By: Elsa Thomas, Pharm.D. c/o 2013

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Human body uses various complex mechanisms to maintain its body temperature within a narrow range despite extreme environmental temperature changes as well as physiological changes. Several factors can affect body temperature such as disease states, growth, exercise, hormonal changes, and medications. Hypothermia can occurs as a result of peripheral vasodilation, decrease in metabolic activity or exposure to cold environmental conditions where as hyperthermia is a condition that can result from excessive heat generation from seizures, muscle rigidity, increased metabolic rate, decreased sweating or from drugs that alter hypothalamic activity. There are numerous  drugs that affect body temperature including barbiturates, cyclic antidepressants, hypoglycemic agents, opiods, antihistamines, anticholinergics etc.[1]

Metformin is a biguanide oral hypoglycemic agent used to treat type 2 diabetes mellitus. Although hypoglycemia is a major adverse effect associated with most agents used to treat diabetes, metfomin is not one of them. But one of the important, yet rare, adverse effect associated with even the therapeutic dose of metformin is lactic acidosis, a condition where metformin accumulates in the intestine leading to an increased production of lactate faster than it can be removed, a condition usually seen in those patients with renal impairment and presents with hypoglycemia, hypothermia, hypotension, and resistant bradyarrhythmias.[2]

Goldfrank’s Toxicologic Emergencies provides  the same information on metformin. The book also adds that ‘insufficient evidence supports the concept that metformin-associated hypoglycemia can develop in a patient who is not critically ill without lactic acidosis’, suggesting that hypoglycemia associated with the use of metformin is solely the characteristic of an overdose.[3] The mechanism by which lactic acidosis directly causes hypothermia is not defined as it is for hypoglycemia causing hypothermia. One case study involving the successful treatment of severe lactic acidosis caused by a suicide attempt of a 43 year old women with a metformin overdose, lists hypoglycemia and hypothermia as symptoms presented by the patient[4] while an article published in ‘Haematologica”, the hematology journal, explains that ‘hypoglycemia causes peripheral vasodilatation, sweating, and inhibits shivering, commonly resulting in hypothermia’.[5] This leads to the conclusion that metformin causes hypoglycemic symptoms under conditions of overdose defined by lactic acidosis and the resultant hypoglycemia leads to symptoms of hypothermia.

Trazodone is a serotonin reuptake inhibitor that is used as an antidepressant. One of its side effects causes significant sedation that leads to it’s off label use as a sedative/hypnotic, to treat insomnia. But another one of its less frequent and non-preferred side effects is the production of night sweats.[6] One study done on 12 healthy volunteers to study the effect of trazodone on core body temperature showed that trazodone decreased the highest rectal temperature (P<0.05), the lowest temperature (P'<0.05) and the average temperature (P<0.01) but did not change the amplitude compared to placebo; this study inconclusive of the hyperthermic nature of trazodone.[7] But the possibility is supported by The American Psychiatric Publishing Textbook of Psychosomatic Medicine by stating that serotonergic agents including trazodone can cause an elevation in body temperature.[8] Furthermore, such drugs can cause a life-threatening condition resulting from increased CNS serotonergic activity called serotonin syndrome and its manifestations include hyperthermia and diaphoresis.[9] Similar to that of metformin, trazodone also causes changes in body temperature characterized mostly by acute toxic conditions and is absent or negligible otherwise.

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Published by Rho Chi Post