Selective serotonin reuptake inhibitors (SSRIs) are replacing tricyclic antidepressants (TCAs) with increasing frequency in the United States. Although SSRI poisoning tends to be less serious than TCA poisoning, the incidence of adverse side effects and drug interactions may be greater. The serotonin syndrome is a potentially severe adverse drug interaction characterized by the triad of altered mental status, autonomic dysfunction, and neuromuscular abnormalities. The serotonin syndrome is similar to the neuroleptic malignant syndrome, leading to misdiagnosis. Although serotonin syndrome may result in death, most patients recover completely with supportive care alone. The main pathophysiologic mechanism appears to be excessive 5-hydroxytryptophan stimulation; this finding is supported by reports of beneficial effects with serotonin-antagonist treatment. The incidence of the serotonin syndrome may increase as SSRIs continue to replace TCAs. Morbidity and costly diagnostic procedures may be avoided if prompt diagnosis and appropriate treatment are provided.

[Martin TG: Serotonin syndrome. Ann Emerg Med November 1996;28:520-526.]