Neuroleptic malignant syndrome and serotonin syndrome

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Abstract

This chapter is focused on drug-induced hyperthermia with special regard to use of antipsychotics and antidepressants for the treatment of schizophrenia and major depression, respectively. Neuroleptic malignant syndrome (NMS) develops during the use of neuroleptics, whereas serotonin syndrome is caused mainly by serotoninergic antidepressants. Although both syndromes show various symptoms, hyperthermia is the main clinical manifestation. In this review we describe the historical background, clinical manifestations, diagnosis, and differential diagnosis of these two syndromes based on our observations on the experimental and clinical data.

Introduction

Antipsychotics and antidepressants are indispensable drugs for the treatment of schizophrenia and major depression, respectively. Nevertheless, these agents induce numerous side effects. Neuroleptic malignant syndrome (NMS) develops during the use of neuroleptics, whereas serotonin syndrome is caused mainly by serotoninergic antidepressants. Although both syndromes show various symptoms, hyperthermia is a main clinical manifestation. The components of these two syndromes are similar, and some researchers consider them to exist on a spectrum of the same disorder (Demirkiran et al., 1986; Fink, 1996). Hyperthermia sometimes occurs in patients who are simultaneously being treated with both a neuroleptic and an antidepressant: in such cases it is often difficult to differentiate which syndrome it is. As described below, the pharmacotherapy for these two syndromes is slightly different and thus it is important to differentiate them. More than 40 years have elapsed since NMS was first reported, and 20 years have passed since serotonin syndrome was first reported, but not much is known about the pathophysiology or pathogenesis of either of them even now. In this chapter we describe the historical background, clinical manifestations, diagnosis, and differential diagnosis of these two syndromes. The clinical data and basic data we have collected this far are presented, and the pathophysiology and pathogenesis of the two syndromes are discussed.

Section snippets

Historical background

Although similar cases had been reported in the late 1950s (Preston, 1959), when neuroleptics began to be used clinically, NMS was first reported in 1960 by Delay et al. (1960) in France as “syndrome malin des neuroleptiques”; and the French term was translated into English as “neuroleptic malignant syndrome” (Delay and Deniker, 1968) and became familiar in English-speaking countries around the world. However, the syndrome was reported only occasionally in the 1960s and 1970s, and did not

Historical background

In the 1970s, the pharmacological effects of serotonin by administering various serotonin agonists to animals and observing their abnormal behavior were studied. The animals exhibited forepaw treading, straub tail, tremor, flat body posture, head weaving, and wet-dog shake. This combination of abnormal behaviors was called “serotonin behavioral syndrome” (Grahame-Smith, 1971; Jacobs, 1976). Thus, the term “serotonin syndrome” was initially used in the field of animal behavioral pharmacology.

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