Imagine this clinical scenario: you work in a companion animal practice with a high surgical caseload. Some colleagues routinely use trazodone to manage cases of iatrogenic stress in canine patients, but others have expressed doubts over its efficacy in reducing stress.
One of your patients, a five-month-old puppy hospitalised after a castration procedure, is displaying stress behaviours by vocalising and trying to dig out of its cage. Your colleague recommends the use of trazodone. You decide to consult the evidence to learn more about the efficacy of trazodone in hospitalised patients or those recovering post-surgery.
The evidence
Three papers were critically reviewed:
- A randomised prospective blinded observational study (Gilbert-Gregory et al., 2016)
- A randomised placebo-controlled clinical trial (Gruen et al., 2017)
- A non-randomised prospective open-label clinical trial (Gruen et al., 2014)
Gilbert-Gregory et al. (2016) observed 120 dogs housed in a stressful environment: a veterinary practice. For analysis, these dogs were split into two groups; one group received trazodone, and the other received nothing. Seventeen signs and behaviours that indicate fear, anxiety or aggression, observed at two intervals after trazodone administration, were evaluated.
Gruen et al. (2017) studied 29 dogs undergoing orthopaedic surgery. The patients were randomly and blindly split into two groups. One group was administered trazodone post-surgery, while the other was given a placebo. The patients were examined pre- and post-administration of trazodone or placebo to see if they displayed a set of stress-related behaviours.
Gruen et al. (2014) studied 41 dogs that were all administered trazodone after orthopaedic surgery. All dogs were initially given 5mg/kg of trazodone, which was later increased to 7mg/kg. Upon client request, 25 patients were given a higher dose of trazodone up to a mean peak dosage of 21.9 ± 39mg/kg PO. Before and after trazodone was administered, owners were asked to rate their pet for a set of behaviours associated with feeling calm. Trazodone dosage and onset and duration of action were also studied, as well as any adverse events post-administration.
Limitations of the evidence
The quality of evidence to support the PICO question is weak, and all three studies had limitations.
The study by Gilbert-Gregory et al. (2016) had several limitations, including control variable shortcomings, the use of concomitant medications, the lack of randomisation, the fact that the sample didn’t take into account the patients’ recovery time and the fact that not all patients had undergone surgery. In addition, the study was observational, with clinicians deciding which dogs to administer trazodone to, based on presumed clinical need. Control dogs were selected because they were housed in an environmentally but not baseline behaviour-matched environment.
The study was observational, with clinicians deciding which dogs to administer trazodone to, based on presumed clinical need.
The limitations of the study by Gruen et al. (2017) were the small sample size, the potential systemic bias and case selection, the lack of supporting evidence for the selection of certain outcomes, the reliance on owner reporting and the potential for the placebo-by-proxy effect to have skewed the study.
Limitations were also seen in the study by Gruen et al. (2014). These included:
- Presence of other concomitant drugs
- Lack of a control group
- No study of differences in behaviour between dogs who received different doses
- Potential mitigating factors, such as placebo-by-proxy
- Changes in owner behaviour
- No consideration of patients’ acclimatisation to a hospital environment
- Reliance on owner reporting
Summary of findings
Gilbert-Gregory et al. (2016) found that administrating trazodone to hospitalised dogs led to a reduction in the display of stress-related behaviours compared to the control group, which showed no significant change. The median total stress-related behaviour scores and median summation scores for frenetic and freeze behaviours were lower in the treatment group than in the control group.
In their study, Gruen et al. (2017) found that the administration of trazodone at home during post-surgical confinement was not more effective at reducing stress-related behaviours when compared to the use of a placebo. No significant differences were found between the trazodone and placebo groups in a variety of stress-related behaviours, including greeting behaviour, calmness, tolerance of confinement at home, willingness to be controlled on a leash and pulling while on a leash.
However, Gruen et al. (2014) found that the administration of trazodone was effective in the management of stress in dogs. Eighty-nine percent (32/36) of dogs improved in calmness and tolerance to confinement either moderately or extremely during their study.
Conclusion
Overall, evidence demonstrating that trazodone reduces stress-related behaviours in hospitalised dogs is weak in these studies. Gilbert-Gregory et al. (2016) have the strongest evidence, but confounding factors weaken the overall conclusions.
Overall, evidence demonstrating that trazodone reduces stress-related behaviours in hospitalised dogs is weak in these studies
Further studies that eliminate these confounding factors are required to produce a stronger quality of evidence. Additionally, a further investigation with a larger sample size would assist in strengthening the evidence of an association between trazodone administration and a reduction in the behavioural signs of stress in dogs.
Further studies are also required to evaluate the efficacy of different doses, the appropriate length of time that trazodone should be administered before a stressful event and the efficacy of trazodone to manage stress in conjunction with other anxiolytic drugs.
| The full Knowledge Summary can be read in RCVS Knowledge’s open access journal Veterinary Evidence. |
Disclaimer
The application of evidence into practice should take into account multiple factors, not limited to individual clinical expertise, patient’s circumstances, owner’s values, the individual case in front of you, the availability of therapies and resources, and the country, location or clinic where you work.
Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.
