Strategy</title><p>A systematic search was conducted in PubMed, Embase, Web of Science, Cochrane Library, and PsycINFO from inception to August 16, 2025. Two independent reviewers (JL and JW) screened titles/abstracts and subsequently assessed full texts, with disagreements resolved by consensus. Search strategies combined controlled vocabulary (MeSH) and free-text terms across 3 concept blocks: AI and methods (eg, &#x201C;artificial intelligence,&#x201D; &#x201C;machine learning,&#x201D; and &#x201C;deep learning&#x201D;), anxiety disorders (eg, &#x201C;anxiety disorders,&#x201D; &#x201C;social anxiety disorder,&#x201D; &#x201C;generalized anxiety disorder,&#x201D; and &#x201C;panic disorder&#x201D;), and CBT (eg, &#x201C;cognitive behavioral therapy,&#x201D; &#x201C;CBT,&#x201D; and &#x201C;cognitive therapy&#x201D;). No language or publication year limits were applied at the initial search stage to minimize selection bias. Detailed database-specific strategies are provided in Table S1 in <xref ref-type="supplementary-material" rid="app1">Multimedia Appendix 1</xref>. Study selection followed a dual-stage independent screening process. Two reviewers (JL and JW) first screened titles/abstracts and then independently assessed full texts of potentially eligible records. Disagreements were resolved by consensus or by third-party arbitration (ZW). The reference lists of included studies were manually screened for additional records. It should be noted that in conducting this systematic review, we did not contact authors, experts, or manufacturers to obtain additional studies or data, and did not adapt or reuse search strategies from previous reviews. Additionally, a formal peer review of the search strategy was not conducted.</p></sec><sec id="s2-4"><title>Inclusion and Exclusion Criteria</title><p>The PITROS framework was used for the inclusion criteria:</p><list list-type="bullet"><list-item><p>Participants (P): patients with anxiety disorders receiving CBT, including separation anxiety disorder, selective mutism, specific phobia, SAD, PD/panic attacks, agoraphobia, GAD, and substance/medication-induced anxiety disorder</p></list-item><list-item><p>Index test (I): AI methods (eg, ML and DL) developed to predict CBT treatment response</p></list-item><list-item><p>Target condition (T): positive cases defined as clinically significant post-CBT improvement (eg, meaningful symptom reduction); negative cases defined as poor or no response</p></list-item><list-item><p>Reference standard (R): validated diagnostic/severity scales for anxiety disorders</p></list-item><list-item><p>Outcomes (O): sensitivity, specificity, area under the curve (AUC), and accuracy</p></list-item><list-item><p>Setting (S): mental health outpatient clinics, psychiatric hospitals, and clinical trial centers; multicenter prospective or retrospective designs using electronic health records or public databases</p></list-item></list><p>The exclusion criteria were as follows: (1) publication in a language other than English at the full-text stage, (2) nonempirical article type (eg, review, case report, conference abstract, meta-analysis, and letter), (3) no assessment of the prediction of CBT response using AI, (4) inclusion of a population that did not have anxiety disorder or that did not undergo CBT, (5) absence of a recognized reference standard or inadequate data to derive the target metrics, and (6) duplicate publication identified using EndNote and manual checking. The database search was unrestricted by language to maximize sensitivity, but non-English publications were excluded during full-text review owing to translation resource constraints. We acknowledge this as a potential limitation, as it may have introduced language bias by excluding relevant studies published in other languages. The independent selection of studies was conducted by 2 reviewers (JL and JW), with disagreements resolved through discussion or by a third reviewer (ZW).</p></sec><sec id="s2-5"><title>Data Extraction</title><p>Two independent reviewers (JL and JW) conducted comprehensive data extraction from full-text articles to assess study eligibility. The extracted data encompassed critical study characteristics, including the authors, year, country, study design, center, response definition, types of disorders, and types of treatments. Specific quantitative elements included the total number of patients in the training and internal validation sets, the number of response patients in the training and internal validation sets, the data-splitting method, predictors, AI algorithms, and AI methods. For internal validation sets, we systematically recorded true positive (TP), true negative (TN), false positive (FP), and false negative (FN) values.</p><p>For studies included in the systematic review but lacking meta-analysis&#x2013;compatible data, we proactively contacted corresponding authors via email to request necessary information. Given the frequent absence of diagnostic contingency tables, we reconstructed 2&#x00D7;2 tables using reported sensitivity, specificity, responder numbers, and total patient counts. Any discrepancies in extraction were resolved through a collaborative discussion, with a third reviewer (ZW) serving as an arbitrator if consensus could not be reached, thereby ensuring methodological rigor and data integrity.</p></sec><sec id="s2-6"><title>Quality Assessment</title><p>The latest PROBAST+AI (Prediction Model Risk of Bias Assessment Tool for Artificial Intelligence) quality assessment tool was used [<xref ref-type="bibr" rid="ref24">24</xref>], which replaced PROBAST 2019. This tool comprises 2 phases: model development and model evaluation. Each phase encompasses 7 domains covering participant and data sources, predictors, outcome assessment, and analysis. Evaluation results for each domain are categorized as &#x201C;low,&#x201D; &#x201C;high,&#x201D; or &#x201C;unclear,&#x201D; determined based on specific signal questions. Signal concerns are rated as &#x201C;yes,&#x201D; &#x201C;probably yes,&#x201D; &#x201C;probably no,&#x201D; &#x201C;no,&#x201D; &#x201C;no information,&#x201D; and, in some cases, &#x201C;not applicable.&#x201D; Signal concerns phrased as &#x201C;yes&#x201D; or &#x201C;probably yes&#x201D; indicate a lower risk of bias. Any signal question rated &#x201C;no&#x201D; or &#x201C;probably no&#x201D; indicates a potential high risk of bias in that domain. If no &#x201C;no&#x201D; or &#x201C;probably no&#x201D; rating exists but &#x201C;no information&#x201D; is present, the domain&#x2019;s bias risk is classified as unclear. The complete list of signal questions and tables is detailed in Tables S2 and S3 in <xref ref-type="supplementary-material" rid="app1">Multimedia Appendix 1</xref>.</p><p>To ensure objectivity and accuracy in the assessment process, 2 reviewers (JL and JW) independently assessed the risk of bias in the included studies using the PROBAST+AI quality assessment tool. During the review process, any discrepancies between reviewers were resolved through in-depth discussions and analyses to achieve consensus, ensuring highly reliable, consistent final assessment results.</p></sec><sec id="s2-7"><title>Outcome Measures</title><p>The primary outcome measures encompassed comprehensive diagnostic performance metrics from internal validation sets, including sensitivity, specificity, accuracy, and AUC. Sensitivity, calculated as TP/(TP+FN), measured the AI model&#x2019;s ability to accurately identify TPs, while specificity, computed as TN/(TN+FP), assessed the model&#x2019;s proficiency in correctly identifying negative cases. AUC provided a holistic assessment of the model&#x2019;s discriminative power between positive and negative instances. Accuracy, defined as (TP+TN)/total patients, represented the proportion of correctly classified samples. We systematically extracted performance metrics from all data sources (eg, imaging, clinical/demographic, and multimodal) and AI algorithms presented in each study. However, for the purpose of meta-analytic pooling, only the primary model from each article, specifically the model based on nonoverlapping patient cohorts, was selected to ensure data independence and avoid double-counting.</p></sec><sec id="s2-8"><title>Statistical Analysis</title><p>While the core analytical plan and reporting adhered to the preregistered protocol, a key methodological deviation was implemented to enhance the robustness of our statistical synthesis. The registered protocol specified the use of the bivariate random-effects model (Reitsma model) as the primary method for pooling sensitivity and specificity. In the final analysis, we maintained this model for generating the summary receiver operating characteristic (SROC) curve and the AUC. However, for the pooled estimates of sensitivity and specificity themselves, we adopted a univariate random-effects model using the Restricted Maximum Likelihood estimator, with CIs adjusted via the Hartung-Knapp-Sidik-Jonkman (HKSJ) method. This adaptation was made to incorporate the HKSJ adjustment, which provides more conservative and reliable CIs, particularly when dealing with a limited number of studies or substantial heterogeneity [<xref ref-type="bibr" rid="ref25">25</xref>]. Prediction intervals (PIs) were calculated and reported alongside these pooled estimates to illustrate the expected distribution of effects in real-world settings. Heterogeneity was quantitatively assessed using the PIs and further explored through subgroup analyses and meta-regression [<xref ref-type="bibr" rid="ref26">26</xref>]. Bivariate boxplots were used to visually identify potential outlier studies contributing to heterogeneity. Prespecified covariates for meta-regression included the number of study centers, anxiety disorder subtype, data splitting method, CBT protocol type, and AI algorithm category. Subgroup analyses were conducted according to data type, algorithm type, and specific anxiety disorder diagnoses. Additionally, a bubble plot was used to assess temporal trends in the accuracy of different algorithms, and funnel plots were used, along with Egger tests, to evaluate potential small-study effects.</p></sec></sec><sec id="s3" sec-type="results"><title>Results</title><sec id="s3-1"><title>Study Selection</title><p>A search across 5 electronic databases yielded 1399 potentially relevant publications. After deleting 399 duplicates, 1000 records were retained for preliminary screening. At this phase, 980 studies were identified as clearly irrelevant based on the title/abstract and the publication type. Thus, 15 articles were selected for full-text review. Following a comprehensive assessment of the full texts, 5 studies were removed because they did not investigate treatment response to CBT. Two studies were excluded due to non-English publication. Three studies were excluded as they were ongoing trials without any published outcome measures. Additionally, 6 qualifying studies were identified from nondatabase sources. Ultimately, 11 studies [<xref ref-type="bibr" rid="ref7">7</xref>,<xref ref-type="bibr" rid="ref17">17</xref>,<xref ref-type="bibr" rid="ref18">18</xref>,<xref ref-type="bibr" rid="ref27">27</xref>-<xref ref-type="bibr" rid="ref34">34</xref>] were included in the meta-analysis as they met predefined inclusion criteria. The identification, screening, eligibility assessment, and inclusion process followed the PRISMA guidelines, and the selection analysis is elaborated in <xref ref-type="fig" rid="figure1">Figure 1</xref>.</p><fig position="float" id="figure1"><label>Figure 1.</label><caption><p>PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) s in Figure 1:</p><p>flow diagram of the systematic literature search and study selection process for studies evaluating artificial intelligence models in predicting treatment response to cognitive behavioral therapy for anxiety disorders.</p></caption><graphic alt-version="no" mimetype="image" position="float" xlink:type="simple" xlink:href="jmir_v28i1e86079_fig01.png"/></fig></sec><sec id="s3-2"><title>Study Description and Quality Assessment</title><p>A total of 11 eligible studies comprising 59,085 samples (training: 38,563; internal validation set: 20,522) were included. Among these, 4 studies exclusively evaluated SAD [<xref ref-type="bibr" rid="ref7">7</xref>,<xref ref-type="bibr" rid="ref29">29</xref>,<xref ref-type="bibr" rid="ref32">32</xref>,<xref ref-type="bibr" rid="ref34">34</xref>], 2 studies focused on PD with agoraphobia [<xref ref-type="bibr" rid="ref30">30</xref>,<xref ref-type="bibr" rid="ref33">33</xref>], 1 study investigated both GAD and PD [<xref ref-type="bibr" rid="ref27">27</xref>], 1 study examined PD and SAD [<xref ref-type="bibr" rid="ref31">31</xref>], and the remaining 3 studies addressed multiple anxiety disorder subtypes [<xref ref-type="bibr" rid="ref17">17</xref>,<xref ref-type="bibr" rid="ref18">18</xref>,<xref ref-type="bibr" rid="ref28">28</xref>]. Nine studies [<xref ref-type="bibr" rid="ref17">17</xref>,<xref ref-type="bibr" rid="ref18">18</xref>,<xref ref-type="bibr" rid="ref27">27</xref>,<xref ref-type="bibr" rid="ref29">29</xref>-<xref ref-type="bibr" rid="ref34">34</xref>] provided data eligible for meta-analysis. The included studies were published between 2014 and 2024, and all were prospective. Definitions of treatment response varied across studies: 2 studies used the CGI-I [<xref ref-type="bibr" rid="ref29">29</xref>,<xref ref-type="bibr" rid="ref32">32</xref>], 2 used the LSAS [<xref ref-type="bibr" rid="ref7">7</xref>,<xref ref-type="bibr" rid="ref34">34</xref>], 2 used the HAM-A [<xref ref-type="bibr" rid="ref30">30</xref>,<xref ref-type="bibr" rid="ref33">33</xref>], 1 used the Overall Anxiety Severity and Impairment Scale (OASIS) [<xref ref-type="bibr" rid="ref27">27</xref>], 1 used the clinical severity rating [<xref ref-type="bibr" rid="ref28">28</xref>], 1 combined HAM-A and the Spider Phobia Questionnaire (SPQ) [<xref ref-type="bibr" rid="ref18">18</xref>], 1 used both the Generalized Anxiety Disorder-7 (GAD-7) and the Patient Health Questionnaire-9 (PHQ-9) [<xref ref-type="bibr" rid="ref17">17</xref>], and 1 applied multiple scales simultaneously [<xref ref-type="bibr" rid="ref31">31</xref>]. Across the 9 datasets, the most frequently used AI algorithms were support vector machines (SVMs; 4/9, 44%) and random forests (RFs; 3/9, 33%). Additionally, of the 9 datasets, 2 were based on clinical/demographic data, 6 on imaging data, and 1 on multimodal data. The clinical, methodological, and technical characteristics of the included studies are summarized in <xref ref-type="table" rid="table1">Table 1</xref> and <xref ref-type="supplementary-material" rid="app2">Multimedia Appendix 2</xref>.</p><table-wrap id="t1" position="float"><label>Table 1.</label><caption><p>Characteristics of the included studies (n=11) and their patient populations.</p></caption><table id="table1" frame="hsides" rules="groups"><thead><tr><td align="left" valign="top">Study (author)</td><td align="left" valign="top">Year</td><td align="left" valign="top">Country</td><td align="left" valign="top">Study design</td><td align="left" valign="top">Center</td><td align="left" valign="top">Response definition</td><td align="left" valign="top">Types of anxiety disorders</td><td align="left" valign="top">Types of treatments</td><td align="left" valign="top">Data source</td><td align="left" valign="top" colspan="2">Total sample size, n</td><td align="left" valign="top" colspan="2">Response sample size, n</td></tr><tr><td align="left" valign="bottom"/><td align="left" valign="bottom"/><td align="left" valign="bottom"/><td align="left" valign="bottom"/><td align="left" valign="bottom"/><td align="left" valign="bottom"/><td align="left" valign="bottom"/><td align="left" valign="bottom"/><td align="left" valign="bottom"/><td align="left" valign="top">Training</td><td align="left" valign="top">Internal validation</td><td align="left" valign="top">Training</td><td align="left" valign="top">Internal validation</td></tr></thead><tbody><tr><td align="left" valign="top">Ball et al [<xref ref-type="bibr" rid="ref27">27</xref>]</td><td align="left" valign="top">2014</td><td align="left" valign="top">America</td><td align="left" valign="top">Pro<sup><xref ref-type="table-fn" rid="table1fn1">a</xref></sup></td><td align="left" valign="top">Single center</td><td align="left" valign="top">OASIS<sup><xref ref-type="table-fn" rid="table1fn2">b</xref></sup> &#x2264;5</td><td align="left" valign="top">GAD<sup><xref ref-type="table-fn" rid="table1fn3">c</xref></sup>, PD<sup><xref ref-type="table-fn" rid="table1fn4">d</xref></sup></td><td align="left" valign="top">Standard CBT<sup><xref ref-type="table-fn" rid="table1fn5">e</xref></sup></td><td align="left" valign="top">Institutional database</td><td align="left" valign="top">48</td><td align="left" valign="top">49</td><td align="left" valign="top">29</td><td align="left" valign="top">49</td></tr><tr><td align="left" valign="top">Bertie et al [<xref ref-type="bibr" rid="ref28">28</xref>]</td><td align="left" valign="top">2024</td><td align="left" valign="top">Multiple countries</td><td align="left" valign="top">Pro</td><td align="left" valign="top">Multiple centers</td><td align="left" valign="top">CSR<sup><xref ref-type="table-fn" rid="table1fn6">f</xref></sup> &#x2265;4</td><td align="left" valign="top">GAD, separation anxiety, SAD<sup><xref ref-type="table-fn" rid="table1fn7">g</xref></sup>, SPH<sup><xref ref-type="table-fn" rid="table1fn8">h</xref></sup></td><td align="left" valign="top">Standard CBT</td><td align="left" valign="top">Institutional database</td><td align="left" valign="top">2214</td><td align="left" valign="top">2214</td><td align="left" valign="top">&#x2014;<sup><xref ref-type="table-fn" rid="table1fn9">i</xref></sup></td><td align="left" valign="top">&#x2014;</td></tr><tr><td align="left" valign="top">Bukhari et al [<xref ref-type="bibr" rid="ref7">7</xref>]</td><td align="left" valign="top">2025</td><td align="left" valign="top">America</td><td align="left" valign="top">Pro</td><td align="left" valign="top">Multiple centers</td><td align="left" valign="top">LSAS<sup><xref ref-type="table-fn" rid="table1fn10">j</xref></sup>&#x2193; &#x2265;50%</td><td align="left" valign="top">SAD</td><td align="left" valign="top">Standard CBT</td><td align="left" valign="top">Institutional database</td><td align="left" valign="top">157</td><td align="left" valign="top">157</td><td align="left" valign="top">&#x2014;</td><td align="left" valign="top">&#x2014;</td></tr><tr><td align="left" valign="top">Frick et al [<xref ref-type="bibr" rid="ref29">29</xref>]</td><td align="left" valign="top">2020</td><td align="left" valign="top">Sweden</td><td align="left" valign="top">Pro</td><td align="left" valign="top">Single center</td><td align="left" valign="top">CGI-I<sup><xref ref-type="table-fn" rid="table1fn11">k</xref></sup> &#x2264;2</td><td align="left" valign="top">SAD</td><td align="left" valign="top">CBT+SSRI<sup><xref ref-type="table-fn" rid="table1fn12">l</xref></sup>, CBT+placebo</td><td align="left" valign="top">Institutional database</td><td align="left" valign="top">47</td><td align="left" valign="top">47</td><td align="left" valign="top">24</td><td align="left" valign="top">24</td></tr><tr><td align="left" valign="top">Hahn et al [<xref ref-type="bibr" rid="ref30">30</xref>]</td><td align="left" valign="top">2015</td><td align="left" valign="top">Germany</td><td align="left" valign="top">Pro</td><td align="left" valign="top">Multiple centers</td><td align="left" valign="top">HAM-A<sup><xref ref-type="table-fn" rid="table1fn13">m</xref></sup>&#x2193; &#x2265;50%</td><td align="left" valign="top">PD with AG<sup><xref ref-type="table-fn" rid="table1fn14">n</xref></sup></td><td align="left" valign="top">Standard CBT</td><td align="left" valign="top">Institutional database</td><td align="left" valign="top">49</td><td align="left" valign="top">49</td><td align="left" valign="top">25</td><td align="left" valign="top">25</td></tr><tr><td align="left" valign="top">Hilbert et al [<xref ref-type="bibr" rid="ref18">18</xref>]</td><td align="left" valign="top">2024</td><td align="left" valign="top">Germany</td><td align="left" valign="top">Pro</td><td align="left" valign="top">Multiple centers</td><td align="left" valign="top">Protect-AD: HAM-A&#x2193; &#x2265;50%; Spider VR: SPQ<sup><xref ref-type="table-fn" rid="table1fn15">o</xref></sup>&#x2193; &#x2265;30%</td><td align="left" valign="top">PD, AG, SAD, SPH</td><td align="left" valign="top">Standard CBT</td><td align="left" valign="top">Institutional database</td><td align="left" valign="top">410</td><td align="left" valign="top">410</td><td align="left" valign="top">213</td><td align="left" valign="top">213</td></tr><tr><td align="left" valign="top">Hentati Isacsson et al [<xref ref-type="bibr" rid="ref31">31</xref>]</td><td align="left" valign="top">2024</td><td align="left" valign="top">Sweden</td><td align="left" valign="top">Pro</td><td align="left" valign="top">Single center</td><td align="left" valign="top">MADRS<sup><xref ref-type="table-fn" rid="table1fn16">p</xref></sup> &#x2264;11, PDSS<sup><xref ref-type="table-fn" rid="table1fn17">q</xref></sup> &#x2264;8, LSAS &#x2264;35</td><td align="left" valign="top">PD, SAD</td><td align="left" valign="top">iCBT<sup><xref ref-type="table-fn" rid="table1fn18">r</xref></sup></td><td align="left" valign="top">Institutional database</td><td align="left" valign="top">3619</td><td align="left" valign="top">3619</td><td align="left" valign="top">&#x2014;</td><td align="left" valign="top">&#x2014;</td></tr><tr><td align="left" valign="top">M&#x00E5;nsson et al [<xref ref-type="bibr" rid="ref32">32</xref>]</td><td align="left" valign="top">2015</td><td align="left" valign="top">Sweden</td><td align="left" valign="top">Pro</td><td align="left" valign="top">Multiple centers</td><td align="left" valign="top">CGI-I &#x2264;2</td><td align="left" valign="top">SAD</td><td align="left" valign="top">iCBT</td><td align="left" valign="top">Institutional database</td><td align="left" valign="top">23</td><td align="left" valign="top">23</td><td align="left" valign="top">12</td><td align="left" valign="top">12</td></tr><tr><td align="left" valign="top">Prasad et al [<xref ref-type="bibr" rid="ref17">17</xref>]</td><td align="left" valign="top">2023</td><td align="left" valign="top">United Kingdom, America</td><td align="left" valign="top">Pro</td><td align="left" valign="top">Multiple centers</td><td align="left" valign="top">GAD-7<sup><xref ref-type="table-fn" rid="table1fn19">s</xref></sup>&#x2193; &#x2265;64, PHQ-9<sup><xref ref-type="table-fn" rid="table1fn20">t</xref></sup>&#x2191; &#x003C;6</td><td align="left" valign="top">Anxiety</td><td align="left" valign="top">iCBT</td><td align="left" valign="top">Institutional database</td><td align="left" valign="top">31,899</td><td align="left" valign="top">13,857</td><td align="left" valign="top">&#x2014;</td><td align="left" valign="top">5232</td></tr><tr><td align="left" valign="top">Sundermann et al [<xref ref-type="bibr" rid="ref33">33</xref>]</td><td align="left" valign="top">2017</td><td align="left" valign="top">Germany</td><td align="left" valign="top">Pro</td><td align="left" valign="top">Multiple centers</td><td align="left" valign="top">HAM-A&#x2193; &#x2265;50%</td><td align="left" valign="top">PD with AG</td><td align="left" valign="top">Standard CBT</td><td align="left" valign="top">Institutional database</td><td align="left" valign="top">59</td><td align="left" valign="top">59</td><td align="left" valign="top">30</td><td align="left" valign="top">30</td></tr><tr><td align="left" valign="top">Whitfield-Gabrieli et al [<xref ref-type="bibr" rid="ref34">34</xref>]</td><td align="left" valign="top">2015</td><td align="left" valign="top">America</td><td align="left" valign="top">Pro</td><td align="left" valign="top">Multiple centers</td><td align="left" valign="top">LSAS&#x2193; &#x2265;50%</td><td align="left" valign="top">SAD</td><td align="left" valign="top">Standard CBT</td><td align="left" valign="top">Institutional database</td><td align="left" valign="top">38</td><td align="left" valign="top">38</td><td align="left" valign="top">19</td><td align="left" valign="top">19</td></tr></tbody></table><table-wrap-foot><fn id="table1fn1"><p><sup>a</sup>Pro: prospective.</p></fn><fn id="table1fn2"><p><sup>b</sup>OASIS: Overall Anxiety Severity and Impairment Scale.</p></fn><fn id="table1fn3"><p><sup>c</sup>GAD: generalized anxiety disorder.</p></fn><fn id="table1fn4"><p><sup>d</sup>PD: panic disorder.</p></fn><fn id="table1fn5"><p><sup>e</sup>CBT: cognitive behavioral therapy.</p></fn><fn id="table1fn6"><p><sup>f</sup>CSR: clinical severity rating.</p></fn><fn id="table1fn7"><p><sup>g</sup>SAD: social anxiety disorder.</p></fn><fn id="table1fn8"><p><sup>h</sup>SPH: specific phobia.</p></fn><fn id="table1fn9"><p><sup>i</sup>Not applicable.</p></fn><fn id="table1fn10"><p><sup>j</sup>LASA: Liebowitz Social Anxiety Scale.</p></fn><fn id="table1fn11"><p><sup>k</sup>CGI-I: clinical global impression-improvement.</p></fn><fn id="table1fn12"><p><sup>l</sup>SSRI: selective serotonin reuptake inhibitor.</p></fn><fn id="table1fn13"><p><sup>m</sup>HAM-A: Hamilton Anxiety Rating Scale.</p></fn><fn id="table1fn14"><p><sup>n</sup>AG: agoraphobia.</p></fn><fn id="table1fn15"><p><sup>o</sup>SPQ: Spider Phobia Questionnaire.</p></fn><fn id="table1fn16"><p><sup>p</sup>MADRS: Montgomery-Asberg Depression Rating Scale.</p></fn><fn id="table1fn17"><p><sup>q</sup>PDSS: Panic Disorder Severity Scale.</p></fn><fn id="table1fn18"><p><sup>r</sup>iCBT: internet-based cognitive behavioral therapy.</p></fn><fn id="table1fn19"><p><sup>s</sup>GAD-7: Generalized Anxiety Disorder-7.</p></fn><fn id="table1fn20"><p><sup>t</sup>PHQ-9: Patient Health Questionnaire-9.</p></fn></table-wrap-foot></table-wrap><p>The risk of bias, as assessed by the PROBAST+AI quality assessment tool, is presented in <xref ref-type="fig" rid="figure2">Figure 2</xref> and Tables S2 and S3 in <xref ref-type="supplementary-material" rid="app1">Multimedia Appendix 1</xref>. For model development, in the overall quality assessment, 55% (6/11) of studies were rated as high risk, while the remaining 45% (5/11) were rated as low risk. Regarding applicability concerns, 9% (1/11) of studies were rated as high risk, while the remaining 91% (10/11) were rated as low risk. For model validation, 55% (6/11) of studies were rated as high risk in the overall risk of bias assessment, with the remaining 45% (5/11) rated as low risk. In the comprehensive evaluation of applicability concerns, 9% (1/11) of studies were rated as high risk, while the remaining 91% (10/11) were rated as low risk.</p><fig position="float" id="figure2"><label>Figure 2.</label><caption><p>Risk of bias and applicability assessment using the PROBAST+AI tool for studies developing or validating AI models to predict treatment response after cognitive behavioral therapy in patients with anxiety disorders. Panel A summarizes the risk of bias for model development studies, and panel B summarizes the risk of bias for model validation studies. PROBAST+AI: Prediction Model Risk of Bias Assessment Tool for Artificial Intelligence.</p></caption><graphic alt-version="no" mimetype="image" position="float" xlink:type="simple" xlink:href="jmir_v28i1e86079_fig02.png"/></fig></sec><sec id="s3-3"><title>Trend in Diagnostic Accuracy Over Time</title><p>The scatter plot in <xref ref-type="fig" rid="figure3">Figure 3</xref> illustrates a negative trend in model accuracy from 2014 to 2024 across logistic regression (LR), recurrent neural network (RNN), RF, and SVM algorithms. A linear regression line confirms that reported accuracy has generally decreased over the decade within this dataset. The highest performance was recorded in 2015 by an SVM model (approximately 0.9), while the lowest scores appeared in 2024, with RF models showing a drop in scores to around 0.5. The shaded region indicates the CI for this downward trajectory (<xref ref-type="fig" rid="figure3">Figure 3</xref>).</p><fig position="float" id="figure3"><label>Figure 3.</label><caption><p>Bubble plot illustrating the accuracy of various artificial intelligence algorithms over time (publication year) for predicting treatment response to cognitive behavioral therapy in patients with anxiety disorders. LR: logistic regression; RF: random forest; RNN: recurrent neural network; SVM: support vector machine.</p></caption><graphic alt-version="no" mimetype="image" position="float" xlink:type="simple" xlink:href="jmir_v28i1e86079_fig03.png"/></fig></sec><sec id="s3-4"><title>Predicting CBT Response to Anxiety Disorders Using AI Models Based on the Primary Model Per Study</title><p>The pooled sensitivity of AI models was 0.73 (95% CI 0.58&#x2010;0.85; 95% PI 0.31&#x2010;0.99; <italic>I</italic>&#x00B2;=82.8%), specificity was 0.75 (95% CI 0.59&#x2010;0.89; 95% PI 0.25&#x2010;1.00; <italic>I</italic>&#x00B2;=96.7%), accuracy was 0.74 (95% CI 0.62&#x2010;0.84; 95% PI 0.39&#x2010;0.97; <italic>I</italic>&#x00B2;=94.6%), and AUC was 0.81 (95% CI 0.78&#x2010;0.85), as shown in <xref ref-type="fig" rid="figure4">Figures 4</xref><xref ref-type="fig" rid="figure5"/><xref ref-type="fig" rid="figure6"/>-<xref ref-type="fig" rid="figure7">7</xref>. Based on a prespecified pretest probability of 20%, the Fagan nomogram indicated a posttest probability of 43% for a positive result and 8% for a negative result (Figure S1 in <xref ref-type="supplementary-material" rid="app1">Multimedia Appendix 1</xref>). The results of the bivariate boxplots indicated that 1 study [<xref ref-type="bibr" rid="ref30">30</xref>] had discrete values, suggesting it may be a source of heterogeneity (<xref ref-type="fig" rid="figure8">Figure 8</xref>). Furthermore, meta-regression analysis indicated that heterogeneity in sensitivity was significantly associated with the number of centers (<italic>P</italic>&#x003C;.001) and the type of anxiety disorder (<italic>P</italic>&#x003C;.001). In contrast, heterogeneity in specificity was significantly associated with CBT type (<italic>P</italic>&#x003C;.001) and AI algorithm category (<italic>P</italic>&#x003C;.001) (<xref ref-type="table" rid="table2">Table 2</xref>).</p><fig position="float" id="figure4"><label>Figure 4.</label><caption><p>Forest plot displaying the pooled sensitivity, with 95% CIs and prediction intervals, of artificial intelligence models for predicting treatment response after cognitive behavioral therapy in patients with anxiety disorders [<xref ref-type="bibr" rid="ref17">17</xref>,<xref ref-type="bibr" rid="ref18">18</xref>,<xref ref-type="bibr" rid="ref27">27</xref>,<xref ref-type="bibr" rid="ref29">29</xref>,<xref ref-type="bibr" rid="ref30">30</xref>,<xref ref-type="bibr" rid="ref32">32</xref>-<xref ref-type="bibr" rid="ref34">34</xref>]. FN: false negative; TP: true positive.</p></caption><graphic alt-version="no" mimetype="image" position="float" xlink:type="simple" xlink:href="jmir_v28i1e86079_fig04.png"/></fig><fig position="float" id="figure5"><label>Figure 5.</label><caption><p>Forest plot displaying the pooled specificity, with 95% CIs and prediction intervals, of artificial intelligence models for predicting treatment response after cognitive behavioral therapy in patients with anxiety disorders [<xref ref-type="bibr" rid="ref17">17</xref>,<xref ref-type="bibr" rid="ref18">18</xref>,<xref ref-type="bibr" rid="ref27">27</xref>,<xref ref-type="bibr" rid="ref29">29</xref>,<xref ref-type="bibr" rid="ref30">30</xref>,<xref ref-type="bibr" rid="ref32">32</xref>-<xref ref-type="bibr" rid="ref34">34</xref>]. FP: false positive; TN: true negative.</p></caption><graphic alt-version="no" mimetype="image" position="float" xlink:type="simple" xlink:href="jmir_v28i1e86079_fig05.png"/></fig><fig position="float" id="figure6"><label>Figure 6.</label><caption><p>Forest plot displaying the pooled accuracy, with 95% CIs and prediction intervals, of artificial intelligence models for predicting treatment response after cognitive behavioral therapy in patients with anxiety disorders [<xref ref-type="bibr" rid="ref17">17</xref>,<xref ref-type="bibr" rid="ref18">18</xref>,<xref ref-type="bibr" rid="ref27">27</xref>,<xref ref-type="bibr" rid="ref29">29</xref>,<xref ref-type="bibr" rid="ref30">30</xref>,<xref ref-type="bibr" rid="ref32">32</xref>-<xref ref-type="bibr" rid="ref34">34</xref>]. TN: true negative; TP: true positive.</p></caption><graphic alt-version="no" mimetype="image" position="float" xlink:type="simple" xlink:href="jmir_v28i1e86079_fig06.png"/></fig><fig position="float" id="figure7"><label>Figure 7.</label><caption><p>Summary receiver operating characteristic (SROC) curve for artificial intelligence models predicting treatment response in patients with anxiety disorders after cognitive behavioral therapy. The summary point estimates for sensitivity (SENS) and specificity (SPEC), and the area under the curve (AUC) are shown.</p></caption><graphic alt-version="no" mimetype="image" position="float" xlink:type="simple" xlink:href="jmir_v28i1e86079_fig07.png"/></fig><fig position="float" id="figure8"><label>Figure 8.</label><caption><p>Bivariate boxplot of the combined logit-transformed sensitivity (SENS) and specificity (SPEC) estimates from the bivariate random-effects meta-analysis for predicting treatment response in patients with anxiety disorders after cognitive behavioral therapy. Squares represent individual study estimates; the box illustrates the joint distribution.</p></caption><graphic alt-version="no" mimetype="image" position="float" xlink:type="simple" xlink:href="jmir_v28i1e86079_fig08.png"/></fig><table-wrap id="t2" position="float"><label>Table 2.</label><caption><p>Results of the univariable meta-regression analysis examining potential sources of heterogeneity in the performance of artificial intelligence models for predicting cognitive behavioral therapy treatment response in anxiety disorders.</p></caption><table id="table2" frame="hsides" rules="groups"><thead><tr><td align="left" valign="top">Subgroup</td><td align="left" valign="top">Number of contingency tables</td><td align="left" valign="top">Sensitivity, value (95% CI)</td><td align="left" valign="top">Meta-regression <italic>P</italic> value</td><td align="left" valign="top">Specificity, value (95% CI)</td><td align="left" valign="top">Meta-regression <italic>P</italic> value</td></tr></thead><tbody><tr><td align="left" valign="top" colspan="3">Number of centers</td><td align="left" valign="top">.02</td><td align="left" valign="top"/><td align="left" valign="top">.89</td></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Single center</td><td align="left" valign="top">2</td><td align="left" valign="top">0.87 (0.76&#x2010;0.99)</td><td align="left" valign="top"/><td align="left" valign="top">0.74 (0.46&#x2010;1.00)</td><td align="left" valign="top"/></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Multiple centers</td><td align="left" valign="top">7</td><td align="left" valign="top">0.69 (0.58&#x2010;0.80)</td><td align="left" valign="top"/><td align="left" valign="top">0.76 (0.61&#x2010;0.90)</td><td align="left" valign="top"/></tr><tr><td align="left" valign="top" colspan="3">Type of anxiety disorder</td><td align="left" valign="top">.01</td><td align="left" valign="top"/><td align="left" valign="top">.10</td></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>SAD<sup><xref ref-type="table-fn" rid="table2fn1">a</xref></sup></td><td align="left" valign="top">3</td><td align="left" valign="top">0.86 (0.74&#x2010;0.98)</td><td align="left" valign="top"/><td align="left" valign="top">0.87 (0.71&#x2010;1.00)</td><td align="left" valign="top"/></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Others</td><td align="left" valign="top">6</td><td align="left" valign="top">0.68 (0.57&#x2010;0.79)</td><td align="left" valign="top"/><td align="left" valign="top">0.69 (0.54&#x2010;0.85)</td><td align="left" valign="top"/></tr><tr><td align="left" valign="top" colspan="3">Data splitting method</td><td align="left" valign="top">.23</td><td align="left" valign="top"/><td align="left" valign="top">.28</td></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>LOOCV<sup><xref ref-type="table-fn" rid="table2fn2">b</xref></sup></td><td align="left" valign="top">4</td><td align="left" valign="top">0.78 (0.62&#x2010;0.93)</td><td align="left" valign="top"/><td align="left" valign="top">0.81 (0.63&#x2010;0.98)</td><td align="left" valign="top"/></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Independent validation</td><td align="left" valign="top">5</td><td align="left" valign="top">0.72 (0.58&#x2010;0.86)</td><td align="left" valign="top"/><td align="left" valign="top">0.71 (0.54&#x2010;0.89)</td><td align="left" valign="top"/></tr><tr><td align="left" valign="top" colspan="3">CBT<sup><xref ref-type="table-fn" rid="table2fn3">c</xref></sup> type</td><td align="left" valign="top">.77</td><td align="left" valign="top"/><td align="left" valign="top">&#x003C;.001</td></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>iCBT<sup><xref ref-type="table-fn" rid="table2fn4">d</xref></sup></td><td align="left" valign="top">2</td><td align="left" valign="top">0.71 (0.48&#x2010;0.94)</td><td align="left" valign="top"/><td align="left" valign="top">0.95 (0.91&#x2010;0.98)</td><td align="left" valign="top"/></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Standard CBT</td><td align="left" valign="top">6</td><td align="left" valign="top">0.74 (0.62&#x2010;0.87)</td><td align="left" valign="top"/><td align="left" valign="top">0.61 (0.51&#x2010;0.71)</td><td align="left" valign="top"/></tr><tr><td align="left" valign="top" colspan="3">AI<sup><xref ref-type="table-fn" rid="table2fn5">e</xref></sup> algorithms</td><td align="left" valign="top">.51</td><td align="left" valign="top"/><td align="left" valign="top">&#x003C;.001</td></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>DL<sup><xref ref-type="table-fn" rid="table2fn6">f</xref></sup></td><td align="left" valign="top">1</td><td align="left" valign="top">0.62 (0.29&#x2010;0.94)</td><td align="left" valign="top"/><td align="left" valign="top">0.93 (0.87&#x2010;1.00)</td><td align="left" valign="top"/></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>ML<sup><xref ref-type="table-fn" rid="table2fn7">g</xref></sup></td><td align="left" valign="top">8</td><td align="left" valign="top">0.78 (0.68&#x2010;0.88)</td><td align="left" valign="top"/><td align="left" valign="top">0.67 (0.57&#x2010;0.78)</td><td align="left" valign="top"/></tr></tbody></table><table-wrap-foot><fn id="table2fn1"><p><sup>a</sup>SAD: social anxiety disorder.</p></fn><fn id="table2fn2"><p><sup>b</sup>LOOCV: leave-one-out cross-validation.</p></fn><fn id="table2fn3"><p><sup>c</sup>CBT: cognitive behavioral therapy.</p></fn><fn id="table2fn4"><p><sup>d</sup>iCBT: internet-based cognitive behavioral therapy.</p></fn><fn id="table2fn5"><p><sup>e</sup>AI: artificial intelligence&#x200C;.</p></fn><fn id="table2fn6"><p><sup>f</sup>DL: deep learning.</p></fn><fn id="table2fn7"><p><sup>g</sup>ML: machine learning.</p></fn></table-wrap-foot></table-wrap></sec><sec id="s3-5"><title>Subgroup Analysis</title><p>Within the data-type subgroup, multimodal AI models appeared to achieve higher pooled sensitivity (0.84, 95% CI 0.60&#x2010;0.97) and accuracy (0.82, 95% CI 0.66&#x2010;0.92) compared with single-modal approaches. In contrast, models based on either clinical/demographic or imaging data alone demonstrated comparatively lower sensitivity and accuracy. Regarding specificity, models developed using clinical/demographic data showed relatively higher estimates (0.81, 95% CI 0.55&#x2010;0.93). Regarding AUC, only 1 study reported data within this subgroup, and in that study, imaging models achieved an AUC of 0.79 (95% CI 0.76&#x2010;0.83) (<xref ref-type="table" rid="table3">Table 3</xref>).</p><table-wrap id="t3" position="float"><label>Table 3.</label><caption><p>Subgroup meta-analysis of the pooled predictive performance of artificial intelligence models for predicting cognitive behavioral therapy response, stratified by input data type, algorithm type, and anxiety disorder classification.</p></caption><table id="table3" frame="hsides" rules="groups"><thead><tr><td align="left" valign="top">Subgroup</td><td align="left" valign="top">Number of contingency tables</td><td align="left" valign="top">Sensitivity, value (95% CI)</td><td align="left" valign="top">Specificity, value (95% CI)</td><td align="left" valign="top">AUC<sup><xref ref-type="table-fn" rid="table3fn1">a</xref></sup>, value (95% CI)</td><td align="left" valign="top">Accuracy, value (95% CI)</td></tr></thead><tbody><tr><td align="left" valign="top">Type of data</td><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" valign="top"/></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Clinical/demographic</td><td align="left" valign="top">2</td><td align="left" valign="top">0.65 (0.42&#x2010;0.82)</td><td align="left" valign="top">0.81 (0.55&#x2010;0.93)</td><td align="left" valign="top">&#x2014;<sup><xref ref-type="table-fn" rid="table3fn2">b</xref></sup></td><td align="left" valign="top">0.73 (0.55&#x2010;0.89)</td></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Imaging</td><td align="left" valign="top">6</td><td align="left" valign="top">0.77 (0.63&#x2010;0.87)</td><td align="left" valign="top">0.71 (0.53&#x2010;0.85)</td><td align="left" valign="top">0.79 (0.76&#x2010;0.83)</td><td align="left" valign="top">0.72 (0.00&#x2010;1.00)</td></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Multimodal</td><td align="left" valign="top">1</td><td align="left" valign="top">0.84 (0.60&#x2010;0.97)</td><td align="left" valign="top">0.79 (0.54&#x2010;0.94)</td><td align="left" valign="top">&#x2014;</td><td align="left" valign="top">0.82 (0.66&#x2010;0.92)</td></tr><tr><td align="left" valign="top">AI<sup><xref ref-type="table-fn" rid="table3fn3">c</xref></sup> algorithms</td><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" valign="top"/></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>RF<sup><xref ref-type="table-fn" rid="table3fn4">d</xref></sup></td><td align="left" valign="top">3</td><td align="left" valign="top">0.64 (0.58&#x2010;0.70)</td><td align="left" valign="top">0.52 (0.45&#x2010;0.59)</td><td align="left" valign="top">0.54 (0.50&#x2010;0.59)</td><td align="left" valign="top">0.63 (0.27&#x2010;0.93)</td></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>SVM<sup><xref ref-type="table-fn" rid="table3fn5">e</xref></sup></td><td align="left" valign="top">4</td><td align="left" valign="top">0.82 (0.61&#x2010;0.93)</td><td align="left" valign="top">0.75 (0.60&#x2010;0.85)</td><td align="left" valign="top">0.83 (0.80&#x2010;0.86)</td><td align="left" valign="top">0.78 (0.50&#x2010;0.97)</td></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>RNN<sup><xref ref-type="table-fn" rid="table3fn6">f</xref></sup></td><td align="left" valign="top">1</td><td align="left" valign="top">0.62 (0.60&#x2010;0.63)</td><td align="left" valign="top">0.93 (0.92&#x2010;0.94)</td><td align="left" valign="top">&#x2014;</td><td align="left" valign="top">0.81 (0.81&#x2010;0.82)</td></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>LR<sup><xref ref-type="table-fn" rid="table3fn7">g</xref></sup></td><td align="left" valign="top">1</td><td align="left" valign="top">0.84 (0.60&#x2010;0.97)</td><td align="left" valign="top">0.79 (0.54&#x2010;0.94)</td><td align="left" valign="top">&#x2014;</td><td align="left" valign="top">0.82 (0.66&#x2010;0.92)</td></tr><tr><td align="left" valign="top">Type of anxiety disorder</td><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" valign="top"/></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>GAD<sup><xref ref-type="table-fn" rid="table3fn8">h</xref></sup> and PD<sup><xref ref-type="table-fn" rid="table3fn9">i</xref></sup></td><td align="left" valign="top">1</td><td align="left" valign="top">0.86 (0.68&#x2010;0.96)</td><td align="left" valign="top">0.68 (0.43&#x2010;0.87)</td><td align="left" valign="top">&#x2014;</td><td align="left" valign="top">0.79 (0.65&#x2010;0.90)</td></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>SAD<sup><xref ref-type="table-fn" rid="table3fn10">j</xref></sup></td><td align="left" valign="top">3</td><td align="left" valign="top">0.86 (0.78&#x2010;0.92)</td><td align="left" valign="top">0.87 (0.41&#x2010;1.00)</td><td align="left" valign="top">0.92 (0.85&#x2010;0.98)</td><td align="left" valign="top">0.85 (0.72&#x2010;0.94)</td></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>PD with AG<sup><xref ref-type="table-fn" rid="table3fn11">k</xref></sup></td><td align="left" valign="top">2</td><td align="left" valign="top">0.69 (0.00&#x2010;1.00)</td><td align="left" valign="top">0.71 (0.00&#x2010;1.00)</td><td align="left" valign="top">&#x2014;</td><td align="left" valign="top">0.69 (0.00&#x2010;1.00)</td></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Multiple anxiety disorders</td><td align="left" valign="top">3</td><td align="left" valign="top">0.61 (0.45&#x2010;0.77)</td><td align="left" valign="top">0.68 (0.05&#x2010;1.00)</td><td align="left" valign="top">0.65 (0.49&#x2010;0.81)</td><td align="left" valign="top">0.65 (0.25&#x2010;0.96)</td></tr></tbody></table><table-wrap-foot><fn id="table3fn1"><p><sup>a</sup>AUC: area under curve.</p></fn><fn id="table3fn2"><p><sup>b</sup>Not applicable.</p></fn><fn id="table3fn3"><p><sup>c</sup>AI: artificial intelligence.</p></fn><fn id="table3fn4"><p><sup>d</sup>RF: random forest.</p></fn><fn id="table3fn5"><p><sup>e</sup>SVM: support vector machine.</p></fn><fn id="table3fn6"><p><sup>f</sup>RNN: recurrent neural network.</p></fn><fn id="table3fn7"><p><sup>g</sup>LR: logistic regression.</p></fn><fn id="table3fn8"><p><sup>h</sup>GAD: generalized anxiety disorder.</p></fn><fn id="table3fn9"><p><sup>i</sup>PD: panic disorder.</p></fn><fn id="table3fn10"><p><sup>j</sup>SAD: social anxiety disorder.</p></fn><fn id="table3fn11"><p><sup>k</sup>AG: agoraphobia.</p></fn></table-wrap-foot></table-wrap><p>Within the AI algorithm subgroup, different algorithms demonstrated distinct advantages across various performance metrics. For sensitivity, LR performed best, achieving a value of 0.84 (95% CI 0.60&#x2010;0.97). Similarly, in terms of accuracy, LR again showed optimal performance, reaching a value of 0.82 (95% CI 0.66&#x2010;0.92). For specificity, the RNN achieved the highest value of 0.93 (95% CI 0.87&#x2010;0.98). Regarding the AUC, only 2 algorithms produced results that could be combined, with the SVM algorithm yielding a relatively high combined AUC of 0.83 (95% CI 0.80&#x2010;0.86).</p><p>Within the type of anxiety disorder subgroup, predictive performance varied across outcome metrics. For sensitivity, GAD and PD demonstrated relatively higher pooled estimates at 0.86 (95% CI 0.68&#x2010;0.96). In contrast, SAD showed comparatively stronger performance in specificity and accuracy, with a pooled specificity of 0.87 (95% CI 0.41&#x2010;1.00) and accuracy of 0.85 (95% CI 0.72&#x2010;0.94). For discrimination, as measured by AUC, pooled estimates were available for 2 disorder types, among which SAD demonstrated a comparatively higher AUC of 0.92 (95% CI 0.85&#x2010;0.98).</p></sec><sec id="s3-6"><title>Publication Bias</title><p>Funnel plots and Egger regression tests were conducted to evaluate potential small-study effects (Figures S2-S4 in <xref ref-type="supplementary-material" rid="app1">Multimedia Appendix 1</xref>). No statistically significant evidence of small-study effects was observed for sensitivity (<italic>t<sub>7</sub></italic>=1.75; <italic>P</italic>=.12; intercept=1.54; SE=0.88) and accuracy (<italic>t</italic><sub>7</sub>=&#x2212;1.51; <italic>P</italic>=.17; intercept=&#x2212;2.40; SE=1.59). In contrast, the test for specificity yielded a statistically significant result (<italic>t</italic><sub>7</sub>=&#x2212;2.58; <italic>P</italic>=.04; intercept=&#x2212;4.29; SE=1.66), suggesting the possible presence of small-study effects.</p></sec></sec><sec id="s4" sec-type="discussion"><title>Discussion</title><sec id="s4-1"><title>Principal Findings</title><p>The systematic review and meta-analysis revealed that the model demonstrated moderate predictive performance in forecasting treatment response to CBT among patients with anxiety disorders, with sensitivity, specificity, accuracy, and AUC values of 0.73, 0.75, 0.74, and 0.81, respectively. This moderate predictive capability reflects the combined influence of multiple complex factors. First, limitations in input variables constitute a key constraint: current models primarily rely on demographic data, psychiatric history, and scale measurements, making it challenging to capture deeper biological and environmental factors [<xref ref-type="bibr" rid="ref7">7</xref>,<xref ref-type="bibr" rid="ref35">35</xref>]. While biomarkers, such as neuroimaging, could theoretically significantly enhance predictive accuracy, their clinical application remains constrained by cost and accessibility [<xref ref-type="bibr" rid="ref32">32</xref>,<xref ref-type="bibr" rid="ref35">35</xref>]. Second, data heterogeneity and sample size issues cannot be overlooked. Significant variations among patient cohorts in symptom severity, comorbid conditions, and treatment modalities diminish the model&#x2019;s generalizability [<xref ref-type="bibr" rid="ref18">18</xref>,<xref ref-type="bibr" rid="ref36">36</xref>]. Small-sample studies often overestimate predictive capability, while large-scale multicenter studies frequently yield reduced accuracy, sometimes approaching random levels [<xref ref-type="bibr" rid="ref18">18</xref>,<xref ref-type="bibr" rid="ref35">35</xref>].</p><p>Furthermore, limitations exist in variable selection and modeling approaches: prediction capabilities relying solely on traditional questionnaires and demographic data are constrained [<xref ref-type="bibr" rid="ref35">35</xref>,<xref ref-type="bibr" rid="ref37">37</xref>]. While integrating multimodal data (eg, neuroimaging, genetic, and behavioral data) may enhance performance, the comprehensive collection of such data remains challenging in real-world clinical settings [<xref ref-type="bibr" rid="ref18">18</xref>]. Finally, challenges in practical application and external validation cannot be overlooked; many models lack independent external validation, resulting in significantly reduced accuracy and interpretability in clinical settings [<xref ref-type="bibr" rid="ref38">38</xref>]. In summary, while current models demonstrate predictive potential, future research requires larger-scale, multicenter, and multimodal studies to enhance model robustness and clinical translation capabilities.</p><p>The subgroup analysis suggested that multimodal data integration was associated with comparatively higher sensitivity (0.84) and accuracy (0.82) than single-modal approaches. Across algorithm categories, no single model consistently outperformed others; LR showed higher sensitivity (0.84) and accuracy (0.82), RNN demonstrated higher specificity (0.93), and SVM had a comparatively higher AUC of 0.83. Predictive performance also varied across anxiety disorder subtypes. GAD and PD showed comparatively higher sensitivity (0.86), whereas SAD demonstrated higher specificity (0.87), accuracy (0.85), and AUC (0.92). Together, these findings suggest that optimal prediction may depend less on a single &#x201C;best&#x201D; algorithm and more on strategically matching the model architecture to the data type and clinical question [<xref ref-type="bibr" rid="ref39">39</xref>]. Future work should therefore focus not only on multimodal data collection but also on developing tailored, interpretable modeling approaches that can be validated in real-world clinical settings [<xref ref-type="bibr" rid="ref40">40</xref>].</p><p>The systematic review revealed that multimodal data demonstrated the most promising performance in predicting CBT treatment response for anxiety disorders, with a sensitivity of 0.84 and an accuracy of 0.82. The superior predictive capability of multimodal approaches could be attributed to several key mechanisms. First, multimodal data integration enabled the comprehensive capture of the multidimensional nature of anxiety disorders by combining neuroimaging, physiological signals, behavioral data, and clinical assessments [<xref ref-type="bibr" rid="ref29">29</xref>,<xref ref-type="bibr" rid="ref30">30</xref>]. Complementary information across modalities enabled AI models to detect nuanced individual differences and potential mechanisms of treatment response [<xref ref-type="bibr" rid="ref27">27</xref>,<xref ref-type="bibr" rid="ref34">34</xref>]. Research indicates that, compared with single-modality approaches, multimodal fusion significantly enhances predictive accuracy, particularly when incorporating models that integrate functional and structural brain connectivity [<xref ref-type="bibr" rid="ref29">29</xref>,<xref ref-type="bibr" rid="ref34">34</xref>]. Moreover, multimodal approaches supported personalized, dynamic prediction models that can identify high-risk nonresponders early, potentially facilitating adaptive treatment strategies [<xref ref-type="bibr" rid="ref17">17</xref>,<xref ref-type="bibr" rid="ref27">27</xref>]. While these findings are promising, careful validation through larger, cross-validated studies is essential to establish the clinical utility and generalizability of such AI-driven prediction models [<xref ref-type="bibr" rid="ref29">29</xref>,<xref ref-type="bibr" rid="ref33">33</xref>].</p><p>The meta-analysis revealed differential performance patterns across ML algorithms in predicting CBT treatment response for anxiety disorders. LR demonstrated comparatively higher sensitivity (0.84) and accuracy (0.82), potentially attributable to its ability to capture linear relationships between clinical features and treatment outcomes [<xref ref-type="bibr" rid="ref7">7</xref>,<xref ref-type="bibr" rid="ref31">31</xref>]. The algorithm&#x2019;s strength lies in its ability to model structured clinical data with minimal risk of overfitting, particularly in scenarios with balanced sample distributions [<xref ref-type="bibr" rid="ref7">7</xref>,<xref ref-type="bibr" rid="ref17">17</xref>]. Conversely, RNNs exhibited superior specificity (0.93), likely due to their ability to process high-dimensional, sequential data and capture complex nonlinear interactions [<xref ref-type="bibr" rid="ref17">17</xref>]. RNN&#x2019;s advanced modeling approach enables more nuanced identification of nonresponders by leveraging temporal patterns in clinical measurements and platform interaction behaviors [<xref ref-type="bibr" rid="ref17">17</xref>]. For overall discrimination, SVM achieved a pooled AUC of 0.83 (95% CI 0.80&#x2010;0.86). Given their kernel-based formulation, SVMs may perform well with moderate sample sizes and complex feature spaces, allowing flexible decision boundaries [<xref ref-type="bibr" rid="ref7">7</xref>,<xref ref-type="bibr" rid="ref31">31</xref>]. Taken together, these findings suggest that algorithmic performance may vary according to data structure and modeling objectives. Rather than indicating a universally superior approach, the results support the importance of aligning model architecture with data characteristics and specific clinical prediction goals [<xref ref-type="bibr" rid="ref31">31</xref>].</p><p>The subgroup analysis indicated that predictive performance varied across anxiety disorder subtypes. GAD and PD demonstrated comparatively higher sensitivity estimates (0.86, 95% CI 0.68&#x2010;0.96), suggesting relatively stronger identification of treatment responders in these populations. In contrast, SAD showed higher pooled specificity (0.87, 95% CI 0.41&#x2010;1.00) and accuracy (0.85, 95% CI 0.72&#x2010;0.94). For discrimination as measured by AUC, pooled estimates were available for 2 disorder types, among which SAD demonstrated a comparatively higher AUC of 0.92 (95% CI 0.85&#x2010;0.98). The variation in predictive performance across anxiety disorder subtypes may partly account for the observed heterogeneity. In the subgroup analysis, GAD and PD demonstrated higher sensitivity, which may be related to the use of structured symptom-based scales that provide relatively stable responder signals for model training [<xref ref-type="bibr" rid="ref27">27</xref>]. First, SAD research often relies on symptom measures that closely align core fear and avoidance dimensions with treatment outcome definitions, which may facilitate clearer model discrimination [<xref ref-type="bibr" rid="ref7">7</xref>,<xref ref-type="bibr" rid="ref34">34</xref>]. Second, some SAD studies incorporate high-information features beyond routine clinical variables, potentially enhancing overall predictive performance [<xref ref-type="bibr" rid="ref29">29</xref>,<xref ref-type="bibr" rid="ref32">32</xref>]. Third, SAD samples are frequently drawn from relatively homogeneous clinical trials with standardized intervention protocols, which may reduce heterogeneity and improve model stability [<xref ref-type="bibr" rid="ref7">7</xref>,<xref ref-type="bibr" rid="ref32">32</xref>].</p></sec><sec id="s4-2"><title>Comparison With Prior Work</title><p>In the systematic review and meta-analysis published by Vieira et al [<xref ref-type="bibr" rid="ref35">35</xref>] in 2022, the authors evaluated ML approaches for predicting CBT treatment response across multiple psychiatric disorders. Their analysis included 24 studies comprising 7497 patients and covered 5 diagnostic groups: major depressive disorder, obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), anxiety disorders, and substance use disorders. The overall pooled accuracy was 0.74 (95% CI 0.70&#x2010;0.78), with variability across diagnostic categories. PTSD, anxiety disorders, and OCD demonstrated comparatively higher accuracy estimates (0.787, 0.776, and 0.761, respectively). In comparison, our study focused specifically on anxiety disorders and yielded a pooled accuracy of 0.74 (95% CI 0.62&#x2010;0.84), which is comparable to the overall estimate reported by Vieira et al [<xref ref-type="bibr" rid="ref35">35</xref>]. However, our analysis extended beyond accuracy by systematically synthesizing sensitivity, specificity, and AUC to provide a more comprehensive assessment of predictive performance. In addition, we conducted subgroup analyses examining the potential influence of data types (eg, clinical and neuroimaging), algorithm types, and disease types on model performance, thereby offering a more granular evaluation within the anxiety disorder domain. Bubble plots were used to illustrate temporal trends and the distribution of study characteristics across performance metrics.</p></sec><sec id="s4-3"><title>Heterogeneity</title><p>The substantial heterogeneity observed across studies may influence the overall strength of evidence for AI-based prediction models. Given the anticipated between-study variability, a bivariate random-effects model was applied to pool sensitivity and specificity estimates. Meta-regression and subgroup analyses were further conducted to explore potential sources of heterogeneity. The results indicated that heterogeneity in sensitivity was significantly associated with the number of study centers (<italic>P</italic>=.02) and the anxiety disorder subtype (<italic>P</italic>=.01). In contrast, heterogeneity in specificity was significantly associated with CBT type (<italic>P</italic>&#x003C;.001) and AI algorithm category (<italic>P</italic>&#x003C;.001). The comparatively higher sensitivity observed in single-center studies, compared with multicenter studies, may reflect more homogeneous samples and more consistent data collection procedures [<xref ref-type="bibr" rid="ref41">41</xref>]. Differences across anxiety disorder types may relate to variations in symptom structure, measurement alignment, and sample characteristics, which could influence the clarity of the responder signals available to the models [<xref ref-type="bibr" rid="ref42">42</xref>]. Meanwhile, differences between iCBT and standard CBT may reflect variations in intervention structure and in the intensity of monitoring [<xref ref-type="bibr" rid="ref43">43</xref>]. Variability in specificity across algorithm categories (DL vs ML) may relate to differences in model complexity and data representation strategies [<xref ref-type="bibr" rid="ref44">44</xref>].</p><p>The bivariate boxplot suggested that 1 study [<xref ref-type="bibr" rid="ref30">30</xref>] may represent a potential source of heterogeneity. Nevertheless, heterogeneity is likely multifactorial. Additional contributors may include differences in patient age, disorder severity, prior treatment exposure, geographic setting, sample size, feature selection strategies, data preprocessing methods, and hyperparameter optimization [<xref ref-type="bibr" rid="ref45">45</xref>-<xref ref-type="bibr" rid="ref48">48</xref>]. The combined influence of these methodological and clinical factors may account for the variability in predictive performance. Future research would benefit from more standardized reporting and systematic consideration of these variables to enhance reproducibility and external validity.</p></sec><sec id="s4-4"><title>Implications for Practice and Research</title><p>Discussing the clinical interpretation of our results, the AI models demonstrated moderate predictive value for CBT treatment response in anxiety disorders, with the strongest performance observed for SAD. Multimodal models, which combine clinical demographics with imaging data, showed relatively superior predictive performance compared with unimodal approaches. This suggests that AI could support clinicians in making earlier, more informed therapeutic decisions and potentially improve patient outcomes by enabling timely treatment adjustments [<xref ref-type="bibr" rid="ref49">49</xref>,<xref ref-type="bibr" rid="ref50">50</xref>]. Specifically, these predictive models could be integrated into clinical workflows at key decision points: (1) during initial assessment to help stratify patients by likelihood of response, informing the intensity of early monitoring or the consideration of augmented treatment protocols, and (2) during the early stages of CBT to identify potential nonresponders, allowing for a timely switch or integration of other evidence-based interventions before disengagement occurs [<xref ref-type="bibr" rid="ref35">35</xref>,<xref ref-type="bibr" rid="ref51">51</xref>].</p><p>However, AI should serve as a decision-support tool rather than replacing clinician judgment, since treatment choices for anxiety disorders are influenced by not only severity but also patient preferences, comorbidity, and functional goals [<xref ref-type="bibr" rid="ref52">52</xref>]. In the treatment of anxiety disorders, complex therapeutic decisions not only depend on assessing disease severity but also closely relate to the patient&#x2019;s individual condition and needs [<xref ref-type="bibr" rid="ref53">53</xref>]. For real-world deployment, developing AI tools as clinician-facing dashboards that present predictive probabilities alongside key clinical context, rather than as autonomous decision systems, is crucial for fostering trust and facilitating shared decision-making [<xref ref-type="bibr" rid="ref54">54</xref>]. Notably, among the studies we included, external validation sets were relatively scarce, and no research has yet focused solely on predicting outcomes for external validation cohorts. Future studies are needed to evaluate the generalization capabilities of AI models. Furthermore, limitations to the future adoption of AI include scarce annotated anxiety disorder data and regulatory hurdles [<xref ref-type="bibr" rid="ref55">55</xref>]. Technical challenges persist in data availability, model interpretability, and transparency [<xref ref-type="bibr" rid="ref56">56</xref>]. Advances in few-shot learning, self-supervised models, and centralized platforms may support an integrated AI ecosystem [<xref ref-type="bibr" rid="ref57">57</xref>].</p></sec><sec id="s4-5"><title>Limitations</title><p>When interpreting the findings of this systematic review and meta-analysis on the AI prediction of CBT treatment response for anxiety disorders, several limitations should be considered. First, the PROBAST+AI assessment indicated a high risk of bias in over half of the included studies, particularly in analytical methodology, which may have influenced the pooled estimates and contributed to between-study heterogeneity. Future studies should adopt more rigorous design and transparent reporting standards. Second, variability in the definition of treatment response across studies may have affected comparability. Although most scales assessed anxiety symptom reduction, differences in operational criteria could influence predictive performance. Greater standardization of outcome definitions would enhance consistency in future research. Third, the substantial heterogeneity and wide PIs suggest that model performance may vary considerably across clinical settings. Therefore, the pooled estimates should be interpreted cautiously and regarded as preliminary within the context of current methodological constraints. Fourth, although heterogeneity was observed across studies, this likely reflects differences in study design, patient characteristics, and modeling approaches. The reported PIs indicate that performance may vary across settings, highlighting the importance of external validation in future research. Finally, due to limited data availability, direct head-to-head comparisons between AI models and routinely used clinical scales were not feasible. Future research should incorporate comparative designs to better assess the incremental value of AI-based prediction tools. Overall, while AI models demonstrate potential for supporting treatment decision-making, stronger evidence from externally validated and methodologically robust studies is needed before clinical implementation.</p></sec><sec id="s4-6"><title>Conclusions</title><p>This meta-analysis quantitatively synthesized AI performance in predicting CBT response for anxiety disorders, moving beyond narrative reviews to provide pooled evidence. In contrast to existing reviews that encompass broader diagnostic groups, our focused approach establishes a precise benchmark for this clinical domain, highlighting the current moderate overall performance. Furthermore, we extend beyond previous work by demonstrating the superior predictive utility of multimodal data, identifying SAD as the most predictable subtype, and systematically evaluating the impact of data modalities and algorithm types. Future efforts should prioritize robustly validated multimodal models, laying essential groundwork for the potential development of AI-assisted tools to personalize treatment planning in anxiety disorders.</p></sec></sec></body><back><ack><p>The authors declare the use of generative artificial intelligence (GAI) in the research and writing process. According to the GAIDeT taxonomy (2025), the following tasks were delegated to GAI tools under full human supervision: proofreading and editing, adapting and adjusting emotional tone, translation, and reformatting. The GAI tool used was Sider. Responsibility for the final manuscript lies entirely with the authors. GAI tools are not listed as authors and do not bear responsibility for the final outcomes. The declaration has been submitted by JL.</p></ack><notes><sec><title>Funding</title><p>The authors declare that no funding was received for this study. No funding body had any role in the study design, data collection, analysis, interpretation, or writing of the manuscript.</p></sec><sec><title>Data Availability</title><p>All data generated or analyzed during this study are included in this published article and its supplementary information files.</p></sec></notes><fn-group><fn fn-type="con"><p>JL contributed to conceptualization, critical revision of the manuscript, and final approval. JL, JW, ZW, and MISBAA contributed to data curation, formal analysis, investigation, and methodology. All authors read and approved the final manuscript.</p></fn><fn fn-type="conflict"><p>None declared.</p></fn></fn-group><glossary><title>Abbreviations</title><def-list><def-item><term id="abb1">AI</term><def><p>artificial intelligence</p></def></def-item><def-item><term id="abb2">AUC</term><def><p>area under the curve</p></def></def-item><def-item><term id="abb3">CBT</term><def><p>cognitive behavioral therapy</p></def></def-item><def-item><term id="abb4">CGI-I</term><def><p>Clinical Global Impressions&#x2013;Improvement</p></def></def-item><def-item><term id="abb5">DL</term><def><p>deep learning</p></def></def-item><def-item><term id="abb6">FN</term><def><p>false negative</p></def></def-item><def-item><term id="abb7">FP</term><def><p>false positive</p></def></def-item><def-item><term id="abb8">GAD</term><def><p>generalized anxiety disorder</p></def></def-item><def-item><term id="abb9">GAD-7</term><def><p>Generalized Anxiety Disorder-7</p></def></def-item><def-item><term id="abb10">HAM-A</term><def><p>Hamilton Anxiety Rating Scale</p></def></def-item><def-item><term id="abb11">HKSJ</term><def><p>Hartung-Knapp-Sidik-Jonkman</p></def></def-item><def-item><term id="abb12">LR</term><def><p>logistic regression</p></def></def-item><def-item><term id="abb13">LSAS</term><def><p>Liebowitz Social Anxiety Scale</p></def></def-item><def-item><term id="abb14">ML</term><def><p>machine learning</p></def></def-item><def-item><term id="abb15">OASIS</term><def><p>Overall Anxiety Severity and Impairment Scale</p></def></def-item><def-item><term id="abb16">OCD</term><def><p>obsessive-compulsive disorder</p></def></def-item><def-item><term id="abb17">PD</term><def><p>panic disorder</p></def></def-item><def-item><term id="abb18">PHQ-9</term><def><p>Patient Health Questionnaire-9</p></def></def-item><def-item><term id="abb19">PI</term><def><p>prediction interval</p></def></def-item><def-item><term id="abb20">PRISMA</term><def><p>Preferred Reporting Items for Systematic Reviews and Meta-Analyses</p></def></def-item><def-item><term id="abb21">PROBAST+AI</term><def><p>Prediction Model Risk of Bias Assessment Tool for Artificial Intelligence</p></def></def-item><def-item><term id="abb22">PTSD</term><def><p>posttraumatic stress disorder</p></def></def-item><def-item><term id="abb23">RF</term><def><p>random forest</p></def></def-item><def-item><term id="abb24">RNN</term><def><p>recurrent neural network</p></def></def-item><def-item><term id="abb25">SAD</term><def><p>social anxiety disorder</p></def></def-item><def-item><term id="abb26">SPQ</term><def><p>Spider Phobia Questionnaire</p></def></def-item><def-item><term id="abb27">SVM</term><def><p>support vector machine</p></def></def-item><def-item><term id="abb28">TN</term><def><p>true negative</p></def></def-item><def-item><term id="abb29">TP</term><def><p>true positive</p></def></def-item></def-list></glossary><ref-list><title>References</title><ref id="ref1"><label>1</label><nlm-citation 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