Biological Perspectives: Are Neuroleptic Malignant Syndrome and Serotonin Syndrome the Same Syndrome?

Neuroleptic malignant syndrome (NMS) and and Serotonin syndrome (SS) are uncommon but potentially fatal reactions associated with the use of psychotropics in the treatment of psychiatric disorders. NMS is known to be caused primarily by dopamine receptor antagonists such as antipsychotics. SS is the result of excess stimulation of central and peripheral nervous system postsynaptic serotonergic receptors by serotonin boosting agents, most often, the antidepressants. It is known to primarily occur when serotonergic agents increase serotonin neurotransmission through inhibition of serotonin reuptake, stimulation of serotonin release, increased serotonin synthesis, direct agonism of serotonin receptors or by inhibition of serotonin breakdown. The development of NMS and SS differ, with SS related to increased levels of serotonin concentration, while NMS appears to be more of an idiosyncratic reaction. Here, Steele et al describe how NMS and SS potentially intersect in their expression and pathophysiology.