Open Journal of Psychiatry, 2012, 2, 281-283 OJPsych Published Online October 2012 (
A psychiatric whodunit: Serotonin syndrome in the
emergency department
Christopher Rodgman, Megan Thompson, Nicolas Vergara
Department of Psychiatry and Behavioral Sciences, Tulane University School of Medicine, New Orleans, USA
Received 8 July 2012; revised 10 August 2012; accepted 20 August 2012
Serotonin syndrome is a life-threatening reaction as-
sociated with serotonergic agents. Its mortality is es-
timated around 11%, hence prompt diagnosis is ne-
cessary [1]. Given the variability of its presentation,
physicians often misdiagnose this devastating condi-
tion. We present a case of serotonin syndrome seen in
the Emergency Department by an on-call psychiatric
resident and review the Hunter Serotonin Toxicity
Criteria, emphasizing the importance of physician fa-
miliarity with these criteria.
Keywords: Serotonin Syndrome; Paroxetine;
Emergency Department
Serotonin syndrome is a life-threatening reaction associ-
ated with serotonergic agents. Its mortality is estimated
around 11%, hence prompt diagnosis is necessary [1].
Given the variability of its presentation, physicians often
misdiagnose this devastating condition. We present a case
of serotonin syndrome seen in the Emergency Depart-
ment by an on-call psychiatric resident.
A 28-year old male was brought to the ED for altered
mental status (AMS). He presented shirtless, shoeless,
diaphoretic, pale with dilated pupils and chapped lips,
and smelled of urine. He was oriented only to self, and
screaming incoher ently wh ile thrash ing about on the b ed.
Initial vitals showed his blood pressure was 139/74, his
heart rate was 120, his respirations were 18 breaths per
minute, and his temperature was 98.3 degrees Fahrenheit.
The ED physician had ordered labs including a CBC,
CMP, urinalysis, urine toxicity, BAL, and TSH. The re-
sults of these labs were all within normal limits. A psy-
chiatric consult was requested by ED staff as the etiology
for this presentation was unclear.
Upon consultation the psychiatry resident noted the
patient to be repeating specific phrases including “Mis-
sissippi, Mississippi, I’m in the military” and “I need to
know the date”. He denied any pertinent medical or sub-
stance abuse issues, and denied taking any daily medica-
tions. He could not provide collateral contact information,
and was not carrying a wallet or phone for any further
information to be obtained. Medical records contained
one note from six years prior detailing outpatient treat-
ment for depression, for which he was discharged due to
non-compliance. Given his history of depression, unsta-
ble vital signs and combative behavior he was initially
thought to have either purposefully or accidentally over-
dosed on drugs or medications. As his lab work did not
identify any substances in his system, the resident be-
came concerned about serotonin syndrome and neurolep-
tic malignant syndrome (NMS), prompting him to order
a CPK. Serotonin syndrome and NMS were considered
as the patient’s presentation, lab results, and physical
exam did not direct the ED staff or psychiatry resident to
a diagnosis, and the resident evaluating the patient wanted
to rule out life-threatening psychiatric causes. His CPK
level was found to be 264 U/L. In males total CPK limits
are 32 - 267 U/L [2].
Given the patient’s elevated CPK level, he was re-
examined by the psychiatric resident who was looking
for signs consistent with serotonin syndrome or NMS.
The patient displayed mild muscle rigidity but no myo-
clonus was present, and his rigidity was considered un-
important. Without myoclonus the resident incorrectly
thought that serotonin syndrome was ruled out. Upon
discussion of the case with the supervising staff, it was
considered that the patient’s agitation could be due to
intoxication with PCP that was not detected by his UDS.
The staff recommended administering vitamin C, which
can disperse PCP from fat cells allowing PCP to then be
detected. 1 gram of vitamin C was administered, and
repeat UDS did not detect PCP. At this point the patient’s
agitation required medication. Over 40 minutes, he re-
ceived 4 mg IV lorazepam and 20 mg olanzapine, neither
of which was effective. He calmed mildly after placed in
soft 4-point restraints. A CT scan was considered, but
C. Rodgman et al. / Open Journal of Psychiatry 2 (2012) 281-283
risks outweighed the benefits. The decision was made to
consult the ICU as although his diagnosis remained un-
clear, he required constant monitoring. Upon ICU eva-
luation, vital signs shifted to the following: BP 98/55,
HR 140, RR 18. Despite the fluctuation s in his v itals, the
ICU was unconvinced of the severity and decompensat-
ing nature of his illness, instead attributing it to intox ica-
tion with some unknown substance. However, they did
agree to admit the patient to provide supportive care and
continuous monitoring.
In the ICU, AMS continued for which he was given
olanzapine (40 mg) and lorazepam (6 mg). He remained
disoriented with fluctuating vitals until day number four
of admission, when his vital signs stabilized, his agita-
tion resolved an d he was fully oriented an d able to effec-
tively communicate. The patient was now able to report
the name of his outpatient psychiatrist. Informed of pa-
tient status, his psychiatrist came to the ICU with two
important documents. The first was a color-coded list of
the patient’s previous doctors and their 20 different treat-
ment courses over the past ten years. His past diagnoses
included bipolar I disorder, bipolar II disorder, attention
deficit hyperactivity disorder, post traumatic stress dis-
order, and major depressive disorder. The second item
the physician provided was a hand-drawn timescale of
medications done by the patient. It involved unconven-
tional medications and dosing schedules being taken by
the patient prior to his admission. His morning medica-
tions included alprazolam (1 mg), aspirin (81 mg), dex-
troamphetamine/amphetamine (30 mg), fish oil (1000 mg),
lamotrigine (100 mg), paroxetine (40 mg), and a vitamin
B6 tablet.
At noon he took alprazolam (1 mg) and dextroam-
phetamine/amphetamine (15 mg). This was followed by
another dose of both alprazolam (1 mg) and dextroam-
phetamine/amphetamine (30 mg) at 3 p.m. His bedtime
regimen consisted of clonazepam (2 mg), fish oil (1000
mg), lamotrigine (100 mg), prazosin (3 mg) and zolpi-
dem (10 mg). This large, inconsistent amount of medica-
tion was due to his doctor-shopping behavior, as he was
seeing at least four providers at once. When confronted
with this information, he readily confessed both his in-
appropriate behavior and his suicide attempt. Prior to ad-
mission, he had become suicidal and had taken a 90-day
supply of paroxetine followed by ondansetron to prevent
vomiting. The attempt was lethal in in tent, and had it not
been for aggressive hydration, monitoring of vitals, and
treatment with benzodiazepines, could have ended in
completed suicide.
3.1. Overview
Serotonin syndrome, a life-threatening reaction to sero-
toninergic medications, can be produced by any seroton-
ergic drug. A search of PubMed with keywords “sero-
tonin syndrome” revealed a variety of sources too innu-
merable to discuss in this brief case report review, but
did clarify the illness. Its proposed etiology is stimulation
of 5-HT2A receptors, causing excess intrasynaptic 5-hydro-
xytryptamine [2]. This syndrome more frequen tly occurs
after administration of a second serotonergic agent, and
is also referred to as serotonin toxicity. Medications from
many different classes have serotonergic properties, such
as the antibiotic linezolid, the pain medication tramadol,
and the antitussive dextromethor-phan. Although any sero-
tonergic agent can be the cause, some medications are
more likely to precipitate serotonin syndrome than others.
It should be noted that the most common symptom of
serotonin syndrome is myoclonus, present in 57% of case s ,
but it is not necessary for diagnosis [1,2].
3.2. Diagnosis
The true incidence of serotonin syndrome is unknown.
Diagnosis involves known exposure to a serotoninergic
agent with alterations in cognition and behavior, auto-
nomic nervous system, and neuromuscular activity. No
diagnostic blood test exists, but with extreme muscle
rigidity CPK may be elevated [1]. Co mpiled from an SSRI-
alone overdose database, The Hunter Serotonin Toxicity
Criteria is used in diagnosis. The Hunter Serotonin Tox-
icity Criteria is as follows: Diagnosis is made in the pre-
sence of a serotonergic agent with spontaneous clonus,
inducible clonus with agitation or diaphoresis, ocular
clonus with agitation or diaphoresis, hyperreflexia with
tremor, or if hypertonic with a temperature over 38˚C
with ocular or inducible clonus. If the patient fails to
meet the above criteria, the diagnosis is not serotonin to-
xicity [3].
In terms of a differential diagnosis, NMS must be
ruled out. Most researchers view the core symptoms of
NMS as fever with muscle ridgitidy, however as with
serotonin syndrome, its presentation is quite v ariable [4].
Adityanjee et al. proposed a complex research criteria for
NMS in 1999 which can help with diagnosis of NMS.
Their work suggests that severe (Type I) NMS can be
diagnosed if all of the fo llowing are present: altered sen-
sorium, extrapyrimidal symptoms, hyperpyrexia, auto-
nomic dysfunction, recent ingestion of dopamine deplete
or cessation of antiparkinsonian or anticholinergic medi-
cation, not due to other condition, and one of another
supporting conditions is present (elevated CPK, leuco-
cytosis, low serum iron, elevated LFT’s, myog lobinuria).
Less severe types II-IV involve meeting less of the above
criteria. Our patient’s presentation was similar and would
meet several of these criteria as well. Unfortunately, the
presence of a dopaminergic or a serotonergic agent was
not known, nor was the physician examining the patient
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C. Rodgman et al. / Open Journal of Psychiatry 2 (2012) 281-283
Copyright © 2012 SciRes. OPEN ACCESS
using Hunter Criteria or Adityanjee Rules to rule out se-
rotonin syndrome or NMS [5-7].
3.3. Treatment
Treatment is necessary for every case of serotonin toxic-
ity, with mortality estimated at 11%. Supportive care is
essential, but no guidelines exist for the use of serotonin
antagonists. Providers should first cease all serotonergic
agents and admit to hospital, with severe cases requiring
ICU transfer. The most common cause of death is hyper-
thermia. [1] Most patients improve within 24 ho urs; 25%
of patients require endotracheal intubation and neuro-
muscular Benzodiazepines are nonspecific serotonin an-
tagonists and likely also work by relaxing the patient, but
cyproheptadine appears most effective. The reasoning
behind this is unclear, but likely involves histamine re-
ceptors. Doses from 4 to 12 mg orally can be repeated in
2 hours if no response to the initial dose is noted. It is,
however, only available orally. Cyproheptadine should
be discontinued if no response is noted after 32 mg. Re-
sponders are given 4 mg every 6 hours for 48 hours.
Chlorpromazine antagonizes 5-HT2A receptors, and can
be given intramuscularly but blocks dopamine receptors
and can exacerbate NMS, increase rigidity and hypoten-
sion, and lower the seizure threshold. Bromocriptine and
other dopamine agonists should not be used, and dantro-
line, a muscle relaxant, should only be considered in
cases of malignant hyperthermia. Once recovered, sero-
tonergic agents should be avoided, and if necessary risks
vs. benefits should be discussed with the patient and
close monitoring should be initiated, as the incidence of
recurrence is unknown [1]. Our patient received multiple
lorazepam doses, and despite ICU reluctance was given
proper hydration and vital sign monit oring. Had he needed
intubation or muscle paralysis, he would have received it
With the frequent misdiagnosis and high mortality of
serotonin syndrome, all physicians, not just psychiatrists,
should familiarize themselves with the Hunter Serotonin
Toxicity Criteria.
The authors would like to thank supportive members of the Department
of Psychiatry and Behavioral Sciences, specifically Dr. L. Lee Tynes,
Dr. Erik Kinzie, and Dr . Daniel Winstead.
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