A 63-year-old man is brought to the emergency department due to restlessness and altered mental status. His wife reports that the patient awakened at 6:00 AM agitated and slightly confused. Over the past 2 hours, his symptoms have worsened. She states that he was well the previous day but went to his primary care doctor due to a persistent, dry cough for 3 weeks following an upper respiratory tract infection. The patient was prescribed dextromethorphan and an albuterol inhaler. He has a history of major depressive disorder that is well controlled with fluoxetine. Temperature is 38.3 C (101 F), blood pressure is 160/90 mm Hg, pulse is 112/min, and respirations are 22/min. Pulse oximetry is 100% on room air. The patient is agitated and confused. Pupils are dilated, and lungs are clear to auscultation bilaterally. Hyperreflexia and ankle clonus are noted on neurological examination. Which of the following is the most appropriate initial therapy for this patient?
Serotonin syndrome | |
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Management |
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MAOI = monoamine oxidase inhibitor; MDMA = 3,4-methylenedioxymethamphetamine; | |
This patient taking a selective serotonin inhibitor (SSRI) has altered mental status, autonomic instability (eg, hyperthermia, hypertension, tachycardia, mydriasis), and neuromuscular excitability (eg, hyperreflexia, ankle clonus), a triad concerning for serotonin syndrome. Although it typically follows an increased SSRI (eg, fluoxetine) dosage, serotonin syndrome can also be precipitated by concomitant use of another serotonergic agent. This patient recently began taking the antitussive dextromethorphan, which primarily activates sigma opioid receptors to inhibit cough but also has serotonergic activity at the 5-hydroxytryptophan (5-HTA) 2 receptors.
Management often includes:
In patients who are unresponsive to benzodiazepines and supportive care, cyproheptadine is used to lower the serotonergic activity through antagonism of 5-HT1A and 5-HT2A receptors. Serotonin syndrome can have a relatively rapid onset and progression; some patients require intubation and sedation (eg, for severe hyperthermia).
(Choice A) Bromocriptine, a dopamine agonist, is used to treat neuroleptic malignant syndrome (NMS). Although NMS can also present with hyperthermia and autonomic dysregulation, severe muscle rigidity is typically a prominent feature; myoclonus and hyperreflexia are less common.
(Choice B) Haloperidol, an antipsychotic that treats psychosis and agitation, should not be used in serotonin syndrome because its anticholinergic properties prevent the dissipation of body heat, exacerbating hyperthermia.
(Choice C) Although pneumonia (treated with levofloxacin) can present with fever and altered mental status after upper respiratory tract symptoms, this patient's normal oxygen saturation and clear lungs make pneumonia less likely. Also, it would be unusual for pneumonia to develop suddenly after 3 weeks of dry cough, and dilated pupils and neuromuscular excitability would not be expected.
(Choice E) Physostigmine is sometimes used to treat anticholinergic toxicity, which can cause delirium, mydriasis, hyperthermia, and hypertension. However, hyperreflexia and clonus would be unexpected, and this patient's combination of serotonergic medications makes serotonin syndrome more likely.
Educational objective:
Serotonin syndrome is characterized by mental status changes, autonomic dysregulation, and neuromuscular excitability. Management includes discontinuation of serotonergic medications, hydration, cooling, and blood pressure control. Benzodiazepines are used to decrease agitation and muscle contractions. Cyproheptadine is used to decrease central serotonergic activity.