Question

Clinical Pearl- Although the selective serotonin reuptake inhibitors are a pharmacological class, they are not a chemical class. Failure to respond to one SSRI does not reliably predict failure to respond to others.

A 47yr old woman presents to her primary care physician with a chief complaint of fatigue. She indicates that she was promoted to senior manager in her company approximately 11 months earlier. Although her promotion was welcome and came with a sizable raise in pay, it resulted in her having to move away from an office and group of colleagues she very much enjoyed. In addition, her level of responsibility increased dramatically. The patient reports that for the last 7 weeks, she has been waking up at 3am every night and been unable to go back to sleep. She dreads the day and the stresses of the workplace. As a consequence, she is not eating as well as she might and has dropped 7% of her body weight in the last 3 months. She also reports being so stressed that she breaks down crying in the office occasionally and has been calling in sick frequently. When she comes home, she finds she is less motivated to attend to chores around the house and has no motivation, interest, or energy to pursue recreational activities that she once enjoyed such as hiking. She describes herself as “chronically miserable and worried all the time.” Her medical history is notable for chronic neck pain from a motor vehicle accident for which she is being treated with tramadol and meperidine. In addition, she is on hydrochlorothiazide and propranolol for hypertension. The patient has a history of one depressive episode after a divorce that was treated successfully with fluoxetine. Medical workup including complete blood cell count, thyroid function tests, and a chemistry panel reveals no abnormalities. She is started on fluoxetine for a presumed major depressive episode and referred for cognitive behavioral psychotherapy.

1. What CYP450 and pharmacodynamic interactions might be associated with fluoxetine use in this patient and why? Hint: Use this drug interaction tool https://www.rxlist.com/drug-interaction- checker.htm (Hint: pg 129 in Lippincott. drugs-drug interactions to consider- tramadol, meperidine, hydrochlorothiazide, propranolol) Sheesh!!!

2. What class of antidepressants would be contraindicated in this patient and why? (list of other Antidepressant classes are in the Antidepressant powerpoint slides and on pg.128 in Lippincott)

3. Compare other antidepressants with SSRIs with regard to adverse effects and relative advantages and disadvantages. (other classes listed in the Antidepressant powerpoint and on pg.128 in Lippincott)

4. MAOIs are associated with two classes of serious drug interactions, explain one of them? Extra star if you can identify and explain both!

Answer 1

a) fluoxetine inhibit CYP3A4 so elevates plasma level of beta blockers. As she is elderly female., she had poor complaints, she is given with fluoxetine. It is along acting drug

b) As she had hypertension Tricyclic antidepressant are contraindicated. Other antidepressant are SNRI, atypical antidepressant, MAOI

c) TCA

Frequent anticolinergic effects

Cardiovascular side effects

Neurological side effects

Low safety margin

Patient respond incompletely

SSRI

no anticolinergic effects

No cardiovascular side effects

No neurological side effects

High safety margin

Patient respond completely

Some patients does not respond to SSRI respond to TCA

d) when reserpine, guanethidine, tricyclic antidepressant are given along with MAOI leads to excitement, increase in Bp, increase in tempeature due to to their initial NA releasing or uptake blocking effect