Dermatology Update: Can dextromethorphan be used to treat repetitive itching and scratching in atopic dogs?

Atopic dermatitis is one of the most common causes of pruritus in dogs. It is diagnosed based on a dog's history and clinical signs and the elimination of other causes of pruritus.

The pathogenesis of pruritus in dogs is still not well understood. To further complicate matters, some clinicians speculate that certain dogs have a combination of sensory irritation (true itch) and repetitive behaviors (self-directed itch), though these dogs are hard to differentiate from dogs with purely sensory irritation. But the dogs that are most suspected of having this combination are those that clients describe as becoming itchy when stressed.

Treatment options for atopy vary depending on a variety of factors, including the severity of signs, whether the signs are year-round or seasonal, the dog's response to medical treatment, and the owner's financial constraints. Dogs receiving immunotherapy often also receive concurrent antipruritic therapy on either a long-term or intermittent basis.

In a recent study, oral dextromethorphan hydrobromide was evaluated in 14 dogs with atopic dermatitis to determine whether the drug had any effect on repetitive behaviors associated with or suggestive of pruritus (e.g. self-licking, self-chewing, self-biting).1 A veterinary dermatologist diagnosed atopic dermatitis in the dogs, and all of the dogs were free of other complicating causes of pruritus (e.g. mites, yeast). After a three-week washout period from any drugs the dogs may have been receiving before the study, the dogs were randomly enrolled in a four-week, placebo-controlled, double blind crossover study. The dogs received 2 mg/kg dextromethorphan in a gelatin capsule every 12 hours and a placebo for two weeks each. During the study, oatmeal soaks were allowed, but no other therapies. Twelve dogs completed the study; two dropped out because of adverse effects (sedation, diarrhea). Because of a lack of compliance with data collection, the investigators were only able to evaluate data from 10 dogs. An important component of the study was the owners' scoring of their dogs' pruritus. The owners were required to record how much time they spent with their dogs and the amount of time the dogs exhibited certain itch behaviors. In addition, a dermatologist examined the dogs at various points in the study.

The investigators used a calculation called the itch percent to evaluate the data. The itch percent was calculated based on the time the owners spent with their dogs and how much time the dogs were observed to be involved in itch-scratch behaviors during these periods. Dogs receiving the placebo were observed to exhibit itch behaviors 8.7% of the time; dogs receiving dextromethorphan exhibited itch behaviors 6% of the time. The difference (2.7%) was statistically significant and represents a 31% decrease in observed itch behaviors. A global dermatology score was calculated for all the dogs, which consisted of three components of the dermatologist's assessment (a pruritus score, an inflammation score, and an overall score). The dermatologist's global assessment was more favorable after the active treatment phase in 11 of the 12 dogs, and the pruritus score during dextromethorphan treatment was significantly less compared with the placebo and baseline. The investigators concluded from these findings that dextromethorphan was beneficial in reducing the time the dogs spent licking, chewing, and self-biting.

Commentary

The findings in this study suggest that dextromethorphan may be clinically useful in atopic dogs with habituated pruritic behaviors. However, a placebo effect may still have been a factor. Moreover, the investigators stated that the oatmeal soaks might have contributed to some of the overall gross improvement in the skin. And the 31% decrease in pruritus represents 23 minutes of itch-scratch behavior when the dogs received the placebo vs. 17 minutes when they received dextromethorphan. I'm not sure that the average client would find a decrease of six minutes of itching to be a great improvement. Finally, in a recent study on the pharmacokinetics of dextromethorphan after intravenous and oral administration in healthy dogs, the investigators found that the drug had a short half-life, was rapidly cleared, and had poor bioavailability.2 The authors of this pharmacokinetics study concluded that the drug's erratic absorption, short elimination half-life, and rapid clearance limit its potential usefulness when administered orally long-term.2

If there is a true benefit from dextromethorphan, it suggests that some central component to pruritus or at least to the repetitive behaviors that clients and veterinarians interpret as pruritus (e.g. licking, biting) exists. Opioid antagonists have been successfully used in other species to treat repetitive behaviors.3,4 For example, dextromethorphan has been effective in treating crib-biting in horses.5 It is hypothesized that dextromethorphan works by N-methyl-D-aspartate blockade and not by opioid blockade. The exact mechanism of action is unknown, but N-methyl-D-aspartate receptors are found in the spinal cord and brain and are involved in learning and memory, tolerance, and sensitization.

When new findings regarding a drug's antipruritic effects are reported, it is tempting to prescribe it as a first-choice drug; however, newer is not always better or appropriate. The long-term safety of dextromethorphan is unknown, and the dogs in this study received the drug for only two weeks. Clients should be aware that this drug is not free of side effects, which include sedation, vomiting, and diarrhea.

Treating dogs with chronic atopy will always require vigilant monitoring for breakthrough infections and secondary parasitic infestations. Traditional therapies for pruritus (immunotherapy, antihistamines, glucocorticoids, and cyclosporine) are indicated initially. Dextromethorphan may be useful in patients with no obvious signs of inflammation or in cases of a suspected repetitive behavior. But it is important to note that no studies are available documenting the existence of habitual pathogenesis. Perhaps there is a place for a drug such as dextromethorphan in the treatment of atopy, but for now my recommendation is to focus on traditional antipruritic therapies and monitoring of underlying disease.

REFERENCES

1. Dodman NH, Shuster L, Nesbitt G, et al. The use of dextromethorphan to treat repetitive self-directed scratching, biting, or chewing in dogs with allergic dermatitis. J Vet Pharmacol Ther 2004;27:99-104.

2. Kukanich B, Papich MG. Plasma profile and pharmacokinetics of dextromethorphan after intravenous and oral administration in healthy dogs. J Vet Pharmacol Ther 2004;27:337-341.

3. Dodman NH, Shuster L, Court MH, et al. Investigation into the use of narcotic antagonists in the treatment of a stereotypic behavior pattern (crib-biting) in the horse. Am J Vet Res 1987;48:311-319.

4. Kenny DE. Use of naltrexone for treatment of psychogenically induced dermatoses in five zoo animals. J Am Vet Med Assoc 1994;205:1021-1023.

5. Rendon RA, Shuster L, Dodman NH. The effect of the NMDA receptor blocker, dextromethorphan, on cribbing in horses. Pharmacol Biochem Behav 2001;68:49-51.

"Dermatology Update" was contributed by Karen A. Moriello, DVM, DACVD, Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706.