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Toxicity, Monoamine Oxidase Inhibitor

  • Authors: Steven Marcus, MD
  • CME/CE Released: 1/4/2011
  • Valid for credit through: 1/4/2013
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  • Laurie E. Scudder, DNP, NP

    Nurse Planner, Continuing Professional Education Department, Medscape, LLC; Clinical Assistant Professor, School of Nursing and Allied Health, George Washington University, Washington, DC


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Toxicity, Monoamine Oxidase Inhibitor: Clinical




The monoamine oxidase inhibitor (MAOI) agents currently available in the United States include phenelzine sulfate (Nardil), tranylcypromine sulfate (Parnate), isocarboxazid (Marplan), and selegiline (Eldepryl [specific for the MAO-B enzyme]), all of which irreversibly bind to MAO. Reversible inhibitors of MAO are available in Europe (eg, brofaromine, cimoxatone, clorgyline, lazabemide, moclobemide). Substances, such as St. John's wort, that may have MAOI-like activity are frequently used for self-treatment of depression. Methylene blue has also been reported to cause serotonin toxicity because of its possible MAO-A inhibitor activity.[14,15,16,17]

According to recent reviews of the experience with one of the newer selective MAOIs, moclobemide (Aurorix, Manerix), little is expected in the way of symptoms and signs from a simple overdose, except in the circumstance of the co-ingestion of another serotonin-active substance.

For food and drug interactions, the history must include a careful search for potential offending agents, including over-the-counter preparations.

Often, a significant lag or so-called latent period occurs between exposure and manifestation of clinical effects. Often, the initial effects are that of progressively severe catecholamine excess, hyperthermia, tachycardia, sweating, hypertension, and agitation followed after a lag of many hours with hypotension, seizures, and coma.

  • Ingestion of an MAOI can induce a complex array of hypermetabolic signs that include the following:
    • Fever
    • Tachycardia
    • Generalized muscle rigidity
    • Tachypnea
    • Metabolic acidosis
    • Hypoxemia
    • Hypercapnia
  • Acute overdose usually does not produce a hypertensive crisis unless the patient provokes the interaction.
  • Early mild symptoms
    • Irritability
    • Anxiety
    • Flushing
    • Sweating
    • Headache
  • Moderate symptoms
    • Anxiousness
    • Restlessness
    • Fever
  • Severe symptoms
    • Severe fever
    • Seizures
    • Sleepiness


Monoamine oxidase inhibitor (MAOI) overdoses or interactions present with excessive catecholamine stimulation toxidromes. Late in the course, the patient may become hypotensive and comatose. Symptoms can be classified into mild, moderate, and severe.

A peculiar nystagmus has been reported in cases of overdose. Rapid jerking movement of the eyes as if watching a tennis or ping pong match termed "ping pong gaze"[18] or opsoclonus has been reported in severe MAOI intoxication.

  • Mild symptoms
    • Agitation
    • Confusion
    • Flushing
    • Diaphoresis
  • Moderate symptoms
    • Altered mental status
    • Hallucination
    • Fever
    • Diplopia
    • Hypertension, which can be very high and precipitate rhabdomyolysis, myocardial infarction, intracranial hemorrhage, renal failure, and other hypertensive emergency complications
    • Tachycardia
    • Tachypnea
  • Severe symptoms
    • Severe hyperpyrexia
    • Seizures
    • CNS depression
    • Coma
    • Cardiorespiratory depression
    • Malignant hyperthermia
    • Muscle rigidity


Monoamine oxidase inhibitors (MAOIs) may have drug interactions with serotonin reuptake inhibitors, several analgesics (particularly meperidine [Demerol]), and tyramine-containing foods. Any drug that releases catecholamines may precipitate life-threatening events in individuals also using MAOIs.

  • Tyramine-containing foods
    • Aged cheeses
    • Aged, pickled, or smoked meats (eg, salami) or fish (eg, herring)
    • Yeast extracts
    • Beer (dark more than light, on tap more than in bottles because tyramine is adsorbed to glass)
    • Red wine more than white wine
    • Avocado
    • Sauerkraut
    • Ginseng
  • Potential drug interactions
    • Meperidine
    • Dextromethorphan
    • Selective serotonin reuptake inhibitors (SSRIs) – Fluoxetine, paroxetine
    • Sertraline
    • Triptans are serotonin agonist at 5-HT1B/D, thus they should have no or less association with serotonin syndrome.[19] Although using triptans and MAOIs together might increase triptans level due to sharing the same metabolic pathway.[20]
    • All serotonergic agents
    • Linezolid, an antibiotic used to treat certain drug-resistant organisms such as methicillin-resistant Staphylococcus aureus (MRSA), has been determined to be a reversible, nonselective MAOI and has been implicated in acute serotonin syndrome, so it may be a risk.[21]
    • Methylene blue has been reported to be associated with serotonin syndrome.[14,15,16] It has been studied as a potent reversible MAO-A inhibitor.[17]
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