Adverse effects of trazodone in dogs on primary hemostasis and electrocardiogram: A single-blinded placebo-controlled crossover study

BACKGROUND: Trazodone is a serotonin antagonist/reuptake inhibitor medication commonly used for anxiety in dogs. Therapy with selective serotonin reuptake inhibitors in humans is associated with bleeding disorders and increased arrhythmogenesis. HYPOTHESIS/OBJECTIVES: To evaluate markers of primary hemostasis and corrected QT (cQT) interval in dogs before and after oral administration of standard dosages of trazodone or placebo. ANIMALS: Fifteen apparently healthy, client-owned dogs. METHODS: A single-blinded, randomized placebo-controlled crossover study was performed. Dogs were administered trazodone (5 to 7.5 mg/kg PO Q12h) or placebo. [Correction added after first online publication on 14 October 2023. In the abstract (methods) section (57.5 mg/kg PO Q12h) changed as (5 to 7.5 mg/kg PO Q12h).] Buccal mucosal bleeding time (BMBT), platelet count, platelet aggregation via Plateletworks, PFA-100 closure time and cQT interval were measured. A Shapiro-Wilk test was performed followed by either a paired t test or a Wilcoxon signed-rank test. RESULTS: No significant difference was detected in the BMBT, PFA-100 closure times, platelet counts, and cQT interval between trazodone or placebo. However, using Plateletworks, there was a significant decrease in platelet aggregation after administration of trazodone (95%; 81-97 vs 62%; 39-89, P = .002) and not placebo (95%; 81-97 vs 91%; 81-96, P = .21). CONCLUSIONS: It is unknown if this represents a clinically relevant change or if dogs with preexisting impairment in primary hemostasis or receiving higher dosages or longer durations of trazodone could have a more substantial change in hemostatic variables.