Three neurotransmitters may play a role in this discontinuation syndrome. Quetiapine is a dopamine D2, serotonin 5-HT1A, and histamine H1 receptor antagonist. Dopamine, serotonin, and histamine receptors are present in the chemoreceptor trigger zone, a medullary site that causes nausea and emesis when stimulated. Dopamine and serotonin also influence autonomic control in brainstem nuclei. Therefore, these neurotransmitters are present in brain regions that could cause nausea and autonomic dysregulation. Ms. A’s symptoms were similar to those reported in patients who were withdrawn from other atypical (2) and typical (3) antipsychotics, implicating dopamine. They also resembled the selective serotonin reuptake inhibitor discontinuation syndrome (4), suggesting a role for serotonin. However, ondansetron, a 5-HT3 antagonist, was ineffective in controlling nausea in this case, whereas prochlorperazine, an H1 and D2 antagonist, mitigated the severest symptoms. These clinical findings and the fact that quetiapine affects predominantly histamine at low doses suggest that Ms. A’s symptoms were due to withdrawal of H1 antagonism. However, her therapeutic improvement at only 100 mg/day raises the possibility that she was highly sensitive to all of quetiapine’s pharmacological effects.