Pediatric Monoamine Oxidase Inhibitor Toxicity Clinical Presentation

Monoamine oxidase inhibitors (MAOIs) are not typically prescribed to children; they are prescribed to adults in a household. Therefore, as in all suspected pediatric ingestions, inquiring about all drugs in the home and evaluating each as a possible cause of the child’s presentation is essential.

MAOIs may not produce symptoms for as long as 24 hours after an acute overdose. Symptoms can be attributed to various physiologic derangements, as follows:

• Symptoms related to a hyperadrenergic state

  • Dizziness
  • Headache
  • Agitation
  • Blurry vision
  • Shortness of breath
  • Chest pain
• Symptoms related to serotonin excess

  • Altered mentation (confusion, anxiety, agitation)
  • Fever
  • Muscle cramps or rigidity
  • Hallucinations
  • Anxiety
  • Agitation
  • Diaphoresis
  • Diarrhea
• Symptoms related to cardiovascular compromise (usually delayed)

  • Pallor
  • Syncope or presyncope
• Weakness

Signs of MAOI overdoses depend on the quantity ingested, the time elapsed since the ingestion, and the presence of co-ingestions.

• Cardiac system

  • Hypertension due to a hyperadrenergic state may be observed early. It may be transient and should not be aggressively treated unless the patient is symptomatic.
  • Orthostatic hypotension and frank hypotension can occur later.
  • Tachycardia is usually present. Arrhythmias are relatively uncommon unless a co-ingestion is involved.
• Pulmonary system - Pulmonary edema (late finding)
• Autonomic findings

  • Hyperpyrexia
  • Mydriasis
  • Diaphoresis
  • Flushing
• CNS

  • Agitation
  • Hyperreflexia
  • Muscular rigidity
  • Tremors/muscle spasms
  • Seizures
  • Coma

Signs and symptoms depend on the time of presentation and whether a co-ingestion occurred. The mechanisms for MAOI-related toxicity can be divided into those related to MAOI overdose alone and those related to MAOI interactions with other substances.

• The adverse effects related to an MAOI overdose alone can be divided into 4 phases.

  • Phase 1 is a period of latency that lasts approximately 6-12 hours. The delayed appearance of signs and symptoms is thought to be related to the gradual accumulation of norepinephrine and serotonin.
  • Phase 2 is characterized by a catecholamine surge that causes sympathetic and CNS excitation.
  • In phase 3, hypotension and CNS depression occur.
  • Phase 4 involves secondary complications such as rhabdomyolysis, renal failure, pulmonary edema, myocardial infarction, and disseminated intravascular coagulopathy.
• Reactions caused by the interactions of MAOIs with other drugs and foods can also cause toxicity.

  • Drug and food interactions related to MAOIs can occur at therapeutic or toxic doses.
  • The effects of indirect-acting adrenergic drugs are markedly potentiated when combined with MAOIs. These agents include methylphenidate (Ritalin), phenylephrine, ephedrine, cocaine, and amphetamines.
  • Direct-acting sympathomimetics such as epinephrine, norepinephrine, isoproterenol, carbidopa, and L-methyldopa directly act on the postsynaptic receptors rather than the releasing presynaptic vesicles, and they do not cause such a marked adrenergic response.
  • Tricyclic antidepressants (TCAs) block the inactivation of norepinephrine and serotonin;^[6] TCAs taken in combination with MAOIs can lead to excessive catecholamine and serotonin activity, a potentially life-threatening situation. Because of the prolonged action of MAOIs, a 2-4 week washout period must be observed before treatment with TCAs is started.
  • In conjunction with selective serotonin reuptake inhibitors (SSRIs), MAOIs can produce a hyperserotoninergic state known as serotonin syndrome. An altered mental status, autonomic instability, and neuromuscular dysfunction characterize the syndrome.
  • Similar toxicity can occur when MAOIs are combined with drugs that have serotonin reuptake inhibitory properties, such as tramadol, linezolid, meperidine, or dextromethorphan.
  • Foods containing tyramine, such as aged cheese, red wine, overripe foods, aged meat, fava beans, beer, avocado, and yeast extracts, can cause a similar hyperadrenergic state, leading to hypertension or stroke, in individuals taking MAOIs.