Real-World Safety of Cyproheptadine-Based Appetite Stimulants: An Electronic Health Record-Based Retrospective Cohort Study in Adult Patients

<b>Background</b>: Cyproheptadine-based appetite stimulants (CAS) have been safely used in Korea for over 30 years. However, in older adults who are vulnerable to malnutrition, sarcopenia, and fall-related morbidity, safety of CAS in nutrition care remains uncertain due to limited evidence and its antihistaminic effects. This study aimed to assess the real-world safety of CAS compared with megestrol and other antihistamines to inform safe pharmacologic support within clinical nutrition practice. <b>Methods</b>: A retrospective observational study was conducted using Seoul National University Hospital's common data model. Patients who were prescribed CAS, megestrol, or antihistamines between 2004 and 2022 were enrolled. To balance covariates, propensity score matching was applied. The primary outcomes-dizziness, sedation, and hypotension-were evaluated within 30 days of drug administration. Additionally, sensitivity analyses and subgroup assessments by age and duration of use were performed to evaluate robustness of the findings. <b>Results</b>: No significant differences were observed in the risk of dizziness, sedation, or hypotension when CAS was compared to megestrol, with adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of 1.02 (0.70-1.50) for dizziness, 0.53 (0.19-1.54) for sedation, and 0.70 (0.34-1.44) for hypotension. Similar findings were noted in the comparison with antihistamines, where the aHRs for dizziness, sedation, or hypotension of 0.56 (0.41-0.78), 1.05 (0.46-2.38), and 0.65 (0.36-1.17), respectively. <b>Conclusions</b>: CAS demonstrated an acceptable safety profile in older adults, with safety comparable to both megestrol and antihistamines.