The case presents a 52-year-old woman with chronic depression and anxiety, who has failed multiple antidepressant therapies while being treated for breast cancer with tamoxifen, which exacerbated her depressive symptoms. The document discusses the patient’s extensive medication history, mental health diagnosis, and the impact of tamoxifen, suggesting alternative antidepressant options and emphasizing guidelines for hormone therapy in oncology. The patient’s condition reflects the challenges in managing depression alongside cancer treatment, highlighting the need for tailored approaches in treatment based on genomic factors and drug interactions.

1. TAMOXIFEN AND
DEPRESSION
PATIENT CASE
PRESENTATION
LEINA EL-TILIB
1

2. Objectives
• Understand the Patient Profile
• Diagnose and Differentiate
Mental Health Conditions
• Apply NCCN Guidelines in
Oncology
• Analyze and Interpret Clinical
Trial Data
• Formulate Evidence-Based
Recommendations
2

3. Chief Complaint
• “Can you switch me to
something that works?”
• Multiple trials of antidepressents
therapy
• Offered PGX testing and result
interpetation
3

4. Patient HPI
• MA 52 yo white women presenting
with chronic depression and anxiety.
She had been trialed on several
antidepressant therapies in the past -
none of which have reduced her
depression/anxiety.
• Previous antidepressants/anxiolytics:
Paroxetine, Sertraline, Citalopram,
Bupropion, Venlafaxine, Buspirone,
Quetiapine, Aripiprazole, and
Clonazepam
4

5. Patient PMH
• Major Depressive Disorder
(MDD)
• Generalized Anxiety Disorder
(GAD)
• Breast Cancer
• Over Active Bladder (OAB)
• Insomnia
• Obesity
5

6. Family & Social
History
Family Hx
• Mother (living) - HTN, depression, T2DM
• Father (deceased) - HTN, COPD
• Grandmother - breast cancer
Social Hx
• Nicotine smoker >30 years, 1 PPD
• Denies drinking alcohol
• Occational Marijuana Use
6

7. Medication Directions Indication
Fluoxetine 20 mg
capsules
2 capsules once daily depression & anxiety
Tamoxifen 20 mg
tablets
1 tablet once daily
breast cancer
prevention
Oxybutynin 5 mg ER
tablets
1 tablet once daily urge incontinence
Trazadone 50 mg
tablets
1 tablet at bedtime
prn
insomnia
Gabapentin 300 mg
2 capsules once daily
at bedtime
hot flashes
Vitamin D3 25 mcg
tablets
1 tablet once daily vitamin d deficiency
Tylenol 500 mg tablets 2 tablets q4-6h prn knee pain
Medications
7

8. Allergies & ADE
• Patient reports allergy to Bupropion
• experiences urticaria = itchy, red,
raised bumps or welts that appear on
the skin
• Bupropion induced Urticara is common
in patients who have trialed several
antidepressants in the past typically
appearing 1-14 days after initiation. 1
8

9. Depression Anxiety
Mood Disorder: Characterized by
persistent sadness.
• Symptoms:
⚬ Lack of motivation.
⚬ Loss of interest in daily activities.
• Impact on Functioning:
⚬ Affects physical energy.
⚬ Disrupts sleep patterns.
⚬ Impairs cognitive focus.
• Emotional Experiences:
⚬ Feelings of hopelessness.
⚬ Low self-worth.
⚬ In severe cases, thoughts of self-
harm.
Condition: Characterized by excessive worry or
fear.
• Characteristics:
⚬ Often disproportionate to the situation.
⚬ Can interfere with daily life.
• Symptoms:
⚬ Restlessness.
⚬ Rapid heartbeat.
⚬ Difficulty concentrating.
Types of Anxiety Disorders:
• Generalized Anxiety Disorder (GAD): Chronic
worry about various aspects of life.
• Panic Disorder: Recurrent panic attacks and
fear of future attacks.
• Social Anxiety Disorder: Intense fear of
social situations and being judged by others.
9

10. Score Date
11 2/2022
8 5/2022
14 9/2022
8 5/2023
13 5/2024
13 9/2024
MDD
MDD is measured using the PHQ9
Questionnaire.
1

11. GAD
GAD is measured using the GAD7
Questionnaire.
Score Date
7 2/2022
9 5/2022
16 9/2022
11 5/2023
11 5/2024
13 9/2024
1

12. PHQ9 GAD7
Based on patient’s scores sshe would
be characterized as moderate-
moderately severe depression
Based on patient’s scores she would
be characterized as having mild-
moderate anxiety
1

13. Antidepressent Trials
• Citalopram – didn’t work
• Venlafaxine – couldn’t tolerate
• Bupropion – allergy
• Sertraline 100 mg 2 tablets daily – had started
taking in 2009 but d/c bc it “wasn’t working &
caused sexual side effects (decrease in libido) then
switched to Paroxetine?
• Paroxetine ER 12.5 mg, 25 mg, 37.5 mg 1 tablet daily
– When using this medication she reported no SE,
but had to stop due to breastfeeding
• Quetiapine 25 mg 1 tablet at bedtime once daily
• Aripiprazole 2 mg, 5 mg, 10 mg 1 tablet every
morning
• Clonazepam 1 mg ½ tablet three-times daily prn for
severe anxiety
• Buspirone 10 mg 1 tablet q12h (5/2023) switched to
Fluoxetine
1

14. Breast Cancer
FUJI MACHINE
• Patient was diagnosed with breast cancer of the left
tissue. Biopsys found masses >7mm, and 2 adjunct
cysts >7 mm on the left breast.
• Genetics testing found to be ER/PR-positive, HER2-
negative, clinical stage 1A (T1BN0M0)
• Tumor, Nodes, Metatsis staging system
1

15. Breast Cancer
• According to the NCCN Guidelines for Breast Cancer
treatment, patients with this dx are indicated to
receive hormone therapy + radiation after excision of
the mass.6
• STAGE 1 TREATMENT
⚬ SURGERY = LUMPECTOMY
⚬ SYSTEMIC THERAPY
￭ HORMONAL THERAPY
• SERMS OR AROMATASE INHIBITORS
• Since she is permenupausal, aromaste inhibitors are
not recommended without endocrine suppression.
• The recommended hormonal therapy is tamoxifen 20
mg once daily for 5-10 years after excision.
1

16. Tamoxifen Induced
Depression
• Patient was started on Tamoxifen
4/2023. Upon initiation, patient reports
that it had caused disturbances in her
mood afterwards. Stating that her
depression became the worst its ever
been.
• According to LexiComp the percentage
of depression (2% to 12%), fatigue,
mood changes (12% to 18%).2
1

17. Switching Hormonal
Therapy?
• Hormonal therapy selection is based on a
womens age.
• Aromatase Inhibitors are preferred in
postmenopausal patients becuase AI are not as
effective without ovarian suppression. This was
proven by the SOFT & TEXT trials.
• Premenopausal women produce too much
estrogen for AI to be effective.
• Its recommended to manage depressive
symptoms with antidepressents.
1

18. SOFT & TEXT trials
Suppression of Ovarian Function Trial (SOFT) & Tamoxifen and
Exemestane Trials were 2 studies that looked at the 5-year
rates of recurrence of breast cancer in premenopausal women
who received the aromatase inhibitor exemestane plus ovarian
suppression than among those who received tamoxifen plus
ovarian suppression, and tamoxifen alone. Ovarian
suppression was achieved with triptorelin (GnRH agonist) at a
dose of 3.75 mg by intramuscular injection every 28 days,
bilateral oophorectomy, or ovarian irradiation. These trials
where 8 years long.3
1

19. SOFT & TEXT Trial Results
Higher rates of
disease free
reoccurence in
combination (92.1%)
& better results than
tamoxifen as well.
Exemestane +
ovarian supression
Tamoxifen +
ovarian supression
Higher rates of
disease free
reoccurence in
combination (83.2%)
vs. tamoxifen alone
(78.9%).
Patients in the ovarian
supressed group had a much
higher incidence of SE (ie.
hot flashes). The results of
this study concluded that
instead of inducing ovarian
suppression, just reserve AI
for postmenopausal women.
Secondary
Findings

20. Recommendation
• NCCN states that using hormonal
therapy for 5-10 yrs post surgery is
the recommended course of
action.6
• Managing depressive symptoms
should be done using
antidepressents that do not interact
with tamoxifen.
• PGX (subtrate of): MAJOR 2D6, 3A4;
MINOR 2A6, 2B6, 2C9, 2E1; INHIBITS
2C9.2
20

21. Drug 1A2 2C9 2C19 2D6 3A4
Citalopram
- - - + -
Escitalopram
- - - + -
Fluoxetine
- ++ + / ++ +++ ++a
Paroxetine
- - - +++ -
Fluvoxamine
+++ ++ +++ - ++
Sertraline
- + + + / ++ +
Duloxetine
+ - - + -
Venlaxfaxine
- - - + -
SSRI/SNRI
PGX
2

22. PGX Results
GENE PHENOTYPE IMPACT
1A2 NM
normal metabolism
expected
2C9 IM
increased drug
levels
2D6 IM
increased drug
levels
3A4/5 NA
normal
metabolism*
*CYP3A5 is normally not expressed in the general public therefore her
genotype of unexpression is considered normal
22

23. • More research is needed to
concluded whether tamoxifen
can induce depression
• One theory is that since
tamoxifen is working to
modulate estrogen, it might
impact the serotonin pathways
- worsening mood.
Tamoxifen &
Depression
23

24. Tying it all together
To recommend a new antidepressent for
this patient you must consider
• genomics
• DDI with tamoxifen
Some options are:
• mirtazepine - minimal 2D6 metabolism +
sleep benefit
• desvenlafaxine - bypasses the CYP
pathway
• nortriptyline - minimal 2D6 interaction
& for treatment resistent depression
• duloxetine - some 2D6 activity but can
help with vasomotor symptoms (dose
reduction)
24

25. Recommendation
National Institute of Health and Care
Excellence (NICE) switching to a different
antidepressant for patients who have
failed other treatment options.
• desvenlafaxine
⚬ avoids CYP metabolism
• Dosing: 50 mg once daily. In patients
who do not respond after 6 weeks (or 7
days in clinically urgent situations),
may increase to 100 mg once daily.1
24

26. References
1.MicroMedex. Tamoxifen Monograph [Internet]. Micromedexsolutions.com. 2019 [cited 2024
Oct 31]. Available from: https://www.micromedexsolutions.com/home/dispatch
2.Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF, et al. Adjuvant
Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer. New England Journal
of Medicine [Internet]. 2018 Jul 12;379(2):111–21. Available from:
https://www.nejm.org/doi/full/10.1056/NEJMoa1804710
3.Francis PA, Pagani O, Fleming GF, Walley BA, Colleoni M, Láng I, et al. Tailoring Adjuvant
Endocrine Therapy for Premenopausal Breast Cancer. New England Journal of Medicine. 2018
Jul 12;379(2):122–37.
4.Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, et al. Tamoxifen
for Prevention of Breast Cancer: Report of the National Surgical Adjuvant Breast and Bowel
Project P-1 Study. JNCI: Journal of the National Cancer Institute. 1998 Sep 16;90(18):1371–88.
5.Gutierrez N, Malik S, Cohen PR, Winn AE. Bupropion-Associated Delayed Onset Urticaria.
Cureus. 2021 Sep 26;
6.Lee R. DynaMed [Internet]. Dynamed.com. 2024 [cited 2024 Nov 1]. Available from:
https://www.dynamed.com/management/endocrine-therapy-for-early-and-locally-advanced-
breast-cancer
2

27. THANK
YOU
26

28. FYI
Gabapentin &
hotflashes
HRT is cxn in this pt
pop. gaba, venlaf,
∴
clon. are non-
hormonal agents
alternatives. due to
vasomotor activity
Why no chemo?
TAILORx study
found that chemo
had no additional
benefit vx.
hormonal therapy
Men & breast
caner
Breast cancer is
rare in men. 1%
of men are
diagnosised with
it
L-methylfolate
Supplement most
people are deficent
in. Increasing this
can boost mood sx
27