Serotonin Syndrome Flashcards
what is the triad of symptoms associated with serotonin syndrome
mental status changes
autonomic hyperactivity
neuromuscular changes (hyperreflexia and clonus)
why does serotonin syndrome occur
due to excess serotonin
what is the range of possible presentations of serotonin syndrome
can vary significantly
mild symptoms (tremor, diarrhea)–> delirium, neuromuscular rigidity and hyperthermia in life threatening cases
what is the incidence of serotonin syndrome
unknown–> mild cases not diagnosed or can be dismissed
more serious presentations can be confounded by other toxidromes
what % of people who overdose on SSRIs develop serotonin syndrome
14-16%
is serotonin syndrome rare
no –> has been identified in elderly, children and newborn infants
what class of antidepressants is strongly associated with severe cases of serotonin syndrome?
what other combinations of drugs increase this risk
MAOIs strong associated with severe cases of serotonin syndrome
especially when used in combo with:
meperidine
dextromethorphan
SSRIs
MDMA
how quickly does serotonin syndrome present/how fast is symptom onset
RAPID onset of symptoms–> within MINUTES after a change in medication or an overdose
approx 60% of patients with serotonin syndrome oresent within SIX HOURS after initial use of medication, an overdose or a change in dosing
how quickly does serotonin syndrome resolve after initiation of treatment
most resolve within 24 hours after initiation of treatment and discontinuation of serotonergic drugs–> symptoms may persist in meds with longer half life
does serotonin syndrome occur only with initiation of serotonergic agents
no–> both initiation AND withdrawal of serotonergic agents have been associated with serotonin syndrome
list classes of medications that have been associated with serotonin syndrome
SSRIs
other antidepressants
MAOIs
anticonvulsants
analgesics
antimigraine drugs
bariatric medications
antibiotics
drugs of abuse
dietary and herbal supplements
mood stabilizers
antiemetics
OTC cold and flu meds
list SSRIs associated with serotonin syndrome
sertraline
fluoxetine
fluvoxamine
paroxetine
citalopram
list other antidepressants associated with serotonin syndrome
trazodone
nefazodone
buspirone
clomipramine
venlafaxine
list MAOIs associated with serotonin syndrome
phenelzine
moclobemide
clorgiline
isocarboxazid
list anticonvulsants associated with serotonin syndrome
valproate
list analgesics associated with serotonin syndrome
meperidone
fentanyl
tramadol
pentazocine
list antiemetics associated with serotonin syndrome
ondansetron
metoclopramide
list antimigraine drugs associated with serotonin syndrome
sumatriptan (because is a 5TH1B/1D agonist)
list bariatric medications associated with serotonin syndrome
sibutramine
list antibiotics associated with serotonin syndrome
linezolid (MAOI)
ritonavir (inhibits CYP3A4)
list OTC cold and flu meds associated with serotonin syndrome
dextromethorphan
list drugs of abuse associated with serotonin syndrome
MDMA
LSD
“foxy methoxy”
Syrian rue (has MAOI components)
list dietary supplements associated with serotonin syndrome
tryptophan
st johns wort
ginseng
list mood stabilizers associated with serotonin syndrome
lithium
what might you find on neurological exam associated with serotonin syndrome
horizontal ocular clonus
intemrittent tremors
myoclonus
hyperreflexia
what is the name of the criteria proposed for diagnosing serotonin syndrome
Hunter critieria
what is a mnemonic to remember the hunter criteria
MOIST
Muscle rigidity + temp above 38 + either ocular or inducible clonus
Ocular clonus and either agitation or diaphoresis
Inducible clonus and either agitation or diaphoresis
Spontaneous clonus
Tremor and hyperreflexia
what is the first decision point in the Hunter’s Decision rules?
is there spontaneous clonus? if yes, then there is serotonin syndrome
what is the decision tree in the Hunter Decision rules?
spontaneous clonus–>
inducible clonus + either agitation or diaphoresis–>
ocular clonus + either agitation or diaphoresis–>
tremor + hyperreflexia–>
hypertonia + temp above 38 + ocular or inducible clonus
*if any any point moving down that tree, all of the conditions are met at that level, then you suspect serotonin toxicity and act accordingly
how is the neurotransmitter serotonin produced
produced by the decarboxylation and hydroxylation of l-tryptophan
which serotonin receptor appears to be most implicated in the development of serotonin syndrome
5HT2A agonism
(though no single receptor appears to be solely responsible)
other than serotonin receptors, what other types of receptors/neurotransmitters also appear to be implicated in serotonin syndrome
NMDA antagonists
GABA
ddx serotonin syndrome
anticholinergic poisoning
malignant hyperthermia
NMS
how do you distinguish serotonin syndrome from anticholinergic poisoning
anticholinergic toxicity presents with NORMAL reflexes and have normal toxidrome of mydriasis, hyperactive delirium, dry oral mucosa and skin, urinary retention, absence of bowel sounds (i.e dry as a bone)
SS–> hyepractive bowel sounds, clonus, hyperreflexia, tremor, diaphoresis, normal skin color (NOT dry as a bone)
how do you distinguish malignant hyperthermia from serotonin syndrome
MH–> after exposure to inhalational anesthesia; skin mottled, cyanotic areas, hyporeflexia
SS–> hyperreflexia
how do you distinguish NMS from serotonin syndrome
NMS generally evolves over several days
SS is more rapid onset and is generally hyperkinetic
are benzos safe to use in serotonin syndrome
yes
are antipsychotics (i.e olanzapine) safe to use in serotonin syndrome
yes, if indicated
is bromocriptine safe to use in serotonin syndrome
no–> worsens serotonin syndrome due to dopamine and serotonin agonist properties
is dantrolene safe to use in serotonin syndrome
no–> not indicated and may worsen outcomes or cause death
is there a single lab investigation that can diagnose serotonin syndrome
no
can see:
metabolic acidosis
rhabdo
elevated AST
elevated Cr
renal failure
DIC
what should you think if you see tremor, clonus, hyperreflexia or akathesia without other signs of EPS
?serotonin syndrome
where is the clonus associated with serotonin syndrome usually most pronounced
lower extremities
what is the single most important clinical finding suggestive of serotonin syndrome
clonus
what is the most important sign to check for when assessing for serotonin syndrome
deep tendon reflexes hyperreflexia
why should you avoid physical restraints in serotonin syndrome unless imminent emergency or risk of injury
may contribute to increased mortality by reinforcing ISOMETRIC muscle contractions that may cause severe LACTIC ACIDOSIS and HYPERTHERMIA
what are the first steps in treating serotonin syndrome
immediately d/c triggering serotonergic agent
supportive care–> IV fluids, correct vitals
control autonomic instability, hyperthermia and agitation
treatment of mild serotonin syndrome
supportive therapy
treatment of moderate serotonin syndrome
aggressively correct all cardiorespiratory and thermal abnormalities
may benefit from admin of 5HT2A antagonists
treatment of severe serotonin syndrome
all people with temp above 41.1 are severely ill
should receive supportive therapy + cardioresp and thermal correction + 5HT2A antagonist
PLUS
immediate sedation, neuromuscular paralysis and intubation
how do you manage agitation in serotonin syndrome
with benzos
why is management of agitation with benzos essential in management of all cases of serotonin syndrome
help blunt hyperadrenergic component of the syndrome
+ control the agitation
list 3 medications that are considered 5HT2A antagonists
cyproheptadine
olanzapine
chlorpromazine
what is cyproheptadine
a first generation antihistamine with anticholinergic, antiserotonergic and local anesthestic properties
how do you dose cyproheptadine in the case of serotonin syndrome treatment
initial dose of 12mg followed by 2mg q2h if symptoms continue
maintenance dose of 8mg q6h recommended
typically 12-32 mg given over 24 hour period will bind to 85-95% of serotonin receptors
what dose of olanzapine can be given in the case of treatment of serotonin syndrome
10mg IM/SL
is there a role for antipyretic agents in the management of serotonin syndrome
no–> the increase in temp is due to increase in muscular activity and not alteration in hypothalamic temp set point
