From the Guidelines
Tamoxifen can cause mood issues in some patients, including depression, anxiety, and emotional lability, due to its effects on estrogen receptors in the brain and neurotransmitter systems involved in mood regulation. This selective estrogen receptor modulator (SERM), commonly prescribed at doses of 20mg daily for breast cancer treatment or prevention, has been associated with mood changes in approximately 10-15% of users 1. These mood changes typically emerge within the first few months of treatment but can occur at any point during therapy, which often continues for 5-10 years.
Key Points to Consider
- The decision to use tamoxifen should be based on a careful consideration of the risks and benefits, including the potential for mood issues 1.
- Women with a history of depression or anxiety may be more susceptible to mood changes while taking tamoxifen.
- If you experience significant mood disturbances while taking tamoxifen, consult your healthcare provider promptly rather than discontinuing the medication on your own.
- Your doctor may recommend supportive strategies like regular exercise, adequate sleep, stress management techniques, or in some cases, antidepressant medication to manage mood issues.
Mechanism of Mood Effects
The mood effects of tamoxifen occur because it blocks estrogen receptors in brain regions that regulate mood and emotion, particularly in the limbic system 1. Estrogen typically has mood-stabilizing effects for many women, so blocking its action can disrupt this balance. Additionally, the hormonal changes induced by tamoxifen can affect neurotransmitter systems involved in mood regulation, including serotonin and dopamine pathways.
Clinical Guidance
The American Society of Clinical Oncology recommends discussing tamoxifen as an option to reduce the risk of invasive breast cancer in premenopausal women who are age 35 years with a 5-year projected absolute breast cancer risk ≥ 1.66% 1. However, tamoxifen is not recommended for use in women with a history of deep vein thrombosis, pulmonary embolus, stroke, transient ischemic attack, or during prolonged immobilization.
From the FDA Drug Label
Other adverse reactions which are seen infrequently are ... depression, dizziness, lightheadedness, headache... Adverse Reactionsn = 104n = 100 ... Depression22 In the NSABP P-1 trial, 15.0% and 9. 7% of participants receiving tamoxifen and placebo therapy, respectively withdrew from the trial for medical reasons... Other Toxicities Mood11.610.8
Tamoxifen and Mood Issues: Tamoxifen can cause mood issues, including depression. The incidence of mood issues, such as depression, is reported in the clinical trials, with 11.6% of women on tamoxifen experiencing mood issues compared to 10.8% on placebo 2.
From the Research
Tamoxifen and Mood Issues
- Tamoxifen, a selective estrogen receptor modulator, has been reported to have both antimanic and depressive effects on mood 3.
- The potential depressive effect of tamoxifen has been repeatedly reported, with 9 cohort studies and 7 case reports describing the onset or exacerbation of depressive episodes 3.
- A study published in the Journal of Clinical Psychopharmacology found that tamoxifen may trigger mood symptoms onset or exacerbation in vulnerable patients, particularly those with a history of mood disorders 3.
- Another study published in The Breast Journal suggested that tamoxifen's antagonist qualities may block the neuroprotective effects of estrogen, leading to down-regulation of neurotransmitters associated with mood regulation, such as serotonin and norepinephrine 4.
Risk of Depression
- A study published in the Journal of the National Cancer Institute found that women in the higher risk depression groups were more likely to experience depressive symptoms, but there was no difference in the proportion of women scoring 16 or higher on the CES-D questionnaire by treatment assignment (tamoxifen versus placebo) 5.
- However, a review of studies published in Frontiers in Neuroendocrinology revealed an overall impairing effect of tamoxifen on cognition in breast cancer patients, hinting at central antiestrogen activity, which may contribute to mood disturbances 6.
Mood Disturbances
- Mood disturbances, including somnolence, anxiety, fatigue, hot flashes, and memory impairment, have been reported among patients receiving tamoxifen as adjuvant therapy 7.
- A case report published in Palliative & Supportive Care described a 56-year-old woman who developed severe mood changes after administration of anastrozole, which resolved after discontinuation of treatment, highlighting the potential for aromatase inhibitors to cause mood disturbances 7.
- The literature suggests that tamoxifen demonstrates promising effects in psychiatric disorders, like bipolar disorder, where its therapeutic action may be independent of interaction with estrogen receptors 6.