A case report of acute hypothermia during initial inpatient clozapine titration with review of current literature on clozapine-induced temperature dysregulations

BACKGROUND: Here we describe a unique case of clozapine-associated hypothermia during initial titration of this medication in an acute inpatient psychiatry setting. Only a handful of cases on this topic have been published. We discuss possible pharmacologic mechanisms supporting or refuting the propensity of clozapine to induce hypothermia, as well as risk factors for clozapine-induced hypothermia, and a comparison to clozapine-induced hyperthermia. CASE PRESENTATION: A 70 year-old African American female with treatment-refractory schizoaffective disorder developed hypothermia with a nadir temperature of 89 °F (31.7 °C) after 7 days on clozapine, on a total dose of 50 mg twice daily. Accompanying symptoms included bradycardia, hypotension, QTc prolongation, tachypnea, hypoxemia, and an absence of shivering. The patient was transferred to the ICU, and rewarmed within 10 h with the discontinuation of her clozapine, ziprasidone, and carvedilol. Broad spectrum antibiotics were initiated, but discontinued shortly after, as the patient had no leukocytosis, and blood cultures were negative. DISCUSSION: While hypoglycemia, hypothyroidism, sepsis, and stroke were effectively ruled out, alternative drug-disease (including chronic kidney disease), and drug-drug interactions were considered possible contributing features. Benzodiazepines, valproic acid, ziprasidone, and the numerous antihypertensive agents the patient was taking were considered as either primary or compounding factors for hypothermia. After exclusion or inclusion of these alternative causes, we calculated a score of 4 (possible) for clozapine-induced hypothermia on the Naranjo Scale. CONCLUSIONS: Clozapine-induced hypothermia may occur more commonly than clinicians believe. Practitioners should be cognizant of this potentially fatal phenomenon, and monitor for temperature dysregulations while on clozapine, especially during initial titration, in those with multiple comorbid factors, and on additional medications that may contribute to hypothermia.