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.
