Antidepressants and kinase inhibitors: considerations on interactions and safety in oncology therapy

Keywords

adjustment disorders - breast neoplasms - drug interactions

Depression is the most common psychiatric disorder among oncology patients, with a prevalence ranging from 20% to 30% in this population. It affects approximately 9% of patients with breast cancer. Factors such as disease progression and symptoms are directly related to the development of depression, as well as issues related to the finitude of life. Given this context, many patients may require antidepressant medication. This therapy can be essential for the patient's overall health recovery. Given that the coadministration of chemotherapy and antidepressants is a common practice, the aim of this study was to evaluate the interactions between antidepressants and cyclin-dependent kinase inhibitors, which are drugs indicated for patients with locally advanced or metastatic cancer. Micromedex® database was used to screen these interactions. The results showed that the main interactions occurred between tricyclic antidepressants, selective serotonin reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors with ribociclib (n:15). The involved antidepressants were imipramine, desipramine, amitriptyline, doxepin, clomipramine, citalopram, escitalopram, paroxetine, sertraline, venlafaxine, and levomilnacipran. Pharmacodynamic interactions (n:12) between these classes altered the QT interval on electrocardiograms, being considered serious reactions that discourage coadministration or recommend monitoring the electrocardiogram if replacement is not feasible. Pharmacokinetic interactions (n:3) occurred due to strong inhibition of the CYP3A4 enzyme by Ribociclib, increasing the serum levels of antidepressants, and when coadministered with another strong inhibitor (nefazodone), there was an increase in serum levels of the chemotherapeutic agent. It is concluded that, aiming to maintain antidepressant therapy, the prescriber should prioritize antidepressants that do not present pharmacokinetic or pharmacodynamic interactions, such as nortriptyline, protriptyline, trimipramine, fluoxetine, duloxetine, bupropion, amoxapine, and maprotiline. If the use of other antidepressants is necessary, the electrocardiogram should be monitored or the dose of ribociclib should be reduced.

Corresponding author: Jéssica Silva Machado (e-mail: [e-mail]).

 

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No conflict of interest has been declared by the author(s).

Publication History

Article published online:
06 May 2025