By Julie Bromberg
Women who are taking tamoxifen to prevent recurrence of breast cancer should avoid the antidepressants paroxetine (Paxil is the brand name) and fluoxetine (Prozac is the brand name). New research has found that using certain antidepressants while taking tamoxifen can increase the risk of death from breast cancer. Other antidepressants, such as citalopram (brand name: Celexa) or venlafaxine (brand name: Effexor), are considered to be safe options.
In the United States, approximately 30% of all women taking tamoxifen are prescribed antidepressants to treat depression or hot flashes that frequently occur while taking tamoxifen. In the past several years, several researchers had raised concerns about certain selective serotonin reuptake inhibitors (SSRI) antidepressants reducing the effectiveness of tamoxifen. [end Desmarais JE and Looper KJ. Interactions between Tamoxifen and Antidepressants via Cytochrome P450 2D6. Journal of Clinical Psychiatry, 2009; 70(12): 1688-1697.] [end Aubert RE, Stanek EJ, Yao J, Teagarden JR, Subar M, Epstein RS, Skaar TC, Desta Z, and Flockhart DA. Risk of Breast Cancer Recurrence in Women Initiating Tamoxifen with CYP2D6 Inhibitors. Journal of Clinical Oncology, 2009; 27(18S): CRA508] [end Jin Y, Desta Z, Stearns V, Ward B, Ho H, Lee KH, et al. CYP2D6 Genotype, Antidepressant Use, and Tamoxifen Metabolism During Adjuvant Breast Cancer Treatment. Journal of the National Cancer Institute, 2005, 97:30-9.] [end Borges S, Desta Z, Li L, Skaar TC, Ward BA, Nguyen A, et al. Quantitative Effect of CYP2D6 Genotype and Inhibitors on Tamoxifen Metabolism: Implication for Optimization of Breast Cancer Treatment. Clinical Pharmacological Therapy, 2006, 80:61-74.] [end Kelly CM, Juurlink DN, Gomes T, Duong-Hua M, Pritchard KI, Austin PC, & Paszat LF. Selective Serotonin Reuptake Inhibitors and Breast Cancer Mortality in Women receiving Tamoxifen: A Population Based Cohort Study. British Medical Journal, 2010; 340: c693.]
Tamoxifen needs to be metabolized (processed) by an enzyme in our body called CYP2D6 in order to make tamoxifen effective at preventing breast cancer. Some SSRIs, such as paroxetine (Paxil) and fluoxetine (Prozac) inhibit CYP2D6, preventing the tamoxifen from being metabolized, so that it is not effective.
While paroxetine and fluoxetine are considered “strong inhibitors,” other SSRIs such as venlafaxine (Effexor), citalopram (Celexa), desvenlafaxine (Pristiq), and mirtazapine (Remeron) 1
only weakly inhibit or do not inhibit CYP2D6. A 2010 study found that venlafaxine (Effexor), citalopram (Celexa), and other SSRIs that moderately inhibit CYP2D6 do not reduce the effectiveness of tamoxifen.5
This study led by Catherine Kelly of Sunnybrook Health Sciences Center and published in the British Medical Journal, examined the survival rates of female breast cancer survivors over the age of 65 who took tamoxifen and an SSRI at the same time. The researchers studied the effects of several SSRIs that have both strong and weak inhibitory effects on CYP2D6. They found that taking paroxetine (Paxil) while on tamoxifen was associated with an increased risk of death from breast cancer and death from any cause. Although they did not find that fluoxetine (Prozac, also a strong inhibitor) was associated with an increased risk of death, the authors believe that this may be because there were not enough women taking fluoxetine in the study.
The researchers also found that the greater overlap of time on tamoxifen and paroxetine was associated with greater risk of death from breast cancer. This association was not seen with any other SSRI. The authors estimated that using paroxetine for 41% of a patient’s time on tamoxifen (the average overlapping time among women in the study) would result in one additional breast cancer death for every 19.7 women treated. If paroxetine was taken for the entire duration of tamoxifen treatment, it would result in one additional death for every 6.9 patients treated.
If you are taking tamoxifen, do not take paroxetine or fluoxetine to treat depression or hot flashes. Remember that the brand name drugs (Paxil and Prozac) are virtually identical to the generic versions of the drugs, so both should be avoided. Ask your doctor about other SSRIs (such as citalopram and venlafaxine) or other types of antidepressants that do not interfere with or weaken the beneficial effects of tamoxifen. Since depression tends to go away over time, you may want to see if you feel equally well without any antidepressant medication.
If you are currently taking tamoxifen and either paroxetine or fluoxetine, do not abruptly stop taking the antidepressant, since this could have a negative impact on your mood. Talk to your doctor as soon as possible about gradually going off the SSRI you are on, or switching to a different antidepressant with no or low inhibition of CYP2D6.
Kelly CM, Juurlink DN, Gomes T, Duong-Hua M, Pritchard KI, Austin PC, & Paszat LF. Selective Serotonin Reuptake Inhibitors and Breast Cancer Mortality in Women receiving Tamoxifen: A Population Based Cohort Study. British Medical Journal, 2010; 340: c693.