Monoamine Oxidase Inhibitor

Aka: Monoamine Oxidase Inhibitor, MAO Inhibitor, MAOI, Moclobemide

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II. Indications

  1. Refractory Major Depression
  2. Anxiety Disorder
  3. Atypical Depression
  4. Refractory Depression
  5. Bulimia
  6. Social Phobia
  7. Narcolepsy
  8. Parkinsonism
  9. Multiple System Atrophy

III. Background

  1. Among the first Antidepressants developed (1950s)

IV. Precautions

  1. Limit use to refractory mental health or neurologic conditions due to high risk of adverse effects and Drug Interactions
  2. Tyramine-free diet must be followed
    1. Continue for two weeks after stopping medication
    2. See Tyramine Containing Foods
  3. Stop 2 weeks before starting another Antidepressant
  4. Taper Phenelzine (Nardil) slowly when stopping
    1. See Antidepressant Withdrawal
    2. Reduce dose by 15 mg/day every 2 weeks (or 10%/week)

V. Mechanism

  1. Inhibits monoamine oxidase
    1. Monoamine Oxidase is the enzyme that breaks down biogenic amines (e.g. Norepinephrine, Serotonin, Dopamine, Tyramine)
      1. Type A Monoamine Oxidase affects Gastrointestinal System (intestinal tract, liver, placenta)
        1. Metabolizes Serotonin and Norepinephrine (as well as Dopamine, tyramine)
      2. Type B Monoamine Oxidase affects Central Nervous System (as well as liver and Platelets)
        1. Metabolizes phenylethylamine, methylhistamine and tryptamine (as well as Dopamine, tyramine)
  2. Most MAO Inhibitors block MAO irreversibly for weeks (only Moclobemide and Safinamide are reversible)
    1. MAO Inhibitors have a similar structure to Amphetamine
    2. Older MAO Inhibitors are nonspecific and affect both Type A and B (e.g. trancypromine, Phenelzine)
    3. Selegiline is specific for Type B and is used in Parkinsonism
  3. MAO Inhibition increases synaptic concentration of monoamines
    1. Serotonin
    2. Norepinephrine
    3. Dopamine
    4. Tyramine
  4. Images
    1. autonomicSynapse.png

VI. Preparations: Non-Selective (Inhibit both MAO-A and MAO-B)

  1. Hydrazine (hepatotoxicity risk)
    1. Isocarboxazid (Marplan): No longer manufactured in U.S.
      1. Dosing: 10 mg PO bid
      2. Maximum: 60 mg per day
    2. Phenelzine (Nardil)
      1. Dosing: 15 mg PO tid
      2. Maximum: 90 mg per day
  2. Non-hydrazine
    1. Tranylcypromine (Parnate)
      1. Dosing: 10-40 mg/day in divided doses
      2. Maximum: 60 mg per day

VII. Preparations: Selective MAO Inhibitors

  1. Selective MAO-A Inhibitors
    1. Moclobemide (reversible MAO Inhibitor)
      1. Major Depression: 150 mg orally twice daily after meals
      2. Maximum dose: 600 mg/day (divided twice daily)
  2. Selective MAO-B Inhibitors (Parkinsonian agents)
    1. Selegiline (Eldepryl, Emsam)
      1. Major Depression: Transdermal patch 6 mg/24 hours (maximum dose 12 mg/24 hours)
      2. Parkinsonism: 5 mg orally twice daily at breakfast and lunch
    2. Rasagiline (Azilect)
      1. Parkinsonism: 0.5 mg orally daily (may be increased to 1 mg orally daily)
    3. Safinamide (Xadago, reversible MAO Inhibitor)
      1. Parkinsonism: 50 mg orally daily (may be increased to 100 mg orally daily after 2 weeks)

VIII. Preparations: Other agents with MAO Inhibitor Activity

  1. Linezolid
  2. St John's Wort
    1. Contains Hypericin and Hyperforin (weak Type A and B MAO Inhibitors)

IX. Complications

  1. Hypertensive Crisis (life-threatening)
    1. Occurs if tyramine or Sympathomimetic exposure
    2. Treat with Phentolamine (alpha-adrenergic Antagonist)
  2. Overdose
    1. Hypotension to cardiovascular collapse
    2. Also presents with Serotonin Syndrome (Agitation, Hallucinations, hyperreflexia, fever, Seizures)
    3. Treat with Intravenous Fluids and direct acting Vasopressors (e.g. Norepinephrine)
  3. Serotonin Syndrome
    1. Occurs with concurrent use of other Serotoninergic drug, or in Overdose

X. Drug Interactions

  1. MAO Inhibitors potentiate Sympathomimetics (Do not use with these medications within 2 weeks)
    1. Tyramine Containing Foods
    2. Sympathomimetics (Ephedra, Ephedrine, pseudophedrine, Phenylephrine)
    3. General Anesthesia
    4. Cyclobenzaprine (Flexeril)
    5. Specific Opioids
      1. Meperidine (Demerol)
      2. Methadone
      3. Tramadol
      4. Dextromethorphan
  2. Serotonergic Medications (Serotonin Syndrome risk)
    1. Selective Serotonin Reuptake Inhibitors (SSRI)
    2. Serotonin Norepinephrine Reuptake Inhibitor
    3. Tricyclic Antidepressant
    4. Atypical Antidepressants (Bupropion, Mirtazapine)
    5. Other Serotonergic Medications (e.g. Tramadol, Meperidine, Methadone, Dextromethorphan, St. John's Wort)

XI. Metabolism

  1. MAO Inhibitors are inactivated by acetylation
    1. Slow acetylators (genetic predisposition) will have elevated serum levels of MAO Inhibitors

XII. Adverse Effects

  1. Anti-Histaminergic effects
    1. Dizziness
    2. Sedation
    3. Orthostatic Hypotension
    4. Weight gain
  2. Dopaminergic effects
    1. Insomnia
    2. Myoclonal jerks
  3. Serotoninergic Effects
    1. Sexual Dysfunction
    2. Headache
  4. Anticholinergic Toxicity
    1. Dry Mouth
    2. Constipation
    3. Blurred Vision
    4. Urinary hesitancy
    5. Nausea
    6. Memory Dysfunction
  5. Other Effects
    1. Peripheral Edema
    2. Weakness
    3. Hepatotoxicity

XIII. References

  1. Sub Laban and Saadabadi (2022) Monoamine Oxidase Inhibitors, StatPearls, Treasure Island
    1. https://www.ncbi.nlm.nih.gov/books/NBK539848/
  2. Nordt and Shoenberger in Herbert (2019) EM:Rap 19(3): 8-9
  3. Olson (2020) Clinical Pharmacology, Medmaster, Miami, p. 36-7

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