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Comparing the effectiveness of clomipramine and fluoxetine in dogs with anxiety-related behaviours
Williamson O.; Varela V.; Tom J...
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In dogs with anxious behaviours, is fluoxetine more effective than clomipramine in reducing anxiety-related behaviours?
Appraisal, application and reflection
Three studies were identified that answer the PICO question. Each study looked at both fluoxetine and clomipramine; Yalcin (2010) and Rapoport et al. (1992) both compared to a placebo control but Unnithan et al. (2021) did not compare to a control. Each study used randomisation to determine treatment groups. All three of these studies include bias due to reliance on scoring done by pet owners. There were no articles published with higher levels of evidence.
Yalcin (2010) found that both fluoxetine and clomipramine were equally effective at reducing tail chasing. Specifically, a significant difference was reported between clomipramine and placebo, and no difference between fluoxetine and clomipramine, but it was not reported whether fluoxetine differed significantly from the placebo. During the final interval (weeks 10–12) of the study, 7/8 dogs in the clomipramine group, 8/9 dogs in the fluoxetine group, and 1/8 dogs in the placebo group had moderate to substantial improvement. A statistical analysis of these results was not provided. As improved scoring improved in all three groups, including the control, age or other factors may contribute to the results.
Rapoport et al. (1992) was a blinded study and used a crossover design, though they did not report on the results of the second phase of the study. The wash out period between the different treatment phases was not directly reported for the study, but was inferred to be 1 week. Fluoxetine and its metabolite would have required a 10 day wash out period, based on the five elimination half-lives of the drug. In this study clomipramine was compared to desipramine as a control, and fluoxetine to fenfluramine. In comparing all the drugs in the study clomipramine and fluoxetine were found to be equally effective.
Unnithan et al. (2021) did not specify any type of blinding in their study. An unspecified number of the dogs in this study were treated with antibiotics for epidermal ulceration associated with licking, though the authors did not state the antibiotics used or the degree to which injuries healed and, instead, reported on changes in licking behaviour as scored by owners. A stronger effect was reported for the fluoxetine treatment group compared to the clomipramine group, though no statistical analysis of the results was provided. Neither Unnithan et al. (2021) or Rapoport et al. (1992) addressed allergy testing or treatment despite environmental and food allergies being possible causes for acral lick granulomas.
Dogs can manifest anxiety through a variety of activities including tail chasing and licking. In the longer-term follow-up reported by Rapoport et al. (1992) three of the patients continued treatment with favourable results for at least 6 months after the study, one with fluoxetine and two with clomipramine. This may indicate some efficacy for longer-term management of acral lick dermatitis. There may also be success in resolving symptoms, as it was also reported that two of the patients on fluoxetine continued improvement following discontinuation of the drug. However, individual responses may vary, because in one instance fluoxetine treatment was discontinued due to no further improvement.
Licking is a behaviour that dogs can exhibit compulsively that can lead to self-injury in the form of acral lick dermatitis, however, acral lick dermatitis is also reported to be caused by environmental and food allergies. Neither Rapoport et al. (1992) or Unnithan et al. (2021) addressed allergies as a potential cause of acral lick granulomas. Had other causes for acral lick dermatitis been included during subject enrollment, those candidates could have been rejected for the study and a higher number of patients may have responded to the drugs. Even without addressing allergies, improvement in treatment groups was reported in both studies. This information could be helpful in the treatment of animals suffering from acral lick dermatitis whose owners are not able to pursue allergy testing or food trials.
Though there is a limited amount of research available to compare clomipramine and fluoxetine in treatment of anxious behaviour, there is evidence that they are both effective treatment options. Since other causes of acral lick dermatitis were not eliminated, a greater proportion of patients could have responded to treatment. Other possible considerations when choosing which of these drugs to prescribe include cost to the owner and durability of response. It is also possible that dogs may have a more robust response to one drug or the other on an individual basis and trial-and-error may be required to find the best treatment. Additional research should be done to compare these two commonly used drugs to strengthen the evidence that currently suggests that the two are similarly effective, along with addressing some of the shortcomings of these trials.
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Affiliation of the authors at the time of publication
College of Veterinary Medicine, Midwestern University, 19555 N 59th AVE, Glendale, AZ 85308Department of Pharmacology, Midwestern University, 19555 N 59th AVE, Glendale, AZ 85308
* Corresponding author email: [email protected]
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