A potentially fatal condition that results from the combination of two or more drugs that overactivate the serotonin system in the central nervous system (CNS)

Characterized by mental status, autonomic, and neuromuscular changes

Occurs when multiple serotonergic agents are used together, or are used in close succession

Risk factors

SSRIs used together with lithium, tryptophan, dextromethorphan, trazodone

Combination of monoamine oxidase inhibitors (MAOIs), SSRIs, clomipramine, or tricyclic antidepressants

Clomipramine

Onset of symptoms is within minutes to hours following an increase in dose or an addition of a serotonergic agent.

Change in mental status include sagitation, euphoria, drowsiness, delirium, confusion, hypomania, dizziness, psychosis, seizures, and coma.

Autonomic instability includes fever, diaphoresis, shivering, tachycardia, hypertension, hypotension, tachypnea, nausea, and diarrhea.

Neuromuscular abnormalities are hyperreflexia, clonus, tremor, increased tone, nystagmus. (Be aware that muscle rigidity can make it difficult to ascertain hyperreflexia and clonus.)

Rule out other causes of fever such as infections, substance abuse or withdrawal, and metabolic disorders.