The serotonin syndrome and its treatment

Abstract

Serotonin syndrome is caused by drug induced excess of intrasynaptic 5-hydroxytryptamine. The clinical manifestations are mediated by the action of 5-hydroxytryptamine on various subtypes of serotonin receptors. There is no effective drug treatment established. The history of the treatment of serotonin syndrome with 5-hydroxytryptamine blocking drugs is reviewed. A literature search was undertaken using both Medline and a manual search of the older literature. Reports of cases treated with the 5-HT2 blockers cyproheptadine and chlorpromazine were identified and analysed. There is some evidence suggesting the efficacy of chlorpromazine and cyproheptadine in the treatment of serotonin syndrome. The evidence for cyproheptadine is less substantial, perhaps because the dose of cyproheptadine necessary to ensure blockade of brain 5-HT2 receptors is 20-30 mg, which is higher than that used in the cases reported to date (4-16 mg).

Evaluation and Management of Children With Acute Mental Health or Behavioral Problems. Part II: Recognition of Clinically Challenging Mental Health Related Conditions Presenting With Medical or Uncertain Symptoms

“…98 Both drugs may be effective, 108 but cyproheptadine is preferred by most experts. 99,100 Low dosages of direct-acting sympathomimetic amines (eg, phenylephrine, norepinephrine, and epinephrine) or short-acting drugs such as esmolol or nitroprusside have been used to manage fluctuating blood pressure and heart rate.…”

Neurological complications of psychiatric drugs: clinical features and management

“…cyproheptadine) can be beneficial (Gillman, 1999). Benzodiazepines can help control agitation and by limiting excessive muscle activity they can also help lower pyrexia (Gillman, 1999).…”

Toxicité sérotoninergique provoquée par une interaction entre le fentanyl et la paroxétine

“…Sedation has been beneficial in animal models 15 and may be used to treat agitation. 16 Severe cases involving hyperpyrexia (> 38.5 o C), marked hypertonia, or rigidity require aggressive, supportive treatment, including active cooling and consideration of neuromuscular paralysis with mechanical respiratory ventilation. 7 Severe cases of serotonin toxicity have a well documented mortality; therefore, the use of specific 5-HT 2A antagonists is recommended.…”

“…7 Severe cases of serotonin toxicity have a well documented mortality; therefore, the use of specific 5-HT 2A antagonists is recommended. 16 Cyproheptadine 17 is only available in an oral formulation, but may be given crushed via a nasogastric tube. Chlorpromazine is the only intravenous 5-HT 2A antagonist available for humans, and this has been successfully used in the treatment of severe serotonin toxicity.…”

“…Chlorpromazine is the only intravenous 5-HT 2A antagonist available for humans, and this has been successfully used in the treatment of severe serotonin toxicity. 16 Chlorpromazine may exacerbate cardiovascular instability due to α 1 antagonist effects. The patient in this report responded to supportive treatment and withdrawal of serotonergic drugs.…”