Drug interactions with vortioxetine, a new multimodal antidepressant Interazioni farmacologiche della vortioxetina, un nuovo antidepressivo ad azione multimodale

Multiple drug therapy is common in clinical psychiatry practice and carries the risk of drug interactions. A drug interaction occurs when the effectiveness or toxicity of a drug is altered by the concomitant administration of another pharmacological agent. In a few cases drug interactions may prove beneficial, leading to increased efficacy or reduced risk of unwanted effects, and therefore certain drug combinations may be used advantageously in clinical practice. However, more often, drug interactions are of concern because the outcome of concurrent drug administration is diminished therapeutic efficacy or increased toxicity of one or more of the administered compounds. The potential for drug interactions represents an important issue in the evaluation of many psychotropic drugs including antidepressants. Antidepressant medications may be involved in drug interactions as they are commonly prescribed in combination with other drugs used to treat concomitant psychiatric, neurological or somatic disorders or to augment antidepressant response in refractory depression1. Currently available antidepressants differ considerably in their potential for pharmacological interactions. Certain first-generation antidepressants, namely monoamine oxidase inhibitors (MAOIs), have been associated with a significant risk of potentially harmful pharmacodynamic drug interactions which has contributed to a gradual decline in their utiSUMMARY. This article summarized the available knowledge on clinically relevant drug interactions of vortioxetine, a new antidepressant with a “multimodal” serotonergic mechanism of action, recently approved for the treatment of major depressive disorder. Although information is still limited and mainly based on studies performed in healthy volunteers, vortioxetine appears to have a favorable drug interaction profile. Concerning the potential for pharmacokinetic drug interactions, vortioxetine has little to no effect on various cytochrome P450 (CYP) isoforms and therefore is not expected to markedly affect plasma concentrations of other medications metabolized by these enzymes. This is a major advantage when compared to other antidepressants which are known to inhibit the activity of one or more CYP isoforms. On the other hand, dosage adjustments may be required when vortioxetine is coadministered with strong CYP2D6 inhibitors or broad-spectrum CYP inducers. Vortioxetine carries a relatively low risk for pharmacodynamic drug interactions, at least as compared to first-generation antidepressants. Like other antidepressants enhancing serotonergic activity, vortioxetine is associated with a potential risk of serotonin syndrome when used in combination with other serotonergic agents. Based on all available clinical data, vortioxetine has no increased risk of serotonin syndrome when used without other serotoninergic agents and at therapeutic doses.