SARS CoV-2 infection or COVID-19 disease has triggered a global pandemic and requires a complex approach, given the multisystemic impairment and lack of specific etiological treatment. The diversity of drug groups, used for non-specific, pathogenetic, and symptomatic treatment, may expose the patient to a significant risk of developing drug interactions. The long-term treatment of a psychiatric patient may predispose to an increased risk for side effects, especially in the association of chronic somatic pathologies that require the administration of specific preparations. Psychotropic drugs are associated with adverse effects on the cardiovascular system (cardiotoxicity, QT prolongation), central nervous system (convulsions), and hematopoietic system (neutropenia, agranulocytosis, lymphopenia), which may overlap with concomitant use with other groups of drugs. Drug interactions in these cases may have an increased incidence with unpredictable manifestations. The elucidation of the mechanisms underlying drug interactions and the possibility of anticipating the occurrence of clinically relevant interactions is extremely important for clinicians.