Interactions between antidepressants, sleep aids and selected breast cancer therapy

Abstract

Depression and insomnia are very significant pathologies in cancer patients as they contribute to the patient's overall cure and quality of life. Moreover, untreated depression and ongoing insomnia are associated with decreased immune responses and lower survival rates. With all disease states and especially with cancer, close attention to drug-drug interactions and the potential impact on the efficacy of therapy is paramount. One area of particular interest due to the lack of well-done clinical trials is drug-drug interaction(s) between antidepressants and cancer treatment. Pharmacokinetics of a certain drug allows for prediction of certain drug interactions based on chemical properties of the agents involved. If the agents depend on their metabolites for activity, active drug level will be decreased through this enzyme inhibition. In this paper, we looked at the cytochrome-P450 drug interactions between antidepressants and sleep aids with Selective Estrogen Receptor Modulators (SERM). Newer SERM metabolisms are less influenced by interactions with medications used to treat depression. However, tamoxifen metabolism could be severely altered by several antidepressants. This has direct consequences as patients on tamoxifen and antidepressant can have double the risk of relapse to cancer in two years. We discussed those interactions and made recommendations for clinical use.

Keywords: cancer patients; depression; drugs interaction; insomnia.

Figure 1.

Cytochrome-P450 Drug Interactions between Antidepressants and Selective Estrogen Receptor Modulators (serms). Classification of antidepressants’ cytochrome P450 inhibition based on available pharmacokinetic data.^, Green (⟷): No inhibition; Yellow (↓): Mild inhibition; Orange (↓↓): Moderate inhibition; Red (↓↓↓): Strong inhibition. Recommendation based on clinical relevance of cytochrome P450 interactions. ^aConsider therapy modification: Evidence available to support clinically significant decrease in efficacy of selected breast cancer pharmacotherapy as measured by all-cause mortality and/or breast cancer recurrence. ^bMonitor therapy: Lack of evidence available or available evidence suggests clinically insignificant decrease in efficacy of selected breast cancer pharmacotherapy as measured by all-cause mortality and/or breast cancer recurrence. ^Cno action required: No known or expected clinically significant interaction.

Figure 2.

Cytochrome-P450 Drug Interactions between Selected Sleep Aids and Selective Estrogen Receptor Modulators (SERMs). Classification of sleep aids’ cytochrome P450 interactions based on available pharmacokinetic data. Green (⟷): No interaction. Recommendation based on clinical relevance of cytochrome P450 interactions. ^cNo action required, No known or expected clinically significant interaction.