TheraAgent: Self-Improving Therapeutic Agent for Precise and Comprehensive Treatment Planning

Large language models show promise for mental health support, yet therapeutic quality improves only when evaluation functions as an actionable control signal rather than a passive metric. We introduce a framework that formulates therapeutic response generation as a decision-refinement problem driven by multi-dimensional, human-aligned evaluation. In Stage I, we introduce TheraJudge, an open-source therapeutic evaluator trained via preference-based optimization on human-annotated data to produce reliable judgments across 7 psychological dimensions. In Stage II, we introduce TheraAgent, which operationalizes TheraJudge's evaluations through a coordinated refinement process with specialized Critic, Coach, and Therapist roles that translate evaluative signals into targeted response revisions. Empirically, TheraJudge achieves strong agreement with clinician ratings, with intraclass correlation coefficients (ICC = 0.87-0.95), surpassing supervised baselines and strong closed-source judges, particularly on critical dimensions such as Safety, Relevance, and Empathy. Acting on these evaluations, TheraAgent yields a +0.43 improvement in human-rated therapeutic quality (on a 5-point scale) under blind evaluation, with 96% clinician inter-rater reliability. Low-quality responses ($\leq 3$) improve by +2.45 points with a 94% recovery rate, demonstrating targeted correction of unsafe outputs. Overall, our results indicate that effective alignment of mental-health LLMs stems from acting on human-aligned evaluation, rather than relying solely on stronger generation. We release code at https://github.com/vis-nlp/TheraAlign.

Treatment reasoning underpins every therapeutic decision, integrating disease context, comorbidities, medications, contraindications, and evolving biomedical knowledge to select an appropriate therapy. It is inherently iterative: candidates are weighed against many constraints, revised as evidence emerges, and grounded in verifiable sources. Here we introduce ATHENA-R1, an AI agent for treatment reasoning across all FDA approved drugs since 1939, trained by reinforcement learning over a universe of 212 biomedical tools. At each step it identifies missing information, selects and runs relevant tools, and incorporates the evidence. To train it without human-annotated traces, we build a two-level self-learning framework: multi-agent systems construct the tools, tasks, and reasoning trajectories for supervised fine-tuning, then reinforcement learning with scientific feedback rewards reasoning quality (evidence gathering, grounded tool use, logical non-redundancy). Across five benchmarks of 3,168 drug reasoning tasks and 456 patient treatment cases, ATHENA-R1 outperforms language models and tool-use systems, reaching 94.7% accuracy on open-ended drug reasoning and 82.9% on treatment reasoning, 17.8 and 10.7 points above GPT-5. In blinded evaluations by experts from 28 rare disease organizations, it is preferred over reference models on all criteria, and physicians rated it favorably on complex hospitalized cardiovascular and infectious-disease cases. Adverse-event hypotheses it generated, tested in electronic health records from 5.4 million patients, reached adjusted odds ratios of 1.48-1.84, with no elevation among negative controls. Because it requires knowing what evidence to seek before concluding, treatment reasoning has long been hard for AI; we show it can be reframed as a learnable process of iterative evidence gathering that reinforcement learning can train AI to perform.

Clinical order generation serves as a critical bridge between clinical decision-making and real-world practice, translating medical decisions into concrete and executable orders. Existing agents mainly focus on coarse-grained decisions and overlook the fine-grained, executable information required for clinical orders. To address this gap, we propose CAREAgent, an agent for clinical order generation. To support its training, we introduce a two-stage agentic reasoning data construction method. First, we design an agent framework that constructs verifiable reasoning trajectories aligned with realistic clinical tool usage. Second, we filter reasoning trajectories by format compliance, order validity, and clinical plausibility. Building on the constructed data, the model is first trained via supervised fine-tuning to acquire fundamental reasoning formats and medical knowledge, and is subsequently optimized through reinforcement learning with multi-dimensional reward functions to enhance complex clinical reasoning capabilities. Experiments on multiple benchmarks demonstrate the effectiveness of CAREAgent. On ClinicalBench (unseen during training), CAREAgent improves the F1 score by 5.05%, 2.09%, and 0.86% over the single-agent, multi-agent, and agentic reasoning methods, respectively.