AA is a 66 yo female patient is being seen in the family medicine clinic for treatment of her depression. The patient reports feeling tired all the time, lack of motivation, inability to focus, and her relationship with her husband and friends has become strained. AA informs her provider that 10 years ago she was diagnosed with depression and her physician at the time put her on Zoloft, but she quit taking it after feeling better. The patient reports this has been ongoing for 6 months despite trying over the counter St. John’s Wort which she heard could help with depressive symptoms. The patient was diagnosed with epilepsy 2 years ago and HER2(+)HR(+) Breast cancer.
PMH: Depression, Epilepsy, HER2(+) HR(+) Breast Cancer
Current Medications: Lamictal PO 400 mg ER QD, Tamoxifen 20 mg PO QD, St. John’s Wort Supplement
Her provider wanted to run some potential pharmacotherapy options by you. Which of the following are true regarding selection of an antidepressant for AA? Select all that apply.
A. Wellbutrin may lower the patient’s seizure threshold and would be contraindicated considering her history of epilepsy.
B. Prozac and Paroxetine may increase tamoxifen's concentrations via inhibition of CYP3A4.
C. Mirtazapine would be a potentially good option for this patient if she is seeking weight loss.
D. St. John’s Wort is not considered first line to treat the patient’s depression and is a CYP3A4 inducer.
E. Paxil has significant anticholinergic side effects and should be avoided in the elderly.
Answers with Rationale:
Brand/Generics Covered: Zoloft (Sertraline), Lamictal (Lamotrigine), Wellbutrin (Bupropion), Paxil (Paroxetine), Prozac (Fluoxetine)
Correct Answers: A, D, E
Answer A is correct: Answer choice A is correct because Bupropion is contraindicated in patients with seizure disorders as is listed in the package insert. Bupropion is known to cause a 4-fold increase in incidence of seizures and is not recommended in patients with a history of seizures.
Answer B is incorrect: Prozac and Paroxetine do not inhibit CYP3A4, thus the nature of the interaction does not have to do with CYP3A4. Both Sarafem (used for premenstrual dysphoric disorder but also fluoxetine) and Paroxetine are strong CYP2D6 inhibitors. Tamoxifen is a prodrug, which means it requires CYP2D6 metabolism to be converted to an active metabolite. When used together these drugs will inhibit metabolism of tamoxifen and may actually reduce the therapeutic effect of tamoxifen by inhibiting the conversion of tamoxifen to its active form. Thus caution should be heeded before using tamoxifen with CYP2D6 inhibitors.
Answer C is incorrect. Mirtazapine does not help with weight loss as it actually stimulates appetite. For patients who have loss of appetite due to their depression, Mirtazapine could prove helpful and actually cause weight gain.
Answer D is correct. St. John’s Wort is a CYP3A4 inducer and it is not considered a first line agent to treat depression. It often gets used OTC similar to this patient but due to its potent inducing activity can decrease concentrations of many drugs, including protease inhibitors used in management of HIV.
Answer E is correct. Paxil does have strong anticholinergic effects and is actually listed on the BEERS list with the side effects of “highly anticholinergic, sedating, and can cause orthostatic hypotension.” The BEERS list also recommends avoiding the use of Paxil in the elderly.
Competencies Covered: Area 2: 2.1(Pharmacology, mechanism of action, or therapeutic class), 2.2(Brand/Generic)
Area 3: 3.6(Drug contraindications, allergies, or precautions), 3.7(Adverse drug effects, toxicology, or overdose), 3.8(Drug interactions)
We are now in March so the exam is fast approaching! Spend some time each day reviewing those most difficult topics for you and you will be prepared well for the exam.