What are examples of Monoamine Oxidase Inhibitors (MAOIs) for a patient with treatment-resistant depression?

Examples of Monoamine Oxidase Inhibitors (MAOIs)

The MAOIs available for treating depression include phenelzine, tranylcypromine, isocarboxazid, selegiline (including transdermal formulation), and moclobemide (selective and reversible MAO-A inhibitor). 1, 2, 3, 4

Traditional (Irreversible, Non-Selective) MAOIs

• Phenelzine is a classic irreversible MAOI used for treatment-resistant depression, atypical depression, and anxiety disorders 1, 3, 4
• Tranylcypromine is another irreversible MAOI indicated for treatment-resistant depression and should be considered before electroconvulsive therapy 2, 3, 4
• Isocarboxazid is the third classic irreversible MAOI with similar indications to phenelzine and tranylcypromine 1, 3, 4

Selective MAOIs

• Selegiline is a selective MAO-B inhibitor available in both oral and transdermal formulations, with the transdermal form requiring fewer dietary restrictions 5, 6, 7
• Moclobemide is a selective and reversible MAO-A inhibitor that does not require strict dietary tyramine restrictions and is better tolerated than traditional MAOIs 4, 7

Other Medications with MAOI Activity

• Linezolid is an antibiotic with MAOI properties that carries risk of serotonin syndrome when combined with serotonergic agents 1, 2

Clinical Context for Use

MAOIs are recommended as third- to fifth-line treatments in current guidelines due to safety concerns, but should be considered earlier in specific populations. 1, 5, 6

Preferred Patient Populations:

• Patients with treatment-resistant depression who have failed multiple other antidepressants 1, 5, 3
• Those with atypical depression (characterized by mood reactivity, increased appetite, hypersomnia, leaden paralysis) 5, 6, 4
• Patients with high levels of anxiety or panic disorder with agoraphobia 1, 5, 6
• Those with anergic bipolar depression 5, 6, 4

When to Consider MAOIs:

• Before proceeding to electroconvulsive therapy in treatment-resistant cases 3
• In selected cases, MAOIs may be considered earlier than traditionally recommended and should not be regarded as drugs of last resort 3

Critical Safety Considerations

Absolute Contraindications:

• Concomitant use with other MAOIs, SSRIs, SNRIs, or tricyclic antidepressants due to serotonin syndrome risk 8, 1, 2
• Stimulants (amphetamines, methylphenidate) due to hypertensive crisis risk 8, 1
• Sympathomimetic decongestants (pseudoephedrine, phenylephrine) due to hypertensive crisis risk 1
• Dextromethorphan (cough suppressant) due to serotonin syndrome risk 1
• Meperidine and other opioids (tramadol, methadone, fentanyl) due to serotonin syndrome risk 1, 2

Required Washout Periods:

• At least 2 weeks must elapse after stopping an MAOI before starting SSRIs, SNRIs, stimulants, or other contraindicated medications 1
• 5 weeks must elapse after stopping fluoxetine before starting an MAOI 1
• At least 2 weeks must elapse after stopping other antidepressants before starting an MAOI 1

Dietary Restrictions:

• Patients must avoid foods and beverages with high tyramine content while taking traditional MAOIs and for 2 weeks after discontinuation to prevent hypertensive crisis 2, 4
• The transdermal selegiline formulation requires fewer dietary restrictions compared to traditional MAOIs 5, 6
• Moclobemide (selective MAO-A inhibitor) is largely free from tyramine interaction risk 4, 7

Hypertensive Crisis Warning Signs:

• Occipital headache (may radiate frontally), palpitations, neck stiffness, nausea, vomiting, sweating, dilated pupils, photophobia 2
• Severe hypertension (>180/120 mm Hg) with organ dysfunction requires immediate blood pressure reduction 2
• Discontinue MAOI immediately if hypertensive crisis symptoms occur 2

Serotonin Syndrome Manifestations:

• Mental status changes (agitation, hallucinations, delirium, coma), autonomic instability (tachycardia, labile blood pressure, hyperthermia), neuromuscular symptoms (tremor, rigidity, myoclonus, hyperreflexia) 2
• Fatal outcomes have been reported with MAOI-induced serotonin syndrome 2

Common Pitfalls to Avoid

• Failure to maintain adequate washout periods when switching between MAOIs and other antidepressants is the most common cause of preventable adverse events 1
• Patients must be explicitly warned to avoid all over-the-counter cold/allergy medications containing sympathomimetics without consulting their provider 1
• All healthcare providers (including dentists, surgeons, emergency physicians) must be informed of MAOI use before prescribing any medications 1
• Do not rely solely on blood pressure readings; patients must also be observed for other signs and symptoms of hypertensive crisis 2