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%.