Serotonin syndrome is a potentially life-threatening condition resulting from increased CNS serotonergic activity that is usually drug related. Symptoms may include mental status changes, hyperthermia, and autonomic and neuromuscular hyperactivity. Diagnosis is clinical. Treatment is supportive.
Serotonin syndrome can occur with therapeutic drug use, self-poisoning, or, most commonly, unintended drug interactions when 2 serotonergic drugs are used (see Table 4: Drugs That Can Cause Serotonin Syndrome). It can occur in all age groups.
Complications in severe serotonin syndrome can include metabolic acidosis, rhabdomyolysis, seizures, acute renal failure, and disseminated intravascular coagulation. Causes probably include severe hyperthermia and muscle activity.
Symptoms and Signs
Manifestations can range widely in severity. They can be grouped into the following categories:
Neuromuscular hyperactivity may be more pronounced in the lower than the upper extremities.
Symptoms usually resolve in 24 h, but symptoms may last longer after use of drugs that have a long half-life or active metabolites (eg, monoamine oxidase inhibitors, SSRIs).
Diagnosis is clinical. Various explicit criteria have been proposed.
The Hunter criteria are currently preferred because of ease of use and high accuracy (almost 85% sensitivity and > 95% specificity compared with diagnosis by a toxicologist). These criteria require that patients have taken a serotonergic drug and have one of the following:
Systemic infections, drug or alcohol withdrawal syndromes, and toxicity caused by sympathomimetic or anticholinergic drugs should also be considered in the differential diagnosis. Differentiation of serotonin syndrome from neuroleptic malignant syndrome (see Neuroleptic Malignant Syndrome) may be difficult because symptoms (eg, muscle rigidity, hyperthermia, autonomic hyperactivity, altered mental status) overlap. Clues to serotonin syndrome include use of serotonergic drugs, rapid onset (eg, within 24 h), and hyperreflexia, in contrast to the often decreased reflex responses in neuroleptic malignant syndrome.
There are no confirmatory tests, but patients should have testing to exclude other disorders (eg, CSF analysis for possible CNS infection, urine testing for drugs of abuse). Also, some tests (eg, serum electrolytes, platelet count, renal function tests, CK, PT, testing for urine myoglobin) may be necessary to identify complications in severe serotonin syndrome.
All serotonergic drugs should be stopped. Mild symptoms are often relieved with sedation using a benzodiazepine. If symptoms rapidly resolve, patients should be observed for at least several hours. Most will require hospitalization for further testing, treatment, and monitoring.
In severe cases, admission to an ICU is required. Hyperthermia is treated by cooling (see Treatment). Neuromuscular blockade with appropriate sedation, muscle paralysis, and other supportive measures may be necessary. Drug treatment of autonomic abnormalities (eg, hypertension, tachycardia) should be with shorter-acting drugs (eg, nitroprusside, esmolol) because autonomic effects can change rapidly.
If symptoms persist despite supportive measures, the serotonin antagonist cyproheptadine can be given orally or, after crushing, via NGT (12 mg, then 2 mg q 2 h until response occurs). Dantrolene is not recommended.
Consultation with a toxicologist is encouraged and can be accomplished by calling the United States Poison Control Network (1-800-222-1222) or accessing the WHO's list of international poison centers (http://www.who.int/gho/phe/chemical_safety/poisons_centres/en/index.html).
Last full review/revision February 2010 by James P. Knochel, MD
Content last modified September 2013