BackgroundPharmacotherapy is necessary for many people with psychiatric disorders and polypharmacy is common. The psychotropic drug-drug interaction (DDI) should be concerned and efficiently monitored by a proper instrument.ObjectivesThis study aimed to investigate the prevalence and associated factors of psychotropic DDI and to compare the identification utility from three databases:Drugs.com®, Lexicomp®, and Epocrates®.MethodsThis was a retrospective cohort design. We collected demographic and clinical data of all patients hospitalised in the psychiatric inpatient unit in 2020. Psychotropic DDI profiles were examined through three databases. Descriptive statistics were used to report comprehensiveness of each database and prevalence of psychotropic DDI. The Fleiss’ kappa index would be analysed to indicate agreement strength of DDI severity classification among three databases.ResultsFrom 149 total admissions, the psychotropic DDIs were found in 148 admissions (99.3%). Thorough the study, there were 182 of both psychotropic and other agents prescribed under 1,357 prescriptions. In total, 2,825 psychotropic DDIs were identified by usingDrugs.com® 2,500 times, Epocrates® 2,269 times, and Lexicomp® 2,265 times. Interactions with clonazepam was the three most frequent agents when co-administrated with quetiapine (n = 56), risperidone (n = 36), and valproic acid and derivatives (n = 36). Serious DDIs were comparatively lower in incidence and there was no evidence of its association with reported clinical adverse consequences. The study revealed slight and fair agreement regarding severity classification among the three databases was found. DDI events detected byDrugs.com® were greatest in number, but Lexicomp® provided the broadest list of medications prescribed in our study.ConclusionAmong three databases, interactions detected byDrugs.com® were greatest in number, whereas Lexicomp® provided the broadest list of medications. Development of such databases, based on both theoretical and clinical conceptions, should be focused to balance safety of patients and weariness of healthcare providers.