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Aligned with the American Nurses Credentialing Center format. Authored & peer-reviewed by PMHNPs.

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A 21-year-old woman with a history of seasonal allergies and major depressive disorder presents to the emergency department complaining of chills and muscle soreness approximately 3 hours after ingesting MDMA. She is visibly agitated but able to convey her history. She reports taking no other illicit substance, but she notes taking an 11 mg oral extended-release tablet of brompheniramine earlier this morning. She describes ongoing episodes of uncontrollable sneezing but reports no chills or soreness prior to taking MDMA. She attests to continued adherence with a daily regimen of fluoxetine 60 mg oral tablet. Her temperature is 102.1°F with a regular pulse of 110 beats/min. Physical exam reveals dilated pupils, persistent ocular clonus, diaphoresis, and sustained ankle jerking after dorsiflexion of the feet bilaterally. Her lungs are clear. There is no sign of edema in the face or limbs. Which of the following is the most likely diagnosis?

A Anaphylaxis
B Influenza
C Serotonin syndrome
D Somatic symptom disorder

Serotonin syndrome is a life-threatening condition that results from the simultaneous use of multiple serotonergic agents. N-methyl-3,4-methylenedioxyamphetamine (MDMA) and selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine elevate mood by increasing serotonin levels in the brain. However, antihistamines vary in serotonin activity. Some first-generation antihistamines, such as brompheniramine and chlorpheniramine, are 5-HT2A agonists and should be used with caution in patients taking SSRIs, while others such as cyproheptadine display 5-HT2A antagonism. Serotonin syndrome is triggered by high levels of serotonin at synapses in the brainstem and manifests as fever, diaphoresis, dilated pupils, ocular clonus, nausea, vomiting, and myoclonus in the extremities. In addition to the drugs listed above (MDMA, brompheniramine, and fluoxetine), serotonin syndrome can also be triggered when the following drugs are used in combination: monoamine oxidase inhibitors, tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitors, St. John’s wort, bupropion, trazodone, meperidine, tramadol, fentanyl, sumatriptan, cocaine, amphetamines, linezolid, dextromethorphan, lithium, tryptophan, and levodopa.

Anaphylaxis (A) is a life-threatening allergic reaction that leads to respiratory distress and circulatory collapse but is not known to cause elevated temperature. Influenza (B) is a viral infection that may manifest as fever, fatigue, rhinorrhea and muscle soreness. However, influenza usually results from contact with an infected individual and is neither associated with serotonergic drugs nor serotonergic signs such as dilated pupils, ocular clonus, or myoclonus. Somatic symptom disorder (D) is evident when a patient has a debilitating preoccupation with multiple perceived physical ailments. In contrast to the woman from the vignette, people with somatic symptom disorder display inappropriate and exaggerated concern for their symptoms. Displaying grave concern is not inappropriate after the acute onset of flu-like symptoms following MDMA ingestion because such symptoms may herald a potentially life-threatening event.


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serotonin syndrome

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Q: Which first-generation antihistamine is used to reverse serotonin syndrome?


A: Cyproheptadine.

Serotonin Syndrome

  • Patient with a history of taking multiple medications that increase the amount of serotonin
  • PE will show mental status changes, autonomic instability, and neuromuscular abnormalities
  • Treatment is benzodiazepines, cyproheptadine, removing the offending agent(s)

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I’ve been a nurse for 10 years and used Rosh Review for my NP exam and loved it. The content is in-depth and did a great job to help me learn what I needed for the exam.


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