Today’s USMLE® Step 1 question of the day features a young man with acute agitation, hyperthermia, and muscle rigidity after a recent antidepressant change. What’s the underlying cause of his presentation? Let’s find out!
A 25-year-old man presents to the emergency department in an incoherent state with flushing, agitation, muscle rigidity, and hyperthermia. Intravenous lorazepam is started, which reduces the patient’s muscle rigidity. However, within 30 minutes, the patient becomes unresponsive and comatose. Intravenous cyproheptadine is started, which eventually helps the patient recover. On obtaining a prescription history, it is noted that the patient had been taking fluoxetine and recently switched to vortioxetine.
Which of the following explains the underlying cause of this patient’s symptoms?
A. Excessive dopamine
B. Excessive serotonin
C. Deficiency of norepinephrine
D. Deficiency of dopamine
E. Deficiency of serotonin
Scroll down for the correct answer!
The correct answer to today’s USMLE® Step 1 Question is…
B. Excessive serotonin
Correct: See Main Explanation.
Incorrect Answer Explanations
A. Excessive dopamine
Incorrect: Excessive dopaminergic activity is linked to schizophrenia, hallucinogenic symptoms, and mania. This patient is exhibiting symptoms of serotonin syndrome.
C. Deficiency of norepinephrine
Incorrect: Low levels of norepinephrine are associated with lethargy, lack of concentration, attention deficit hyperactivity disorder, and depression. In contrast, this patient’s symptoms are more consistent with serotonin syndrome.
D. Deficiency of dopamine
Incorrect: This answer choice describes the underlying pathology of Parkinson disease. In contrast, this patient’s symptoms are more suggestive of serotonin syndrome, which is caused by excessive serotonin release.
E. Deficiency of serotonin
Incorrect: A deficiency of serotonin is linked to symptoms of depression. This patient is suffering from serotonin syndrome, which is due to an excess of serotonergic activity.
Main Explanation
This patient’s symptoms of flushing, agitation, muscle rigidity, hyperthermia, and altered mental status are characteristic of serotonin syndrome. Serotonin syndrome arises from an excess of serotonergic potentiation, which can arise from excessive use of antidepressants or drugs that increase serotonin levels. Serotonin syndrome arises within 24-hours of medication use and typically resolves within 24-hours after its discontinuation.
Two antidepressants, namely vortioxetine and vilazodone, have been associated with serotonin syndrome due to their powerful effects in increasing serotonin levels. They exert this effect via two mechanisms: 1) inhibition of serotonin reuptake transporters, and 2) partial agonism of 5-HT1A receptors (in vilazodone) or full agonism of 5-HT1A receptors (in vortioxetine). The combined action of these mechanisms creates a potent antidepressant effect.
To treat serotonin syndrome, cyproheptadine, a 5-HT2A blocker, should be administered. It is important to distinguish serotonin syndrome from other conditions with similar presentations, reference the table below.
Major Takeaway
Serotonin syndrome is characterized by altered mental status, muscle rigidity, hyperreflexia, and hyperthermia. It can be precipitated by antidepressants such as vortioxetine and vilazodone. The condition can be potentially life-threatening and should be treated promptly with cyproheptadine.
Want to learn more about this topic?
Watch this Osmosis video: Atypical antidepressants
References
- Volpi-Abadie, J., Kaye, A.M., Kaye, A.D. (2013) Serotonin syndrome. The Ochsner Journal. 13(4), 533-540. PMID: 24358002.
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