Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

severe serotonin toxicity

1st line – emergency supportive care

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ACUTE
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severe serotonin toxicity
1st line – 

emergency supportive care

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 and hyperthermia treated with rapid cooling depending on the patient's temperature.[2][3]

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, avoiding fentanyl. Propofol allows for a more rapid wake-up afterwards compared with morphine and midazolam. Advice from a Poison Centre is essential, poison centres may differ between countries and regions.

Consider – activated charcoal

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ACUTE
|
severe serotonin toxicity
Consider – 

activated charcoal

Additional treatment recommended for SOME patients in selected patient group

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 2 hours.

Primary options

activated charcoal: 25-100 g orally as a single dose

Consider – chlorpromazine or cyproheptadine

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ACUTE
|
severe serotonin toxicity
Consider – 

chlorpromazine or cyproheptadine

Additional treatment recommended for SOME patients in selected patient group

Although there is limited evidence for the use of specific 5-HT antagonists in severe serotonin toxicity, intravenous chlorpromazine has been anecdotally successful.[25][27]

Hypotension due to peripheral alpha-antagonism must be avoided by pre-administration of intravenous fluids.

There is limited experience with chlorpromazine in this setting, and careful clinical judgement is required to determine whether there are adequate benefits versus the risk of hypotension.

For patients with neuromuscular excitation and agitation a single high dose of cyproheptadine (a non-specific 5-HT2 antagonist and antihistamine) may be used.[27][28][29][30] For longer-acting serotonergic agents (e.g., fluoxetine), regular lower doses should be used. It also has sedative effects that are useful.

Primary options

chlorpromazine: consult specialist for guidance on dose

OR

cyproheptadine: consult specialist for guidance on dose

Consider – cessation of offending medication(s)

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ACUTE
|
severe serotonin toxicity
Consider – 

cessation of offending medication(s)

Additional treatment recommended for SOME patients in selected patient group

Once the patient has been stabilised, consideration should be given to stopping all serotonergic medications.

Plus – muscle paralysis and cooling

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ACUTE
|
severe serotonin toxicity
|
with rhabdomyolysis
Plus – 

muscle paralysis and cooling

Treatment recommended for ALL patients in selected patient group

Rhabdomyolysis develops acutely in untreated, severe serotonin toxicity due to prolonged tonic-clonic muscle activity in association with hyperthermia. Characterised by a rising creatine phosphokinase level.

Can be prevented with early treatment of severe serotonin toxicity plus muscle paralysis and cooling.[24][25][26] See Rhabdomyolysis.

moderate serotonin toxicity

1st line – cessation of offending medication(s) plus observation

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ACUTE
|
moderate serotonin toxicity
1st line – 

cessation of offending medication(s) plus observation

All serotonergic drugs must be ceased.

Patients should be observed in hospital for at least 6 hours, 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.[8]

If toxicity becomes life-threatening, patients should be treated as per guidelines for severe toxicity.

Consider – benzodiazepine or cyproheptadine

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ACUTE
|
moderate serotonin toxicity
Consider – 

benzodiazepine or cyproheptadine

Additional treatment recommended for SOME patients in selected patient group

Benzodiazepines may be used to treat anxiety and also provide sedation.

For patients with neuromuscular excitation and agitation that is distressing or unpleasant, a single high dose of cyproheptadine (a non-specific 5-HT2 antagonist and antihistamine) may be used.[27][28][29][30] For longer-acting serotonergic agents (e.g., fluoxetine), regular lower doses should be used. It also has sedative effects that are useful.

Primary options

diazepam: 5-10 mg orally as a single dose, may repeat in 30-60 minutes according to response

OR

cyproheptadine: consult specialist for guidance on dose

mild serotonin toxicity

1st line – cessation of offending medication(s) or dose reduction

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ACUTE
|
mild serotonin toxicity
1st line – 

cessation of offending medication(s) or dose reduction

No treatment is required in these patients, except ceasing the offending medication(s) or reducing the dose of the medication, if appropriate.[4]

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 the benefits of treatment.

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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