The basic difference between these two conditions is the neurotransmitters involved. In serotonin syndrome the problem is serotonin; for neuroleptic malignant syndrome (NMS) it’s dopamine.

Yet, the direction of the problem is opposite in each case. Serotonin syndrome is characterized by pathologically high levels of serotonin (usually due to overdosing on serotonin-increasing drugs), but NMS usually occurs when dopamine activity is extremely low (often due to dopamine-blocking drugs prescribed for schizophrenia).

This reveals that there is an optimum concentration of each type of neurotransmitter, going far above or below which is likely to cause neurological problems. Thus, in contrast to serotonin syndrome’s high levels, when serotonin is extremely low it tends to lead to symptoms of depression. And, in contrast to NMS’s low dopamine levels, extremely high dopamine levels are associated with aggressive and addictive behaviors as well as, in some cases, the psychotic symptoms of schizophrenia.

Balance is key.

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Gordon, M. F., Frucht, S. J., Leder, A. N., & Ketigan, L. A. (2021). 8 - Serotonin Syndrome. In D. Tarsy (Ed.), Movement Disorder Emergencies: Diagnosis and Treatment (3rd ed., Ser. Current Clinical Neurology, pp. 139–166). essay, Springer Nature Switzerland AG.

Kaye, A. D., Kaye, A. M., & Urman, R. D. (Eds.). (2015). Essentials of pharmacology for anesthesia, pain medicine, and critical care. Springer New York.
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