Moderate serotonergic toxidrome
Oral therapy
Patients with moderate serotonergic toxidrome who are distressed by their symptoms may require sedation with an oral benzodiazepine.
For a cooperative patient with mild to moderate agitation, use:
diazepam 5 to 20 mg (child: 0.2 mg/kg up to 10 mg) orally; repeat after 30 minutes if required. Usually no more than 120 mg is required in 24 hours. serotonergic toxidrome diazepam
If there is no improvement with a benzodiazepine, antidotal therapy with cyproheptadine can be tried. Cyproheptadine has been used successfully in clinical practice, but there are no controlled trials to confirm its efficacy for serotonergic toxidrome. For patients with significant neuromuscular excitation (eg sustained clonus) and agitation, use:
cyproheptadine 12 mg (child younger than 7 years: 2 mg; child 7 years or older: 4 mg) orally, as a single dose. serotonergic toxidrome
A longer course of cyproheptadine may be needed for prolonged effects of serotonergic toxidrome due to drugs with long half-lives (eg fluoxetine) or modified-release preparations (eg tramadol). Use:
cyproheptadine 8 mg (child younger than 7 years: 2 mg; child 7 years or older: 4 mg) orally, 3 times daily until symptoms resolve (usually within 24 hours).
Parenteral therapy
If patients cannot take or are unwilling to take oral therapy, parenteral sedation is required for agitation due to moderate serotonergic toxidrome.
For adults, use:
1 diazepam 5 to 10 mg intravenously over 2 to 5 minutes, every 10 minutes until the patient is sedated but rousable. Maximum dose is 30 mg per event and 60 mg in 24 hours1
OR
1 midazolam 2.5 to 5 mg intravenously, every 3 to 4 minutes until the patient is sedated but rousable. Maximum dose is 20 mg in 24 hours. serotonergic toxidrome midazolam
For children, use:
1 diazepam 0.05 to 0.1 mg/kg up to 5 mg intravenously, over 2 to 5 minutes; repeat once after 15 minutes if required. Maximum dose is 0.2 mg/kg up to 10 mg per event
OR
2 midazolam 0.05 to 0.1 mg/kg up to 5 mg intramuscularly or intravenously, every 3 to 4 minutes until the patient is sedated but rousable. Maximum dose is 0.4 mg/kg up to 20 mg per event. midazolam
Intravenous chlorpromazine can be used as an alternative to an intravenous benzodiazepine. Consider the harms and benefits; postural hypotension is a common adverse effect, and chlorpromazine can be particularly harmful if the diagnosis is incorrect (eg potentially fatal in a patient with neuroleptic malignant syndrome). Symptoms can take up to 24 hours to resolve.
For adults, use:
chlorpromazine 25 mg in sodium chloride 0.9% 1000mL intravenously, over 30 to 60 minutes. Repeat the dose every 6 to 8 hours until symptoms resolve, provided the patient is not hypotensive. serotonergic toxidrome chlorpromazine
For children, use:
chlorpromazine 0.5 mg/kg up to 25 mg in sodium chloride 0.9% 10 mL/kg up to 500 mL intravenously, over 30 to 60 minutes. Repeat the dose every 6 to 8 hours until symptoms resolve, provided the patient is not hypotensive . chlorpromazine