Clinically significant hypothermia is a commonly evaluated condition in emergency medicine. Most cases are related to prolonged exposure to the environment, infection, or endocrinopathies.

Presented here is a case of hypothermia likely induced by an atypical antipsychotic medication.

A 69-year-old incarcerated man presented to our emergency department with an oral temperature of 85°F (29.4°C). The patient was taking ziprasidone (Geodon, Pfizer, New York, NY) 80 mg twice daily.

Atypical antipsychotic medications have been implicated in numerous cases of clinically significant hypothermia. The mechanism of action for antipsychotics has not been fully elucidated, but the hypothermia induced by this class of medications is believed to be driven through the antagonism of the dopamine (D_1-4) and 5-hydroxytryptamine-2 (5-HT2) receptors. It has been theorized that under normal conditions, there is a balance between dopamine acting to reduce the body temperature and 5-HT2 acting to elevate body temperature. Atypical antipsychotics, particularly ziprasidone, appear to have a higher affinity to antagonize the 5-HT2 receptor and less at the D₂ receptor, therefore creating an imbalance favoring the lowering of core body temperature. Other theories include the antagonism of α₁ receptors by these medications causing vasodilatation and shunting of blood to the skin causing profound heat loss.

An antipsychotic medication can be the sole cause of hypothermia or it can be one of a number of possible causes coexisting in the individual with hypothermia.