NAPLEX Question of the Week: Antidepressants

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JF is a 65 year old female who two months ago lost her husband due to lung cancer. His PMH is significant for hypertension, hyperlipidemia, and allergic rhinitis for which she takes lisinopril 20mg daily, rosuvastatin 20mg daily, and clarinex 5mg once daily. Her vitals today in clinic are BP 135/80, HR 70, T 98.8 F, RR 12. She reports to her PCM a 6-week history of nightly insomnia, lack of energy, inability to concentrate at her job, a 10 pound weight loss, and overall feeling fatigued.  Her primary care provider is considering prescribing fluoxetine for what is consistent with a major depressive disorder. Which of the following are true regarding fluoxetine therapy for JF? Select all that apply.

A. While paroxetine may benefit some symptoms within the first two weeks, maximal benefit often takes up to 4-6 weeks to occur.

B. While no SSRI should be stopped abruptly due to risk of discontinuation side effects, fluoxetine likely has the least risk among SSRIs due to the long half-life of its metabolite, norfluoxetine.

C. The most common adverse effects in the initiation phase are gastrointestinal (nausea/vomiting/abdominal discomfort).

D. Fluoxetine may inhibit metabolism of medication substrates that pass through CYP 2D6.

E. Fluoxetine when used with NSAIDs, aspirin, warfarin, or direct oral anticoagulants may increase the risk of bleeding.

Answer with Rationale:

All answers are correct. SSRIs are one of the most prescribed medications in the United States, primarily for depression. While intended in most patients to be given for a short time, often they are given for much longer. JF due to the death of her husband hopefully can be given a short course and then taper off in 6-9 months. Answers A, B, and C are very important for patients to understand and know as these could lead to nonadherence. While fluoxetine's risk of discontinuation syndrome is lower than other SSRIs, it is not zero.  While GI side effects can happen when initiated, they often abate quickly with continued therapy. Medications such as risperidone, metoprolol, or tamoxifen, that are CYP 2D6 substrates, may be affected by coadministration with fluoxetine (answer D). Another commonly used SSRI, paroxetine,  also possesses significant 2D6 inhibition properties. Any SSRI may increase the risk of bleeding when given with an agent that can cause bleeding on its own (answer E).

A full chapter on depression can be found in our newly released NAPLEX Review Guide 4th edition found here:

Congrats to all who have passed the examination! For those about to take the exam, good luck!

Dr. Bland

Christopher M. Bland

Clinical Professor, University of Georgia College of Pharmacy

Dr. Christopher M. Bland is a Clinical Professor at the University of Georgia College of Pharmacy at the Southeast GA campus in Savannah, GA. Dr. Bland has over 20 years of academic and clinical experience in a number of clinical areas. He is a Fellow of both the Infectious Diseases Society of America as well as the American College of Clinical Pharmacy. He is co-founder of the Southeastern Research Group Endeavor, SERGE-45, with over 80 practitioners across 14 states involved. Dr. Bland serves as Associate Editor for the NAPLEX Review Guide 4th edition as well as Editor-In-Chief for the Question of the Week. He has provided live, interactive reviews for more than 10 Colleges/Schools of Pharmacy over the course of his career.