Exploratory prescribing risk profiles and drug drug interaction burden in older adults with depressive episodes.

Introduction: Older adults with depressive episodes are frequently treated in the context of psychiatric multimorbidity, somatic co-treatment, and polypharmacy, increasing their vulnerability to drug-drug interactions (DDIs) and cumulative medication-related risk. This study characterized DDI burden and exploratory prescribing risk profiles among psychogeriatric outpatients, focusing on patients with depressive episodes. Methods: We conducted a retrospective observational study of psychiatric outpatient visits in 2023. The primary subgroup consisted of those diagnosed with a depressive episode. Patients with at least one diagnosis of a depressive episode formed the primary depression-focused subgroup. Potential DDIs were assessed using DrugBank and classified as major, moderate, or minor. These potential DDIs were database-identified and were not clinically confirmed adverse drug events. Visit-and patient-level analyses described potential DDI burden, medication risk burden, psychiatric co-diagnoses, and diagnosis-specific potential DDI pairs. Multivariable logistic and negative binomial regression models were fitted among patients with depressive episodes. Patient-level exploratory prescribing risk profiles were derived in the full cohort using DDI and medication risk burden features. Results: The cohort included 309 patients and 1242 eligible visits; 242 patients had at least one depressive episode diagnosis. Anxiety disorders were the predominant co-diagnosis among patients with depressive episodes, being recorded in 193 patients (79.8%) and co-occurring with depressive episode at the same visit in 177 patients (73.1%). Nearly half (50.4%) of visits from depressive-episode patients included at least one database-identified major potential DDI, while 93.7% had at least one moderate potential DDI. Leading moderate DDI pairs mainly involved benzodiazepine/Z-drug and benzodiazepine/antidepressant combinations. Leading major DDI pairs included cardiovascular, carbamazepine-related, and trazodone-related interactions. Medication load was the variable most consistently associated with potential DDI burden, while diagnostic complexity contributed to cumulative annual major DDI burden. A higher-burden exploratory prescribing risk profile identified 86 patients with depressive episodes (35.5%), highlighting a clinically important subgroup characterized by greater polypharmacy, potential DDI burden, and geriatric medication risk scores. Conclusion: Database-identified potential DDI burden was substantial among older adults with depressive episodes and was driven mainly by medication load. Anxiety overlap, recurrent sedative-related moderate potential DDIs, and higher-burden prescribing risk profiles highlight the need for structured, regimen-level medication review.