Serotonin Syndrome Versus Neuroleptic Malignant Syndrome

Serotonin syndrome and neuroleptic malignant syndrome (NMS) are two commonly taught drug-induced syndromes but are rarely encountered in practice. I wanted to put together some important differences between these two syndromes because many of the symptoms overlap. Some of those classic overlapping symptoms include hyperthermia, hypertension, and tachycardia. Here are some tips that may help you differentiate between these drug-induced phenomena.

The easiest place to start is the patient medication list. Neuroleptic malignant syndrome (NMS) is typically caused by agents with dopamine blocking activity (antipsychotics, metoclopramide, other miscellaneous nausea/vomiting medications) while serotonin syndrome is (obviously) caused by agents with serotonin-agonist effects (SSRIs, SNRIs, TCAs, tramadol, etc.). Reviewing the medication list is one of the most consequential actions you will take, but let’s face the fact that many patients on antipsychotics, may also be taking other psychotropics that have serotonergic activity.

From a clinical standpoint, there may be some notable items on assessment that may help differentiate serotonin syndrome versus NMS. The GI tract is an important assessment. With NMS, the gut is typically relatively unaffected. With serotonin syndrome, diarrhea, nausea, and vomiting are all possible. The easiest way that I remember this is to recognize that sertraline is considered the most highly serotonergic agent of the SSRIs. Due to this higher serotonergic activity, sertraline has a higher incidence of diarrhea and is often nicknamed “Squirtraline”. Increased bowel sounds will likely be present in serotonin syndrome.

A review of the skeletomuscular system is also important. Hyperreflexia is much more common in serotonin syndrome compared to neuroleptic malignant syndrome. HYPOreflexia is more common in NMS.

Pupil dilation may be more prominent in patients with serotonin syndrome. In addition, the onset of the symptoms of serotonin syndrome may be quicker than NMS but this can be variable so isn’t a great differentiating factor.

Hopefully, that gives you a little sense of what to look for if you encounter some of the overlapping clinical symptoms of serotonin syndrome versus neuroleptic malignant syndrome.

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Written By Eric Christianson

September 21, 2022

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