A psychiatric whodunit: Serotonin syndrome in the emergency department

doi:10.4236/ojpsych.2012.24039

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Open Journal of Psychiatry, 2012, 2, 281-283 OJPsych

http://dx.doi.org/10.4236/ojpsych.2012.24039 Published Online October 2012 (http://www.SciRP.org/journal/ojpsych/)

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

Email: [email protected]

Received 8 July 2012; revised 10 August 2012; accepted 20 August 2012

ABSTRACT

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

1. INTRODUCTION

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.

2. CASE

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

OPEN ACCESS

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282

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. DISCUSSION

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

C. Rodgman et al. / Open Journal of Psychiatry 2 (2012) 281-283

283

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

rapidly.

4. CONCLUSION

With the frequent misdiagnosis and high mortality of

serotonin syndrome, all physicians, not just psychiatrists,

should familiarize themselves with the Hunter Serotonin

Toxicity Criteria.

5. ACKNOWLEDGEMENTS

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.

REFERENCES

[1] Mills, K.C. and Bora, K.M. (2011) A typical antidepres-

sants, serotonin reuptake inhibitors, and serotonin syn-

drome. In: Tintinalli, J.E., Stapczy nski, J.S., Cline, D.M.,

Ma, O.J., Cydulka, R.K. and Meckler, G.D., Eds., Tinti-

nalli’s Emergency Medicine: A Comprehensive Study Guide,

7th Edition, McGraw-Hill, New York.

http://www.accessmedicine.com/content.aspx?aID=6384

959

[2] Nicoll, D., McPhee, S.J., Pignone, M., Lu and Chuanyi

Mark, Pocket Guide to Diagnostic Tests:

http://www.accessmedicine.com/pocketDiagnostic.aspx

[3] Gillman, P.K. (1999) The serotonin syndrome and its

treatment. Journal of Psychopharmacology, 13, 100-109.

doi:10.1177/026988119901300111

[4] Dunkley, E.J., Isbister, G.K., Sibbritt, D., Dawson, A.H.

and Whyte, I.M. (2003) The hunter serotonin toxicity

criteria: Simple and accurate diagnostic decision rules for

serotonin toxicity. QJM: An International Journal of

Medicine, 96, 635-642. doi:10.1093/qjmed/hcg109

[5] Gillman, K. (2010) Neuroleptic malignant syndrome: Me-

chanisms, interactions, and causality. Movement Disor-

ders, 25, 1780-1790. doi:10.1002/mds.23220

[6] Adityanjee, M.T. and Aderibigbe Y. (1999) Proposed re-

search diagnostic criteria for neuroleptic malignant syn-

drome. The International Journal of Neuropsychophar-

macology, 2, 129-144. doi:10.1017/S1461145799001388

[7] Ables, A.Z. and Nagubilli, R. (2010) Prevention, recogni-

tion, and management of serotonin syndrome. American

Family Physician, 81, 1139-1142.