The impact of single‐dose trazodone administration on plasma endogenous adrenocorticotropic hormone and serum cortisol concentrations in healthy dogs

Abstract Background Conditions affecting the hypothalamic‐pituitary‐adrenal (HPA) axis are common in dogs. Testing the function of the HPA axis includes measurement of endogenous adrenocorticotropic hormone (eACTH) and performance of an adrenocorticotropic hormone (ACTH) stimulation test. Trazodone is commonly administered to dogs to decrease stress. In humans, trazodone significantly decreases plasma cortisol concentration via alpha‐1 adrenergic activity. Objectives Determine the influence of trazodone on eACTH and serum cortisol concentrations in healthy dogs. Animals Fourteen healthy, adult, companion dogs. Methods Prospective, randomized placebo‐controlled study. Trazodone (8‐10 mg/kg) or placebo was administered PO 1 hour before eACTH measurement and ACTH stimulation testing. After a ≥7‐day wash‐out period, dogs received the opposite treatment. Differences in eACTH, pre‐ and post‐ACTH stimulation cortisol concentrations, and delta (difference between pre‐ and post‐ACTH) cortisol concentrations were analyzed using a paired t or signed‐rank test with a P < .05 significance level. Results The eACTH concentrations were not significantly different (P = .23) between treatments. Similarly, no significant differences were found in the pre‐ACTH cortisol concentrations between treatments (P = .40). Post‐ACTH cortisol concentrations (P = .05) and delta cortisol concentrations (P = .04) were significantly lower when the dogs were treated with trazodone. Conclusions Preliminary data suggest trazodone administration dampens the adrenocortical response to stimulation in healthy dogs. If similar effects are found in dogs with adrenal disease, the use of trazodone may affect diagnosis and clinical decision making in these populations.