What are the uses, contraindications, and drug interactions of Monoamine Oxidase Inhibitors (MAOIs)?

Monoamine Oxidase Inhibitors (MAOIs): Uses, Contraindications, and Drug Interactions

MAOIs are effective for treatment-resistant depression and certain anxiety disorders but require strict adherence to dietary restrictions and medication precautions due to potentially life-threatening interactions with numerous drugs and foods. 1, 2

Clinical Uses

• MAOIs are indicated for treatment-resistant depression that has failed to respond to first-line antidepressants, particularly depression with atypical features 1, 3
• They are also used in the management of certain anxiety disorders with high anxiety levels 1, 4
• Specific MAOIs include tranylcypromine, phenelzine, isocarboxazid, and selegiline 1, 5
• MAOIs work by inhibiting the monoamine oxidase enzyme, preventing the breakdown of neurotransmitters like serotonin, norepinephrine, and dopamine 6, 3

Absolute Contraindications

• Concurrent use with other MAOIs 2, 5
• Concurrent use with SSRIs, SNRIs, or tricyclic antidepressants 1, 2
• Concurrent use with opioids, especially meperidine, tramadol, methadone, and fentanyl 1, 2
• Concurrent use with sympathomimetics (including amphetamines and cold medications containing pseudoephedrine, phenylephrine, or ephedrine) 2, 5
• Concurrent use with dextromethorphan 2, 6
• Cerebrovascular disease, cardiovascular disease, or hypertension 5
• Pheochromocytoma 5
• Liver disease or abnormal liver function tests 5
• Severe renal impairment 5

Drug Interactions

Medications that can cause Serotonin Syndrome when combined with MAOIs:

• All antidepressants including SSRIs, SNRIs, TCAs, bupropion, mirtazapine, trazodone, and vilazodone 2, 5
• Triptans 2
• Tramadol and other opioids 1, 2
• St. John's Wort and L-tryptophan supplements 7, 6
• Dextromethorphan and certain antihistamines like chlorpheniramine 6

Medications that can cause Hypertensive Crisis when combined with MAOIs:

• Sympathomimetics including amphetamines and stimulants 2, 5
• Decongestants containing pseudoephedrine, phenylephrine, or ephedrine 2, 6
• Levodopa and dopamine 2
• Certain illicit drugs including MDMA (ecstasy), cocaine, and methamphetamine 7, 6

Required Washout Periods

• When switching from an SSRI to an MAOI: minimum 2 weeks (5 weeks for fluoxetine due to its long half-life) 1, 2
• When switching from an MAOI to another antidepressant: minimum 1 week 2, 5
• When switching between different MAOIs: minimum 1 week 5

Dietary Restrictions

• Patients must avoid foods with high tyramine content, which can precipitate hypertensive crisis 2, 6
• Foods to avoid include:
  • Aged cheeses 2, 8
  • Aged, fermented, or smoked meats (salami, pepperoni, etc.) 2
  • Pickled herring and improperly stored fish or meat 2
  • Broad bean pods (fava beans) 2
  • Tap beer and unpasteurized beer 2, 8
  • Concentrated yeast extracts, sauerkraut, and some soybean products 2

Common Pitfalls and Practical Considerations

• Failure to maintain adequate washout periods when switching between MAOIs and other antidepressants can lead to serotonin syndrome 1, 2
• Overlooking over-the-counter medications that may contain contraindicated ingredients (e.g., cold medicines with pseudoephedrine or dextromethorphan) 7, 6
• Not informing all healthcare providers about MAOI use, which can lead to inadvertent prescription of contraindicated medications 6
• Inadequate patient education about dietary restrictions and recognition of hypertensive crisis symptoms 6, 8
• Gradual tapering is essential when discontinuing MAOIs to avoid withdrawal symptoms 1, 2

Monitoring and Safety

• Monitor for signs of serotonin syndrome: mental status changes, neuromuscular hyperactivity, and autonomic instability 7
• Watch for symptoms of hypertensive crisis: severe headache, neck stiffness, nausea, vomiting, sweating, and elevated blood pressure 6, 8
• If serotonin syndrome or hypertensive crisis is suspected, immediately discontinue the MAOI and seek emergency medical attention 7
• Consider starting with lower doses when initiating MAOI therapy and increase gradually 7, 4

Despite their effectiveness for treatment-resistant depression, MAOIs are underutilized due to concerns about their safety profile. However, with proper education, monitoring, and adherence to dietary and medication restrictions, they can be valuable treatment options for patients who have failed other therapies 9, 4.