Drug Interaction in Psycho-Oncology: Antidepressants and Antineoplastics

Abstract

Background and Objectives: Although there is a growing impact of psychiatric and depressive disorders in cancer patients, literature on the idiosyncrasies of antidepressants (ADs) used in those conditions and their interactions with antineoplastic agents (ANs) is scarce. Sharing the same biotransformation pathways enhances the risk of drug interaction between ADs and ANs, specifically when compounds are inducers, inhibitors or substrates of cytochrome P450 (CYP 450). In cancer patients, such drug interactions may result in less efficacy of the drug and/or increase of their side effects. Therefore, the choice of AD should be cautious (safe and effective) and well supported. The main purpose of this review was to analyze the individual pharmacokinetic properties of the most used ADs and ANs in order to summarize the risk of possible drug interactions between them, anticipating the consequences of their coadministration. Methods: The authors reviewed books and PubMed online articles published in the last 6 years. Results: Most of the ANs are subject to transformation by CYP 450 3A4 and their coadministration with ADs, that have inhibitory properties of this CYP isoform, such as fluoxetine, sertraline, paroxetine and fluvoxamine, may result in the loss of the AN’s efficacy or higher toxicity. Conclusion: Among the ADs, escitalopram, citalopram, venlafaxine, mirtazapine and milnacipran stand out for their weak CYP 450 inhibitory potential and their safety profile in those patients.

Optimizing Patient Outcomes with PD‐1/PD‐L1 Immune Checkpoint Inhibitors for the First‐Line Treatment of Advanced Non–Small Cell Lung Cancer

“…A phase I trial was conducted to assess PK interactions between ipilimumab and dacarbazine or carboplatin/paclitaxel chemotherapy used for melanoma . Ipilimumab, a CTLA‐4–targeted ICI, induces cytokines (e.g., IL‐1, IL‐2, interferon‐β, and IL‐6) that modulate the activity of CYP enzymes, potentially altering the PK/PD of dacarbazine and paclitaxel that are metabolized by CYP1A2/2E1 and CYP2C8/3A4, respectively . The study found that the estimated fold changes in geometric mean ratios (GMRs) for peak concentration (C max ) and area under the curve (AUC) of ipilimumab when administered with dacarbazine were 0.982 and 0.917, respectively.…”

Depresión y cáncer: una revisión orientada a la práctica clínica

“…Con pacientes oncológicos sometidos a varias quimioterapias, es importante tener precaución con las interacciones farmacológicas. Antidepresivos como la fluoxetina, la sertralina, la paroxetina y la fluvoxamina inhiben la transformación de agentes antineoplásicos a través del CYP450 3A4, lo que produce una disminución de su eficacia o mayor toxicidad de los mismos 35 . Otros fármacos como el citalopram, el escitalopram, la venlafaxina y la mirtazapina son inhibidores débiles, lo que los convierte en una elección más segura 35 .…”

Drug Interaction in Psycho-Oncology: A Retrospective Glance over the Polymedication and Comorbidities in a Portuguese Psycho-Oncology Service

“…The mourning of current and anticipated losses, the fear of death, concerns with the loved ones, the effect of some chemotherapeutics in mood and biological characteristics of the tumor [1] have been implicated in the genesis of this suffering. According to the literature, about 50% of these patients are people with mental illness, mainly adjustment disorders (4-35%) followed by major depressive disorder (3-36%) [3,[4][5][6] and, for some authors, delirium [7]. However, only 30% of the clinical psychiatric syndromes associated with cancer are identified by their doctors [8].…”

“…Depression is associated with lower quality of life, increased subjective perception of pain, suicidal thoughts, wish for hastened death and a worse prognosis [3,[9][10][11].…”

“…in the control of anorexia, nausea, vomiting and pain management) [12]. However, drug interactions can lead to increased toxicity or loss of effectiveness when certain medications are prescribed at the same time [3]. Drugs such as antihypertensives, corticosteroids and/or antineoplastic agents (procarbazine, vincristine, L-asparaginase, interferon, tamoxifen) have been considered in several studies as medical risk factors for depression in patients with cancer [7,13].…”