# A 38-year-old patient with refractory major depression has been taking fluoxetine 20 mg PO daily for 4 weeks but reports no improvement. The prescriber plans to transition to tranylcypromine. Which patient teaching reflects safe transition?

> source: MyMerci (mymerci.kr)  
> url: https://mymerci.kr/pages/nclex_q.php?qn_id=375261&lang=en  
> language: en  
> subject: Medical Emergencies  
> category: PA

## Question

A 38-year-old patient with refractory major depression has been taking fluoxetine 20 mg PO daily for 4 weeks but reports no improvement. The prescriber plans to transition to tranylcypromine. Which patient teaching reflects safe transition?

## Option

1. No washout is required because MAOIs are well tolerated when combined with SSRIs.
2. Stop fluoxetine in the morning and start tranylcypromine the same evening to avoid a depressive gap.
3. Take fluoxetine and tranylcypromine together for 1 week to bridge the medication change.
4. Stop fluoxetine and wait at least 5 weeks before starting tranylcypromine, then begin a tyramine-restricted diet on day 1 of the MAOI. **✔ Correct answer**

**Correct answer: 4**

## Explanation

Combining a serotonergic SSRI with a MAOI causes serotonin syndrome — a potentially fatal triad of mental status change, autonomic instability, and neuromuscular hyperactivity. The standard rule before starting a MAOI is 14 days off most antidepressants, but 5 weeks (≥35 days) off fluoxetine because of its long-acting active metabolite norfluoxetine (half-life 7–15 days). When the MAOI is started, the patient also begins the tyramine-restricted diet (no aged cheese, cured meats, fermented soy, draft beer, red wine, fava beans, etc.), avoids sympathomimetic OTCs, and carries a MAOI wallet card. Same-day, overlap, or no-washout strategies all create a dangerous serotonergic stack.

## In-depth explanation

Other MAOI washout: 14 days from sertraline, paroxetine, escitalopram, citalopram, venlafaxine, duloxetine, TCAs; 5 weeks from fluoxetine; 24 hours from SSRIs to most other antidepressants is NOT enough when transitioning to a MAOI.

## Clinical scenario

Scenario 38-year-old, refractory MDD, on fluoxetine 20 mg PO daily for 4 weeks with no symptomatic response. Prescriber plans to switch to tranylcypromine. No SI/HI today, no medical contraindications, normal LFTs and BP, and willing to follow dietary restrictions. Other meds: oral contraceptive, multivitamin. No OTC decongestants.

## Key concepts

- **MAOI washout periods** — Standard 14-day washout between most antidepressants and a MAOI in either direction. Exception: fluoxetine requires 5 weeks before starting a MAOI because norfluoxetine has a half-life of 7–15 days.
- **Serotonin syndrome** — Triad of mental status change, autonomic instability, and neuromuscular hyperactivity (clonus, hyperreflexia, tremor) caused by stacking serotonergic agents (SSRI/SNRI/TCA + MAOI/tramadol/triptan/St. John wort/linezolid). Treatment: stop offending drugs, supportive care, cyproheptadine in severe cases.
- **MAOI patient education** — Tyramine-restricted diet from day 1 of MAOI therapy, MAOI wallet card with emergency drug list, avoid OTC sympathomimetics (pseudoephedrine, phenylephrine), no meperidine or dextromethorphan, sit/stand slowly for orthostatic hypotension, report severe headache or chest pain immediately.

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