What are Monoamine Oxidase Inhibitors (MAOIs)?

Monoamine Oxidase Inhibitors (MAOIs)

Monoamine oxidase inhibitors (MAOIs) are a class of antidepressant medications that work by inhibiting the enzyme monoamine oxidase, which breaks down neurotransmitters like serotonin, norepinephrine, and dopamine in the brain, thereby increasing their availability and improving mood. 1, 2

Types and Mechanism of Action

• MAOIs inhibit monoamine oxidase, a complex enzyme system widely distributed throughout the body, preventing the oxidative deamination of various monoamines and catecholamines 1, 3
• Common MAOIs include phenelzine, isocarboxazid, moclobemide, isoniazid, and linezolid 4
• MAOIs can be classified as:
  • Irreversible vs. reversible inhibitors 3
  • Selective vs. non-selective (targeting MAO-A, MAO-B, or both) 3
• The exact mechanism by which MAOIs act as antidepressants is not fully understood but is thought to involve elevation of brain levels of biogenic amines 2

Clinical Uses

• MAOIs were among the first licensed pharmacological treatments for depression 5
• Current indications include:
  • Treatment-resistant depression 6
  • Atypical depression with high levels of anxiety 6
  • Anergic bipolar depression 6
  • Some anxiety disorders 4

Safety Concerns and Contraindications

• MAOIs are contraindicated with:
  • Other MAOIs - can cause serotonin syndrome 4
  • SSRIs, SNRIs, TCAs - risk of serotonin syndrome 4
  • Opioids (especially tramadol, meperidine, methadone, fentanyl) 4
  • Stimulants (amphetamines, possibly methylphenidate) 4
  • Certain cough/cold medications (dextromethorphan, chlorpheniramine) 4
  • Certain over-the-counter products (St. John's wort, L-tryptophan, diet pills) 4
  • Illicit drugs (ecstasy, methamphetamine, cocaine, LSD) 4
  • Foods high in tyramine (aged cheeses, aged meats) - can cause hypertensive crisis 3

Serious Adverse Effects

• Serotonin syndrome: characterized by 4

  • Mental status changes (confusion, agitation, anxiety)
  • Neuromuscular hyperactivity (tremors, clonus, hyperreflexia, muscle rigidity)
  • Autonomic hyperactivity (hypertension, tachycardia, arrhythmias, tachypnea)
  • Advanced symptoms: fever, seizures, arrhythmias, unconsciousness, potentially fatal

• Hypertensive crisis: 3

  • Can occur with tyramine-rich foods
  • Results from excessive norepinephrine release
  • Presents with severe headache, hypertension, and potentially stroke

Drug Interactions

• MAOIs have numerous significant drug interactions: 4, 3
  • Combining with other serotonergic medications can cause serotonin syndrome
  • Sympathomimetic drugs (e.g., phenylephrine, oxymetazoline) can cause hypertensive crisis
  • Meperidine is specifically contraindicated with MAOIs 4
  • Concomitant use with SSRIs is absolutely contraindicated 4

Special Considerations

• When switching to or from MAOIs: 3, 5

  • Adequate washout periods are essential (typically 2 weeks, 5 weeks for fluoxetine)
  • Gradual tapering is recommended to avoid withdrawal symptoms

• Dietary restrictions: 3, 7

  • Traditional MAOIs require strict dietary restrictions to avoid tyramine-rich foods
  • As little as 8-10 mg of tyramine can cause dangerous blood pressure elevations in patients on MAOIs
  • Newer formulations like transdermal selegiline may have fewer dietary restrictions 8

Current Place in Treatment Guidelines

• MAOIs are generally recommended as third-, fourth-, or fifth-line treatments due to safety concerns and dietary restrictions 6
• Despite proven efficacy, MAOIs are underused due to safety concerns and the need for dietary restrictions 6, 7
• The availability of newer, safer formulations (like transdermal delivery systems) may increase their clinical utility 8

Patient Education

• Patients on MAOIs must be educated about: 3
  • Required dietary restrictions
  • Avoiding over-the-counter medications without consulting a healthcare provider
  • Informing all healthcare providers about MAOI use
  • Recognizing signs of serotonin syndrome and hypertensive crisis
  • Carrying medical identification indicating MAOI use

Common Pitfalls and Caveats

• Failure to maintain adequate washout periods when switching between MAOIs and other antidepressants 4
• Inadequate patient education about dietary restrictions and drug interactions 3, 7
• Overlooking MAOIs as an option for treatment-resistant depression 6
• Not recognizing early signs of serotonin syndrome or hypertensive crisis 4