BACKGROUND: Electronic drug interaction databases are often utilized in clinical practice to detect for possible drug-drug interactions between drug pairs. It is uncertain, however, whether most of these detections interactions are clinically important in practice. To demonstrate these issues, this study utilized a comprehensive drug-drug interaction (DDI) electronic database to elucidate the prevalence of DDIs at a cancer centre between antidepressants and oral anticancer drugs (ACDs). METHODS: Drug utilization reports were retrieved to determine the patients who were prescribed with antidepressants oral ACDs between 2006 and 2009 at a cancer center. Medication records of these patients were retrospectively examined using OncoRx, an internet-based oncology-specific database that allows the identification of DDIs. RESULTS: Out of 910 users of antidepressants, about one-third (281 patients, 30.9%) used an oral ACD and an antidepressant concomitantly. From these patients, about one-fifth (21.0%) had potential DDIs. These patients were users of 17 potentially interacting drug pairs. Ten out of the 17 drug pairs could potentially cause pharmacokinetic interactions, and the rest were pharmacodynamic interactions, with only three out of the 17 drug pairs were clinically documented to cause interacting events. CONCLUSION: The lack of screening conditions may have led to an over detection of DDI combinations by electronic DDI databases. Many of the detected interactions may not deem high significance in clinical practice. This study exposed a major weakness of current electronic DDI databases for detecting oral ACDs and antidepressants DDIs.