MAO Inhibitors for Depression Treatment
MAO inhibitors (MAOIs) are recommended only as third-, fourth-, or fifth-line treatments for depression due to safety concerns, dietary restrictions, and potential for serious drug interactions. 1
Position in Treatment Algorithm
MAOIs have proven efficacy for treating depression, particularly in specific patient populations, but are not recommended as first-line therapy:
- First-line treatments: SSRIs and SNRIs 2
- Second-line treatments: Alternative SSRIs/SNRIs, other antidepressant classes
- Third-line or later: MAOIs 1, 3
Specific Indications for MAOIs
MAOIs may be considered for patients with:
- Treatment-resistant depression (after failure of multiple other antidepressants) 1, 4
- Atypical depression (with hypersomnia, increased appetite, rejection sensitivity) 1
- Depression with high levels of anxiety 1
- Anergic bipolar depression 1
Available MAOIs and Dosing
| Medication | Starting Dose | Target Dose | Maximum Dose |
|---|---|---|---|
| Tranylcypromine | 30 mg daily (divided) | 30-60 mg daily | 60 mg daily [5] |
| Phenelzine | 15 mg 3 times daily | 45-90 mg daily | 90 mg daily |
| Selegiline (transdermal) | 6 mg/24 hours | 6-12 mg/24 hours | 12 mg/24 hours |
When initiating therapy with tranylcypromine, start with 30 mg daily in divided doses. If no adequate response, increase in increments of 10 mg per day every 1-3 weeks to a maximum of 60 mg per day 5.
Major Safety Concerns
1. Hypertensive Crisis
- Can occur with consumption of tyramine-rich foods or beverages 5, 6
- Symptoms include severe headache, neck stiffness, nausea, vomiting, sweating, and elevated blood pressure
- Can lead to intracranial hemorrhage if severe
2. Serotonin Syndrome
- Risk increases with concomitant use of serotonergic medications 7, 5
- Symptoms include agitation, hyperthermia, hyperreflexia, incoordination, and mental status changes
- Can be life-threatening in severe cases
3. Drug Interactions
- Absolute contraindications: Other MAOIs, SSRIs, SNRIs, tricyclic antidepressants, sympathomimetic drugs 7, 5
- Stimulant medications (including over-the-counter decongestants) 7
- Many other medications (see full prescribing information) 5
Dietary Restrictions
Patients must avoid foods and beverages with high tyramine content, including:
- Aged cheeses
- Cured meats
- Fermented foods
- Certain alcoholic beverages (tap beers, red wines)
- Fava beans
- Sauerkraut
- Soy sauce and other fermented soy products
Medication Washout Periods
When switching between antidepressants and MAOIs, strict washout periods are essential:
- From SSRI to MAOI: 2-5 weeks (depending on the SSRI) 7
- From MAOI to other antidepressants: At least 14 days 7
- Between different MAOIs: At least 14 days 7
Monitoring Requirements
- Blood pressure monitoring before and during treatment
- Liver function tests at baseline and periodically during treatment 7
- Assessment for serotonin syndrome symptoms
- Monitoring for psychiatric symptoms, including suicidal thoughts 5
Special Considerations
Transdermal Selegiline
- At lower doses (6 mg/24h), dietary restrictions may not be necessary due to selective MAO-B inhibition 1, 3
- Has fewer side effects than oral MAOIs 3
- May be considered before other MAOIs due to improved safety profile
Anesthesia and Surgery
- If possible, discontinue MAOIs prior to elective surgery due to risk of hypotension or hypertension during anesthesia 5
Discontinuation
- Consider gradual tapering to minimize withdrawal effects 5
- Monitor for withdrawal symptoms and depression recurrence
Combination Therapy
Combination of MAOIs with other antidepressants or stimulants is generally contraindicated due to risk of serotonin syndrome and hypertensive crisis 7, 5. However, in treatment-resistant cases under close specialist supervision, some combinations have been cautiously used 4.
Future Directions
Recent research is exploring MAOIs with improved safety profiles and novel delivery methods that may reduce dietary restrictions and drug interactions 3, 8.
MAOIs remain valuable but underutilized tools in the psychiatrist's armamentarium, particularly for patients who have not responded to multiple other antidepressant trials 1, 3.