Early recognition and quick action prevent poor outcome
- Serotonin syndrome manifests with a combination of cognitive, autonomic, and somatic symptoms, including agitation, tachycardia, hyperreflexia, tremors, and hyperthermia, typically arising from the use or combination of serotonergic medications.
- Effective management involves the immediate discontinuation of serotonergic agents, administration of supportive care such as I.V. fluids and benzodiazepines, and the use of serotonin antagonists like cyproheptadine in severe cases.
- Prompt recognition and intervention are crucial for preventing severe complications such as rhabdomyolysis and multi-organ failure.
MICHELLE ANDERSON*, a 54-year-old woman, arrives at the ED with flu-like symptoms, including fatigue, muscle aches, and a mild fever. Her medical history includes depression, which she manages with a selective serotonin reuptake inhibitor (SSRI), and recurrent migraines treated with a triptan. Two days earlier, Ms. Anderson sprained her ankle and received a prescription for tramadol.
On the day of her ED visit, Ms. Anderson experienced a migraine and took her usual triptan. Paul, the ED nurse, notes the patient’s restlessness and mild tremors. Ms. Anderson’s vital signs are HR 98 bpm, BP 140/90 mmHg, temperature 99.2° F, RR 24, and SpO2 95%.
Symptom escalation
Ms. Anderson becomes increasingly confused, agitated, and tachycardic, while also exhibiting hyperreflexia (exaggerated reflex responses). Hyperreflexia can lead to uncontrolled muscle contractions, which increase energy demand and heat production in muscles, causing mechanical stress, ischemia, and cellular disruption. This cascade results in rhabdomyolysis (breakdown of muscle fibers with release of myoglobin, potassium, and creatine kinase into the bloodstream). Myoglobin can damage kidneys and elevate potassium, ultimately resulting in life-threatening cardiac arrhythmias.
Paul implements continuous cardiac monitoring and increases vital sign frequency. He recognizes the possibility of serotonin syndrome and holds tramadol and triptan, which, in combination with the patient’s SSRI, may have synergistically elevated her serotonin levels. Her vital signs are now HR 130, BP 160/106 mmHg, temperature 101.2° F, RR 34, and SpO2 92%
Paul administers oxygen at 3 L/min via nasal and initiates an I.V. for hydration as ordered to manage hyperthermia and prevent rhabdomyolysis. He administers lorazepam 2 mg I.V. to control agitation and muscle rigidity and then prepares cyproheptadine, an antihistamine with 5-HT2A antagonistic properties. He administers an initial dose of 12 mg orally, followed by 2 mg every hour as needed. However, Ms. Anderson’s symptoms intensify. Paul calls the rapid response team (RRT).
Taking action
The RRT provides aggressive hydration with I.V. normal saline at 100 mL/hr, administers additional benzodiazepines to maintain muscle relaxation, and continues cyproheptadine to antagonize excessive serotonin activity.
Given Ms. Anderson’s persistent tachycardia and hypertension, the team monitors her cardiovascular status closely, ready to administer beta-blockers if necessary. To prevent potential respiratory compromise, the RRT decides to intubate the patient.
Education
Serotonin regulates mood, cognition, and various physiological functions, including thermoregulation and neuromuscular activity. Levels that surpass normal limits disrupt neurotransmitter balance, leading to a range of symptoms.
Serotonin syndrome is a potentially life-threatening condition caused by excessive accumulation of serotonin in the central nervous system. It occurs when medications or combinations of medications overstimulate serotonin receptors, especially the 5-HT1A and 5-HT2A subtypes.
Outcome
Ms. Anderson’s symptoms subside, and her vital signs stabilize. After 48 hours in acute care, Ms. Anderson is transferred back to primary care for ongoing management. Before discharge, the provider discontinues cyproheptadine and the nurse offers Ms. Anderson education about how to avoid toxic levels of serotonin. Paul’s quick recognition of Ms. Anderson’s deterioration and the RRT’s swift action prevented progression to severe complications and a potentially catastrophic outcome.
About serotonin syndrome
Serotonin syndrome can develop rapidly, often within hours of starting or increasing a serotonergic agent. Symptoms include
the following:
- Diaphoresis
- Diarrhea
- Hypertension
- Hyperthermia
- Mydriasis
- Nausea and vomiting
- Shivering
- Tachycardia
- Agitation
- Coma
- Confusion
- Hallucinations
- Clonus
- Hyperreflexia
- Muscle rigidity
- Rhabdomyolysis
- Seizures
- Tremors
Medications associated with serotonin syndrome
*Individuals who accidentally or intentionally take large amounts of 5-HTP (5-Hydroxytryptophan) dietary supplements, in addition to prescribed serotonergic medications, put themselves at significant risk of developing serotonin syndrome.
5-HTP, a naturally occurring amino acid and chemical precursor to serotonin (5-HT), is derived from L-tryptophan, an essential amino acid found in food. It’s commonly sold over-the-counter as, or as an ingredient in, a supplement (such as St. John’s Wort). Once ingested, 5-HTP is converted into serotonin in the brain, potentially increasing serotonin levels.
Differential diagnoses
Serotonin syndrome can be confused with other conditions, including the following:
Differential diagnoses
Management of serotonin syndrome includes immediate cessation of offending agents and supportive care. If serotonin
syndrome remains unrecognized or untreated, it can swiftly progress to irreversible organ damage and death.
Cyproheptadine reduces serotonin syndrome symptoms such as hyperthermia, neuromuscular excitation, and autonomic
instability. It’s preferred over chlorpromazine to avoid risks like orthostatic hypotension and worsening hyperthermia.
Cyproheptadine may be administered up to a maximum of 32 mg in 24 hours, followed by a maintenance dose of 8 mg every
6 hours.
*Name is fictitious.
Trae Stewart is a professor of nursing at Massachusetts College of Pharmacy & Health Sciences in Boston and a psychiatric-mental health nurse practitioner at PsychMatters in Las Vegas, Nevada.
American Nurse Journal. 2025; 20(10). Doi: 10.51256/ANJ102546
References
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Morarasu S, Coman AE, Bologa C, et al. Recognition and management of serotonin toxidrome in the emergency department—Case based review. J Pers Med. 2022;12(12):2069. doi:10.3390/jpm12122069
Nagy A, Nasir A, Haque M, Judge R, Lee J. Therapeutic cyproheptadine regimen in serotonin syndrome: Complications after cardiovascular surgery. Clin Case Rep. 2023;11(7):e7720. doi:10.1002/ccr3.7720
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Key words: serotonin syndrome, SSRI, tramadol, clinical management
