Pathophysiology and management of the serotonin syndrome.

OBJECTIVE: To review the symptoms, pathophysiology, and treatment of the serotonin syndrome (SS). DATA SOURCES: A MEDLINE search (1957-1995) of the English-language literature pertaining to the SS was performed. Additional literature was obtained from reference lists of pertinent articles identified through the search. STUDY SELECTION AND DATA EXTRACTION: All articles were considered for possible inclusion in the review. Pertinent information, as judged by the authors, was selected for discussion. DATA SYNTHESIS: The SS, an occasionally fatal disorder, is characterized by symptoms such as mental status changes, seizures, myoclonus, and blood dyscrasias. Both the central and peripheral serotonergic systems and several serotonin receptor types are involved in the symptomatology of the SS. The pathogenesis of SS may be due to endogenous as well as iatrogenic deficits in peripheral serotonin metabolism, a stimulus for release of serotonin, and interactions with other neurotransmitter systems. Lorazepam, serotonin-blockers, and nitroglycerin have been used successfully to treat SS. CONCLUSIONS: The SS is increasingly recognized and reported in the literature. Clinical and basic science research have increased our understanding of the pathophysiology, conditions, and agents that may predispose to the development of the syndrome. Newer treatment strategies are discussed.

Potential vascular and bleeding complications of treatment with selective serotonin reuptake inhibitors.

Selective serotonin reuptake inhibitors (SSRIs) alter peripheral handling of serotonin, leading to potential side effects. Further, the majority of the body's serotonin is found outside the central nervous system. Peripheral serotonin is important in platelet aggregation and the modulation of vascular tone. SSRIs block platelet uptake and pulmonary endothelial metabolism of serotonin, and use of these agents may conceivably result in bleeding and vasospastic complications.

The serotonin syndrome associated with paroxetine, an over-the-counter cold remedy, and vascular disease.

There is a new, potentially fatal disorder that is infrequently reported. The apparent rareness may be because of a lack of recognition of the syndrome or its predisposing factors. Fluoxetine (Prozac, Dista Products Co, Division of Eli Lilly Co, Indianapolis, IN), sertraline (Zoloft, Roerig Division, Pfizer Inc, New York, NY), and paroxetine (Paxil, SmithKline Beecham Pharmaceuticals, Philadelphia, PA) belong to a new class of antidepressant medication: the serotonin reuptake-inhibitors (SRIs). The relative safety profile of the SRIs has led to their widespread use. However, a syndrome of excessive serotonergic activity, the "serotonin syndrome" (SS), has recently been recognized. It is characterized by changes in mental status, hypertension, restlessness, myoclonus, hyperreflexia, diaphoresis, shivering, and tremor. A high index of suspicion is required to make the diagnosis in these acutely ill patients. The most common agents implicated in SS are the monoamine oxidase inhibitors in combination with L-tryptophan or fluoxetine. A case of a patient with significant peripheral vascular disease who developed SS while taking paroxetine and an over-the-counter cold medicine is reported. There have been no prior reports of this interaction. Discontinuation of the offending agents, sedation, and supportive care are the mainstays of treatment. The interactions of serotonin with platelets and vascular endothelium are also discussed.