Rationale, aims and objectives The study aimed to investigate the rate of the potential cytochrome P450 (CYP450)-mediated drug-drug interactions (DDIs) between selective serotonin reuptake inhibitors (SSRI) and other drugs, and identify the most common CYP450-interacted SSRI-drug combinations in real-life clinical practice. Methods This is a retrospective analysis of SSRI prescribing data from the Akdeniz University Hospital database, a tertiary hospital database in Turkey. Prescriptions which were included an SSRI had been selected (from January 2014 to December 2018). Lexicomp® Online™ was used to identify potential CYP450-mediated DDIs. Results A total of 7.5% of SSRI prescriptions were at risk of potential CYP450-mediated DDIs; 74.4% (n = 67) of the pDDIs were identified as category D modification of treatment should be considered. Antipsychotics were involved in 71.8% category D potential DDIs and 83.6% category C potential DDIs. The medications most frequently identified in combination with SSRIs were risperidone (31.7%) and aripiprazole (31.6%). Finally, CYP2D6 and CYP3A4 were the two most commonly affected CYP450 isozymes. Conclusions Prescribing antipsychotic-SSRI pairs interacting via CYP450 may increase serum concentrations of antipsychotics. Using DDI alert software while writing electronic prescriptions during clinical practice may reduce the frequency of ADRs.