Abstract
BACKGROUND: Shortages in mental healthcare lead to long periods of inadequate support for many patients. While digital interventions offer a scalable solution to this unmet clinical need, patient engagement remains a key challenge. Generative artificial intelligence (genAI) presents an opportunity to deliver highly engaging, personalized mental health treatment at scale. METHODS: In a pre-registered (ClinicalTrials.gov: NCT06459128, 10 June 2024), parallel, 2-arm, unblinded, randomized controlled trial (N = 540), we evaluate whether a genAI-enabled cognitive behavioral therapy (CBT) app enhances engagement or symptom reduction compared with digital CBT workbooks. Eligible participants are adults residing in the United States with elevated self-reported symptoms of anxiety (GAD-7 ≥ 7) or depression (PHQ-9 ≥ 9), recruited online. After an online baseline assessment, participants are automatically randomly allocated (3:2) to receive either the genAI-enabled app or a digital workbook, both self-guided over six weeks. Primary outcomes are: 1) engagement frequency and duration, and 2) change in anxiety (GAD-7) and depression (PHQ-9) symptom severity. Secondary outcomes include adverse events and functional impairment. The study is unblinded to participants and researchers due to the nature of the digital interventions. RESULTS: A total of 540 participants are recruited and randomized to each group (intervention: n = 322, active control: n = 218). Nine participants from the control group are excluded from analysis due to protocol deviations. Over six weeks, the genAI solution (n = 322) increases engagement frequency (2.4×) and duration (3.8×) compared to digital workbooks (n = 209), with moderate to large effect sizes. We observe comparable outcomes for anxiety (GAD-7) and depression (PHQ-9) with no differences in adverse events. Moreover, exploratory analyses suggest that participants who choose to engage with clinical personalization features powered by genAI experience stronger anxiety symptom reduction and improved overall wellbeing. CONCLUSIONS: Our findings suggest that, in self-directed usage, tailored genAI-enabled therapy safely enhances user engagement above and beyond static materials, without showing an overall enhancement in anxiety or depression symptom reduction.