Phenelzine
Phenelzine is a potent, non-selective monoamine oxidase inhibitor (MAOI) indicated for the treatment of atypical depression, particularly in patients who have not responded to other antidepressants. It is also effective for certain anxiety disorders, including social anxiety disorder and panic disorder with agoraphobia.
Clinical Overview
Primary Clinical Applications
Phenelzine is indicated for depression that is characterized as atypical, nonendogenous, or neurotic, particularly when patients have not responded to tricyclic antidepressants or other therapies. It shows particular efficacy in depression with anxiety, phobic symptoms, or hypochondriasis.
Mechanism and Clinical Considerations
By irreversibly inhibiting both MAO-A and MAO-B enzymes, phenelzine increases levels of norepinephrine, serotonin, and dopamine. This broad mechanism provides antidepressant and anxiolytic effects but requires strict dietary restrictions and careful drug interaction monitoring.
Specialized Usage Requirements
Due to potentially life-threatening interactions with tyramine-containing foods and numerous medications, phenelzine requires extensive patient education, dietary counseling, and careful monitoring. It is typically reserved for treatment-resistant cases.
Key Clinical Points
Washout of two to five weeks from an SSRI
Longer than the standard fourteen days where the previous drug was fluoxetine, because of norfluoxetine's persistence. Getting this wrong risks serotonin syndrome.
Strict tyramine restriction
Aged cheeses, cured meats, fermented products, broad beans, soy sauce, yeast extracts, and alcoholic beverages including Chianti. Dietary counselling is a prerequisite, not a follow-up item.
Broad cardiovascular contraindications
Congestive heart failure, cardiovascular and cerebrovascular disease, hypertension, phaeochromocytoma, liver disease, and severe renal impairment all rule it out. A history of headache is also listed.
Particular efficacy in atypical depression
Depression with anxiety, phobic symptoms, or hypochondriasis responds notably well, which is why phenelzine retains a place despite the burden of restrictions.
Stop ten days before elective surgery
Interactions with general anaesthetics are dangerous. Meperidine and dextromethorphan are contraindicated outright, and orthostatic hypotension is the most common day-to-day effect.
Prescribing Information
Dosing & Administration
Depression:
- Initial: 15 mg three times daily
- Increase: To 60 mg daily fairly rapidly as tolerated
- Maximum: 90 mg daily
- Maintenance: Reduce to lowest effective dose after response
Elderly:
- Start with lower doses (15 mg daily)
- Increase more gradually
Indications
- Atypical depression
- Depression unresponsive to other treatments
- Off-label: Social anxiety disorder, panic disorder
Contraindications
- Congestive heart failure
- Pheochromocytoma
- Liver disease or abnormal liver function
- Severe renal impairment
- Cerebrovascular disease
- Cardiovascular disease
- Hypertension
- History of headache
Warnings & Precautions
- Hypertensive crisis: Avoid tyramine-containing foods
- Serotonin syndrome: Contraindicated with SSRIs, SNRIs
- Suicidal thoughts: Monitor especially in young adults
- Orthostatic hypotension: Common side effect
- Withdrawal: Discontinue gradually
Drug Interactions
- SSRIs/SNRIs: Contraindicated – 2-5 week washout required
- Sympathomimetics: Risk of hypertensive crisis
- Meperidine: Contraindicated – risk of serotonin syndrome
- Dextromethorphan: Contraindicated
- General anesthetics: Discontinue 10 days before surgery
Dietary Restrictions
- High tyramine foods: Aged cheeses, cured meats, fermented products
- Alcoholic beverages: Beer, wine, especially Chianti
- Other: Broad beans, soy sauce, yeast extracts
Adverse Reactions
Common:
- Orthostatic hypotension, dizziness, headache, drowsiness
Serious:
- Hypertensive crisis, serotonin syndrome, hepatotoxicity
Special Populations
- Pregnancy: Category C – use only if clearly needed
- Elderly: Increased sensitivity to hypotensive effects
- Hepatic impairment: Contraindicated
Frequently Asked Questions
What is Phenelzine used for?
Phenelzine is a potent, non-selective monoamine oxidase inhibitor (MAOI) indicated for the treatment of atypical depression, particularly in patients who have not responded to other antidepressants. It is also effective for certain anxiety disorders, including social anxiety disorder and panic disorder with agoraphobia.
What class of drug is Phenelzine?
Phenelzine is classified as: Monoamine Oxidase Inhibitor (MAOI).
Washout of two to five weeks from an SSRI?
Longer than the standard fourteen days where the previous drug was fluoxetine, because of norfluoxetine's persistence. Getting this wrong risks serotonin syndrome.
Strict tyramine restriction?
Aged cheeses, cured meats, fermented products, broad beans, soy sauce, yeast extracts, and alcoholic beverages including Chianti. Dietary counselling is a prerequisite, not a follow-up item.
Broad cardiovascular contraindications?
Congestive heart failure, cardiovascular and cerebrovascular disease, hypertension, phaeochromocytoma, liver disease, and severe renal impairment all rule it out. A history of headache is also listed.
Particular efficacy in atypical depression?
Depression with anxiety, phobic symptoms, or hypochondriasis responds notably well, which is why phenelzine retains a place despite the burden of restrictions.
Source: FDA prescribing information (DailyMed)