Efficacy of a Conversational AI Agent for Psychiatric Symptoms and Digital Therapeutic Alliance

Importance: Accessible, scalable interventions for psychiatric symptoms are needed to address global mental health care gaps. Conversational artificial intelligence (AI) may extend access by providing personalized support, yet rigorous evidence of efficacy and therapeutic mechanisms remains scarce. Objectives: To evaluate the efficacy of a conversational AI-based mental health platform for psychiatric symptoms, and to assess how perceived therapeutic alliance contributes to user engagement and psychological outcomes. Design, Setting, and Participants: This 3-arm randomized clinical trial was conducted in Israel from April 1 to October 27, 2025, including the 12-week intervention and 3-month follow-up period. Participants were university students who reported psychological distress. Interventions: Participants were randomly assigned 1:1:1 to a 12-week AI-based conversational platform, face-to-face group therapy, or waiting list control. Main Outcomes and Measures: The primary outcomes were anxiety (Generalized Anxiety Disorder-7), depression (Patient Health Questionnaire-9), posttraumatic stress disorder (PTSD; PTSD Checklist for DSM-5), well-being (World Health Organization-5 Well-Being Index), and life satisfaction (Brief Multidimensional Students' Life Satisfaction Scale) measures at the end of the 12-week intervention. Analyses followed the intention-to-treat principle. Results: In total, 995 participants (mean [SD] age, 23.1 [2.4] years; 504 [50.7%] female) were included in analyses, with 336 randomized to the AI intervention, 331 to group therapy, and 328 to waiting list control. After the intervention, participants in the AI group showed greater anxiety reduction than those in group therapy (mean difference [MD], -2.17 [95% CI, -2.67 to -1.67]) or control (MD, -2.15 [95% CI, -2.65 to -1.65]) and greater depression reduction than control (MD, -1.99 [95% CI, -2.63 to -1.35]). PTSD symptoms did not differ among groups. The AI group also showed greater improvements in well-being than group therapy (MD, 5.72 [95% CI, 2.71 to 8.73]) and control (MD, 9.16 [95% CI, 6.14 to 12.18]). Structural equation modeling indicated that perceived therapeutic alliance was associated with engagement (β = 0.31 [95% CI, 0.16 to 0.43]; P < .001) and symptom improvement (β = -0.58 [95% CI, -0.69 to -0.46]; P < .001). Conclusions and Relevance: In this randomized clinical trial of university students with psychological distress, the use of a conversational AI agent was associated with improvements in anxiety, depression, well-being, and life satisfaction, and its perceived therapeutic alliance was associated with engagement and psychological improvement. These findings suggest that conversational AI may serve as a scalable resource within mental health frameworks. Trial Registration: ISRCTN Registry Identifier: ISRCTN61075527.