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Serotonin Syndrome
Evalyn Kennedy, RN, BSN
What is Serotonin Syndrome?
▪ Definition: Excess serotonin levels existing on serotonin receptors
and in synaptic clefts causing CNS instability
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Decrease in serotonin reuptake (SSRIs, SNRIs)
Decrease in serotonin degradation (MAOIs)
Increase in serotonin stimulation and release (Cocaine, amphetamines)
Serotonin receptor agonists (St. John’s wort, triptans)
Pathogenesis
www.cmaj.ca
Patient Presentation
▪ Mild
– Shakiness, slight tremors, twitching,
restlessness
▪ Moderate
– Agitation, pressured speech, diaphoresis
▪ Severe
– Shock, seizures, hallucinations, delirium,
comatose
Review of Systems
▪ Fevers
▪ N/V/D or abdominal pain
▪ Changes in mood, euphoric or depressed, suicidal ideation
▪ Frequent sweats
▪ Shakiness or tremors
▪ Muscle aches or stiffness
▪ Palpitations
▪ Headaches or confusion
▪ Obtain a THOROUGH list of medications past and present and any
changes to dosages or schedules
Physical Exam
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Tachycardia
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Tachypnea
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Hypertension
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Hyperreflexia
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Febrile
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Dilated Pupils
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Dry Mucous Membranes
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Clonus
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Pathologic reflexes
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Diaphoresis
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Hyperactive Bowel Sounds
Diagnostics
▪ No specific lab or radiologic
tests to confirm
▪ Diagnosis based on clinical
presentation
▪ Must roll out other differential
diagnoses
– Spinal tap
– UDS
– CT head
Differentials…
▪ Anticholinergic Toxicity (diphenhydramine, amitriptyline)
▪ Sympathomimetic Toxicity (MDMA, Psychoactive Bath Salts)
▪ Drug or ETOH Withdrawal (Delirium Tremens)
▪ Neuroleptic Malignant Syndrome (Onset of Symptoms, Bradyreflexia)
▪ Malignant Hyperthermia
▪ Meningitis (Meningeal irritation)
▪ Encephalitis
Treatment
▪ Stop the offending agent!
▪ Cooling
▪ Sedation
▪ Beta-Blockers
▪ Intubation
▪ Cyproheptadine 12mg initial dose; 2mg Q2H until response seen
▪ Rapid referral to Toxicologist
Management
▪ Symptoms can be self-limiting
if caught and agent stopped in
time
▪ F/U in 2-3 days with telephone
contact every day with updates
until visit
▪ F/U within 5 days after hospital
discharge if
admission/observation was
necessary
▪ Teach s/s of worsening
condition
▪ Reassess risk vs benefit for
medication needs
List of Substances that can Cause
Serotonin Syndrome…
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Amphetamine
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Fluvoxamine (SSRI)
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Cocaine
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Paroxetine (SSRI)
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Diethylpropion
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Sertraline (SSRI)
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Isocarboxazid (MAOI)
Linezolid (MAOI)
Phenelzine (MAOI)
Selegiline (MAOI)
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Naratriptan (triptan)
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Rizatriptan (triptan)
Methamphetamine
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Sumatriptan (triptan)
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MDA
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Zolmitriptan (triptan)
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Bupreorphine (opioid)
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Amitriptyline (tricyclic)
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MDMA
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Amoxapine (tricyclic)
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Methylphenidate
Phentermine
Fentanyl (opioid)
Desipramine (tricyclic)
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Sibutramine
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Hydrocodone (opioid)
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Meperidine (opioid)
Tranylcypromine (MAOI)
Buproprion (SNRI)
Nefazodone (SNRI)
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Doxepin (tricyclic)
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LSD
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Imipramine (tricyclic)
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Nutmeg
Panax Ginseng
Oxycodone (opioid)
Maprotiline (tricyclic)
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St John’s wort
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Pentazocine (opioid)
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Pethidine (opioid)
Trazodone (SNRI)
Venlafaxine (SNRI)
Citalopram (SSRI)
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Nortriptyline (tricyclic)
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Syrian Rue
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Protriptyline (tricyclic)
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Almotriptan (triptan)
Eletriptan (triptan)
Tramadol (opioid)
Trimiprimine (tricyclic
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Frovatriptan (triptan)
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Buspirone
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Granesitron
Esitalopram (SSRI)
Fluoxetine (SSRI)
Chlorpheniramine
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Dextromethorphan
References
▪ Ables, A. C., & Nagubilli, R. (2010). Prevention, diagnosis, and management of serotonin
syndrome. American Family Physician, 81(9), 1139-1142. Retrieved from
http://www.aafp.org
▪ Basil, M. J., Iqbal, M. M., Iqbal, T., & Kaplan, J. (2012). Overview of serotonin syndrome.
Annals of Clinical Psychiatry, 24(4), 310-318. Retrieved from http://www.aacp.org
▪ Boyer, E. W. (2016). Serotonin syndrome (serotonin toxicity). Up to Date. Retrieved from
http://www.uptodate.com
▪ Dawson, A. H., Dunkley, E. J. C., Isbister, G. K., Sibbritt, D., & Whyte, I. M. (2003). The
hunter serotonin toxicity criteria: simple and accurate diagnostic decision rules for
serotonin toxicity. QJM, 96(9), 635-642. doi: http://dx.doi.org/10.1093/qjmed/hcg109
▪ Lissoway, J., & Weiss, E. A. (2014). Serotonin syndrome. Merck Manual. Retrieved from
http://www.merckmanuals.com
▪ Practor, B. C. (2006). Serotonin syndrome. The Journal of Neuroscience Nursing, 38(2), 102105. Retrieved fromhttp://www.medscape.com