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Serotonin Syndrome
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Serotonin Syndrome
See Also
Serotonin
Neurotransmitter Physiology
Neuroleptic Malignant Syndrome
Malignant Hyperthermia
Background
History
Libby Zion was a young patient who died of Serotonin Syndrome in 1984 and set historic precedent
Provider education regarding Serotonin Syndrome
Principal case that limited intern and resident shift hours
http://en.wikipedia.org/wiki/Libby_Zion_law
Epidemiology
Complicates 14-16% of SSRI
Overdose
s
Isbister (2004) J Toxicol Clin Toxicol 42(3): 277-85 [PubMed]
Etiology
Excessive
Serotonin
levels at the receptor sites
Associated with combinations of
Serotoninergic
drugs
Exacerbated by drugs that increase
Serotonin
levels
Psychiatric medications
Selective Serotonin Reuptake Inhibitor
s -
SSRI
(e.g.
Paroxetine
-
Paxil
)
Serotonin
-
Norepinephrine
Reuptake Inhibitors -
SNRI
(e.g.
Venlafaxine
-
Effexor
)
MAO inhibitor
s (e.g.
Phenelzine
or
Nardil
)
Tricyclic Antidepressant
s (e.g.
Amitriptyline
)
Lithium
Buspar
Trazodone
Some
Antipsychotic Medication
s (e.g.
Olanzapine
or
Zyprexa
)
Stimulant Medication
s
Methylphenidate
(
Ritalin
)
Sibutramine
(
Meridia
)
Antiemetic
s
Metoclopramide (Reglan)
Ondansetron
(
Zofran
)
Droperidol
(
Inapsine
)
Migraine
and
Seizure
Medications
Triptan
s (e.g.
Sumatriptan
Imitrex
)
Ergot Alkaloids
Valproic Acid
(
Depakote
,
Depakene
)
Carbamazepine
(
Tegretol
)
Synthetic
Opioid Analgesic
s
Tramadol
(
Ultram
)
Meperidine
(
Demerol
)
Fentanyl
(
Duragesic
)
Methadone
Dextromethorphan
Rare case reports with
Buprenorphine
(
Suboxone
),
Hydromorphone
,
Oxycodone
or
Hydrocodone
Muscle Relaxants
Cyclobenzaprine
(
Flexeril
)
Metaxalone
(
Skelaxin
)
Miscellaneous medications
Chlorpheniramine
Linezolid
(
Zyvox
) -
MAO inhibitor
effect
Reserpine
Ritonavir
(
Norvir
)
Herbals
and supplements
St. John's Wort
Ginkgo Biloba
Ginseng
L-Tryptophan
5-Hydroxytryptophan (dietary supplement) -
Serotonin
precursor
Yohimbine
Recreational drugs
Cocaine
3,4-methylenedioxmethamphetamine (Ecstacy)
Methamphetamine
Risk Factors
Medications with serotonergic effects (see above)
Combined use of multiple serotonergic drugs
Inadequate washout period between transitioning to a new serotonergic drug
Higher
Incidence
with
Monoamine Oxidase Inhibitor
s,
St. John's Wort
and
Linezolid
Cytochrome P450
Drug Interaction
s or specific patient
Phenotype
s making them more susceptible to Serotonin Syndrome
Medical conditions that decrease the available monoamine oxidase
Hypertension
Atherosclerosis
Hyperlipidemia
Diagnosis
Mental Status Changes
Confusion or
Disorientation
(51%)
Agitation
or irritability (34%)
Coma
or unresponsiveness (29%)
Autonomic changes
Fever
or hyperthermia (45%)
Diaphoresis (45%)
Sinus Tachycardia
(36%)
Hypertension
(35%)
Mydriasis
(28%) or unreactive pupils (20%)
Tachypnea
(26%)
Nausea
(23%)
Neuromuscular changes
Myoclonic Jerk
s (58%)
Hyperreflexia (52%)
Muscle rigidity (51%)
Restlessness or hyperactivity (48%)
Tremor
(43%)
Ataxia
or
Incoordination
(40%)
Clonus
(23%)
Spontaneous
Clonus
with a history of
Serotoninergic
agent use is pathognomonic for Serotonin Syndrome
Dunkley (2003) QJM 96 (9): 635-642 [PubMed]
Exclude other possible causes
Infectious, metabolic,
Substance Abuse
or withdrawal
No recent
Neuroleptic
changes
Differential Diagnosis
Meningitis
or
Encephalitis
Anticholinergic Syndrome
Malignant Hyperthermia
Neuroleptic Malignant Syndrome
Occurs with
Dopamine
blocking agents
Classic triad of fever, muscle rigidity and
Altered Mental Status
Management
Discontinue
Serotoninergic
medication
Provide supportive care
Treat muscle rigidity,
Tremor
and hyperthermia
First line
Benzodiazepine
s
Refractory (severe, critically ill patients)
Intubation
Sedation and
Paralytic Agent
s
Consider
Serotonin
antagonists
Cyproheptadine
(
Periactin
)
Initial protocol
Bolus: 12 mg oral bolus dose for 1 dose
Continued symptoms: 2 mg every 2 hours until symptoms controlled
Maintenance protocol (once stabilized)
Dose: 8 mg every 6 hours or 4 mg every 2-4 hours
Maximum: 0.5 mg/kg/day
Other medications that have been used for Serotonin Syndrome symptom control
Propranolol
Precautions
Avoid
Antipsychotic
s (e.g.
Haloperidol
) as has serotonergic effects and may exacerbate condition
Avoid antipyretics
Hyperthermia of Serotonin Syndrome is due to increased muscle activity (not the
Hypothalamus
)
Course
Many cases likely go undiagnosed and resolve spontaneously when patients stop the medications themselves
Resolution after stopping
Serotoninergic
medication
Within 24 hours in 70% of cases
Within 96 hours in almost all cases
High acuity care
Intensive Care
admission in up to 40% of cases
Mechanical Ventilation
in up to 25% of cases
Rarely fatal: 11 deaths in literature
References
Herbert and Jhun in Herbert (2015) EM:Rap 15(4):14
Nordt and Swadron in Majoewsky (2012) EM:Rap 12(2): 3
Ables (2010) Am Fam Physician 81(9): 1139-42 [PubMed]
Bodner (1995) Neurology 45:219-23 [PubMed]
Brown (1996) Ann Pharmacother 30:529-33 [PubMed]
Corkeron (1995) Med J Aust 163:481-2 [PubMed]
Erner (2003) Pain Med 4(1): 63-74 [PubMed]
Iqbal (2012) Ann Clin Psychiatry 24(4): 310-8 [PubMed]
Kovich (2015) Am Fam Physician 92(2): 94-100 [PubMed]
Mills (1995) Am Fam Physician 52(5):1475-82 [PubMed]
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