What are the treatment options for depression using Monoamine Oxidase Inhibitors (MAOIs)?

Treatment Options for Depression Using Monoamine Oxidase Inhibitors (MAOIs)

Monoamine oxidase inhibitors (MAOIs) are indicated for the treatment of major depressive disorder in adult patients who have not responded adequately to other antidepressants, but they are not recommended as first-line therapy due to safety concerns, drug interactions, and dietary restrictions. 1

Overview of MAOIs in Depression Treatment

• MAOIs were among the first antidepressants developed but are now considered third-, fourth-, or fifth-line treatments due to safety concerns and dietary restrictions 2
• MAOIs have proven efficacy for specific depression subtypes including atypical depression, high anxiety levels, anergic bipolar depression, and treatment-resistant depression 3, 4
• First-generation antidepressants (including MAOIs) are very rarely used because second-generation antidepressants have lower toxicity in overdose with similar efficacy 2

Available MAOI Medications

• Irreversible, non-selective MAOIs:

  • Phenelzine 5
  • Tranylcypromine 1
  • Isocarboxazid 5

• Selective MAOIs:

  • Moclobemide (MAO-A selective, reversible) 5
  • Selegiline (MAO-B selective at lower doses; transdermal formulation has fewer dietary restrictions) 3, 6

Indications and Patient Selection

• MAOIs are specifically indicated for patients who have failed to respond to other antidepressant treatments 1
• Particularly effective for:
  • Atypical depression (characterized by mood reactivity, hypersomnia, increased appetite) 3, 4
  • Depression with high anxiety levels 3, 4
  • Anergic bipolar depression 3, 4
  • Treatment-resistant depression 3, 4

Dosing and Administration

• Tranylcypromine:

  • Starting dose: 30 mg daily in divided doses 1
  • If inadequate response, increase by 10 mg/day every 1-3 weeks
  • Maximum dose: 60 mg/day (30 mg twice daily)
  • More gradual dose increases recommended for patients at risk for hypotension 1

• Gradual discontinuation is recommended to minimize withdrawal effects 1

Safety Considerations and Contraindications

Dietary Restrictions

• Patients must avoid foods high in tyramine content to prevent hypertensive crisis 1, 6
• Transdermal selegiline may require fewer dietary restrictions at lower doses 3, 4

Drug Interactions

• MAOIs are contraindicated with:

  • Other MAOIs 2
  • SSRIs, SNRIs, and tricyclic antidepressants 2
  • Sympathomimetic drugs 2
  • Opioids (especially meperidine) 2
  • Dextromethorphan and other cough/cold medications 2
  • St. John's wort and other serotonergic supplements 2

• A medication-free interval is required when switching to or from MAOIs 1

  • 14 days is typically required when switching from an SSRI to an MAOI 2
  • Fluoxetine requires a 5-week washout period due to its longer half-life 6

Major Risks

• Serotonin syndrome: Potentially life-threatening condition characterized by:

  • Mental status changes (confusion, agitation)
  • Neuromuscular hyperactivity (tremors, clonus, hyperreflexia)
  • Autonomic hyperactivity (hypertension, tachycardia, hyperthermia)
  • Can be fatal if not promptly treated 2

• Hypertensive crisis:

  • Can occur with consumption of tyramine-rich foods or certain medications
  • Symptoms include severe headache, nausea, vomiting, and dangerously elevated blood pressure
  • Can lead to stroke or death if untreated 1, 6

• Suicidal thoughts and behaviors:

  • Increased risk, especially in young adults
  • Close monitoring required, especially during initial treatment and dose changes 1

Common Side Effects

• Dry mouth, dizziness, insomnia, sedation, headache, overexcitement, constipation, blurred vision, and tremor 1
• Orthostatic hypotension 2
• Sexual dysfunction 6

Combination Therapy Considerations

• Combination of MAOIs with other antidepressants is generally contraindicated due to risk of serotonin syndrome 2
• In treatment-resistant cases, some literature supports cautious use of MAOIs in combination with other antidepressants under close supervision by experienced psychiatrists 7
• Such combinations should only be attempted by specialists with extensive experience in managing complex depression cases 7, 6

Monitoring Requirements

• Blood pressure monitoring, especially during initiation and dose changes 1
• Assessment for signs of serotonin syndrome or hypertensive crisis 2
• Monitoring for activation of mania/hypomania in patients with bipolar disorder 1
• Liver function tests as hepatitis and elevated liver enzymes can occur 1

Special Considerations

• MAOIs should be discontinued prior to elective surgery when possible due to risk of interactions with anesthetics 1
• Patient education regarding dietary restrictions, medication interactions, and recognition of adverse effects is essential 6
• Transdermal selegiline may be considered when dietary restrictions are a barrier to MAOI use 3, 4