What is the major side effect of Monoamine Oxidase Inhibitors (MAOIs)?

Major Side Effects of MAOIs

The major side effect of Monoamine Oxidase Inhibitors (MAOIs) is potentially fatal hypertensive crisis, which occurs when these medications interact with foods containing tyramine or with certain medications, including SSRIs, tricyclic antidepressants, and tramadol. 1

Hypertensive Crisis and Serotonin Syndrome

MAOIs inhibit the enzyme monoamine oxidase, which normally breaks down neurotransmitters like serotonin, norepinephrine, and dopamine. This inhibition leads to two primary dangerous interactions:

1. Tyramine-Induced Hypertensive Crisis:

   • When MAOIs inhibit MAO-A, the body loses its ability to metabolize tyramine from foods
   • As little as 8-10 mg of tyramine can trigger dangerous blood pressure elevations 2
   • Symptoms include severe headache, neck stiffness, sweating, nausea, vomiting, and markedly elevated blood pressure
   • Can lead to intracranial hemorrhage and death if severe

2. Serotonin Syndrome:

   • Occurs when MAOIs are combined with other serotonergic medications
   • Characterized by mental status changes (confusion, agitation), neuromuscular hyperactivity (tremors, hyperreflexia), and autonomic instability (hypertension, tachycardia) 1
   • Advanced symptoms include fever, seizures, arrhythmias, and unconsciousness
   • Can be fatal if not promptly treated

Other Common Side Effects

Beyond these life-threatening reactions, MAOIs cause several other significant side effects:

• Hypotension: Particularly postural hypotension, which may result in syncope 3
• Insomnia: One of the most frequently reported side effects 4
• Sexual dysfunction: Common with both phenelzine and tranylcypromine 4
• Weight gain/edema: Reported in multiple studies 4
• Hepatotoxicity: Hepatitis and elevated liver enzymes have been reported 3
• Discontinuation syndrome: Abrupt discontinuation can cause dizziness, nausea, headache, irritability, and other symptoms 3

Medication and Food Interactions

MAOIs have extensive interaction profiles:

• Contraindicated medications:

  • Other MAOIs (including linezolid)
  • Serotonergic drugs (SSRIs, SNRIs, TCAs)
  • Sympathomimetic drugs (decongestants with phenylephrine)
  • Opioids (especially meperidine, tramadol, methadone)
  • Certain OTC medications (dextromethorphan, chlorpheniramine) 1, 2

• Foods to avoid:

  • Aged cheeses
  • Cured or smoked meats
  • Fermented foods
  • Certain alcoholic beverages
  • Foods high in tyramine 5

Clinical Implications and Management

1. Patient education is critical regarding:

   • Dietary restrictions
   • Medication interactions
   • Recognition of hypertensive crisis symptoms

2. Monitoring:

   • Blood pressure (especially when initiating therapy)
   • Liver function tests
   • Signs of serotonin syndrome when adding new medications

3. Discontinuation:

   • Gradual tapering to avoid withdrawal symptoms
   • MAO inhibition may persist up to 10 days after discontinuation 3

4. Emergency treatment of hypertensive crisis:

   • Alpha-blockade is the primary treatment 6
   • Hospital-based supportive care

MAOIs remain valuable medications for treatment-resistant depression and certain anxiety disorders, but their significant side effect profile and interaction potential require careful patient selection, thorough education, and close monitoring.