Transcript Serotonin syndrome: A literature review of therapeutic

Serotonin syndrome:
A literature review of
therapeutic options?
Rob Hall MD, PGY4
FRCPC Emergency Medicine
Nov 8, 2003
Case: I just want to die
• 45yo male
• OD on paxil, gravol,
ibuprofen tonight
• Smoked some crack
• Recent abstinence
from EtOH
• Headache, fever X
1week
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HR125 sinus
BP 165/105
Temp 38.0
RR20, sats 95%
C/S normal
Agitation
Pupils 6 mm
Hyperreflexic, clonus
Tremulous
Very diaphoretic
Neck stiff
No bowel sounds
Case Questions
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Is this serotonin syndrome?
What is the differential dx?
What tests should be done?
What are the main treatments of
serotonin syndrome?
• Is there any evidence for the use of
cyproheptidine?
What is Serotonin?
• Neurotransmitter
• Mood, personality,
sleep, sex, motor,
temp, pain functions
• Very complex
• 14 receptors
• Excitatory and
inhibitory functions
What is Serotonin Syndrome?
• Serotonin syndrome is a constellation of
findings related to excessive stimulation
of serotonin receptors and is manifested
by cognitive, autonomic, and
neuromuscular abnormalities
CAN you diagnosis serotonin syndrome?
C
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COGNITIVE CHANGES:
Agitation, confusion, euphoria, insomnia,
hypomania, hallucinations
AUTONOMIC CHANGES:
Tachycardia, HTN, fever, diaphoresis,
mydriasis, arrythmias, tachypnea
NEUROMUSCULAR CHANGES:
Tremor, hyperreflexia, clonus, ataxia,
incoordination, seizures
Sternbach’s Criteria
• Addition or increased dose of a known
serotonergic agent
• At least three of the
C.A.N. criteria
• Other etiologies excluded
– Withdrawl, sympathomimetics, anticholinergics,
CNS infections, neuroleptic malignant syndrome
• No neuroleptics that have been started or
increased prior to the onset of symptoms
What causes serotonin syndrome?
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SSRIs
SNRIs
MAOIs
Cocaine
Amphetamines
LSD
Lithium
Wellbutrin
And many more!!
How is Seritonin Syndrome Managed?
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Supportive Care
Temperature control
Benzodiazepines
Fluids
Other therapies
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Cyprohepatadine
Beta – blockers
Chlorpromazine
Dantrolene
What is Cyproheptadine?
• Antihistamine with anticholinergic and
antiserotonergic properties
• Blocks 5HT1a and 5HT2 receptors
• Used as antihistamine or for appetite
stimulant in anorexia
• Recommended dosage: 4 mg po tid
• No intravenous formulation
Does Cyproheptadine work?
• Nisijima. Brain Research 2001
– Rat model of serotonin syndrome
– Gave rats an MAOI + serotonin precursor
– All died in 90 min untreated
– Looked at different drug treatments
Does Cyproheptadine work?
Nisijima. Brain Research 2001
DRUG
DEATHS
Cyproheptadine 5 mg/kg
5/5
Cyproheptadine 10 mg/kg
0/5
Dantrolene 20 mg/kg
6/6
Propranolol 10 mg/kg
5/5
Chlorpromazine 20 mg/kg
6/6
Chlorpromazine 40 mg/kg
0/5
Does Cyproheptadine work?
• Isbister. Ann Pharm. 2001
– “We have used cyproheptadine in 62
patients with moderate seritonin syndrome
with success”
– No specific data reported
Does Cyproheptadine work?
• Lappin. NEJM 1994
– Case report
– Seritonin syndrome of moderate severity
– Symptoms subsided 30 min after a 4 mg
po dose
– Dose repeated in 3hrs for recurrence of
symptoms
Does Cyproheptadine work?
• Baigel. Eur Acad Anaesth 2003
– Case report
– Severe serotonin syndrome
– Cyproheptadine 8 mg po
– Level of consciousness promptly improved,
hypertonia resolved, temperature
normalized
Does Cyproheptadine work?
• Gillman. J Clinical Psychopharmacology
– Case report
– Moderate serotonin syndrome
– Treated with cyproheptadine 8 mg po with
no effect, repeat dose at 8 hours with no
effect
– Chlorpromazine 50 mg im and symptoms
improved steadily over next 2hrs
Does Cyproheptadine work?
• McDaniel. Ann Pharmacoltherapy 2001.
– Case series of 4 patients
– All mild to moderate serotonin syndromes
– Dosing: 8 mg po and repeat q8hr
– Responses seen within hours
– No serious side – effects noted (some
anticholinergic effects)
Does Cyproheptadine work?
• Graudins. J Emerg Med 1998
– Case series of 5 patients
– Generally moderate severities
– Initial dose 4-8mg po
– A few got subsequent doses of 4 mg
– Responses seen within 1-2 hours
– No serious complicated reported
Does Cyproheptadine work?
• Maybe
• VERY little literature
• Appears effective
• Appears safe
• Probably not much down side to trying
? Other treatments for Serotonin
Syndrome
• Chlorpromazine
– One case report: Gillmann J Clin
Psychopharmacology
• Propranolol
– One case report: Guze. J Clinical Pharmacol
1986
• Dantrolene
– Drew a blank_______________
The End…