Imagine this clinical scenario: you are presented with a client-owned dog that exhibits anxiety-related behaviours, including acral lick dermatitis and tail chasing. The owner has attempted to put their dog through behavioural training, but they have not seen any positive results. Previous veterinary check-ups have ruled out allergies, parasitism and infection. The owner has asked whether there is any medication that can help reduce these repetitive behaviours. You identify two medications that are used to treat anxiety in dogs: fluoxetine and clomipramine. They both take four to eight weeks to have a therapeutic effect; with this in mind, you consult the evidence to see which is more effective.
The evidence
Three papers were identified that compared fluoxetine and clomipramine: one randomised controlled trial (Unnithan et al., 2021) and two randomised controlled double-blinded trials (Rapoport et al., 1992; Yalcin, 2010). Each of the papers reviewed looked at the effect of the two medications when administered to dogs showing different anxiety-related symptoms.
Rapoport et al. (1992) studied 37 dogs of different breeds, ages and sexes with a history of at least six months of chronic acral licking that produced lesions and had been unresponsive to treatment. The dogs were split into three groups, with half of the patients in each given one drug and the other half given another. The drugs administered to each of the groups were as follows: clomipramine versus desipramine hydrochloride; fluoxetine hydrochloride versus fenfluramine hydrochloride; and sertraline hydrochloride versus placebo. The latter does not relate to the topic at hand and will not be commented on further. The patients in each group were administered one drug for five weeks before being moved onto the drug it was being compared with. The owners were interviewed each week to give feedback on the severity of their dog’s licking behaviour, rated on a 0 to 10 scale (with 0 being an absence of licking).
Yalcin (2010) studied 25 dogs of different ages, sexes and breeds experiencing tail chasing episodes that lasted for a minimum of 60 seconds per episode. The dogs were put into three groups: eight were given clomipramine hydrochloride; nine were given fluoxetine hydrochloride; and eight were given a placebo. The treatments were carried out over 12 weeks, after which the dogs’ owners were asked to assign a score on a scale from 0 to 4, with 0 being no improvement and 4 being substantial improvement.
Unnithan et al. (2021) studied 16 dogs of unspecified age and sex with visible alopecia and ulcerations on their limbs from excessive licking. The patients were split into two groups, with eight given clomipramine and the other eight given fluoxetine. The treatment was administered twice daily for six weeks. Beneficial changes in licking behaviour were recorded using a Likert scale.
Limitations of the evidence
All of the papers reviewed were limited by their short time frames and small numbers of participants
The overall strength of evidence is moderate due to some limitations being present. All of the papers reviewed were limited by their short time frames and small numbers of participants. Two papers were limited by a reliance on subjective owner reports, which could have introduced bias (Rapoport et al., 1992; Yalcin, 2010). Two studies (Rapoport et al., 1992; Unnithan et al., 2021) also failed to rule out the possibility of food allergy as a cause for acral licking before administering treatment.
Rapoport et al. (1992) had the following additional limitations: the standard deviation was not reported; there was a lack of clarity on dosages given to patients; the duration of the washout period was not stated; and the rationale was not given for the different dosages used in each study.
Yalcin (2010) had the following additional limitations: German Shepherds and Anatolian Sheepdogs were over-represented while female dogs were under-represented in the sample; there was a lack of information on how double-blinding and randomisation were achieved; behavioural outcomes may have been affected by differing home environments; and no long-term outcomes were recorded.
Unnithan et al. (2021) had the following additional limitations: the possibility that different antibiotics were given to each subject prior to testing; the breeds, ages and sexes were unspecified; the authors did not specify that the study was blinded; results of Likert scales and Whitney U tests were not provided; and no control groups were used.
Summary of findings
Two of the three papers found no significant difference between the efficacy of fluoxetine and clomipramine at reducing behavioural signs of anxiety in dogs
Two of the three papers (Rapoport et al., 1992; Yalcin, 2010) found no significant difference between the efficacy of fluoxetine and clomipramine at reducing behavioural signs of anxiety in dogs. Unnithan et al. (2021) found that fluoxetine was more effective, but the findings were not statistically significant.
Rapoport et al. (1992) found that the clomipramine group saw a 43 percent decrease in acral licking after treatment, whereas the fluoxetine group saw a 39 percent decrease. The paper found that these two medications were more effective than any of the others studied, but didn’t find any significant difference between the two.
Yalcin (2010) found that both clomipramine and fluoxetine were more effective at reducing signs of tail chasing than the placebo. However, the results of both drugs were not significantly different from one another at any point during the study.
Unnithan et al. (2021) found that patients treated with clomipramine saw a 30 percent decrease in licking after six weeks, whereas patients treated with fluoxetine saw a 40 percent decrease.
Conclusion
The evidence indicates that both are effective treatment options for dogs experiencing anxiety-related symptoms, and when compared to one another, they have a similar level of efficacy
There is moderate evidence to show that both clomipramine and fluoxetine are effective at reducing acral licking and tail chasing in dogs, two symptoms that may indicate anxiety. Therefore, the evidence indicates that both are effective treatment options for dogs experiencing anxiety-related symptoms, and when compared to one another, they have a similar level of efficacy. However, further research is required to compare these two drugs to strengthen the quality of evidence.
Additionally, it is possible that dogs may have different responses to each drug on an individual basis, so a trial-and-error approach may be required to find the most effective treatment.
| 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 and owner’s values; country, location or clinic where you work; the individual case in front of you; and the availability of therapies and resources.
