Question 1

A 58-year-old man on phenelzine for treatment-resistant depression presents to the emergency department with sudden severe occipital headache, blood pressure of 220/130 mmHg, diaphoresis, and tachycardia. He reports eating at a wine and cheese reception two hours ago. What is the most likely diagnosis and most appropriate acute pharmacological treatment?

Accepted Answer

This is a classic tyramine crisis. The patient on an MAOI ingested aged cheese (and likely wine), both high in tyramine. With intestinal MAO-A inhibited, tyramine entered the systemic circulation, entered noradrenergic nerve terminals, and caused massive norepinephrine release — producing severe hypertension, headache, and diaphoresis. The treatment is phentolamine, an alpha-adrenergic blocker that directly counteracts the norepinephrine surge. This is not serotonin syndrome (no clonus, hyperreflexia, or altered mental status suggesting serotonergic excess) and not a panic attack (blood pressure of 220/130 is not a panic attack). Phenoxybenzamine (answer C) is used for pheochromocytoma but is a long-acting agent not ideal for acute crisis management.

Question 2

A psychiatrist plans to switch a patient from fluoxetine 40mg daily to phenelzine for treatment-resistant depression. Fluoxetine is discontinued today. What is the minimum washout period before phenelzine can be safely started?

Accepted Answer

Fluoxetine is unique among SSRIs because its active metabolite, norfluoxetine, has a half-life of 4 to 16 days. Even after fluoxetine itself is cleared, norfluoxetine persists at pharmacologically active concentrations for weeks. The standard two-week washout that applies to other SSRIs is dangerously insufficient for fluoxetine. Five weeks is the established minimum to ensure norfluoxetine levels have fallen low enough to safely introduce an MAOI without risking serotonin syndrome. This is one of the most commonly tested drug interaction facts on psychiatry board exams, and getting it wrong in practice can be fatal.

Question 3

A 45-year-old woman with treatment-resistant depression is started on selegiline transdermal patch at 6mg/24hr. She asks whether she needs to follow the dietary restrictions she has read about for MAOIs. What is the correct guidance?

Accepted Answer

The selegiline transdermal patch at 6mg/24hr is the only MAOI that does not require dietary restrictions. By bypassing the GI tract, it reaches the brain while leaving intestinal MAO-A largely intact to metabolize dietary tyramine. However, this applies only at the 6mg dose. At 9mg and 12mg, systemic levels are high enough to inhibit intestinal MAO-A, and full dietary restrictions apply. Critically, the serotonergic drug interactions remain contraindicated at all doses — the patch eliminates the food restriction problem but not the drug interaction problem. Answer B is a dangerous oversimplification.

Monoamine Oxidase Inhibitors (MAOIs)

Side Effects Worth Knowing

Hypertensive crisis (tyramine reaction)

Serotonin syndrome (with serotonergic drugs)

Orthostatic hypotension

Weight gain

Sexual dysfunction

Insomnia

Peripheral edema

Hepatotoxicity (phenelzine)

References & Further Reading