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SEROTONIN SYNDROME
ELIZABETH BOLDON, BSN, MSN
Elizabeth Boldon is a Nursing Education
Supervisor at Mayo Clinic in Rochester,
Minnesota. She oversees the Nurse Educators
in the Intensive and Progressive care units
and the Simulation Center. She has a passion
for nursing education and continues to teach
in areas such as recognition of the deteriorating patient, communication, and the
transition of new staff into practice. She received a BSN from Allen College in
Waterloo, Iowa in 2002 and an MSN with a focus in education from the University of
Phoenix in 2008. She has bedside nursing experience in medical neurology and the
neuroscience ICU.
ABSTRACT
Drugs can react to cause the body to have too much serotonin and
lead to serotonin syndrome, which is a potentially life threatening
condition. Serotonin syndrome is caused by therapeutic doses, drug
interactions, or overdoses of medications that directly or indirectly
affect the serotonergic system. An excess stimulation of the
serotonergic receptors is what causes serotonin syndrome. The
stimulation is excitatory and causes symptoms, such as tachycardia,
hypertension, agitation, excessive muscular activity. There is no
proven antidote for serotonin syndrome that is effective and safe. The
best treatment is supportive care. Health clinicians must consider the
possibility of serotonin syndrome in the setting of serotonergic
medications where mental status changes and neurological
hyperexcitability occur.
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Policy Statement
This activity has been planned and implemented in accordance with
the policies of NurseCe4Less.com and the continuing nursing education
requirements of the American Nurses Credentialing Center's
Commission on Accreditation for registered nurses. It is the policy of
NurseCe4Less.com to ensure objectivity, transparency, and best
practice in clinical education for all continuing nursing education (CNE)
activities.
Continuing Education Credit Designation
This educational activity is credited for 2.5 hours. Nurses may only
claim credit commensurate with the credit awarded for completion of
this course activity. Pharmacology content is 30 minutes.
Statement of Learning Need
Health clinician knowledge to identify serotonin syndrome and to help
patients avoid it is imperative to prevent an adverse clinical outcome.
Patients that are prescribed serotonergic medications need to be
educated and warned about the possibility of serotonin syndrome and
subtle changes that could lead to severe physical symptoms.
Course Purpose
To help clinicians identify signs and symptoms of serotonin syndrome
and to follow recommended treatment.
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Target Audience
Advanced Practice Registered Nurses and Registered Nurses
(Interdisciplinary Health Team Members, including Vocational Nurses
and Medical Assistants may obtain a Certificate of Completion)
Course Author & Planning Team Conflict of Interest Disclosures
Elizabeth Boldon, BSN, MSN, William S. Cook, PhD,
Douglas Lawrence, MA, Susan DePasquale, MSN, FPMHNP-BC –
All have no disclosures
Acknowledgement of Commercial Support
There is no commercial support for this course.
Please take time to complete a self-assessment of knowledge,
on page 4, sample questions before reading the article.
Opportunity to complete a self-assessment of knowledge
learned will be provided at the end of the course.
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1. Which of the following is the correct definition of serotonin
syndrome?
a. Signs and symptoms caused by excessive stimulation of the
serotonergic system.
b. Signs/symptoms caused by serotonergic drug overdose.
c. A clinical condition that closely resembles neuroleptic
malignant syndrome.
d. A clinical condition characterized hyperthermia, clonus, and
agitation.
2. Which of these classes of drugs inhibits the reuptake of
serotonin?
a.
b.
c.
d.
Common analgesics
Illicit drugs
Sympathomimetics
SSRIs
3. Three illicit drugs that may cause serotonin syndrome are:
a.
b.
c.
d.
Methamphetamine, heroin, marijuana
Cocaine, LSD, ecstasy
Marijuana, ecstasy, cocaine
Dextromethorphan, LSD, methamphetamine
4. The criteria used to diagnose serotonin syndrome is/are
a.
b.
c.
d.
Sternbach’s criteria
the Hunter criteria
Modified Glasgow scale
Romberg criteria
5. True or False: Neuroleptic malignant syndrome may be
mistaken for serotonin syndrome.
a. True
b. False
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Introduction
Serotonin syndrome is a group of signs and symptoms caused by
excessive stimulation of the serotonin receptors. Serotonin syndrome
is caused by therapeutic drug doses, drug interactions, or overdoses of
drugs that directly or indirectly affect the serotonergic system. The
clinical presentation of serotonin syndrome can be intense and
dramatic, but it can also be mild and subtle. Serotonin syndrome can
be mistaken for an infectious or metabolic disorder or for the clinical
syndromes caused by anticholinergic or sympathomimetic poisoning,
and for the neuroleptic malignant syndrome or malignant
hyperthermia. Although it is unusual for serotonin syndrome to cause
a fatality, a severe case is a medical emergency that can rapidly cause
multisystem organ failure. Medical and nursing clinicians must be
aware of serotonin syndrome because drugs that can cause it are in
common use, and intentional overdoses with drugs that can cause
serotonin syndrome are being seen with increasing frequency. This
makes it difficult to detect and clinicians can easily mistake serotonin
syndrome for other pathologies.
Serotonergic System
Serotonin (also called 5-hydroxytryptamine) is a monoamine
neurotransmitter that acts centrally and peripherally. It is synthesized
in the central nervous system and in enterochromaffin cells in the
gastrointestinal (GI) tract. Serotonin has many complex functions, and
the full range and activity of these is not known.1
In the brain, serotonin is involved in mood, personality, appetite,
motor function, temperature regulation, sexual activity, pain
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perception, and sleep induction. Serotonin also inhibits gastric
secretion, acts as a smooth muscle stimulant, promotes platelet
aggregation, affects vascular tone, and is a central and peripheral
neurotransmitter.1
Serotonin is stored in vesicles in
presynaptic neurons. It is
released into the synaptic cleft
and binds to a serotonin receptor
on the postsynaptic neuron.
There are seven families of
serotonin receptors (5-HT1 to
5HT7) and several of these have
different subtypes, for example,
5-HT1A. Serotonin binding to a 5HT receptor initiates a wide
variety of effects on the postsynaptic neuron (decreasing or
increasing intracellular cAMP
levels, causing Na+ and Ca2+ influx and depolarization action), however
the basic effect of serotonin is excitatory. After binding to the receptor,
serotonin is transported back to the presynaptic neuron where it
reenters the vesicles or is broken down by monoamine oxidase.1
Neurotransmitters such as serotonin, dopamine, and glycine, function
by binding to receptors on the membranes of post-synaptic neurons.
These receptors are ligand-gated ion channels or G protein receptors.
When a neurotransmitter binds to a ligand-gated ion channel, the
channel opens and ions enter or leave the cell: depending on which
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ions enter or leave, the effect of the neurotransmitter can be
excitatory (causing cell depolarization) or inhibitory (preventing cell
depolarization). When a neurotransmitter binds to a G protein, the
same effects occur.
When serotonin binds to G proteins of the 5-HT1 receptors, potassium
ions channels open, potassium leaves the cell – increasing membrane
potential and inhibiting depolarization – and cAMP concentrations are
decreased, and the effect is inhibitory. It is important to remember
that the terms inhibition and excitation refer to how the
neurotransmitter affects the cell. The physiological action produced by
excitation may be a decrease in a particular function (i.e., decreased
peristalsis) and the physiological action produced by inhibition may be
an increase in a particular function (i.e., muscle tremor or
hyperreflexia).
Serotonin Syndrome: Epidemiology
Serotonin syndrome is not a recent phenomenon. It was first
recognized in animals, and the first case described in a human was
reported in 1959; however, case reports of unrecognized serotonin
syndrome predate that by at least 20 years.2 The term serotonin
syndrome was first used by Insel, et al. in 1982 to describe a patient
who developed serotonin syndrome from a combination of a
monoamine oxidase (MAO) inhibitor and a tricyclic antidepressant.2,3
The exact incidence of serotonin syndrome is not known. Prior
research investigating the use of selective serotonin reuptake
inhibitors (SSRIs) compared to other antidepressant medication report
that SSRIs rarely result in serious outcomes and death. Tricyclic
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antidepressants and monoamine oxidase inhibitors (MAOIs) have been
found to be more toxic than SSRIs. It has been found that 31 to 32
percent of TCA ingestions required intubation as compared to 4% to
6% of SSRI ingestions. Similarly, 31% to 35% of TCA ingestions
required intensive care unit admission as compared with 0% to 6% of
SSRI ingestions. Death rates were reported as 1.6 per million for SSRI
prescriptions as compared with 34.8 for TCAs and 20 for MAOIs.4
Serotonin syndrome has been described in all ages groups, including
neonates, children, and the elderly.
Clinical Presentation of Serotonin Syndrome
The essential cause of serotonin syndrome is an excess stimulation of
the serotonergic receptors. The stimulation is excitatory and causes
tachycardia, hypertension, agitation, and excessive muscular activity
and other signs and symptoms of the syndrome. The excess
stimulation occurs by one of the following six mechanisms.4-6
Direct Stimulation of the Serotonergic Receptors
Direct stimulation of the serotonergic receptors occurs with the
medications of buspirone, carbamazapine, lithium, as well as with the
psychedelic drug LSD.
Excessive Release of Serotonin
Excessive release of serotonin occurs with amphetamines, cocaine,
dextromethorphan, levodopa, monoamine oxidase inhibitors,
reserpine, as well as with ecstasy/MDMA.
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Decreased Breakdown of Serotonin
Decreased breakdown of serotonin occurs with monoamine oxidase
inhibitors and St. John’s wort.
Enzyme Inhibition
Cytochrome P450 enzymes that metabolize certain serotonergic drugs
can be inhibited by these drugs, i.e., dextromethorphan, methadone,
oxycodone, tramadol, venlafaxine.
Increase in Serotonin Precursors
Increase in serotonin precursors occurs with the essential amino acid,
Tryptophan.
Decreased Serotonin Reuptake
Decreased serotonin reuptake occurs with selective serotonin-reuptake
inhibitors (SSRIs), such as citalopram, escitalopram, fluoxetine,
fluvoxamine, paroxetine, and sertraline, as well as, with
dextromethorphan, monoamine oxidase inhibitors, methadone, and
trazodone. It is not known exactly what families and subtype of
serotonin receptors are involved in serotonin syndrome, which could
be one of the factors accounting for the variability of the clinical
presentation of this pathology. Some authors, however, have identified
the 5-HT1C and the 5-HT2 receptors as the ones affected in cases of
serotonin syndrome.
Although there is a wide range of signs and symptoms that are
possible, serotonin syndrome is definitely characterized and diagnosed
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by abnormal autonomic, cognitive, and neuromuscular changes.5,6
These are further outlined below:

Autonomic:
Autonomic changes include hyperthermia, hypertension,
tachycardia, diaphoresis, flushing, increased bowel sounds,
diarrhea, and mydriasis. The hyperthermia can be very severe
with a body temperature ≥ 38.5° C and higher.

Cognitive:
There are many cognitive changes associated with serotonin
syndrome such as agitation, drowsiness, coma, hypomania,
anxiety, confusion, hallucinations, and delirium.

Neuromuscular:
Symptoms may include akathisia, clonus, hyperreflexia,
myoclonus, rigidity, shivering, and tremor.
Clonus (inducible, ocular, or spontaneous) is the most reliable finding
when diagnosing serotonin syndrome. Clonus is defined as alternate
muscular contraction and relaxation in rapid succession. The signs and
symptoms reviewed above have been observed in patients who have
serotonin syndrome. The clinical presentation and the severity of signs
and symptoms are quite variable; serotonin syndrome can be mild and
quite subtle in presentation or severe and life threatening.
Patients with a mild case of serotonin syndrome may feel restless and
anxious, they may have a low-grade fever, and mild, intermittent
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tremors, and it is easy to overlook or misdiagnose these types of
cases. A severe case of serotonin syndrome is a medical emergency.
These patients may have a body temperature >41° C. Coma,
metabolic acidosis, renal failure, rhabdomyolysis, and disseminated
intravascular coagulation (DIC) may occur and all of this can develop
very rapidly.7
Serotonin syndrome typically begins very quickly. Onset can be within
minutes after exposure. In most cases the patient will develop signs
and symptoms within six hours after exposure to a drug or drugs, but
a delay of up to 24 hours is possible. Most cases resolve within 24
hours, but there have been reports of serotonin syndrome cases
lasting for several days.7-9
Drugs That Cause Serotonin Syndrome
Certain classes of medications have been definitively identified as
drugs that can cause serotonin syndrome, and this makes sense
because their therapeutic effect is based on their action on the
serotonergic system. The SSRIs such as fluoxetine and sertraline, and
monoamine oxidase inhibitors (MAOIs), such as phenelzine and
moclobemide, are common examples of these drugs.
Other drugs may cause serotonin syndrome. However, the connection
between the syndrome and the drug is not as obvious because many
drugs affect uptake or metabolism of multiple neurotransmitters that
does not always translate to a measurable or observable clinical effect.
Two such examples are bromocriptine and tramadol. Both drugs do
have an in vivo effect on the serotenergic system, but the therapeutic
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effect of bromocriptine is caused by dopamine receptor agonist
activity, and the therapeutic effect of tramadol is caused by agonism
of the mu opioid receptors. Yet, both bromocriptine and tramodol can
cause serotonin syndrome.
A recent study looked at delirium occurring in the ICU where an excess
of serotonin was found, which is associated with altered mental status.
Because drugs with serotonergic properties are frequently, for
extended times, administered to patients in ICUs it was theorized that
central serotonergic toxicity may constitute a predisposing,
contributing or precipitating factor in the emergence of delirium in the
ICU setting. Study findings suggested a significant number of patients
diagnosed with delirium had, in fact, drugs prescribed that potentially
contributed to serotonergic toxicity; 16% of patients showed physical
signs of serotonin toxicity and met the Hunter serotonin toxicity
criteria.
The potential for serotonin toxicity in patients, including in the ICU
setting, needs to be understood by clinicians, including the drugs and
supplements that cause it. Drugs associated with, or suspected of
causing serotonin syndrome include those outlined here.4,9-12
Sympathomimetics:
Fenfluramine, phentermine, phenylpropanolamine
5-HT1 Agonists:
Almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan,
sumatriptan, zolmitriptan
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Monoamine Oxidase Inhibitors (MAOIs):
Isocarboxazid, moclobemide, phenelzine, selegiline, and
tranylcypromine
Selective serotonin reuptake inhibitors (SSRIs):
Citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine,
sertraline
Tricyclic Antidepressants:
Amitriptyline, amoxapine, clomipramine, desipramine, doxepin,
imipramine, maprotiline, nortriptyline, protriptyline, trimipramine
Opiates/Analgesics:
Buprenorphine, codeine, levomethorphan, levorphanol, meperidine,
methadone, oxycodone, pentazocine, pethidine, tapentadol, tramadol,
fentanyl, hydrocodone, and meperidine
Antimigraine Medications:
Triptans, carbamazepine and valproic acid
Illicit Drugs:
Amphetamine, bath salts, cocaine, ecstasy/MDMA, LSD (unconfirmed)
Antidepressants and Anxiolytics:
Bupropion, buspirone, duloxetine, mirtazapine, nefazodone, trazodone,
venlafaxine.
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Antiemetics:
Droperidol, granisetron, metoclopramide, ondansetron
Dietary Supplements/Herbal Product:
Ginseng, St. John’s wort, tryptophan, yohimbe
Other Drugs:
Amantadine, bromocriptine, carbamazapine, carisoprodol,
chlorpheniramine, dextromethorphan, dihydroergotamine, fluconazole,
levodopa, linezolid, lithium, methylene blue, olanzapine, reserpine,
ritonavir, and 5-methoxydiisopropyltryptamine (a.k.a. foxy methoxy)
An increased dose of a serotonergic drug, or the addition of a
serotonergic drug to the medication regimen of a patient already
taking a SSRI, MAO, or others (discussed further below) usually
causes serotonin syndrome. It can also be a consequence of overdose.
Serotonin syndrome after a single dose of a serotonergic drug is
unusual, but this has been reported. It is far more common for
serotonin syndrome to be caused by a combination of drugs that act at
different 5-HT receptor sites.4-6
Drug interactions can also be a cause of serotonin syndrome, even if
one of the drugs does not affect the serotonergic system. If a patient
who is taking an SSRI is prescribed a medication that inhibits the
cytochrome P450 enzyme that metabolizes the SSRI, serotonin
syndrome is possible.
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Furthermore, discontinued serotonergic medications can cause
serotonin syndrome if there is an insufficient period of time between
the discontinuation of one medication and beginning therapy with
another. An example is Norfluoxetine, which is a metabolite of
fluoxetine that has a half-life of approximately 2.5 weeks. Because of
the long half-life of this drug and its metabolite, fluoxetine may cause
serotonin syndrome if a patient is given another serotonergic drug
within several weeks of the discontinuation of fluoxetine.
It’s important for health clinicians to continuously review an approved
drug database for current information when prescribing or
administering any form of mono- or combination drug therapy. Drugdrug interactions are one possible cause of serotonin syndrome.
Underlying medical conditions must also be considered. The list below
includes known drug combinations that can cause serotonin syndrome,
and the FDA continuously provides updates on drug combinations and
case reports alerting clinicians to the potential for serotonin toxicity.

MAOIs and amphetamines, dextromethorphan, meperidine,
SSRIs, TCAs, and serotonin-norepinephrine re-uptake inhibitors
(SNRIs).

SSRIs and amphetamines, buspirone, carbamazapine,
dextromethorphan, fluconazole, MAOIs, opiates, L-tryptophan,
phentermine, SNRIs, other SSRIs, TCAs, or St John’s wort.

Opiates and ciprofloxacin, MAOIs, SSRIs, SNRIs, or tramadol.

Tramadol and mirtazapine, olanzapine, opiates, SSRIS, or
sertraline.

Other antidepressants, such as buspirone and SSRIs;
mirtazapine and SSRIs; trazodone and amitriptyline, buspirone, or
lithium; venlafaxine and amitriptyline, ciprofloxacin, fluoxetine or
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other SSRIs, linezolid, lithium, meperidine, methadone,
moclobemide, quietiapine, or trazodone.

Atypical antipsychotics and mood stabilizers, such as Olanzapine
and citalopram or lithium, risperidone and dextromethorphan,
fluoxetine, or paroxetine.

Linezolid and amitriptyline, citalopram, duloxetine escitalopram,
fentanyl, fluoxetine, meperidine, paroxetine, sertraline, and
venlafaxine.
Severe cases of serotonin syndrome appear to be more common if
multiple drugs are taken than when a single serotonergic drug is taken
in overdose or therapeutically. Monoamine oxidase inhibitors are
particularly dangerous when combined with selective serotoninreuptake inhibitors, ecstasy, dextromethorphan, or meperidine.
Diagnosing Serotonin Syndrome
Serotonin syndrome is a clinical diagnosis. There is no way to confirm
the diagnosis by using laboratory tests. The clinician must make the
diagnosis of serotonin syndrome by: 1) a physical exam, 2) taking a
health and medication history, and 3) ruling out other clinical
syndromes that can resemble serotonin syndrome.
Outlined in that manner, making the diagnosis of serotonin syndrome
might appear to be relatively simple, but it can be difficult to do. Mild
or even moderately symptomatic cases can easily be overlooked or
misdiagnosed. For example, serotonin syndrome has been frequently
misdiagnosed as neuroleptic malignant syndrome (NMS), which can be
differentiated through careful history taking and physical evaluation,
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and by bearing in mind that serotonin syndrome develops over 24
hours as compared to symptom development over days to weeks.
Diagnostic Criteria
Although making the diagnosis of serotonin syndrome can be
challenging, there are different diagnostic criteria available that can
help.
Sternbach’s Criteria
Sternbach’s criteria were the first developed for diagnosing serotonin
syndrome. Sternbach’s criteria involves a list of 10 clinical findings and
three clinical situations.4,5,16 The clinical findings of Sternbach’s criteria
are: 1) ataxia, 2) changes in mental status (agitation, confusion,
hypomania), 3) diaphoresis, 4) diarrhea, 5) fever, 6) hyperreflexia,
7) myoclonus, 8) restlessness, 9) shivering, and 10) tremor.
The clinical situations are: 1) a recent addition, or increase in dose of a
known serotonergic drug, 2) confirmed absence of other etiologies that
could explain the patient’s clinical condition such as an infectious
disease, metabolic abnormality, or substance intoxication or
withdrawal, and 3) no recent addition or increase in dose of a
neuroleptic drug.
According to Sternbach’s criteria, a patient has serotonin syndrome if
the patient has three or more of the clinical findings and the patient
has been exposed to a serotonergic drug, has not been exposed to a
neuroleptic, and other likely causes of the signs and symptoms have
been ruled out.
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Hunter Criteria
The Hunter criteria were developed in 2003. The authors were
dissatisfied with Sternbach’s criteria, and they reviewed 2,222 cases of
serotonergic drug overdose. The physical findings in these patients
were noted, and then the ones that were seen most often in patients
who been diagnosed by a clinical toxicologist as having serotonin
syndrome were considered to be the criteria for diagnosing serotonin
syndrome.4,5,16
The Hunter criteria state that a patient has serotonin syndrome if they
have taken a serotonergic agent and meet one of the following
conditions:

Spontaneous clonus

Inducible clonus PLUS agitation or diaphoresis

Ocular clonus PLUS agitation or diaphoresis

Tremor PLUS hyperreflexia

Hypertonia PLUS temperature above 38ºC PLUS ocular clonus or
inducible clonus
Radomski Criteria
The Radomski criteria were developed in 2000 and use many of the
same clinical findings as Sternbach’s criteria and the Hunter criteria.
However, the Radomski criteria are intended to provide diagnostic
criteria for establishing the severity of the serotonin syndrome.4,5,16
The Hunter criteria (or those criteria slightly adapted) is the system
that is used most often and is recommended. The Sternbach criteria
appear to be biased towards mental status changes, and the Hunter
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criteria are felt to be more sensitive and specific and less likely than
the Sternbach criteria to miss incipient or mild cases of serotonin
syndrome. The Radomski criteria do not appear to be popular and
although other diagnostic criteria have been developed (i.e., the
serotonin syndrome scale) these do not appear to be in common use.
THE HUNTER CRITERIA
Ingestion of a serotonergic drug within 5 weeks
or overdose of a serotonergic drug
↓
Spontaneous clonus → Yes → Serotonin syndrome
↓
No
↓
Inducible clonus, ocular clonus → Yes → Agitation,
↓
diaphoresis,
No
fever > 38°
↓
Tremor → Yes → Hyperreflexia →
Serotonin Syndrome
↓
No
↓
Not Serotonin Syndrome
It has been suggested by some researchers that the term serotonin
syndrome may contribute to the confusion surrounding this condition
and the under-diagnosis of serotonin syndrome.5 The work of Dunkley,
et al. has been referenced in ongoing reviews on serotonin syndrome,
which suggested that the diagnostic criteria - or perhaps the
physicians using these criteria - overemphasized the more dramatic
signs of serotonin syndrome. This may result in milder forms of the
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syndrome being missed; hence the suggestion that serotonin toxicity
might be a better term than serotonin syndrome as a syndrome is
typically thought of as a defined clinical entity.
The key point clinicians must realize is that serotonin syndrome is a
spectrum of toxicity that is caused by an excess of serotonin.
Serotonin syndrome along the spectrum can be diagnosed by using the
Hunter criteria to look for the characteristic autonomic, cognitive, and
neuromuscular changes.
Health and Medication History
Taking an accurate health and medication history is very important. It
is fundamental to determine what medications the patient is taking
and has been taking. The clinician must be cognizant of the fact that
some drugs can cause serotonin syndrome even when the patient has
not been taking them for many weeks.
It is good practice for clinicians to ask patients whether medication
doses have recently been changed. Additionally, clinicians should ask if
the patient has been taking any dietary or herbal supplements, and
determine if the medication regimen has been changed in the past five
to six weeks. The clinician will also need to determine the recent state
of the patient’s health; for example, whether there was any evidence
of an ongoing infectious process and other medical conditions the
patient may report. Each time clinicians review patient medication
regimes it’s necessary to include both the existing treatment plan (i.e.,
new medications, and how they have been taking their prescriptions)
and any new organic issues in the patient’s health state.
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Serotonin Toxicity In The Newborn
Although outside the scope of this study, clinicians should be aware of
current considerations given to serotonin toxicity in newborns. The
literature on SSRI effects on newborns is generally obtained from
health databases and case reports. Investigators note that the
predominant data pertains to paroxetine, fluoxetine and sertraline,
which are the most prescribed SSRIs for pregnant women, correlating
with 10% to 30% of newborn babies showing symptoms of respiratory,
motor, central nervous system and gastrointestinal symptoms,
including tachypnea, cyanosis, jitteriness/tremors, increased muscle
tone, and feeding disturbance. Newborn babies exposed in utero will
manifest mild signs and symptoms of serotonin toxicity usually within
hours that resolve within two weeks. Rarely have seizures been
reported.15
Once the baby is born the exposure to SSRI medication stops. The
signs and symptoms observed in newborns exposed in utero to SSRI
may be due to neonatal withdrawal, neonatal toxicity following in utero
exposure or a combination of both withdrawal and serotoninergic
toxicity. Since symptoms resolve after birth, these signs and
symptoms have been termed neonatal abstinence syndrome. Canadian
researchers also coined the phrase SSRI neonatal behavioural
syndrome (SNBS) to describe these signs and symptoms.15 The most
serious potential outcome related to SSRI in utero exposure noted by
some researchers is persistent pulmonary hypertension of the newborn
(PPHN), which is associated with significant infant morbidity and
mortality.15 However, the association of PPHN to maternal use of SSRI
during pregnancy has not been confirmed by subsequent studies.
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While the research is ongoing on the effects of in utero exposure to
SSRI, to date, studies have shown that paroxetine and fluoxetine have
been found to cause neonatal abstinence syndrome more than any of
the other serotonergic drugs. PPHN may be a rare occurrence related
to fetal exposure to SSRIs, although this remains under investigation.
Also, other potential health outcomes to newborns exposed to SSRIs in
utero include low birth weight and gestational age, respiratory distress
and possible admission to the neonatal intensive care unit (NICU).
There is no evidence of adverse effects on the infant exposed to SSRIs
during the course of breastfeeding. All of the current research and
hypotheses related to infant exposure to SSRIs require ongoing review
involving population-based studies and case outcomes.
Clinical Conditions Resembling Serotonin Syndrome
This section covers some clinical conditions that can resemble
serotonin syndrome.2,10,16
Neuroleptic Malignant Syndrome
Neuroleptic malignant syndrome (NMS) is an idiosyncratic drug
reaction to treatment with, or withdrawal from drugs such as levodopa
and antipsychotics that act as dopamine antagonists. Important
differences between serotonin syndrome and NMS are:

The causative agents act on a different neurotransmitter

NMS develops slowly over several days

The clinical findings are different than those of serotonin
syndrome, i.e., the pupils are not mydriatic, the patient will have
normal bowel sounds, and bradyreflexia and a rigid “lead-pipe
like” muscle tone will be noted

NMS is not caused by an overdose
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Anticholinergic Syndrome
The anticholinergic toxidrome (or syndrome caused by a dangerous
drug level) is caused by overdose of drugs that act as antagonists of
acetylcholine at peripheral and central muscarinic receptors; examples
are antihistamines, benztropine, and phenothiazines. Important
differences between serotonin syndrome and anticholinergic syndrome
are highlighted below.

The causative agents act on a different neurotransmitter
receptor site

The temperature is usually 38.8°C or less

The patient will have dry mucous membranes, hot, dry, and
flushed skin, decreased or absent bowel sounds, normal
muscular tone and reflexes, and urinary retention
Malignant Hyperthermia
Malignant hyperthermia is an idiosyncratic response to inhalational
anesthesia. Important differences between serotonin syndrome and
malignant hyperthermia are:

The causative agent

Malignant hyperthermia is an idiosyncratic response, but
serotonin syndrome is a normal physiological response to an
excess of a neurotransmitter

The patient will have hyporeflexia and the temperature is
extremely high, as high as 46°C
Other clinical conditions that could be mistaken for serotonin syndrome
include acute baclofen overdose, cocaine or ecstasy intoxication, drug
withdrawal, dystonic reactions, encephalitis, meningitis, non-
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convulsive seizures, sympathomimetic syndrome caused by a large
dose (or an overdose of sympathomimetic drugs), sepsis, serotonin
discontinuation syndrome, thyroid storm, and tetanus.
There are many clinical conditions that can be mistaken for serotonin
syndrome, and trying to remember them all and their distinguishing
features can be difficult for clinicians. However, by far the most
commonly occurring are NMS and anticholinergic syndrome. To
distinguish between NMS, anticholinergic syndrome and serotonin
syndrome, the clinician needs to pay special attention to: 1) The drug
ingested, 2) Body temperature, 3) Onset and development of the signs
and symptoms, 4) Bowel sounds, 5) Presence or absence of
hyperreflexia, and 5) Presence or absence of clonus.
Serotonin Discontinuation Syndrome
When checking for the presence of serotonin syndrome, it is important
to know what medications the patient has been taking, as was
previously raised. However, if a symptomatic patient had been taking
an SSRI or another drug that affects the serotonergic system, this can
confuse the issue of assessment because if these drugs are not
tapered correctly the patient may develop serotonin discontinuation
syndrome. The syndrome occurs in approximately 20% to 33% of all
patients who stop taking a serotonergic drug.18
The signs and symptoms of serotonin discontinuation syndrome
usually start within one to seven days of decreasing the dose or
discontinuing the drug and they last approximately two weeks.
Somatic signs and symptoms of serotonin discontinuation syndrome
include chills, diarrhea, dizziness, fatigue, fever, nausea, paresthesias,
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unsteady gait, and vomiting. Mood disturbances such as agitation,
anxiety, insomnia, irritation, and lethargy are common, as well.18 Most
cases are mild, but severe effects have been reported.
Treatment Of Serotonin Syndrome
Most cases of serotonin syndrome will improve dramatically or resolve
within 24 hours but if the patient has taken a drug with a long half-life,
a drug with pharmacologically active metabolites, or an extended
release form of a drug, the signs and symptoms can last for weeks.
Mild cases can be observed for six hours and if the patient responds
well to treatment or improves spontaneously, he/she can be
discharged. Those with moderate and severe cases should be
admitted, and patients who have ingested an extended release
preparation should be admitted or observed for longer than six
hours.2,4-6,20
Serotonin syndrome can be caused by an overdose of serotonergic
medications, but what is considered to be an overdose? The amount of
medication that could cause serotonin syndrome cannot be precisely
quantified, but evidence-based clinical guidelines for the SSRIs are
available to help guide clinical decision-making. The U.S. Food and
Drug Administration (FDA) publishes updated safety alerts relative to
drugs that can cause serotonin toxicity, and list serotonergic drugs to
avoid or monitor, if prescribed. For example, in March 2016 a FDA
Safety Alert announced that “Opioids can interact with antidepressants
and migraine medicines to cause a serious central nervous system
reaction called serotonin syndrome, in which high levels of the
chemical serotonin build up in the brain and cause toxicity.”19
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The majority of serotonin syndrome cases occur because of the
ingestion of synergistic medication either unintentionally or
intentionally. Drugs known to inhibit the cytochrome P450 2D6 and/or
3A4 (CYP3A4) isoenzymes are often implicated as causing serotonin
syndrome when added to therapeutic regimens of selective serotonin
reuptake inhibitors (SSRIs). In one case report, serotonin syndrome
was precipitated in a 12-year-old patient taking a stable dosage of
sertraline when erythromycin, a CYP3A4 inhibitor, was also prescribed.
A remarkable number of drugs from different classes have been
implicated as causing serotonin syndrome.21 Most reported cases are
in patients taking multiple serotonergic agents or who have had
considerable exposure to a single serotonin-augmenting drug.
Death from serotonin syndrome is unusual, but severe cases do occur
and the condition of patients who have severe serotonin syndrome
deteriorates very quickly. Patients who have severe serotonin
syndrome should be admitted to intensive care. The use of the drugs
suspected of causing the serotonin syndrome must be immediately
stopped; in mild cases this may be enough to allow the patient to
recover.4,5
In order to avoid serious harm and to successfully treat serotonin
syndrome, it is critical to quickly identify serotonin syndrome and
aggressively provide supportive care. Antidotal therapies have been
tried, but supportive care is the keystone of caring for a patient who
has serotonin syndrome.
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Supportive Care
The mainstay of treatment for serotonin syndrome is supportive care.
It includes the following diagnostic tests and therapy.4-6
Laboratory Tests
If the diagnosis of serotonin syndrome is thought to be likely or the
diagnosis seems certain, BUN and creatinine, coagulation studies,
complete blood count (CBC), creatine phosphokinase, and serum
transaminases should be obtained.
Other tests that may be needed for making the diagnosis of serotonin
syndrome would be blood cultures, urinalysis and urine culture,
cerebrospinal fluid analysis and culture, chest X-ray, and CT scan of
the head.
Aggressive Cooling
Aggressive cooling should be used for patients who are hyperthermic.
Acetaminophen will not help because hyperthermia in serotonin
syndrome is caused by excessive muscular activity, not by a change in
central thermoregulation.
Intubation and Neuromuscular Paralysis
Intubation and neuromuscular paralysis will treat the hyperthermia as
well as the basic cause of hyperthermia. The neuromuscular blocker
succinylcholine should not be used during the intubation process. A
nondepolarzing drug such as vercuronium should be used.
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Patients who are hyperthermic often have rhabdomyolysis.
Rhabdomyolysis increases serum potassium and increases the risk of
arrhythmias, and succinylcholine can cause hyperkalemia.
Benzodiazepines
Benzodiazpines are one of the mainstays of treatment for serotonin
syndrome, and in animal models they have been shown to increase
survival rates. They decrease muscular rigidity, provide sedation and
their use alone may be all that is needed for a mild to moderate case
of serotonin syndrome.
Direct-acting Sympathomimetic
If the patient is hypotensive a direct-acting sympathomimetic should
be used; i.e., epinephrine, norepinephrine, or phenylephrine.
Dopamine acts indirectly. It must be metabolized to epinephrine and
norepinephrine before it can work and in cases of serotonin syndrome
the metabolizing enzyme (monoamine oxidase) may be inhibited.
Nitroprusside
Nitroprusside is a good drug to use for treating hypertension caused
by serotonin syndrome because its effects are very short-acting; the
half-life of nitroprusside is two to three minutes. The autonomic
instability in severe cases of serotonin syndrome means that blood
pressure can be very unstable and unpredictable so using a drug that
can be tightly controlled is a big advantage.
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Hydration Status
Hydration is a very important treatment for serotonin syndrome.
Intravenous infusion for severe volume depletion is recommended.
Complications of Serotonin Syndrome
There should be monitoring of the complications of serotonin
syndrome, which are coma, disseminated intravascular coagulation
(DIC), metabolic acidosis, renal failure, and rhabdomyolysis.
Special Therapies
There is no antidote for serotonin syndrome that has been proven to
be effective and safe or for which there is extensive clinical evidence.
Bromocriptine, chlorpromazine, cyproheptadine, dantrolene,
intravenous lipid, olanzapine, propranolol, and other drugs/therapies
have been used. However, the evidence that supports or does not
support the use of these drugs can be categorized as Level II, and
there are no controlled studies that compare these drugs or truly
determine their efficacy. For example, there are case reports that
suggest use of chlorpromazine, cyproheptadine, and olanzapine helped
control and shorten the duration of the signs and symptoms of
serotonin syndrome, but it may simply be that these cases
represented a natural process of recovery and the drugs had no effect.
The drugs associated with the treatment of serotonin syndrome are
reviewed below.
Chlorpromazine
Chlorpromazine (commonly known as Thorazine®) is an antipsychotic.
The therapeutic effect of chlorpromazine is due to its action as a
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centrally acting dopamine antagonist. But chlorpromazine also blocks
serotonin binding to 5-HT2A receptors and there are several case
reports of chlorpromazine being an effective drug for treating
serotonin syndrome. However, chlorpromazine can cause hypotension,
it can cause dystonias, and it may aggravate hyperthermia, so it
should be used cautiously when treating serotonin syndrome.
Chlorpomazine is contraindicated for treating NMS because it is a
dopamine antagonist.
Cyproheptadine
Cyproheptadine (Periactin®) is an antihistamine that acts as a 5-HT2A
antagonist, and it has been successfully used to treat cases of
serotonin syndrome, and, in some of these case reports, the resolution
of the signs and symptoms was rapid and considerable. However,
treatment failures have been noted, and several authors point out that
although cyproheptadine may be helpful it does not shorten the time
course of serotonin syndrome. Cooper, B.E. (2013) noted there are no
controlled studies that have evaluated the use of cyproheptadine for
the treatment of serotonin syndrome, the evidence for its efficacy is all
from case reports, and these case reports described mild to moderate
cases of serotonin syndrome.20 Despite these uncertainties,
cyproheptadine is still recommended as an adjunct, as it is a serotonin
receptor antagonist and has sedative properties.
Cyproheptadine is given orally, and if the patient cannot tolerate oral
intake it can be crushed and given via a nasogastric tube. The dose is
12 mg followed by 2 mg doses every two hours if the symptoms
persist. The maintenance dose is 8 mg every six hours. The pediatric
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dosing is 0.25 mg/kg/day, every two hours until improvement of
symptoms.
Olanzapine
Olanzapine (Zyprexa®) is an atypical antipsychotic. One of its actions
is 5-HT2 receptor antagonism, and sublingual olanzapine has been
used successfully to treat cases of serotonin syndrome. Although most
of the patients studied had a very quick and complete resolution of
their signs and symptoms, the clinical experience with using
olanzapine to treat these cases consists of small case trials.
Bromocriptine
Bromocriptine has been used to treat serotonin syndrome. However, it
has serotonergic effects and its use has caused one fatality. The drug
should not be used to treat serotonin syndrome.
Dantrolene
Dantrolene is a skeletal muscle relaxant that is used to treat malignant
hyperthermia. It should not be used to treat serotonin syndrome.
There is no clinical evidence that it is effective, and, animal studies
showed that it is not effective. Dantrolene may actually cause
serotonin syndrome, and its use in a suspected case of serotonin
syndrome was associated with a fatality.
Propranolol
Propranolol acts as a 5-HT1A antagonist but it can cause hypotension.
It also decreases heart rate, making it difficult to assess the patient’s
condition. It should not be used to treat serotonin syndrome.
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Intravenous Lipid
There is one case report of intravenous lipid being used for the
treatment of serotonin syndrome. The authors noted that there was a
temporal association between administration of the lipid therapy and a
decrease in hyperreflexia and rigidity.
Summary
Serotonin syndrome is a group of signs and symptoms caused by
excessive stimulation of serotonin receptors. Serotonin syndrome is
caused by therapeutic doses, overdoses, or drug interactions between
medications that directly or indirectly affect the serotonergic system.
Direct stimulation of serotonin receptors, decreased breakdown of
serotonin, increased inhibition of serotonin reuptake, an increase in
serotonin precursors, or an excessive release of serotonin cause
serotonin syndrome.
Medications that can cause serotonin syndrome include SSRIS, MAOIs,
illicit drugs such as cocaine and amphetamines, atypical
antipsychotics, and analgesics such as fentanyl, meperidine, and
tramadol, and dextromethorphan. The incidence and severity of
serotonin syndrome are greatest when multiple drugs have been
ingested. A particularly dangerous drug combination is the MAOIs
combined with SSRIs, dextromethorphan, ecstasy, or meperidine.
Serotonin syndrome is characterized by autonomic, cognitive, and
neuromuscular derangements. Agitation, tachycardia, hypertension,
hyperthermia, muscle rigidity, clonus, hyperreflexia, diaphoresis,
diarrhea are commonly seen. Signs and symptoms usually start within
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six hours, and typically last 24 hours. Clonus (inducible, spontaneous
or ocular) is the most reliable clinical finding for diagnosing serotonin
syndrome.
To distinguish serotonin syndrome, determine what drug was ingested,
determine when the signs and symptom started, observe for clonus
and hyperreflexia, and check body temperature and bowel sounds. A
severe case of serotonin syndrome is a medical emergency; patients
who have severe serotonin syndrome should be admitted to the
intensive care unit.
The best treatment for serotonin syndrome is supportive care.
Epinephrine, norepinephrine, or phenylephrine is recommended to
treat hypotension; alternatively, nitroprusside is recommended to
control hypertension. Additionally, aggressive cooling, neuromuscular
paralysis and intubation, benzodiazepines, and IV hydration were
raised as the most important and effective therapies.
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1. Which of the following is the correct definition of serotonin
syndrome?
a. Signs and symptoms caused by excessive stimulation of the
serotonergic system.
b. Signs/symptoms caused by serotonergic drug overdose.
c. A clinical condition that closely resembles neuroleptic
malignant syndrome.
d. A clinical condition characterized hyperthermia, clonus, and
agitation.
2. Which of these classes of drugs inhibits the reuptake of
serotonin?
a.
b.
c.
d.
Common analgesics
Illicit drugs
Sympathomimetics
SSRIs
3. Three illicit drugs that may cause serotonin syndrome are:
a.
b.
c.
d.
Methamphetamine, heroin, marijuana
Cocaine, LSD, ecstasy
Marijuana, ecstasy, cocaine
Dextromethorphan, LSD, methamphetamine
4. The criteria most often used and recommended to diagnose
serotonin syndrome are the
a.
b.
c.
d.
Sternbach criteria.
Hunter criteria.
Radomski criteria.
Romberg criteria.
5. True or False: Neuroleptic malignant syndrome may be
mistaken for serotonin syndrome.
a. True
b. False
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6. The diagnostic sign that is most reliably noted in cases of
serotonin syndrome is:
a.
b.
c.
d.
Hyperthermia
Hallucinations
Tremor
Clonus
7. The best therapy for serotonin syndrome and three specific
treatments include:
a. Supportive care: intubation, fluids, dantrolene
b. Supportive care: aggressive cooling, benzodiazepines,
cyproheptadine
c. Antidotal therapy: cyproheptadine, chlorpromazine
d. Discontinuation of the drug: supportive care
8. Drugs that should not be used to treat serotonin syndrome
are:
a.
b.
c.
d.
Cyproheptadine, acetaminophen
Dopamine, epinephrine, chlorpromazine
Olanzapine, tramadol, phenylephrine
Bromocriptine, dantrolene, propranolol
9. The causes of serotonin syndrome are:
a. Prolonged use of drugs that affect the serotonergic system.
b. Therapeutic use, overdose, or drug interaction
c. Improper tapering of medications that affect the serotonergic
system.
d. It is an inevitable consequence for some people who take
serotonergic drugs.
10. The three categories of signs/symptoms that are
diagnostic of serotonin syndrome are:
a.
b.
c.
d.
Cardiovascular, autonomic, cognitive
Metabolic, neuromuscular, cognitive
Cognitive, neuromuscular, autonomic
Psychiatric, metabolic, cardiovascular
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11. True or False: Serotonin is synthesized in the central
nervous system and in enterochromaffin cells in the
gastrointestinal (GI) tract.
a. True
b. False
12. When treating serotonin syndrome hyperthermia, during
the intubation process the clinician should use
a.
b.
c.
d.
the neuromuscular blocker succinylcholine.
chlorpomazine.
acetaminophen.
a nondepolarzing drug such as vercuronium.
13. Patients who are hyperthermic often have rhabdomyolysis,
which
a.
b.
c.
d.
leads to decreased or absent bowel sounds.
causes bradyreflexia and a rigid, lead-pipe like muscle tone.
increases serum potassium and the risk of arrhythmias.
leads to hypokalemia and urinary retention.
14. When a patient, who has the symptoms of serotonin
syndrome, has been taking an SSRI or another drug that
affects serotonergic system, the patient may develop
serotonin discontinuation syndrome
a.
b.
c.
d.
if these drugs are not stopped immediately.
if these drugs are not tapered correctly.
unless the dosage is increased.
if these drugs are combined with succinylcholine.
15. ______________ may actually cause serotonin syndrome,
and its use in a suspected case of serotonin syndrome was
associated with a fatality.
a.
b.
c.
d.
Dantrolene
Vercuronium
Chlorpromazine
Cyproheptadine
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CORRECT ANSWERS:
1. Which of the following is the correct definition of serotonin
syndrome?
a. Signs and symptoms caused by excessive stimulation of
the serotonergic system.
“Serotonin syndrome is a group of signs and symptoms
caused by excessive stimulation of the serotonin receptors.
The essential cause of serotonin syndrome is an excess
stimulation of the serotonergic receptors. The stimulation is
excitatory and causes the tachycardia, hypertension,
agitation, and excessive muscular activity and the other signs
and symptoms of the syndrome.”
2. Which of these classes of drugs inhibits the reuptake of
serotonin?
d. SSRIs
“Decreased serotonin reuptake occurs with selective
serotonin-reuptake inhibitors (SSRIs), such as citalopram,
escitalopram, fluoxetine, fluvoxamine, paroxetine, and
sertraline; as well as, dextromethorphan, monoamine oxidase
inhibitors, methadone, and trazodone.”
3. Three illicit drugs that may cause serotonin syndrome are:
b. Cocaine, LSD, ecstasy
“The essential cause of serotonin syndrome is an excess
stimulation of the serotonergic receptors. The stimulation is
excitatory and causes the tachycardia, hypertension,
agitation, and excessive muscular activity and the other signs
and symptoms of the syndrome. The excess stimulation
occurs by one of the following six mechanisms: ... Direct
stimulation of the serotonergic receptors occurs with the
medications of buspirone, carbamazapine, lithium, as well as
with the psychedelic drug LSD.... Excessive release of
serotonin occurs with amphetamines, cocaine,
dextromethorphan, levodopa, monoamine oxidase inhibitors,
reserpine, as well as with ecstasy/MDMA.”
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4. The criteria most often used and recommended to diagnose
serotonin syndrome are the
b. Hunter criteria.
“... the Radomski criteria are intended to provide diagnostic
criteria for establishing the severity of the serotonin
syndrome. The Hunter criteria (or those criteria slightly
adapted) is the system that is used most often and is
recommended. The Sternbach criteria appear to be biased
towards mental status changes, and the Hunter criteria are
felt to be more sensitive and specific and less likely than the
Sternbach criteria to miss incipient or mild cases of serotonin
syndrome. The Radomski criteria do not appear to be popular
and although other diagnostic criteria have been developed
(i.e., the serotonin syndrome scale) these do not appear to be
in common use.... Serotonin syndrome along the spectrum
can be diagnosed by using the Hunter criteria to look for the
characteristic autonomic, cognitive, and neuromuscular
changes.”
5. True or False: Neuroleptic malignant syndrome may be
mistaken for serotonin syndrome.
a. True
“Serotonin syndrome can be mistaken for an infectious or
metabolic disorder or for the clinical syndromes caused by
anticholinergic or sympathomimetic poisoning, or for the
neuroleptic malignant syndrome or malignant hyperthermia.”
6. The diagnostic sign that is most reliably noted in cases of
serotonin syndrome is:
d. Clonus
“Clonus - inducible, spontaneous or ocular- is the most
reliable clinical finding for diagnosing serotonin syndrome.”
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7. The best therapy for serotonin syndrome and three specific
treatments include:
b. Supportive care: aggressive cooling, benzodiazepines,
cyproheptadine
“The mainstay of treatment for serotonin syndrome is
supportive care. It includes the following diagnostic tests and
therapy.... Aggressive cooling should be used for patients who
are hyperthermic.... Benzodiazpines are one of the mainstays
of treatment for serotonin syndrome, and in animal models
they have been shown to increase survival rates....
Cyproheptadine (Periactin®) is an antihistamine that acts as
a 5-HT2A antagonist, and it has been successfully used to treat
cases of serotonin syndrome, and, in some of these case
reports, the resolution of the signs and symptoms was rapid
and considerable.”
8. Drugs that should not be used to treat serotonin syndrome
are:
d. Bromocriptine, dantrolene, propranolol
“Bromocriptine has been used to treat serotonin syndrome.
However, it has serotonergic effects and its use has caused
one fatality. The drug should not be used to treat serotonin
syndrome.... Dantrolene is a skeletal muscle relaxant that is
used to treat malignant hyperthermia. It should not be used
to treat serotonin syndrome. There is no clinical evidence that
it is effective, and, animal studies showed that it is not
effective. Dantrolene may actually cause serotonin syndrome,
and its use in a suspected case of serotonin syndrome was
associated with a fatality.... Propranolol acts as a 5-HT1A
antagonist but it can cause hypotension. It also decreases
heart rate, making it difficult to assess the patient’s condition.
It should not be used to treat serotonin syndrome.”
9. The causes of serotonin syndrome are:
b. Therapeutic use, overdose, or drug interaction
“Serotonin syndrome is caused by therapeutic doses, drug
interactions, or overdoses of medications that directly or
indirectly affect the serotonergic system.”
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10. The three categories of signs/symptoms that are
diagnostic of serotonin syndrome are:
c. Cognitive, neuromuscular, autonomic
“Serotonin syndrome is characterized by autonomic,
cognitive, and neuromuscular derangements.... Serotonin
syndrome along the spectrum can be diagnosed by using the
Hunter criteria to look for the characteristic autonomic,
cognitive, and neuromuscular changes.”
11. True or False: Serotonin is synthesized in the central
nervous system and in enterochromaffin cells in the
gastrointestinal (GI) tract.
a. True
“Serotonin (also called 5-hydroxytryptamine) is a monoamine
neurotransmitter that acts centrally and peripherally. It is
synthesized in the central nervous system and in
enterochromaffin cells in the gastrointestinal (GI) tract.”
12. When treating serotonin syndrome hyperthermia, during
the intubation process the clinician should use
d. a nondepolarzing drug such as vercuronium.
“Aggressive cooling should be used for patients who are
hyperthermic. Acetaminophen will not help because
hyperthermia in serotonin syndrome is caused by excessive
muscular activity, not by a change in central
thermoregulation.... Intubation and Neuromuscular Paralysis:
This will treat the hyperthermia as well as the basic cause of
hyperthermia. Do not use the neuromuscular blocker
succinylcholine during the intubation process. Use a
nondepolarzing drug such as vercuronium.... chlorpromazine
can cause hypotension, it can cause dystonias, and it may
aggravate hyperthermia, so it should be used cautiously when
treating serotonin syndrome. Chlorpomazine is
contraindicated for treating NMS because it is a dopamine
antagonist.”
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13. Patients who are hyperthermic often have rhabdomyolysis,
which
c. increases serum potassium and the risk of arrhythmias.
“Patients who are hyperthermic often have rhabdomyolysis.
Rhabdomyolysis increases serum potassium and increases the
risk of arrhythmias, and succinylcholine can cause
hyperkalemia.”
14. When a patient, who has the symptoms of serotonin
syndrome, has been taking an SSRI or another drug that
affects serotonergic system, the patient may develop
serotonin discontinuation syndrome
b. if these drugs are not tapered correctly.
“When checking for the presence of the serotonin syndrome,
it is important to know what medications the patient has been
taking; this was previously discussed. However, if a
symptomatic patient had been taking an SSRI or another
drug that affects serotonergic system, this can confuse the
issue of assessment because if these drugs are not tapered
correctly the patient may develop serotonin discontinuation
syndrome. The syndrome occurs in approximately 20%-25%
of all patients who stop taking a serotonergic drug.”
15. ______________ may actually cause serotonin syndrome,
and its use in a suspected case of serotonin syndrome was
associated with a fatality.
a. Dantrolene
“Dantrolene may actually cause serotonin syndrome, and its
use in a suspected case of serotonin syndrome was
associated with a fatality.”
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References Section
The References below include published works and in-text citations of
published works that are intended as helpful material for your further
reading.
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
Lesch, K.P. and Waider, J. (2012). Serotonin in the Modulation
of Neural Plasticity and Networks: Implications for
Neurodevelopmental Disorders. Neuron 76, October 4, 2012
a2012 Elsevier Inc. Retrieved online at
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