The effects of orally administered trazodone on ambulation and recumbency in healthy horses

Background: Trazodone, a serotonin receptor antagonist and reuptake inhibitor, might be a useful adjunctive treatment in the initial management of horses with acute laminitis if it minimizes ambulation or encourages recumbency. Objectives: (1) Evaluate the effects of PO trazodone on ambulatory activity and recumbency in healthy horses; and (2) assess the pharmacokinetics of multiple PO doses of trazodone. Animals/Methods: In a randomized cross-over design, 8 healthy horses received placebo or trazodone at 2 doses (2.5 and 7.5 mg/kg) PO q12h for 48 hours with a 14-day washout period between treatments. Forelimb step frequency was measured using a hoof-mounted accelerometer and continuous video monitoring was used to detect recumbency. Groups were compared using repeated measures analysis of variance with Tukey's post hoc test. Trazodone and m-chlorophenylpiperazine (m-CPP) plasma concentrations were determined by ultra-high performance liquid chromatography-tandem mass spectrometry and pharmacokinetics were analyzed using noncompartmental methods. Results: Step frequency was lower in horses receiving 7.5 mg/kg trazodone than in the control group (mean step reduction: 44% ± 11%). Steps-area under the curve were significantly lower in the 7.5 mg/kg group (mean ± SD: 3375 ± 525 steps × hour) as compared to the 2.5 mg/kg group (mean ± SD: 5901 ± 2232; P =.02) and compared to control (mean ± SD: 6590 ± 1241; P =.001). No difference was found in the number of recumbent episodes (P =.92) or total duration of recumbency (P =.9). Trazodone and m-CPP achieved steady-state concentrations, with an accumulation ratio of 1.45 ± 0.2. Conclusions and Clinical Importance: Although it did not affect recumbency, trazodone at 7.5 mg/kg q12h decreased step frequency by approximately 44%.