Article Reviews

The use of dextromethorphan to treat repetitive self-directed scratching, biting, or chewing in dogs with allergic dermatitis

This article examines the efficacy of dextromethorphan, an NMDA (N-methyl-D-aspartate) antagonist, on repetitive behavior (licking, chewing, itching) in dogs with allergic dermatitis. Dextromethorphan, commonly used as an antitussive or analgesic in small animals, has been found effective in the treatment of equine repetitive behavior (cribbing). Other NMDA blockers have found to lessen pruritic behavior in mice and humans.

Reviewed by Ahna Brutlag, DVM

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 Therap. 27: 99-104, 2004.

Dextromethorphan binds to and blocks receptors for N-methyl-D-aspartate (NMDA). These receptors are found in the neuronal membranes of the brain and spinal cord and are activated by glutamate. These receptors play an active role in memory, learning, pain sensation, and tolerance and sensitization to drugs of abuse. Blocking these receptors has been found to reduce repetitive or stereotypic behaviors such as cribbing in horses or obsessive self-scratching in humans. In unpublished experiments, mice given intradermal injections of compounds that cause mast cell degranulation (pruritus models), NDMA blockers markedly decrease scratching.

Self-scratching and other pruritic conditions have a central component and can be exacerbated by anxiety and other central influences. The traditional model used to study canine compulsive behavior is the lick granuloma or acral lick dermatitis (ALD). Though ALD can have numerous physical instigators, the behavioral component of this compulsion is now appreciated. Opioid antagonists have been proven effective in the treatment of ALD; however, treating ALD in dogs (and self-scratching in humans) with opioids also seem to be effective. The purposed theory for this paradox is that both opioids and their antagonists block NMDA receptors, therefore it appears to be the blocking of these central receptors that actually contribute to the lessening of symptoms.

The double-blind crossover study followed 14 dogs, each previously diagnosed with allergic dermatitis and showing chronic signs of self-licking/chewing/scratching. The dogs were treated with a two week trial of oral dextromethorphan (2 mg/kg PO BID) and two weeks of a placebo (in random order). All medications were withdrawn for at least three weeks prior to the trial. Skin scrapings and ear cytologies were done on all dogs to rule out parasitic and/or secondary infections.

Three main categories were evaluated to determine the drug's effectiveness: gross dermatology score, pruritus score, and “itch percent”. Each dog was examined by a veterinary dermatologist three times during the four week trial (at the beginning to establish baseline values, at the end of the second week, and at the end of the fourth week). At each visit, nine areas of the dog were examined for a variety of dermatologic findings (i.e. alopecia, pustules, papules, erythema, etc.) and each dog was given a gross dermatology score. The level of self-licking/chewing/biting was also assessed (the pruritus score). Each dog was also given a global dermatology assessment of its overall condition as compared to baseline values. At home, the owners were asked to record the amount of time they spent with their dogs and the amount of time the dogs spent engaged in self-directed behavior (scratching, chewing, licking, etc) during the four week trial. The time spent scratching divided by the amount of observed time, multiplied by 100% was dubbed the itch percent.

Based on the owner's observations, dogs treated with dextromethorphan were found to spend significantly less time (31%) engaged in self-directed behavior when compared to the placebo. Likewise, the dermatologist that observed the dogs noted a significant improvement (P = 0.002) in the pruritus score during the active treatment phase. The gross dermatology scores were significantly improved as compared to the baseline but did not differ significantly from each other. The authors attribute this lack of statistical difference to the fact that, for humane reasons, each dog was given a weekly oatmeal bath throughout the entire trial.

Two dogs developed side effects during the active phase of the trial. One dog became lethargic and the other developed diarrhea. Both dogs were removed from the study and symptoms resolved following discontinuation of the drug.

Dr. Brutlag's comments:

The study provides compelling evidence that NMDA blockers may assist in the treatment of repetitive behavioral disorders. Unfortunately, the number of dogs used in the study is small and the criteria used to grade each dog quite subjective. Given the extreme frustration faced by treating veterinarians and dog owners with allergic dogs, dextromethorphan may be a useful tool in the arsenal of atopic therapies.

Because of the short half-life of dextromethorphan, use of a time release formula is recommended. An example of this form is found in Delsym™, an OTC cough suppressant that contains 6 mg/ml dextromethorphan in a sweet syrup base. Oral extended release tablets are also available.

Duncan KL, Hare WR, Buck WB. Malignant hyperthermia-like reaction secondary to ingestion of hops in five dogs. JAVMA 220(1):31-33, 1997.

This article, although not current, serves as a timely reminder of a potential animal toxicity associated with making beer. Many people receive home brew kits for Christmas and are just now trying them out. The article reviews five cases of hops ingestion and notes that ingestion of hops may result in a malignant hyperthermia type reaction in susceptible dogs. A key point, in terms of toxicity, is that hops plugs contain compressed whole leaves and are generally the culprits with little or no toxicity expected from the more popular processed hops pellets.

Article review :

The cases of five dogs (4 Greyhounds and 1 Labrador Retriever) known to ingest hops were reviewed. Three of the five dogs had no history of anesthesia. The onset of clinical signs occurred from 2.5 to 8 hours after ingestion. Signs included panting, restlessness, abdominal pain, tachycardia and tachypnea. Evidence of gaseous distension in the proximal SI and colon was present on X-Rays. Rectal temperature in all five dogs was elevated, with temperatures in three dogs > 41.7C. Four of the five dogs died despite aggressive therapy. Rigor mortis, when reported, occurred within 10 minutes. The surviving dog was treated early and aggressively with gastric lavage, removing about 250 ml of hops from the washings, and IV sodium bicarbonate.

Cultivated members of the genus Humulus are referred to as hop. Hops, used to provide flavor and aroma while brewing beer, are obtained from the flowers of the female Humulus lupulus . Resins, essential oils, phenols, and nitrogenous compounds are found in Humulus lupulus . Any of these can have a toxic effect on animals.

Resins, especially soft resins, contain acids that provide the bitter taste to beer. Soft resins are generally phenolic compounds that are unstable and their content decreases with the age of hops. Essential oils are present in 0.5 to 2.5% concentrations and include hydrocarbons, sulfur containing compounds, and oxygenated compounds. Essential oils impart the aroma to hops. Essential oils are also unstable and most are evaporated 10-15 minutes after boiling. Phenolic compounds vary from 2 to 4%. Included are tannins (coumaric acid, gallic acid, and caffeic acid) and many other polyphenolic compounds. Of the 20 different polyphenolic compounds identified, xanthohumol is the most widely recognized. It is rapidly oxidized, even in cold states. Nitrogenous compounds are present in 2 to 3.5 % concentrations; 0.5% are soluble. An “uncharacterized alkaloid” has been isolated. Betaine, adenine, hypoxanthine, choline, and most essential amino acids are other nitrogenous constituents present in hops.

Most of these biologically active compounds are volatile and would be lost during the boiling portion of brewing. The authors surmise, however, that if hops are steeped and not boiled, then one or more of the biologically active compounds would be present in used or discard hops plugs. They further postulate that ingestion of a hops plug containing one or more of these biologically active compounds was the cause of clinical signs in all five dogs. They suspected malignant hyperthermia in these dogs based on breed, presence of hyperthermia, lack of response to cooling measures, rapid onset of rigor mortis, and serum electrolyte/muscle enzyme abnormalities.

Malignant hyperthermia has been reported in human beings, pigs, dogs, cats, and horses. Stress, excitement, and anesthetic agents are the most common triggers in susceptible animals. Clinical signs develop from minutes to a few hours. The most common signs include hyperthermia, tachycardia, metabolic acidosis, and increases in serum magnesium potassium, calcium and phosphorous. A presumptive diagnosis is made based on clinical signs, familial history, and breed of dog. A definitive diagnosis can be obtained by using one or more of diagnostic tests (RBC fragility, muscle contracture, and halothane-succinylcholine challenge exposure test).

Any dog exposed to hops plugs that presents with an increased heart rate and elevated temperature should be treated aggressively. Treatment includes emesis, gastric lavage followed by activated charcoal with a cathartic, IV fluids to lower body temperature and increase urine output, and other cooling measures. Acid base status should be assessed and IV sodium bicarbonate administered as needed. Cardiac arrhythmias should be treated with procainamide and not lidocaine as lidocaine has an effect on the myoplasmic calcium concentration. Dantrolene, although not used in these dogs, is recommended (2-3 mg/kg IV or 3.5 mg/kg PO as soon as possible; followed by 100 mg PO every 12 hours for 3 days).

Any dog that survives should have a diagnostic test to confirm susceptibility to malignant hyperthermia. The authors suggest either an RBC fragility test or caffeine muscle contracture. Animal owners brewing beer should dispose of spent hops in a manner not likely to harm dogs. Hops plugs, which contain whole leaf hops, are generally felt to be the most toxic. The more popular hops pellets, with little or not particulate matter left for dogs to consume, are generally felt to be safer and less likely to result in toxicity.

Dr. Hovda's Comments: This article presents timely information regarding the potential for susceptible dogs to develop malignant hyperthermia when exposed to hops plugs. While recommended but not used in any of the dogs in this review, dantrolene has been used successfully in a number of more recent cases and should be considered in all cases similar to these. Finally, veterinarians should remember that the more popular and very processed hops pellets may not be as toxic as spent hops plugs.