Trazodone: A Review of Its Pharmacological Properties and Its Off-Label Use in Dogs and Cats

Chea, Bunna; Giorgi, Mario

doi:10.3844/ajavsp.2017.188.194

Cited by 17 publications

(16 citation statements)

References 27 publications

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“…In humans, trazodone has been shown to decrease plasma cortisol concentrations compared with placebo and is commonly prescribed for the treatment of anxiety, depression, and to facilitate sleep (7,32). While trazodone is not currently labeled for use in dogs, off-label use of trazodone is common for the treatment of anxiety disorders as well as to reduce the agitation and distress associated with post-surgery confinement and reduced exercise (33,34). In this experiment, treatment with trazodone lowered blood cortisol concentrations compared to all other treatments.…”

Section: Discussionmentioning

confidence: 82%

The Impact of Feeding Cannabidiol (CBD) Containing Treats on Canine Response to a Noise-Induced Fear Response Test

et al. 2020

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Interest is increasing regarding use of Cannabidiol (CBD) in companion animals due to anecdotal evidence of beneficial behavioral and health effects. The purpose of this investigation was to evaluate the influence of CBD on behavioral responses to fear-inducing stimuli in dogs. Sixteen dogs (18.1 ± 0.2 kg) were utilized in a replicated 4 × 4 Latin square design experiment with treatments arranged in a 2 × 2 factorial, consisting of control, 25 mg CBD, trazodone (100 mg for 10-20 kg BW, 200 mg for 20.1-40 kg BW), and the combination of CBD and trazodone. A fireworks model of noise-induced fear was used to assess CBD effectiveness after 7 d of supplementation. Each test lasted a total of 6 min and consisted of a 3 min environmental habituation phase with no noise and a 3 min noise phase with a fireworks track. Plasma was collected 1 h before, immediately after, and 1 h following testing for cortisol analysis. Behaviors in each 3 min block were video recorded, and heart rate (HR) sensors were fitted for collection of HR and HR variability parameters. Research personnel administering treats and analyzing behavioral data were blinded as to the treatments administered. Data were tested for normality using the UNIVARIATE procedure in SAS, then differences examined using the MIXED procedure with fixed effects of treatment, period, time, and treatment x time interaction. Inactivity duration and HR increased during the first minute of the fireworks track compared with 1 min prior (P < 0.001 and P = 0.011, respectively), indicating the fireworks model successfully generated a fear response. Trazodone lowered plasma cortisol (P < 0.001), which was unaffected by CBD (P = 0.104) or the combination with CBD (P = 0.238). Neither CBD nor trazodone affected the duration of inactivity (P = 0.918 and 0.329, respectively). Trazodone increased time spent with tail relaxed (P = 0.001). CBD tended to increase HR (P = 0.093) and decreased the peak of low-and high-frequency bands (LF and HF, P = 0.011 and 0.022, respectively). These results do not support an anxiolytic effect of CBD in dogs given 1.4 mg CBD/kg BW/d.

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Section: Discussionmentioning

confidence: 82%

The Impact of Feeding Cannabidiol (CBD) Containing Treats on Canine Response to a Noise-Induced Fear Response Test

et al. 2020

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“…It is thought that the wide range of time to maximum concentration may be due to changes in gastric residence time in fed versus fasted dogs 2 . A previous study reported a maximum concentration within the range of 2.5–7.5 hours in fasted dogs 22,23 . Unfortunately, there are no studies that have investigated the metabolites of trazodone in the dog.…”

Section: Discussionmentioning

confidence: 99%

Suspected hepatotoxicity secondary to trazodone therapy in a dog

Arnold¹,

Davis²,

Wismer

et al. 2020

J Vet Emergen Crit Care

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Objective To describe a case of suspected hepatotoxicity in a dog secondary to administration of trazodone. Case Summary A 6‐year‐old, neutered, mixed breed dog was evaluated for a progressive increased liver enzyme activity over a 6‐week period. The patient originally presented for raisin toxicosis, and hence, was having serial blood work monitoring performed. Trazodone was initially started at that time due to severe separation anxiety while hospitalized (consistently 5 out of 7 days of the week, for a 6‐week duration). Due to continued increased liver enzyme activity, extensive workup was performed which included abdominal ultrasound, leptospirosis titers, bile acids, and liver biopsies. Histopathologic findings were consistent with acute hepatotoxicity. In the absence of other toxicants and the close proximity to drug administration, a drug‐induced hepatopathy secondary to trazodone was presumed. Following discontinuation of trazodone therapy, the hepatopathy completely resolved and the patient fully recovered. New or Unique Information Provided While acute hepatotoxicity has been reported in human medicine secondary to the administration of trazodone, this is the first reported case of suspected hepatotoxicity in a dog secondary to trazodone therapy. Veterinary professionals should be aware of the rare potential adverse effect that may be seen in canine patients secondary to trazodone therapy. Appropriate clinicopathologic monitoring should occur in patients on chronic trazodone therapy.

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“…In veterinary medicine, trazodone (TRZ), another phenylpiperazine chemical derivative, has gained popularity as adjunctive off label medication for long term treatment of anxiety disorders in dogs (Gruen and Sherman, 2008) and as an anxiolytic for short-term management of patients after surgery (Jay et al, 2013;Chea and Giorgi, 2017). VLZ might have the potential to have better pharmacokinetic, pharmacodynamic and safety profiles than trazodone in the dog as theorized in human beings.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Effect of feeding on the pharmacokinetics of vilazodone in dogs

Sartini

Gbylik-Sikorska

Łebkowska‐Wieruszewska

et al. 2019

Research in Veterinary Science

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Vilazodone (VLZ) is a drug approved for the treatment of major depressive disorder in humans but no data are available for dogs. The present study aimed to evaluate the pharmacokinetics of a single oral 40 mg dose of VLZ in healthy Labrador dogs (n=6) in fasted and fed conditions. Dogs were randomly divided in two (n=3) groups in a cross-over study design (2x2). Group I was administered with VLZ at 40 mg/dog after fasting overnight. Group II was fed prior to and after administration of the same dose. A two-week wash-out period was observed. Plasma samples collected underwent LC-MS/MS analysis. VLZ concentrations were quantified in dogs' plasma in two different windows of time: 30 min to 10 h for the fasted group and 4 h to 35 h for the fed group. The values for t1/2z were statistically different between the groups (fed, 4.6 ± 1.1 h vs fasted, 1.7 ± 0.2 h). Tmax drastically changed between the groups (fed, 10 h vs fasted, 1.5 h), while Cmax did not significantly vary (fed, 39.4 ± 5.6 ng/mL vs fasted, 38.7 ± 4.8 ng/mL). The AUC value was always statistically higher in the fed group. As a result, the average relative oral fasted bioavailability of VLZ was low, 28.8 ± 6.1%. In conclusion, feeding can affect the pharmacokinetics of VLZ in the dog.

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Trazodone: A Review of Its Pharmacological Properties and Its Off-Label Use in Dogs and Cats

Cited by 17 publications

References 27 publications

The Impact of Feeding Cannabidiol (CBD) Containing Treats on Canine Response to a Noise-Induced Fear Response Test

The Impact of Feeding Cannabidiol (CBD) Containing Treats on Canine Response to a Noise-Induced Fear Response Test

Suspected hepatotoxicity secondary to trazodone therapy in a dog

Effect of feeding on the pharmacokinetics of vilazodone in dogs

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