Interactions Between Tamoxifen and Antidepressants via Cytochrome P450 2D6

Desmarais, Julie Eve; Looper, Karl

doi:10.4088/jcp.08r04856blu

Cited by 120 publications

(99 citation statements)

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“…16 SSRIs in these women may also speed the metabolism of tamoxifen to inactive metabolites, possibly reducing the severity of side effects, including hot flashes. 39 Therefore, our findings relate to women suffering from natural peri-and post-menopausal symptoms.…”

Section: Implications For Practice and Researchmentioning

confidence: 87%

SSRIs for Hot Flashes: A Systematic Review and Meta-Analysis of Randomized Trials

et al. 2013

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BACKGROUND: Hot flashes are the most commonly reported vasomotor symptom during the peri-and early post-menopausal period. OBJECTIVES: To systematically review, appraise and summarize the evidence of the impact of different SSRIs on peri-menopausal hot flashes in healthy women in randomized, controlled trials. METHODS: A comprehensive literature search was conducted of MEDLINE™, EMBASE, the Cochrane Central Register of Controlled Trials, Web of Science and Scopus through March 2013. Two independent reviewers selected studies and extracted data. Random effects meta-analysis was used to pool outcomes across studies, and Bayesian mixed treatment methods were used to rank SSRIs in terms of effectiveness. RESULTS: We included a total of 11 randomized controlled trials with good methodological quality enrolling 2,069 menopausal and post-menopausal women (follow-up 1-9 months, mean age 36-76 years, mean time since menopause 2.3-6.6 years). Compared with placebo, SSRIs were associated with a statistically significant decrease in hot flash frequency (difference in means −0.93; 95 % CI −1.46 to −0.37; I 2 = 21 %) and severity assessed by various scales (standardized difference in means −0.34; 95 % CI −0.59 to −0.10; I 2 = 47 %). Adverse events did not differ from placebo. Mixed treatment comparison analysis demonstrated the superiority of escitalopram compared to other SSRIs in terms of efficacy. CONCLUSION: SSRI use is associated with modest improvement in the severity and frequency of hot flashes but can also be associated with the typical profile of SSRI adverse effects.

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Section: Implications For Practice and Researchmentioning

confidence: 87%

SSRIs for Hot Flashes: A Systematic Review and Meta-Analysis of Randomized Trials

et al. 2013

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“…Agents such as fluoxetine, paroxetine, bupropion quinidine and cinacalcet act as strong inhibitors of CYP2D6 and should therefore be cautiously prescribed in combination with tamoxifen [31] . Unfortunately, there is little and inconsistent data within the majority of available studies, regarding the co-administration of a CYP2D6-inhibitor.…”

Section: Discussionmentioning

confidence: 99%

Impact of CYP2D*6 in the adjuvant treatment of breast cancer patients with tamoxifen

Markopoulos

Kykalos

Mantas

2014

WJCO

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Biotransformation of tamoxifen to the potent antiestrogen endoxifen is performed by cytochrome P450 (CYP) enzymes, in particular the CYP2D6 isoform. CYP2D6*4 is one of the most frequent alleles associated with loss of enzymatic activity. The incidence of CYP2D6*4 among Caucasians is estimated up to 27%, while it is present in up to 90% of all poor metabolizers within the Caucasian population. The hypothesis under question is whether the presence of one or two non-functioning (null) alleles predicts an inferior outcome in postmenopausal women with breast cancer receiving adjuvant treatment with tamoxifen. The numerous existing studies investigating the association of CYP2D6 with treatment failure in breast cancer are inconsistent and give rather conflicting results. Currently, routine CYP2D6 testing among women with breast cancer is not recommended and the significance of CYP2D6 phenotype in decision making regarding the administration of tamoxifen is unclear. The present study summarizes current literature regarding clinical studies on CYP2D6*4, particularly in terms of response to tamoxifen therapy and breast cancer outcome.© 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: CYP2D6; Tamoxifen; Breast cancer; Adjuvant treatment Core tip: Currently, routine cytochrome P450 (CYP)2D6 testing among women with breast cancer is not recommended and the significance of CYP2D6 phenotype in decision making regarding the administration of tamoxifen is unclear. The present study summarizes current literature regarding clinical studies on CYP2D6*4, particularly in terms of response to tamoxifen therapy and breast cancer outcome.Markopoulos C, Kykalos S, Mantas D. Impact of CYP2D*6 in the adjuvant treatment of breast cancer patients with tamoxifen.

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“…Sertraline and duloxetine are moderate inhibitors of CYP2D6 [15]. Venlafaxine, escitalopram and citalopram are weak inhibitors of CYP2D6, with little effect on the metabolism of tamoxifen [15,16].…”

Section: Tamoxifen Metabolismmentioning

confidence: 99%

“…Although mirtazapine has not been extensively studied, existing data suggest there is a minimum effect on CYP2D6 [16].…”

Section: Tamoxifen Metabolismmentioning

confidence: 99%

Treatment of Depression in Patients under Breast Cancer Therapy: Antidepressant-Tamoxifen Drug Interactions

Aguiar¹,

Aguiar²,

Rocha³

2017

J Drug Metab Toxicol

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The hormone therapy with tamoxifen is used in patients with breast cancer. The tamoxifen mechanism of action is based on the antagonist action of selective estrogen receptors. Depression and anxiety are psychiatric disorders which frequently coexist in patients with breast cancer. In the last decades, there has been an increase in the use of antidepressants. This literature review aims to provide a general view of pharmacokinetic knowledge of drug interactions between tamoxifen and antidepressants. Since tamoxifen is metabolized by CYP2D6, the use of antidepressants that are inhibitors of this is enzyme, such as paroxetine, fluoxetine and bupropion must be avoided. Based on cytochrome p450 drug interactions, it can be concluded that the use of citalopram, escitalopram, desvenlafaxine and venlafaxine are safe and effective treatment unlikely to alter tamoxifen efficacy.

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Interactions Between Tamoxifen and Antidepressants via Cytochrome P450 2D6

Cited by 120 publications

References 0 publications

SSRIs for Hot Flashes: A Systematic Review and Meta-Analysis of Randomized Trials

SSRIs for Hot Flashes: A Systematic Review and Meta-Analysis of Randomized Trials

Impact of CYP2D*6 in the adjuvant treatment of breast cancer patients with tamoxifen

Treatment of Depression in Patients under Breast Cancer Therapy: Antidepressant-Tamoxifen Drug Interactions

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