Diagnosis
The diagnosis is based on a history of taking a serotonergic agent PLUS specific clinical findings. See the Hunter Serotonin Toxicity Criteria.
H&P:
Risk factors:
Typical presentation:
DDx: NMS, Malignant hyperthermia, Anticholinergic syndrome, others.
Cause: Excessive serotonergic activity in the CNS and PNS.
Complications:
Diagnostic testing: Consider a CBC, CMP (Electrolytes, BUN, Cr, liver enzymes), Creatine phosphokinase, Coag studies, UA/UCx, Urine Drug Screen, blood culture, CXR, CT scan, LP (CSF analysis and culture). Note: the purpose is not to diagnose SS but to r/o other things on the DDx and monitor the patient for potential complications.
Treatment
Stop all serotonergic agents (offending drugs) + Give supportive care till the vital signs are normal. Most patients improve without further tx.
-Hospitalize patients with moderate or severe SS.
-ICU care for Critically ill patients. They may need sedation, neuromuscular paralysis, and intubation.
-Oxygen to keep SpO2 ≥90 percent; IV fluids if volume depleted; Continuous cardiac monitoring
Benzodiazepines to treat agitation and tremor. IV benzo like lorazepam or diazepam is the drug of choice.
Give serotonin antagonists. The antidote is cyproheptadine. Only use it if there is no response to Benzos
-After symptoms resolve, assess the need to resume using serotonergic agents.

Background
SS is potentially life-threatening.  The cause is an increased serotonergic activity in the central nervous system (CNS). Clinical findings of SS include mental status changes, autonomic hyperactivity, and neuromuscular hyperactivity.
The excess serotonergic activity is due to either 1) taking a high dose of a single serotonergic agent; 2) taking multiple serotonergic agents;  3) taking a drug like Erythromycin that inhibits cytochrome P450 isoenzymes that metabolize a serotonergic agent like SSRI that the patient is taking. SS is seen in patients using meds for treatment purposes, inadvertent drugs interactions, and suicide attempts (intentional self-poisoning).

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For tachycardia, Avoid propranolol because if it’s long activity.

Clonus.

Typical presentation (s): Patient comes in with acute onset agitation, restlessness and tremulousness. Pt started taking cyclobenzaprine TID as needed for acute MSK back pain. To sleep, he took an extra dose of sleeping pill given by PCP.  PMH: Depression treated with SSRI.
PE: Fever (T 100.7), P 99. The patient is diaphoretic + has a resting symmetrical tremor. Patellar and biceps reflexes are 4+. RRR, CTAB. Normal Abd. exam. Normal Strength.

Recognizing it early is important because most cases can be treated in the outpatient setting by stopping of the precipitating agent(s) and providing supportive care.

Reference

Prevention, recognition, and management of serotonin syndrome. Am Fam Physician 2010;81(9):1139-1142. http://www.aafp.org/afp/2010/0501/p1139.html

Crit Care Med 2012;40(9):2662-2670. http://journals.lww.com/ccmjournal/Abstract/2012/09000/Treatment_of_four_psychiatric_emergencies_in_the.17.aspx

Perioperative Diagnosis and Treatment of Serotonin Syndrome Following Administration of Methylene Blue. The American Journal of Case Reports. 2016;17:347-351. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4917068/

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