A chilling complication
Mr. S experiences recurrent hypothermia during treatment for multiple medical problems and psychotic symptoms. Could antipsychotics be the cause?
GABA may have a role in hypothermia. Experiments with rats have shown that L-methionine-DL-sulfoximine infusions into the dorsal raphe nucleus of rats slows serotonin turnover, which decreases the release of GABA synthesis, and both induce hypothermia.5
Other neurotransmitter systems involved include dopamine and norepinephrine and their increased metabolism. One study compared clozapine with risperidone, quetiapine, and olanzapine with regard to dopamine receptor affinity in rats.5 Clozapine had a greater affinity for D1 compared with D2 receptors. Researchers used antipsychotic-induced hypothermia to measure this. Clozapine, olanzapine, and risperidone produced dose-dependent hypothermia, which researchers were able to prevent by blocking the D1 receptor.
Other factors can contribute to hypothermia in patients taking antipsychotics, including:
- pre-existing brain damage
- lesions of the preoptic anterior hypothalamic region
- neurotensin, a thermoregulatory neuropeptide
- ambient temperature
- apathy and indifference resulting from antipsychotic use, which may dampen behavior aimed toward thermoregulation, such as using blankets when sleeping.
OUTCOME: Multiple infections
Mr. S remains hospitalized because of complications related to his diabetes, which contribute to fluctuations in mental status consistent with delirium. Two months into Mr. S’ hospital stay, the psychiatrist decides to address these symptoms by restarting risperidone, 0.5 mg in the morning and 1 mg in the evening. Within several days of restarting risperidone, Mr. S’ temperature drops from 37°C to 35.1°C. One day after another dose of risperidone, 0.5 mg, is added at noon, the patient’s temperature drops to 33.1°C. Mr. S continues to be lethargic and confused and is hypoglycemic.
Mr. S eventually decompensates and is admitted to the ICU, where he is intubated. There, the patient has positive cultures for methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. While in the ICU Mr. S continues to receive risperidone, and his temperature drops to 30.5°C.
Mr. S improves and he is subsequently sent to the medical floor, then he is discharged to a long-term acute care facility. His temperature continues to range between 33°C and 34°C for 2 weeks, then returns to normal after all antipsychotics are discontinued.
The author’s observations
This case report documents periods of hypothermia in a male patient who received various antipsychotics during treatment. It appears that his hypothermia occurred in conjunction with starting and changing antipsychotics and increasing dosages (Table 2).
Mr. S’ case is unique in that it involves hypothermia apparently in response to multiple atypical antipsychotics in 1 patient over a prolonged time; to our knowledge, no other such cases exist. This was a complicated case of a patient with multiple serious comorbidities. We feel, however, that antipsychotics were the major contributor to Mr. S’ hypothermia because the drops in temperature occurred as discrete periods tied to times of antipsychotic use.
Close monitoring of drug serum levels—particularly when starting, changing, or increasing a dosage—may help prevent antipsychotic-induced hypothermia. Be vigilant for behavioral changes and problems that could contribute to hypothermia, such as social isolation and inappropriate dress, as well as comorbidities such as infection. It is unclear at what core body temperature to consider stopping an antipsychotic or decreasing the dosage.
Table 2
Mr. S’ temperature during hospitalization
| Hospitalized day | Core body temperature (°C)* | Antipsychotic |
|---|---|---|
| Admission | 35.5 | None |
| 8 | 36.8 | Started risperidone, 1 mg bid |
| 11 | 35.2 | Added quetiapine, 100 mg po qhs |
| 14 | 36.8 | Stopped risperidone, increased quetiapine to 150 mg bid |
| 18 | 35.4 | Switched to ziprasidone, 40 mg bid |
| 23 | 35.7 | Switched to aripiprazole, 10 mg/d |
| 30 | 34.7 | Increased aripiprazole to 15 mg/d |
| 38 | 34.1 | Increased aripiprazole to 20 mg/d |
| 76 | 33.1 | Switched to risperidone, 0.5 mg am and noon and 1 mg qhs |
| 107 | 37.0 | None |
| *Normal core body temperature is 37°C (98.6°F) | ||
- Gibbons GM, Wein DA, Paula R. Profound hypothermia secondary to normal ziprasidone use. Am J Emerg Med. 2008;26(6):737.
- Aripiprazole • Abilify
- Clozapine • Clozaril
- Olanzapine • Zyprexa
- Quetiapine • Seroquel
- Risperidone • Risperdal
- Vancomycin • Vancocin
- Ziprasidone • Geodon
The authors report no financial relationship with an company whose products are mentioned in this article or with manufacturers of competing products.
