Phenelzine Side Effects: What to Expect and When to Call Your Doctor

Phenelzine (Nardil) has a distinct side effect profile compared to SSRIs and other modern antidepressants. Many patients tolerate it well when they understand what to expect — and when to take symptoms seriously. Here's a comprehensive, plain-language guide to phenelzine side effects in 2026.

The Boxed Warning: What You Must Know First

Like all antidepressants, phenelzine carries an FDA boxed warning — the strongest safety warning required. It states that antidepressants, including phenelzine, can increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (ages 18–24) with major depressive disorder and other psychiatric conditions. Phenelzine is not FDA-approved for use in children under 16.

If you or someone you know is having thoughts of self-harm, call 988 (Suicide and Crisis Lifeline) or go to the nearest emergency room.

Common Side Effects of Phenelzine

These are the most frequently reported side effects. Many improve over the first few weeks of treatment:

Sedation and drowsiness: Among the most common complaints, especially early in treatment. Often improves with time. Taking the largest dose in the evening can help.

Weight gain: One of the most significant tolerability issues with phenelzine. Unlike tranylcypromine, phenelzine (a hydrazine MAOI) is associated with notable weight gain in many patients.

Sexual dysfunction: Delayed orgasm and impotence are common. This may be dose-dependent; discuss with your prescriber if it's a significant concern.

Orthostatic hypotension: Dizziness when standing up (postural hypotension). Rise slowly from sitting or lying positions. Blood pressure usually returns to normal if phenelzine is reduced or stopped.

Dry mouth: Stay hydrated and consider sugar-free gum or lozenges.

Constipation: Increase fiber and water intake. Discuss with your prescriber if severe.

Muscle stiffness: Especially in legs. Usually mild and manageable.

Insomnia: Avoid taking phenelzine late in the day. Discuss sleep aids with your prescriber if needed.

Blurred vision: Usually mild. Contact your prescriber if significant.

Serious Side Effects: Call Your Doctor

Elevated blood pressure: Phenelzine can raise blood pressure even without dietary violations. Monitor your BP regularly. Contact your prescriber if you notice a persistent increase.

Mania or hypomania: If you have bipolar disorder, phenelzine may trigger manic episodes. Call your doctor immediately if you notice sudden elevated mood, decreased sleep need, racing thoughts, or impulsive behavior.

Liver damage: Phenelzine (as a hydrazine compound) carries a risk of hepatotoxicity. Report any yellowing of skin or eyes, dark urine, or upper abdominal pain immediately.

Vitamin B6 (pyridoxine) deficiency: Phenelzine can deplete pyridoxine, causing peripheral neuropathy (tingling, numbness in hands and feet). Your prescriber may recommend B6 supplementation.

Emergency Side Effects: Call 911 or Go to the ER

Hypertensive crisis: Severe, sudden headache (especially at the back of the head), stiff neck, nausea/vomiting, chest pain, sweating, and dilated pupils. This is a medical emergency. Call 911 immediately.

Serotonin syndrome: Agitation, confusion, rapid heart rate, high blood pressure, dilated pupils, muscle twitching or rigidity, fever. Usually occurs if phenelzine is combined with serotonergic drugs. This is a life-threatening emergency.

The Tyramine Connection: Why Diet Matters

Phenelzine blocks the enzyme that normally breaks down tyramine in food. Eating high-tyramine foods while on phenelzine can trigger a dangerous spike in blood pressure (hypertensive crisis). Foods to strictly avoid include: aged cheeses, fermented meats (salami, pepperoni), tap or draft beer, soy sauce, fava beans, and yeast extracts (like Marmite).

For a complete list of drug and food interactions, see our guide to phenelzine drug interactions. And if you're having trouble filling your prescription, medfinder can help you find a pharmacy with it in stock.