Monoamine Oxidase Inhibitor Toxicity in Emergency Medicine Clinical Presentation

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.^{[15, 16, 17, 18]}

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. Literature suggests that a large number of individuals use either over-the-counter products and/or nutritional products, some of which might precipitate serious interactions when taken with MAOIs.^[19]

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. The most common event is the patient's ingestion of a precipitating medication or food, see causes below.
• 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"^[20] 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 is probably the most infamous of medications known to produce significant illness when administered to an individual taking an MAOI. Meperidine produces a release of serotonin precipitating a potentially fatal outcome. Libby Zion was a young woman admitted to a major hospital with abdominal pain. There is a great deal of controversy about the historical information, but the point was made that she had been receiving an MAOI and this was either not known or the interaction was not appreciated by the young house officer caring for her when the house officer ordered meperidine for the patient's abdominal pain, which resulted in severe hyperpyrexia and her eventual death. This case led to the modern emphasis on shorter house officer work hours and greater supervision by more senior physicians.
  • Dextromethorphan
  • Selective serotonin reuptake inhibitors (SSRIs) – Fluoxetine, paroxetine. Tramadol, since it exerts some MAOI-like effects, perhaps some release of serotonin, and some serotonin-reuptake inhibition has been thought to potentially precipitate toxicity and is considered by some a contraindicated medication to use in a patient receiving an MAOI.^[21]
  • Sertraline
  • Triptans are serotonin agonist at 5-HT1B/D, thus they should have no or less association with serotonin syndrome.^[22] Although using triptans and MAOIs together might increase triptans level due to sharing the same metabolic pathway.^[23]
  • 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.^[24]
  • Methylene blue has been reported to be associated with serotonin syndrome.^{[15, 16, 17]} It has been studied as a potent reversible MAO-A inhibitor.^[18]