Cited by 14Artificial Intelligence in Healthcare and EducationMachine Learning in HealthcareClinical Reasoning and Diagnostic Skills

Large language models management of complex medication regimens: a case-based evaluation

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Chase, Aaron, Most, Amoreena, Xu, Shaochen, Barreto, Erin, Murray, Brian, Henry, Kelli, Smith, Susan, Hedrick, Tanner +4 more·2025·Frontiers in Pharmacology

Abstract

Background: Large language models (LLMs) have shown the ability to diagnose complex medical cases, but only limited studies have evaluated the performance of LLMs in the development of evidence-based treatment plans. The purpose of this evaluation was to test four LLMs on their ability to develop safe and efficacious treatment plans on complex patients managed in the intensive care unit (ICU). Methods: Eight high-fidelity patient cases focusing on medication management were developed by critical care clinicians including history of present illness, laboratory values, vital signs, home medications, and current medications. Four LLMs [ChatGPT (GPT-3.5), ChatGPT (GPT-4), Claude-2, and Llama-2-70b] were prompted to develop an optimized medication regimen for each case. LLM generated medication regimens were then reviewed by a panel of seven critical care clinicians to assess safety and efficacy, as defined by medication errors identified and appropriate treatment for the clinical conditions. Appropriate treatment was measured by the average rate of clinician agreement to continue each medication in the regimen and compared using analysis of variance (ANOVA). Results: Clinicians identified a median of 4.1-6.9 medication errors per recommended regimen, and life-threatening medication recommendations were present in 16.3%-57.1% of the regimens, depending on LLM. Clinicians continued LLM-recommended medications at a rate of 54.6%-67.3%, with GPT-4 having the highest rate of medication continuation among all LLMs tested (p < 0.001) and the lowest rate of life-threatening medication errors (p < 0.001). Conclusion: Caution is warranted using present LLMs for medication regimens given the number of medication errors that were identified in this pilot study. However, LLMs did demonstrate potential to serve as clinical decision support for the management of complex medication regimens given the need for domain specific prompting and testing.

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  • Another study reported fabricated references in medication information generated by ChatGPT-3.5.

    “Another study also reported fabricated references in medication information generated by ChatGPT-3.5.67”

    From Large Language Models in Pharmacist-Led Direct Patient Care: A Rapid Review of Published Evaluations (2026) · cites this paper as [67]

    The Results report medication-regimen errors in GPT-3.5 output, but do not say it generated fabricated references. A search of our copy for fabricated or invented citations and references found no passage addressing that claim. (LLM, conf=0.75)

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References 24 · Cited by 14

Research works printed but not linked: 3

  1. Guan Z. Wu Z. Liu Z. Wu D. Ren H. Li Q. (2023). “ CohortGPT: an enhanced GPT for participant recruitment in clinical study”. arXiv preprint. 10.48550/arXiv:2307.11346 · DOI
  2. Tariq R. A. Vashisht R. Sinha A. Scherbak Y. (2024). Medication dispensing errors and prevention. StatPearls. Available online at: https://www.ncbi.nlm.nih.gov/books/NBK519065/. 30085607
  3. Zhang H. Diao S. Lin Y. Fung Y. R. Lian Q. Wang X. (2024). R-Tuning: instructing large language models to say ‘I don’t know’. Mexico City, Mexico: Association for Computational Linguistics, 7113– 7139.

Authors
Chase, A., Most, A., Xu, S., Barreto, E., Murray, B., Henry, K., Smith, S., Hedrick, T., Chen, X., Li, S., Liu, T., & Sikora, A.
Affiliations
  • University of New Mexico Hospital (US)
  • University of Georgia (US)
  • Mayo Clinic (US)
  • University of North Carolina at Chapel Hill (US)
  • University of Virginia (US)
Corresponding author
Sikora, Andrea
Venue
Frontiers in Pharmacology
Published
2025-11-24
Volume
16
Pages
1514445-1514445
ISSN
1663-9812 (ISSN-L)
OpenAlex
W4416607794
Cited by
14
References
24
Citations by year
2026: 14
FWCI
3.37
Type
journal article
Language
en
Open access
Locations
  • Frontiers in Pharmacology (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Agency for Healthcare Research and Quality
Topics
  • Health Sciences › Medicine › Health Informatics › Artificial Intelligence in Healthcare and Education
  • Physical Sciences › Computer Science › Artificial Intelligence › Machine Learning in Healthcare
  • Health Sciences › Medicine › Family Practice › Clinical Reasoning and Diagnostic Skills
Keywords
large language models, intensive care unit, medication errors, clinical decision support, ChatGPT, GPT-4, Llama 2, Claude 2, clinician agreement

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