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An Anxiety Reaction Requiring ICU Level of Care: Serotonin Syndrome
Allcorn, M, D.O., PGY-3, Colyer, E, D.O.
Kent Hospital, Department of Emergency Medicine, Warwick, RI
INTRODUCTION: The diagnosis of serotonin syndrome can be life-threatening, as well as difficult to
diagnose due to its variability of presentation, spectrum of severity, and unpredictable rate of
progression. Acquiring a thorough history, developing a firm foundation of knowledge in psychiatric
medications, having a high index of suspicion, early discussion with your regional Poison Control
Center, and a low threshold for administration of cyproheptadine are all important aspects for the
management of this devastating reaction. Today we present a case in which a 50 year-old male
presented to a community hospital emergency department complaining of “the worst panic attack of
my life”.
CASE: A 50 yr old man presented to the emergency department with the “worst panic attack of my
life.” The man stated he had been increasingly anxious over the past three days. He reported a
history of anxiety and panic attacks, but stated he declined the use of benzodiazepines due to a
history of alcohol abuse and subsequent benzodiazepine dependence after alcohol detoxification. He
reports that earlier that evening he had been in the shower and heard his sister calling for him
multiple times, but later discovered his sister was not present in the house. It was these auditory
hallucinations which prompted him to come in and be evaluated. At this time, it was also elicited that
the patient had recently had two changes in his medications. A few weeks prior to presentation the
patient had been started on Cymbalta 60mg daily, in addition to his buspirone 15mg BID and
Mirtazipine 50mg QHS. He reported that the addition of Cymbalta had been causing him GI upset and
vomiting every morning, so he was subsequently instructed to attempt taking this medication at
bedtime, which he began with success 5 days prior to presentation. The patient also reported a
recent “pinched nerve” in his left shoulder, for which he was seen 3 days prior to presentation in the
same ED and started on cyclobenzaprine (Flexeril) 10mg every 8 hours. At the time of presentation
the patient had a heart rate varying from 110 up to the 140. His presenting blood pressure was
162/97, but at the time of initial exam by the resident, he was normotensive. He was afebrile, and
aside from his tachycardia he had no abnormal findings on physical exam. He received an IV fluid
bolus, but refused benzodiazepines to treat his anxiety due to his history. Therefore, he was initially
given 12.5mg quitiapine IV to treat this symptom. He had no resolution of his anxiety approximately
30 minutes after this, and remained tachycardic in the 130’s. The diagnosis of serotonin syndrome
was brought up discussion, but his only sign of autonomic instability was his tachycardia and he had
no clonus or altered mental status. Of note, there was still some suspicion, despite his adamant
refusal, that this was alcohol withdrawal. After no improvement with quitiapine, he agreed to 1mg of
IV lorazepam. Approximately 30 minutes after this, he became more altered and developed
spontaneous clonus. At that time, the diagnosis was made and the patient was treated with a loading
dose of cyproheptadine, admitted to the ICU, and the regional Poison Control Center was consulted,
who agreed with this plan. Once in the ICU, the patient’s temperature rose to 39ºC and he became
more altered, requiring sedation and mechanical ventilation. He was continued on cyproheptadine
until his fever and clonus resolved, on ICU day 4.
DISCUSSION: As stated above, knowledge of the pharmacology of psychiatric medications is
essential. While none of the patient’s medications were specifically SSRI’s, all three have
serotonergic properties. Cyclobenzaprine is structurally similar to TCA’s, which have weak
serotonergic properties, while Cymbalta (which had been being thrown up, but was now tolerated with
bedtime dosing) and buspirone both also carry weak serotonergic properties. A thorough history
noting the addition of two of these medications should have, and did, raise the suspicion of serotonin
syndrome. However, as previously mentioned serotonin syndrome is a spectrum of clinical
presentation and should have been suspected at the earliest signs of autonomic instability,
hyperreflexia, or altered mental status. This case also emphasizes the importance of listening to the
patient. His anxiety, disorientation, and delirium were early indicators of the impending development
of serotonin syndrome, not alcohol withdrawal.