Simulating Psychotherapeutic Sessions with Generative Artificial Intelligence: A Proof-of-Concept Study of In Silico Psychotherapy Research
Abstract
Abstract Background Across biomedicine, in silico models increasingly complement in vivo and in vitro research. Psychotherapy science, however, remains constrained by methodological limitations, resource-intensive trials, challenges in manipulating clinically meaningful features experimentally, and a potential ceiling in efficacy. Leveraging generative AI and large language models (LLMs), we propose a framework for “ in silico psychotherapy research”: controlled simulations of psychotherapeutic interactions under reproducible experimental conditions. Objective We test whether such simulation experiments can recover a theoretically expected effect of an isolated psychotherapy-process manipulation. Methods In a preregistered proof-of-concept study, we generated 512 fully automated motivational interviewing (MI) sessions by linking locally deployed Llama-3.3-70B-In-struct based therapist and patient models across eight vignettes and eight therapist personas. Therapist, but not patient, prompts manipulated common therapeutic factors (CTF), contrasting high versus low empathy, affirmation, and alliance building behaviour in a controlled design. The primary outcome was MI treatment integrity (MITI 4.2 global ratings), assessed by a blinded LLM with repeated ratings and analysed using linear mixed-effects models. Secondary outcomes included observer-inferred importance/confidence rulers based on simulated patient utterances; Therapist Empathy Scale (TES) and Working Alliance Inventory–Short Observer (WAI-S-O) served as manipulation fidelity checks. Human coders rated a stratified subsample. Results Of the 512 simulations, 506 (98.8%) yielded complete transcripts and 480 (93.75) were retained for analysis. Manipulation checks confirmed the fidelity of the CTF manipulation (WAI-S-O total scores β=3.14; [2.65,3.63], p<0.001, TES β=14.48 [13.92,15.04], p<0.001). High versus low CTF produced a theoretically expected improvement in all MITI global ratings, including the MI-specific features not directly targeted by the CTF manipulation (β=0.54–0.95; all p<0.001). Simulated patient confidence but not importance for change increased more under high CTF (β=0.17 [0.09,0.26], p<0.001). Human ratings confirmed the direction of the primary contrast. Conclusions LLM-based psychotherapy simulations were technically feasible, demonstrated experimental fidelity, and showed theoretically concordant effects beyond directly manipulated constructs and simulation participants. These findings provide proof of concept for in silico psychotherapy research as a promising complementary pre-clinical experimental paradigm for hypothesis generation and testing to support accelerated intervention development. The applicability of this approach across patient populations, therapeutic modalities and model architectures requires further evaluation. Trial Pre-registration ClinicalTrials.gov NCT06813066 ; https://clinicaltrials.gov/study/NCT06813066?term=NCT06813066
Authors 11
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University of Basel · University Hospital of Basel · Universität Trier
Affiliation as printed
Clinical Psychology and Psychotherapy – Methods and Approaches, Department of Psychology, Trier University, Trier, Germany
Department of Digital and Blended Psychosomatics and Psychotherapy, Psychosomatic Medicine, University Hospital and University of Basel, Basel, Switzerland
Department of Psychosomatic Medicine, University Hospital and University of Basel, Basel, Switzerland
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Affiliation as printed
Clinical Psychology and Psychotherapy – Methods and Approaches, Department of Psychology, Trier University, Trier, Germany
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University of Basel · University Hospital of Basel
Affiliation as printed
Department of Digital and Blended Psychosomatics and Psychotherapy, Psychosomatic Medicine, University Hospital and University of Basel, Basel, Switzerland
Department of Psychosomatic Medicine, University Hospital and University of Basel, Basel, Switzerland
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University of Basel · University of Zurich · University Hospital of Basel · University Hospital Zurich
Affiliation as printed
Department of Digital and Blended Psychosomatics and Psychotherapy, Psychosomatic Medicine, University Hospital and University of Basel, Basel, Switzerland
Department of Ophthalmology, University Hospital Zurich and University of Zurich, Zurich, Switzerland
Department of Psychosomatic Medicine, University Hospital and University of Basel, Basel, Switzerland
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University of Basel · University Hospital of Basel
Affiliation as printed
Department of Psychosomatic Medicine, University Hospital and University of Basel, Basel, Switzerland
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Affiliation as printed
Department of Health Psychology, Institute of Psychology, RWTH Aachen, Aachen, Germany
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Affiliation as printed
Clinical Psychology and Psychotherapy – Methods and Approaches, Department of Psychology, Trier University, Trier, Germany
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Affiliation as printed
Clinical Psychology and Psychotherapy – Methods and Approaches, Department of Psychology, Trier University, Trier, Germany
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German Research Centre for Artificial Intelligence · Universität Trier
Affiliation as printed
Business Informatics I, Department IV, Trier University, Trier, Germany
German Research Center for Artificial Intelligence (DFKI). Research Department Cognitive Social Simulation, Trier, Germany
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German Research Centre for Artificial Intelligence · University of Haifa
Affiliation as printed
Faculty of Education, School of Therapy Counselling and Human Development, University of Haifa, Haifa, Israel
German Research Center for Artificial Intelligence (DFKI). Research Department Cognitive Social Simulation, Trier, Germany
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Gunther Pascal Meinlschmidt corresponding
University of Basel · University Hospital of Basel · Universität Trier
Affiliation as printed
Clinical Psychology and Psychotherapy – Methods and Approaches, Department of Psychology, Trier University, Trier, Germany
Department of Digital and Blended Psychosomatics and Psychotherapy, Psychosomatic Medicine, University Hospital and University of Basel, Basel, Switzerland
Department of Psychosomatic Medicine, University Hospital and University of Basel, Basel, Switzerland