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One Pill Can Kill: The Case of the Serotonin Socialite
One Pill Can Kill is an online column based on real-life pediatric toxicology cases.
This installment of One Pill Can Kill isn’t an overdose case. It’s a case of a known but uncommon reaction to serotonin agonists.
A 16-year-old girl who started fluoxetine for depression and social anxiety three months ago has had a satisfactory response to the antidepressant. She has become more outgoing and recently made a number of new friendships. She is invited to a party being thrown by her classmates. She arrives home at 2 a.m. intoxicated, and is scolded by her parents. She goes to sleep in her room.
The next morning she is found confused and altered. Her parents call 9-1-1. Your unit arrives 9 minutes later. You find her lying in bed, drenched in sweat. Her pupils are normal, she looks at you when you call her name, and you find otherwise normal vitals.
On exam, she has normal respirations and pulse and a soft abdomen. When you touch her feet, they beat forcefully as if trying to tap a brake pedal, slowly weakening in strength over about 12 movements. When you buckle up the leg straps, her legs jerk with a very strong reflex. She seems very anxious and tense, but is not in trismus or seizure.
You initiate an IV and transport her to the hospital. En route, she says the occasional word, but it is nonsense. Her glucose is normal, and her vitals trend toward tachycardia and hypertension, but only modestly so.
You record an ECG that shows a QTc of 454 and a QRS of 101 milliseconds. At the ER, you are immediately offloaded and the patient is given 1 liter of Ringer's lactate crystalloid.
The emergency physician places her hand on the sole of the patient's left foot and pushes the toes toward her face, and again the patient’s foot beats dramatically. She orders 2mg of midazolam and a toxicologic bloodwork panel.
Serotonin Syndrome
Serotonin is a central nervous system neurotransmitter. Other neurotransmitters include dopamine, glutamate and norepinephrine.
Excessive serotonin in neurosynapses results from either decreased serotonin metabolism or decreased serotonin reuptake into neurons. This excess serotonin causes postsynaptic activity to increase, leading to excess muscle activity. Hyperreflexia, such as clonus, hyperthermia and a sympathomimetic-like effect are observed.
Serotonin syndrome can occur when starting a new serotonergic medication or in settings of overdose of serotonergic medications. Classes include SSRIs (fluvoxamine, fluoxetine, paroxetine, sertraline), SNRIs (duloxetine, venlafaxine), TCAs (amitriptyline, nortriptyline), MAOIs (phenelzine), and trazadone.
Serotonin syndrome can also occur when someone taking a serotonergic medication also takes a medication known to provoke the syndrome, such as fentanyl, codeine, amantadine, sumatriptan, cocaine, MDMA (ecstasy), LSD, lithium and St John’s wort, and dextromethorphan (in many cough syrups).
The Hunter criteria have been established to define the syndrome, the hallmark sign of which is clonus. Fever, diaphoresis, agitation and hyperreflexia round out additional signs.
Many conditions can mimic serotonin syndrome, including neuroleptic malignant syndrome (NMS), malignant hyperthermia, meningitis, and sympathomimetic overdose (SS). SS and NMS have different triggers; rather than by serotonergic medications, NMS is triggered by neuroleptic medications that block dopamine.
Antipsychotics such as haloperidol, quetiapine, risperidone, olanzapine and paliperidone are the most common class of medicines associated with NMS. Other dopamine antagonists include metoclopramide, amantadine, lithium and some antiepileptic drugs.
NMS presents with rigidity and hyporeflexia, which are not features of serotonin syndrome, and usually has an onset of days to weeks, unlike the hours-long onset found with serotonin syndrome.
Back to the Case
The teenager is supported in the hospital with benzodiazepines and cyproheptadine, and her symptoms resolve. Three days after admission, she is oriented and admits to trying fentanyl at the party.
A psychiatric interview concludes that there was no overdose. She is discharged home on escitalopram, an SSRI with a lower incidence of serotonin syndrome in adolescents, and outpatient followup with a psychiatrist is scheduled.
Reference
Blair Bigham, MD, MSc, EMT-P, is an award-winning journalist, scientist and physician who trained in emergency and critical care medicine at McMaster and Stanford Universities. He spent the first decade of his career as a flight paramedic before pursing medical school. He was a Global Journalism Fellow at the Munk School of Global Affairs and associate scientist at St Michael’s Hospital. His work has appeared in newspapers, magazines, newscasts, podcasts and medical journals. His first book, Death Interrupted: How Modern Medicine is Complicating the Way we Die, was published in September 2022. He is a member of EMS World’s Editorial Advisory Board.
Comments
Superb case study! Very thorough! This ought to be thought in all EMS agencies and I’ll be sure to point it out to our training division.
—Alexander von Guggenberg