Serotonin Syndrome

Serotoninergic syndrome is characterised by an excess of serotonin in the central nervous system, associated with the use of various agents, including selective serotonin reuptake inhibitors (SSRIs).

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.

Diagnostic methods

Diagnosis is based on clinical examination and compatible medical history. Additional investigations (ECG, laboratory examinations, toxicological analysis) 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 (see this term), 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.