Clinical Geriatrics

This is the first part of a two-part series that examines central serotonin syndrome in the elderly. Part I reviews the history and prevalence of the disorder, causative agents, presentation and diagnostic criteria, and ways to distinguish the condition from other similar states, such as neuroleptic malignant syndrome. Part II will focus on the pathophysiology, opiate and psychiatric drug interactions, and treatment approaches for central serotonin syndrome in the elderly.

INTRODUCTION
The term serotonin syndrome was first used in a case report in 1982, but study of this condition dates back to the 1950s and 1960s. At that time, unusual drug interactions involving monoamine oxidase inhibitors (MAOIs) were observed in research animals.1-5 When rats were exposed to elevated central serotonergic levels, they displayed a condition that became known as serotonin behavioral syndrome. The pathophysiology of central serotonin syndrome evolved from a study of these animals. In 1991, Sternbach6 published the first diagnostic criteria for serotonin syndrome in humans based on his review of the 38 cases then published. Since that early definition, serotonin syndrome has become more clinically prominent due to the increasing number of available drugs that intentionally affect the level of central nervous system serotonin, and the dramatically increased number of prescriptions for these drugs (eg, selective serotonin reuptake inhibitors [SSRIs]).2,3,7 The additional prominence is also related to the growing exposure to other prescribed medications (eg, linezolid), over-the-counter remedies (eg, cold medications), pain medications (eg, meperidine), and street drugs (eg, ecstasy) with unintended serotonergic properties.

Patients and physicians are often unaware of the additive serotonergic effects of various medications and the resulting increased risk for developing serotonin syndrome. A 1999 study of general practitioners showed that 85.4% were not familiar with serotonin syndrome.8 This finding raises concern since primary care physicians write more prescriptions for SSRIs than psychiatrists.8,9 Compounding physicians’ general lack of knowledge about the syndrome is a lack of clear, definitive diagnostic criteria, which is in part due to serotonin syndrome’s various presentations. It is hoped that this article will educate physicians about the condition, its most common presentations, and the drugs that most frequently cause it.

RATE AND CAUSATIVE AGENTS
Serotonin syndrome is not considered to be an idiosyncratic drug reaction since there is a clear correlation between the level of serotonin-enhancing effect of various medications, either alone or in combination, and the risk for developing the condition10 (Table I).