Синдром серотонина: симптомы, диагностика и лечение.

Symptoms caused by an excess of serotonin in the central nervous system

Serotonin is a neurotransmitter involved in multiple complex biological processes including aggression, pain, sleep, appetite, anxiety, depression, migraine, and vomiting. The syndrome is caused by increased serotonin in the CNS. The 5 HT1A receptor may still contribute through a pharmacodynamic interaction in which increased synaptic concentrations of a serotonin agonist saturate all receptor subtypes.

A postulated "spectrum concept" of serotonin toxicity emphasises the role that progressively increasing serotonin levels play in mediating the clinical picture as side effects merge into toxicity. The dose response relationship is the effect of progressive elevation of serotonin, either by raising the dose of one drug, or combining it with another serotonergic drug which may produce large elevations in serotonin levels.

There is no specific test for SS. Diagnosis is by symptom observation and investigation of the person's history. Researchers later developed the Hunter Toxicity Criteria Decision Rules, which have better sensitivity and specificity, 84% and 97%, respectively, when compared with the gold standard of diagnosis by a medical toxicologist. The condition most often confused with serotonin syndrome is neuroleptic malignant syndrome (NMS). The clinical features of neuroleptic malignant syndrome and SS share some features which can make differentiating them difficult. In both conditions, autonomic dysfunction and altered mental status develop.

Management is based primarily on stopping the usage of the precipitating drugs, the administration of serotonin antagonists such as cyproheptadine (with a regimen of 12 mg for the initial dose followed by 2 mg every 2 hours until clinical), and supportive care including the control of agitation, the control of autonomic instability, and the control of hyperthermia. Additionally, those who ingest large doses of serotonergic agents may benefit from gastrointestinal decontamination with activated charcoal if it can be administered within an hour of overdose. Despite the absence of controlled trials, there are a number of case reports detailing apparent improvement after people have been administered cyproheptadine. Cyproheptadine is only available as tablets and therefore can only be administered orally or via a nasogastric tube; it is unlikely to be effective in people administered activated charcoal and has limited use in severe cases.

Treatment for hyperthermia includes reducing muscle overactivity via sedation with a benzodiazepine. More severe cases may require muscular paralysis with vecuronium, intubation, and artificial ventilation. although in some cases delirium may persist for a number of days. and antidepressant discontinuation may contribute to ongoing features. Following appropriate medical management, SS is generally associated with a favorable prognosis.

Epidemiological studies of SS are difficult as many physicians are unaware of the diagnosis or they may miss the syndrome due to its variable manifestations. In 1998 a survey conducted in England found that 85% of the general practitioners that had prescribed the antidepressant nefazodone were unaware of SS. The incidence may be increasing as a larger number of pro serotonergic drugs (drugs which increase serotonin levels) are now being used in clinical practice. One postmarketing surveillance study identified an incidence of 0.4 cases per 1000 patient months for patients who were taking nefazodone. Zion was a freshman at Bennington College at her death on March 5, 1984, at age 18. She died within 8 hours of her emergency admission to the New York Hospital Cornell Medical Center. She had an ongoing history of depression, and came to the Manhattan hospital on the evening of March 4, 1984, with a fever, agitation and "strange jerking motions" of her body. She also seemed disoriented at times. The emergency room physicians were unable to diagnose her condition definitively but admitted her for hydration and observation. Her death was caused by a combination of pethidine and phenelzine. A medical intern prescribed the pethidine. The case influenced graduate medical education and residency work hours. Limits were set on working hours for medical postgraduates, commonly referred to as interns or residents, in hospital training programs, and they also now require closer senior physician supervision.