Which of the following statements concerning the pathogenesis of serotonin syndrome is correct?

A. Any drug, or combination of drugs, that increases serotonin type 1A activity, can produce serotonin syndrome.
B. Drug interactions rarely precipitate serotonin syndrome.
C. Drugs that increase central nervous system dopamine concentrations are not expected to cause serotonin syndrome.
D. Many different mechanisms, including an increase in serotonin metabolism, may be responsible for an increase in serotonin type 1A activity.
E. Meperidine and dextromethorphan are safe when given to patients taking a serotonergic agent.
 
 

• Answer A is correct.  Most authors would agree that serotonin type 1A activity appears to be the most important mechanism.  However, this is an area of active research and it is probably much more complicated than simply excess serotonin type 1A activity.

• Drugs that are selective for other types of serotonin would not be expected to precipitate serotonin syndrome, in therapeutic doses.

• Because serotonin syndrome most commonly occurs when two or more serotonin- enhancing agents are used in combination, it is imperative to recognize and avoid potential serotonergic drug interactions.

• Drugs that increase brain dopamine concentrations, such as levodopa (Sinemet), bromocriptine (Parlodel), or selegiline (Eldepryl), have the potential to precipitate serotonin syndrome, as they cause indirect serotonin release.  These agents should be used cautiously, if at all, with other drugs that enhance serotonin.

• Many different mechanisms may be responsible for an increase in serotonin type 1A activity including:

• Increased serotonin production or release.
• Decreased serotonin metabolism.
• Inhibition of serotonin uptake.
• Direct stimulation of serotonin type1A receptors.

• Meperidine and dextromethorphan are examples of potent inhibitors of serotonin uptake and have been associated with serotonin syndrome, especially for patients taking MAO inhibitors.

References: 1, 2, and 3

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