Serotonin syndrome

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
What causes serotonin syndrome?

• SSRIs
• SNRIs
• MAOIs
• Cocaine
• Amphetamines
• LSD
• Lithium
• Wellbutrin
• And many more!!
 Serotonin syndrome

• Life threatening
• Overload of central serotonergic
neurotransmission
• Use of antidepressants can cause this
• Risk increases with combination of
antidepressants
 Diagnosis serotonin syndrome

C
COGNITIVE CHANGES:
Agitation, confusion, euphoria, insomnia,
hypomania, hallucinations

A
AUTONOMIC CHANGES:
Tachycardia, HTN, fever, diaphoresis,
mydriasis, arrythmias, tachypnea

N
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
– Withdrawal, sympathomimetics, anticholinergics, CNS
infections, neuroleptic malignant syndrome
• No neuroleptics that have been started or increased
prior to the onset of symptoms
Hunter Serotonin Toxicity Criteria (HSTC)
In the presence of a
serotonergic agent, serotonin
toxicity exists:
• If spontaneous clonus is
present OR
• If inducible clonus AND
agitation or diaphoresis
are present OR
• If ocular clonus AND
agitation or diaphoresis
are present OR
• If tremor AND hyper-
reflexia are present OR
• If hypertonia AND pyrexia
(temperature >38°C
[>100.4°F]) AND ocular
clonus or inducible clonus
are present.
How is Serotonin Syndrome Managed?

• Supportive Care
• Temperature control
• Benzodiazepines
• Fluids • Other therapies
– Cyprohepatadine
– Beta – blockers
– Chlorpromazine
– Dantrolene
 Management approach
• The treatment of serotonin toxicity consists of
– ceasing the serotonergic medication
– assessing the severity of toxicity
– providing supportive care
– in moderate and severe cases, the use of specific
antiserotonergic agents.
– Severe serotonin toxicity is a medical emergency
that often requires emergency treatment.
 Assessment of severity
• The spectrum of serotonin toxicity can be
divided into 3 groups of severity based on the
requirement for medical intervention
• The severity should be assessed early so
appropriate treatment can be started
immediately.
• Mild toxicity
– Serotonergic features that may or may not concern the patient.
– Such features include hyper-reflexia (almost always universally present in
patients prescribed selective serotonin-reuptake inhibitors), inducible
clonus, tremor, myoclonic jerks, and diaphoresis, or sometimes more non-
specific symptoms such as headache or sweating.
– These patients do not meet the Hunter Serotonin Toxicity Criteria (HSTC).
• Moderate toxicity
– Causes significant distress and requires treatment but is not life-
threatening.
– Characterised by anxiety and agitation. Tachycardia is also common.
– Patients meet the HSTC, but hyperthermia (temperature >38.5°C
[>101.3°F] or rapidly rising) and hypertonia are absent.
• Severe toxicity
– Considered a medical emergency, as it progresses to multi-organ failure if
not treated.
– Almost always associated with exposure to a combination of serotonergic
drugs that act by different pharmacological mechanisms.
– Patients meet the HSTC and have hyperthermia and hypertonia.
 Severe serotonin toxicity
– All serotonergic drugs must be ceased.
– This is a medical emergency and the patient needs to be treated in a critical care
area.
• Initial assessment of airway, breathing, and circulation should be undertaken.
• Hyperthermia should be treated with rapid cooling.
– In the majority of patients it is best to sedate, intubate, and ventilate early, including induction of
muscle paralysis to treat spontaneous clonus and hyperthermia.
• Sedation can be achieved either with morphine and midazolam or with propofol.
– Propofol allows for a more rapid wake-up afterwards compared with morphine and midazolam.
– The aim is to prevent major complications, including rhabdomyolysis, multi-organ failure, and death.
– Early treatment may prevent the development of these complications. In patients with
rhabdomyolysis, muscle paralysis and cooling are indicated. [
– If severe serotonin toxicity is a result of an overdose, then decontamination with a
single dose of activated charcoal may be considered if the overdose occurred
within the last hour.
– Although there is limited evidence for the use of specific 5-HT antagonists,
intravenous chlorpromazine has been anecdotally successful.
• Repeat doses can be used, and often a dose can be used to sedate the patient rather than
using a benzodiazepine.
• Hypotension due to peripheral alpha-antagonism must be avoided by pre-administration of
intravenous fluids.
 Moderate serotonin toxicity
• All serotonergic drugs must be ceased.
• Patients should be observed in hospital for at least a 6-hour period,
although they are unlikely to develop severe or life-threatening
toxicity.
• Occasionally, severe serotonin toxicity may present early as
moderate toxicity, such as with extended-release venlafaxine.
• If toxicity becomes life-threatening, patients should be treated as
per guidelines for severe toxicity.
• Treatment focuses on symptomatic relief of anxiety and agitation
and the distressing effects of neuromuscular excitation.
– There is no evidence to support best treatment, except the existence
of case reports.
• Benzodiazepines may be used to treat anxiety and also sedate the patient.
• For patients with neuromuscular excitation and agitation that is distressing or
unpleasant, cyproheptadine (a non-specific 5-HT2 antagonist and
antihistamine) may be used. It also has sedative effects that are useful.
 Mild serotonin toxicity
• No treatment is required in these patients,
except possibly ceasing the offending
medication(s) or reducing the dose of the
medication, if appropriate.
• Often, simple identification of the
serotonergic symptoms may be sufficient, and
continuation of the medication can then be
decided on based upon the patient's tolerance
of these effects and benefits of the treatment.
 Restarting treatment
• Depending on the situation that has led to the
serotonin toxicity (e.g., increased dose,
overdose, drug-drug interaction), a single
serotonergic medication may be re-started at
a lower dose after the condition has resolved,
while the patient is monitored closely.