HypeMed: Enhancing Medication Recommendations with Hypergraph-Based Patient Relationships

Medication recommendation aims to generate safe and effective medication sets from health records. However, accurately recommending medications hinges on inferring a patient's latent clinical condition from sparse and noisy observations, which requires both (i) preserving the visit-level combinatorial semantics of co-occurring diagnoses/procedures and (ii) leveraging informative historical references through effective, visit-conditioned retrieval. Most existing methods fall short in one of these aspects: graph-based modeling often fragments higher-order intra-visit patterns into pairwise relations, while inter-visit augmentation methods commonly exhibit an imbalance between learning a globally stable representation space and performing dynamic retrieval within it. To address these limitations, this paper proposes HypeMed , a two-stage hypergraph-based framework unifying intra-visit coherence modeling and inter-visit augmentation. HypeMed consists of two components: MedRep for representation pre-training and SimMR for similarity-enhanced recommendation. In the first stage, MedRep encodes clinical visits as hyperedges via knowledge-aware contrastive pre-training, creating a globally consistent, retrieval-friendly embedding space. In the second stage, SimMR performs dynamic retrieval within this space, fusing retrieved references with the patient's longitudinal data to refine medication prediction. Evaluation on real-world benchmarks shows that HypeMed outperforms state-of-the-art baselines in both recommendation precision and DDI reduction, simultaneously enhancing the effectiveness and safety of clinical decision support. The implementation is publicly available at https://github.com/xansar/HypeMed .