Case 2 – A Little Jumpy

Case #2: A Little Jumpy
Author: Jami Hickey, MD
Peer Reviewer: Mark Mycyk, MD

A 34 year old man is brought to the emergency department by his wife who states that he has had confusion and difficulty walking for the past two hours. Per his wife, he was acting normally last night before going to bed, but after breakfast this morning was “just not himself”. His only past medical history is depression, but he has recently been complaining of nasal congestion and a dry cough.

Vitals: T: 102.2, HR: 112, BP: 120/80, RR: 20, O2 Sat: 98% on RA

On physical examination the patient is able to tell you his name and knows he is in the hospital but is unclear on the date and seems very sleepy. He is mildly diaphoretic. The remainder of his exam is significant only for increased tone and hyperreflexia of the bilateral lower extremities.

What two toxidromes should you consider in this patient?
Serotonin Syndrome and Neuroleptic Malignant Syndrome
In light of this patient’s history, what additional information should you ask for?
Medication history is extremely important!  You ask his wife and she states that he takes a medication for his depression every morning, but she doesn’t recall the name. He has also been taking some over-the-counter (OTC) medications for his cold for the past few days.
What are your concerns based on the wife’s answer?
This patient may be taking an SSRI for his depression and is at risk for Serotonin Syndrome. Many OTC cold preparations contain dextromethorphan. Dextromethorphan is a cough suppressant that has been well-described in the literature to also have pro-serotonergic properties, which could have precipitated Serotonin Syndrome in this case.
What are some common medications associated with Serotonin Syndrome?
SSRIs/SNRIs and MAOIs are the most common culprits. Serotonin Syndrome predominantly occurs when the dose has recently been increased or when multiple pro-serotonergic medications are taken together.

Drugs can increase serotonin levels via:
1. Inhibition of serotonin breakdown (MAOIs)
2. Blockade of serotonin reuptake (Cocaine, Dextromethorphan, SSRIs, Trazodone, Venlafaxine, and Mepiridine)
3. Supplying excess serotonin precursors (L-Tryptophan and LSD)
4. Enhancing serotonin release (Amphetamines, Cocaine, MDMA, and Lithium)

What are the symptoms and signs of Serotonin Syndrome?
There are three main features of Serotonin Syndrome:
1. Cognitive/Behavioral Changes: Confusion, Agitation, Anxiety, Hallucinations
2. Autonomic dysfunction: Hyperthermia, Diaphoresis, HTN, Tachycardia, and Mydriasis
3. Neuromuscular dysfunction: Myoclonus (most common), Hyperreflexia, Rigidity, Hyperactivity, Ataxia
How do you distinguish Serotonin Syndrome from Neuroleptic Malignant Syndrome?

  Serotonin Syndrome Neuroleptic Malignant Syndrome
Mechanism Serotonin Excess Dopamine Antagonism
Onset Hours Insidious (Days to weeks)
Resolution Hours Days to weeks
Hyperthermia Common Common
Altered Mental Status Common Common
Lead pipe rigidity, tremors, myoclonus Uncommon Common
Hyperreflexia Common Uncommon
Bradykinesia Uncommon Common

What should your initial management be?
-All serotonergic medications should be discontinued.
-The patient should be placed on a monitor with IV access.
-Supportive care is the mainstay of treatment for Serotonin Syndrome with active cooling measures as needed.
-Control muscular rigidity/hyperactivity, using paralytics if necessary.
What pharmacologic option can be considered for treatment of this condition?
Cyproheptadine: an anti-serotoninergic agent that comes in oral formulation only.


Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005 Mar 17;352(11):1112-20.

Thorpe EL, Pizon AF, Lynch MJ, et al. Bupropion induced serotonin syndrome: a case report. J Med Toxicol. 2010 Jun;6(2):168-71.

Zand L, Hoffman SJ, Nyman MA. 74-year-old woman with new-onset myoclonus. Mayo Clin Proc. 2010 Oct;85(10):955-8.

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