Large Language Models in Adverse Drug Reaction Detection and Pharmacovigilance: A Systematic Review of Current Applications, Challenges, and Future Directions

Abstract

Background/Objectives: Pharmacovigilance workflows rely heavily on unstructured text across diverse sources. Here, we systematically reviewed how large language models (LLMs) are being explored as support tools for adverse drug reaction (ADR) detection, extraction, triage, and documentation, highlighting their potential for precision medicine and big data-enabled safety monitoring. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, we systematically searched PubMed, Scopus, and Web of Science for studies published between January 2022 and March 2026. Ultimately, 83 empirical studies satisfied the inclusion criteria. A narrative synthesis was conducted to address methodological heterogeneity across these studies. Results: LLM applications were concentrated in constrained information-extraction and classification tasks, including signal evaluation, clinical-note extraction, social media surveillance, and literature screening. Quantitative performance varied substantially by system design: error-correction prompting yielded an F1-score of 0.921 for ADR named entity recognition, whereas retrieval-augmented generation improved data-retrieval accuracy from 8.3% to 78.3%. Most studies were retrospective, benchmark-based, or proof-of-concept evaluations. Across 581 paired pre-consensus domain judgements, observed inter-rater agreement was 90.4% and Cohen’s κ was 0.837 (95% CI 0.772–0.895). Hallucination, low specificity, prompt sensitivity, narrow datasets, and weak external validation remained common limitations. Conclusions: Current evidence supports supervised, task-specific applications of LLMs for extraction, triage, retrieval, and documentation rather than autonomous pharmacovigilance decision-making. Prospective evaluation, external validation, transparent reporting, and accountable human oversight are required before high-stakes clinical or regulatory deployment.