Neuroleptic malignant syndrome versus serotonin syndrome: the search for a diagnostic tool

To evaluate the use of urine dopamine and catecholamine concentrations as diagnostic aids in a patient with neuroleptic malignant syndrome (NMS) in the emergency department setting.

A 61-year-old female on multiple medications, including several antipsychotics, rapidly deteriorated, with fever, lead-pipe rigidity, and decreased level of consciousness. The patient died 20 days after initial presentation to an emergency department. The Naranjo probability scale indicated probable causality for NMS due to quetiapine, haloperidol, and risperidone in this patient, whereas the Naranjo scale assigned only possible causality for serotonin syndrome developing with serotonergic agents. Laboratory investigations of blood and urine revealed elevations in dopamine, metanephrines, and epinephrines, as well as trazodone and risperidone. Serotonin metabolites were not elevated.

NMS is a rare and potentially severe adverse effect associated with the use of antipsychotic medications. It is mainly characterized by hyperthermia, altered mental state, hemodynamic dysregulation, elevated serum creatine kinase, and rigors. It has been associated with multisystem organ failure potentially leading to rhabdomyolysis, acute respiratory distress syndrome, and disseminated intravascular coagulation. The prevalence of this syndrome is associated with the use of neuroleptics. Serotonin syndrome is another adverse drug reaction leading to NMS associated with elevated serotonin. It occurs when multiple serotonergic medications are ingested and is associated with rapid onset of altered mental status, myoclonus, and autonomic instability. Differentiating between NMS and serotonin syndrome can be challenging because of their similar clinical presentation. This case highlights the importance of a diagnostic aid being available to help distinguish between the 2 syndromes.

We propose that laboratory findings that include dopamine and serotonin metabolites can be used as adjuncts to clinical and prescription histories in the diagnosis of NMS. The use of urinary catecholamine as a diagnostic aid in NMS needs further evaluation.