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Serotonin syndrome

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Disease definition

A rare neurologic disease characterized by an excess of serotonin in the central nervous system, associated with the use of various agents, including selective serotonin reuptake inhibitors (SSRIs) and recreational stimulants.

ORPHA:43116

Classification level: Disorder

Synonym(s):
  • Serotonergic syndrome
  • Serotonin storm
  • Serotonin toxicity
  • Serotonin toxidrome

Prevalence: Unknown

Inheritance: Not applicable

Age of onset: All ages

ICD-10: T43.1

ICD-11: 8D85

UMLS: C0699828

MeSH: D020230

MedDRA: 10040108

Summary
Epidemiology

Data regarding prevalence in Europe are not available.

Clinical description

Serotoninergic syndrome may result in muscle rigidity, myoclonus, agitation, confusion, hyperthermia, hyperreflexia as well as dysautonomic symptoms, with a risk of shock with low peripheral vascular resistance, seizures, coma, rhabdomyolysis and/or disseminated intravascular coagulation (DIC).

Etiology

SSRIs and monoamine oxidase inhibitors (MAOIs) may be responsible for this syndrome at toxic but also at therapeutic concentrations. The syndrome may appear: a few hours to a few days after the initiation of the treatment; following simultaneous combination (counter-indication) of MAOIs-A (toloxatone, moclobemide) and SSRIs or successive combination with an excessively short pill-free interval; as the result of drug-drug interactions; or in some cases of acute poisoning. Individual susceptibility and severity of clinical effects may be explained by interindividual pharmacokinetic and pharmacodynamic differences. Various recreational stimulants including amphetamines (especially MDMA), synthetic cathinones, and cannabinoids are also increasingly involved.

Diagnostic methods

Diagnosis is based on clinical examination and compatible medical history. Additional investigations (electrocardiogram, laboratory examinations, toxicological analysis, electroencephalogram) are essential as clinical manifestations are not specific. Any acute infectious, neurological or metabolic diseases should be first excluded.

Differential diagnosis

Differential toxicological diagnoses include neuroleptic malignant syndrome, adrenergic or anticholinergic syndromes as well as alcohol withdrawal syndrome.

Management and treatment

Treatment is mainly supportive, based on sedation (benzodiazepines), mechanical ventilation, and even neuromuscular blockade, if necessary. In case of malignant hyperthermia, body cooling is mandatory. Dantrolene was proved inefficient. Cyproheptadine is the specific antidote for serotonin syndrome.

Prognosis

Prognosis is generally good if adequate supportive treatments are administered. However, deaths have been reported, due to multiorgan failure or brain anoxia.

Last update: January 2024 - Expert reviewer(s): Pr Bruno MÉGARBANE
A summary on this disease is available in Français, Español, Deutsch, Italiano, Português, Nederlands
Detailed information

Logo ERN: produced/endorsed by ERN(s) Logo FSMR: produced/endorsed by FSMR(s)

Guidelines
Emergency guidelines
Français (2018.pdf) - Orphanet Urgences
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