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in Journal of the American Veterinary Medical Association
in Journal of the American Veterinary Medical Association
in Journal of the American Veterinary Medical Association


Objective—To determine bioavailability, pharmacokinetics, and safety for transdermal (TD) and oral administration of fluoxetine hydrochloride to healthy cats.

Animals—12 healthy mixed-breed sexually intact 1- to 4-year-old purpose-bred cats.

Procedure—A single-dose pharmacokinetic study involving 3 groups of 4 cats each was conducted in parallel. Fluoxetine in a formulation of pluronic lecithin organogel (PLO gel) was applied to the hairless portion of the pinnae of cats at 2 dosages (5 or 10 mg/kg), or it was administered orally in capsules at a dosage of 1 mg/kg. Plasma samples were obtained and submitted for liquid chromatography-mass spectrometry- mass spectrometry analysis of fluoxetine and its active metabolite, norfluoxetine.

Results—Peak fluoxetine concentration (Cmax) was lower and time to Cmax longer for TD administration versus oral administration. Relative bioavailability of each dose administered via the TD route was 10% of the value for oral administration of the drug. Mean plasma elimination half-life after oral administration was 47 and 55 hours for fluoxetine and norfluoxetine, respectively.

Conclusions and Clinical Relevance—This study provides evidence that fluoxetine in a 15% (wt:vol) PLO gel formulation can be absorbed through the skin of cats into the systemic circulation. However, the relative bioavailability for TD administration is approximately only 10% of that for the oral route of administration. (Am J Vet Res 2003;64:994–998)

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in American Journal of Veterinary Research


Objective—To evaluate efficacy of fluoxetine hydrochloride for treatment of compulsive disorders in dogs.

Design—Randomized, controlled clinical trial.

Animals—63 dogs with compulsive disorders.

Procedures—The diagnosis was confirmed on the basis of analysis of videotapes of the dogs' behavior by 3 veterinary behaviorists, results of physical examination and clinicopathologic testing, and, when necessary, telephone interviews with owners. Dogs were randomly assigned to treatment with fluoxetine (1 to 2 mg/kg [0.45 to 0.9 mg/lb], PO, q 24 h) or a placebo. Owners did not receive any advice regarding behavioral or environmental modifications. Severity of episodes was measured through telephone interviews every 2 weeks and on the basis of a daily diary kept by each owner.

Results—42 days after the initiation of treatment, the proportion of dogs with a decrease in severity of the compulsive disorder, as reported by the owners, was significantly higher for dogs treated with fluoxetine than for control dogs, and dogs treated with fluoxetine were significantly more likely (odds ratio, 8.7) to have a decrease in severity of the compulsive disorder. However, mean number and duration of compulsive episodes, as determined from daily diary entries, did not differ significantly between groups. The most common adverse effects were decreased appetite and mild lethargy.

Conclusions and Clinical Relevance—Results suggested that fluoxetine may be efficacious in the treatment of compulsive disorders in dogs, although results were equivocal. The present study did not examine whether fluoxetine was more efficacious than or synergistic with behavioral and environment modifications.

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in Journal of the American Veterinary Medical Association


To assess the efficacy of clomipramine for treatment of canine compulsive disorder (CCD).


Randomized, placebo-controlled, double-blind, balanced AB-BA crossover clinical study


51 dogs with CCD.


Dogs were given clomipramine (3 mg/kg [1.3 mg/lb] of body weight, PO, q 12 h) for 4 weeks and placebo for 4 weeks. At the end of each treatment each owner rated the severity of their dog's behavior, using 2 validated rating scales. Statistical analysis was made by ordinal regression. Compliance, adverse effects, and the effectiveness of masking were also assessed. Each dog's behavior was reevaluated 1 to 2 years after completing the study.


Behaviors included spinning (n = 17) and self-mutilation by licking (acral lick dermatitis, 12). Both rating scales demonstrated a treatment effect. Compliance was satisfactory, and masking was effective. Sedation and reduced appetite were reported more commonly when dogs were given clomipramine than when they were given placebo. Forty-five dogs available for follow-up evaluation still had their behaviors; 6 dogs were lost to follow-up evaluation.

Clinical Implications

Results suggest that clomipramine was effective in dogs with CCD and was not associated with serious adverse effects. However, treatment for 4 weeks was not curative. Behavior modification is likely to be necessary to manage CCD. (J Am Vet Med Assoc 1998;213:1760–1766)

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in Journal of the American Veterinary Medical Association


To determine the effect that feeding diets containing a low (17%), medium (25%), or high (32%) protein content would have on behavior in dogs.


Prospective, controlled study.


12 dogs with dominance aggression, 12 dogs with hyperactivity, 12 dogs with territorial aggression, and 14 control dogs without behavioral problems.


Dogs were fed each of the diets for a 2-week period, and owners were instructed to score their dogs' behavior on a daily basis.


Behavior of the dogs with dominance aggression, dogs with hyperactivity, and control dogs was unchanged by the dietary manipulations. Territorial aggression was significantly reduced when dogs were fed the low- or medium-protein diet, compared with territorial aggression when fed the high-protein diet. Post hoc analysis indicated that this effect was attributable to a marked reduction in aggression in a subset of the group (n = 7) in which territorial aggression was a result of fear.

Clinical Implications—

Results of this study suggest that a reduction in dietary protein content is not generally useful in the treatment of behavior problems in dogs, but may be appropriate in dogs with territorial aggression that is a result of fear. (J Am Vet Med Assoc 1996;208:376-379)

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in Journal of the American Veterinary Medical Association