Atomoxetine Induced Hypothermia: A Case Report

Introduction

Attention-deficit-hyperactivity disorder (ADHD) is a common, chronic neuropsychiatric disorder that impairs social, academic, and occupational functioning in children, adolescents, and adults. The prevalence of this disorder in the United States is 6–9% in youth (i.e., children and adolescents) and 3–5% in adults.¹ As a highly selective noradrenaline reuptake inhibitor, atomoxetine hydrochloride, is the first non-stimulant drug that has been indicated for the treatment of ADHD. According to the data collected from clinical trials, atomoxetine hydrochloride is considered to be safe, effective and associated with relatively few adverse drug reactions: dyspepsia, nausea, vomiting, fatigue, rash, irritability, headache, somnolence, dizziness, decreased appetite and weight loss.² Hypothermia, a condition in which core body temperature drops below 35.0°C, is a rarely seen side effect of stimulant drug use. Here we would like to present an 11-year-old treatment-naïve and healthy adolescent who developed hypothermia after treatment of ADHD with atomoxetine.

Case Report

An 11-year-old male adolescent was referred to our outpatient clinic due to his poor attention, having difficulties in finishing work and poor academic performance. He was diagnosed with ADHD, predominantly inattentive type, according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria.³ He had normal physical examination and no history of significant medical illness. He was started on atomoxetine 10 mg per day. After taking the drug, his mother noticed that his face and his hands were cold, but they disregarded. On the second day of the treatment, he felt “cold” and a little tired. His temperature was found 34.0°C at home and upon his admittance to the hospital his rectal temperature was 34.2°C. Complete blood count and biochemical analysis revealed no abnormality. Passive external rewarming techniques (blanket and a heating lamp) were applied. His body temperature rose to 35.2°C an hour later and was gradually normalized (36.3°C) in 3 hours, under close monitoring of his body temperature every 30 min. The medication was discontinued and no other adverse effect was seen during the following two weeks. The patient has provided permission to publish these features of his case, and the identity of the patient has been protected.

Discussion

Stimulant drugs used in the treatment of ADHD can influence thermoregulation and hypothermia in patients using stimulants is a serious and unpredictable adverse effect that may result in hospitalization. Nocturnal enuresis, seizure disorder, debilitating physical illness, and mental retardation are determined as conditions to increase the risk of hypothermia in psychiatric patients. Drugs used in psychiatry such as antipsychotics, beta-adrenergic antagonists, benzodiazepines, and other sedatives might have an additional effect on the risk of hypothermia.⁴ The mechanism of action of atomoxetine is thought to be related to its selective inhibition of presynaptic norepinephrine reuptake in the prefrontal cortex. It has a high affinity and selectivity for norepinephrine transporters, but little or no affinity for other various neurotransmitter receptors.⁵ The mechanism of hypothermia induced by atomoxetine is not clear. Besides, it was emphasized that, in rats, intraperitoneally administrated atomoxetine significantly increases extracellular norepinephrine and dopamine levels in the prefrontal cortex by up to 290% and 323% of basal levels; while serotonin levels did not significantly differ from baseline.⁶ It is mentioned that under normal condition, dopamine tends to act to reduce body temperature, while serotonin elevates body temperature.⁷ In our case, elevated levels of dopamine, particularly in the mesolimbic area, might have resulted in hypothermia.

Conclusion

To our best knowledge, this is the first report in the literature of an adolescent with ADHD who developed hypothermia after administration of atomoxetine. Our case suggests that clinicians should be aware of the development of thermoregulatory changes when prescribing atomoxetine for patients with ADHD.