Statement of the Problem

A dog was evaluated for daily repetitive circling behavior (spinning).

Signalment

The dog was a 13-month-old 2.5-kg (5.5-lb) spayed female Miniature Dachshund.

History

The dog resided with a single female owner who was fostering dogs for a Dachshund rescue organization. At the time the dog was acquired, 8 other Dachshunds and a Cocker Spaniel lived in the household.

The dog had been released by the breeder to the Dachshund rescue organization at the age of 8 weeks. It reportedly showed the circling behavior from the age of 6 weeks. The current owner had acquired this dog for fostering when it was 4 months old. At the same time, the owner had acquired a 3-month-old half-sibling of this dog for fostering; the 2 dogs had the same sire. The half-sibling showed compulsive pacing in wide circles, especially at night, and was eventually euthanized at the age of 8 months because of severe injuries sustained while pacing. The breeder acknowledged later that another puppy from the same sire also had similar neurologic abnormalities.

The dog that is the subject of the present report was kept inside the owner's home together with the other dogs, but was separated from those dogs by a baby gate in the kitchen when the owner was not at home. A crate was used from time to time to reduce the risk of the dog injuring itself when it was spinning.

Ever since the current owner had obtained the dog, it had spun in tight circles to the left, pivoting on its hind limbs. During the dog's first estrus at 8 months, the circling episodes improved slightly for a short while. The dog was subsequently spayed and, at around that time, started circling to the right from time to time. When circling to the right, the dog would spin in tight circles, but with its forelimbs as the pivot point. The circling behavior was especially marked in the evening, and the owner described the behavior as being more obsessive and intense at that time. On days when the behavior was particularly severe, the dog would not eat its evening meal but circled instead. When offered a toy, the dog sometimes stopped for a moment to grab the toy and then spun with the toy in its mouth. The owner found indications that the dog was also spinning in her absence (eg, scratch marks on her hardwood floor and the dog's blanket rucked in a circle) when she came home from work. Furthermore, the dog sometimes followed the owner around the house in the evening, running in close proximity to her feet. If the owner stood still for a moment, the dog started spinning. When spinning, the only way to interrupt the dog was to pick it up and hold it tightly until it calmed down. While being held, the dog would keep struggling and moving as if trying to break free. The owner said that the dog displayed circling behavior for a total of 6 to 10 hours each day. The only observed changes in frequency and appearance of the circling behavior were the slight improvement and the circling to the right at the time of the first estrus and improvement for a short while when it first arrived in its new home. The owner made sure to pay no attention to the circling behavior except when the dog was in danger of injuring itself. The dog would not stop spinning even when it bumped into furniture and injured itself.

On some nights, the dog did not spin but stared at an imaginary spot on the floor while yelping and crying. The owner was able to interrupt this behavior by interacting with the dog. As soon as the interaction ended, the dog engaged again in yelping and focusing on a spot on the floor.

The dog did not interact much with the owner or the other dogs in the household. Initially, the dog would not even make eye contact with the owner or respond to its name when called. This improved somewhat over time. When together with the other dogs, the dog sometimes ran around with them, but started spinning whenever they stopped running. The dog rarely played with the other dogs or interacted with them for any length of time.

The owner described the dog as being excited and constantly moving around every day before bedtime. If the owner was not present, the dog was not able to fall asleep. To calm the dog down at bedtime, the owner resorted to holding the dog tightly until it had calmed down enough to fall asleep. This daily struggle could last up to 30 minutes. On rare occasions when the dog woke up at night, it panted heavily and had a high heart rate. The dog would then drink water or stand with its front feet in the water bowl for a while, apparently to cool down. One week before examination at the Tufts University Behavior Clinic, the dog exhibited one of these nighttime excitement episodes. During this event, the dog fell over, paddled with all 4 legs, and eventually became limp for a while. On the basis of the description of this episode, a veterinary neurologist with whom the owner consulted commented that the event sounded, in retrospect, like a grand mal seizure.

The owner was not able to identify clear triggers for the circling behavior or for the dog's fixating on an imaginary spot. She could only determine that excitement among her other dogs during the evening could result in increased spinning activity.

Laboratory Results, Previous Treatment, and Physical Examination Findings

When the dog was about 5 months old, the owner had brought it and its half-sibling to be examined by a veterinary neurologist. The neurologist repeated a CBC and serum biochemical analyses that the local veterinarian had already performed and, in addition, measured serum bile acids concentrations before and after eating. Subsequently, the local veterinarian tested the dog for lead poisoning and lysosomal storage disease. All test results were within reference limits. Magnetic resonance imaging and computed tomography were performed to rule out hydrocephalus, neoplasia, and other CNS problems, and no clinically important abnormalities were found.

The dog was treated with fluoxetine (dosage unknown) for 3 weeks. However, because this did not have the desired effect and made the dog lethargic, treatment with clomipramine (2 mg/kg [0.9 mg/lb], PO, q 12 h) was begun. The dog was maintained on this treatment for 4 weeks without any substantial improvement. The same treatment regimen was tried with the half-sibling, also without success. After the purported grand mal seizure, the dog was treated with diazepam (2.5 to 5 mg, PO) each night to help it fall asleep. The neurologist stated that the dog's brain development might be abnormal and recommended consultation with a veterinary behaviorist at Tufts University.

On initial examination at the Tufts University Behavior Clinic, the dog was in good physical condition, but had a scar over the left eye that had resulted from an injury incurred during a spinning episode. The circling behavior was not seen in the consulting room, but the owner provided videotapes for later viewing.

Diagnosis

Previous evaluations and testing had ruled out many possible medical reasons for the dog's circling behavior, such as neoplasia, hydrocephalus, inflammatory and infectious processes, toxins, organ dysfunction, and storage disease. Attention-seeking behavior was ruled out because the behavior occurred in the owner's absence. Given the consistent, repetitive nature of the circling behavior, the fact that the behavior was sometimes increased during excitement among the dog's housemates, and the fact that circling occurred in either direction, a preliminary diagnosis of CCD was made. However, an idiopathic seizure disorder could not be completely ruled out.

Treatment

Because no improvement had occurred when the dog was treated with a serotonin reuptake inhibitor (either fluoxetine or clomipramine) for 7 weeks, the owner agreed to try a new treatment option. Accordingly, the dog was treated with the NMDA receptor antagonist memantine. The starting dosage was 0.4 mg/kg (0.18 mg/lb), PO, every 12 hours; a liquid preparation of memantine (2 mg/mL) was used. The owner was notified that possible adverse effects might include ataxia, tremors, a prone position, and bradypnea and was instructed to immediately report back if any of these or any other adverse effects were seen. Further treatment recommendations included daily aerobic exercise and avoidance of any punishment. Environmental enrichment, including the use of chew toys and food puzzles, was advised as a form of occupational therapy and to redirect the dog when it was about to spin. Because compulsive disorders are anxiety disorders, the importance of structure and consistent interactions with the dog were discussed as measures to reduce anxiety. The owner was also advised to keep trying to identify possible triggers for the circling behavior. To aid this, she was asked to keep a daily log of situations during which the dog started to spin. If she was able to identify a pattern, the owner was to contact the Behavior Clinic to discuss avoidance of these situations. The owner was also asked to report back on a daily basis to assess changes in the circling behavior and was advised to take into account both the intensity and frequency of the behavior when assessing improvement or worsening.

Follow-up

On the second day of treatment, the owner reported a 25% improvement in the dog's circling behavior. The dog also engaged more in playing with food and chew toys. Before treatment, the owner had not been able to distract the dog with toys for any length of time. Because the authors of the present report believed the effects of memantine to be relatively acute, a period of 3 to 5 days at a particular dosage was considered sufficient to see drug-related behavioral changes. Dosage changes were made according to the owner's reports of the drug's positive and adverse effects. After 3 days, the dosage of memantine was increased to 0.5 mg/kg (0.23 mg/lb), PO, every 12 hours to see whether further improvement could be achieved. After this first dosage adjustment, the owner reported more and longer social interactions between the dog and her, as well as between the dog and the other dogs in the household. Furthermore, the intensity and frequency of the spinning were decreased. The owner was able to interrupt the behavior and redirect the dog to food or toys more easily and rated the compulsive behavior as 50% improved, compared with the pretreatment level. The owner also reported that the dog appeared happier and was more active. After 5 days at a dosage of 0.5 mg/kg, PO, every 12 hours with stable improvement, the memantine dosage was increased to 0.8 mg/kg (0.36 mg/ lb), PO, every 12 hours for 1 day and then to 1 mg/kg (0.45 mg/lb), PO, every 12 hours in an attempt to gain further improvement. The owner reported regression at this higher dosage rate and believed that the behavior had returned to its pretreatment level. Therefore, the dosage was reduced to 0.6 mg/kg (0.27 mg/lb) in the morning and 0.8 mg/kg at night. At this reduced dosage, the owner once again reported improvement, but not to the earlier level of 50% improvement. Because the owner wanted to regain the initial improvement, after 3 days, fluoxetine (1 mg/kg [0.45 mg/lb], PO, q 24 h) was added to the treatment regimen and the dosage of memantine was reduced to 0.4 mg/kg, PO, every 12 hours. The owner did not see any adverse effects associated with fluoxetine treatment this time. The dog was treated with this combination of fluoxetine and memantine for 2 weeks, and the owner reported between 50% and 75% improvement in the compulsive circling behavior during that time.

To find out how much of the dog's improvement was attributable to treatment with memantine, the owner was advised to discontinue this drug and to treat the dog with fluoxetine alone. This treatment plan was followed for 5 weeks. A setback in the improvement was noticed during this time, and the owner reported an average improvement of not more than 50%. The owner also noticed that it was harder to interrupt the dog and that the intensity and frequency of the circling behavior had increased.

After the 5 weeks of treatment with fluoxetine alone, the NMDA receptor antagonist dextromethorphan was added to the treatment regimen. Dextromethorphan was chosen instead of memantine for reasons of cost. Chewable dog treats containing dextromethorphan at a dosage of 2 mg/kg were compounded and given to the dog twice a day. The owner did not see any major changes in the dog's behavior, compared with the period during treatment with fluoxetine alone. During the third week of dextromethorphan treatment, the dextromethorphan dosage was increased to 2 mg/kg, PO, every 8 hours. At this dosage, the dog had between 50% and 75% improvement, similar to when the combination of memantine and fluoxetine was used. After 1 week, the dosage of dextromethorphan was increased to 3 mg/kg (0.14 mg/lb), PO, every 8 hours to determine whether further improvement was possible. The owner reported little change, and 1 week later, the dosage of fluoxetine was increased to 2 mg/kg, PO, every 24 hours. During treatment with this combination, the owner reported up to 85% improvement in the dog's behavior. On some days, the dog spun for a total of only 30 minutes to 1 hour. In addition, the dog continued to interact more with the other dogs in the household, engaging in games of tugof-war and chase. The dog also fell asleep more easily and could be redirected when spinning. This degree of improvement was stable for 2 months. However, from time to time, the owner reported some backsliding, with less improvement on certain days. In every instance, it was possible to attribute these bad days to increased stress for the dog, such as occurred when there were visitors to the house, the dog was traveling with the owner, or the owner was under a lot of personal stress. Overall, the owner rated the spinning as manageable and started to look for people willing to adopt the dog.

Two months later, the owner moved to a larger home and started a less stressful job. After that change, the dog's improvement remained consistent and was rated as 85% to 90% each day. On some days, the owner did not witness any spinning episodes until the evening. Even these episodes were minor and could easily be interrupted. During the entire treatment period, no adverse effects associated with memantine, dextromethorphan, or fluoxetine were reported by the owner.

Discussion

Canine compulsive disorders are characterized by repetitive activity that seems to serve no true purpose. They can become disruptive to a dog's functioning and also to the dog's relationship with its owner. Compulsive behavior can be a manifestation of anxiety or stress the dog cannot control,¹ and CCD is diagnosed in between 2% and 5% of dogs examined by veterinary behaviorists.² Although behavior modification can be used to treat CCDs, medication is still an important part of the treatment regimen. However, pharmacologic treatments for CCDs are limited. Amitriptyline, which was formerly widely used, has been stated to be relatively ineffective.³ At the present time, selective serotonin reuptake inhibitors such as fluoxetine, sertraline, or paroxetine as well as clomipramine, a tertiary tricyclic antidepressant, are the most commonly used treatment options. However, these medications are not successful in all dogs with CCD, and other treatment options are needed.

Altered glutamatergic neurotransmission appears to be involved in the pathogenesis of obsessive-compulsive disorders in humans,⁴ and ongoing discussions suggest that drugs with selective action on the glutamate system (eg, by blocking NMDA receptors) may provide a valuable new treatment option.⁵ Various NMDA receptor antagonists have already been used successfully to treat repetitive and compulsive disorders in animals^6,7 and have been patented for the treatment of stereotypic self-injurious and compulsive behaviors in people and animals.⁸

Most of the currently available NMDA receptor antagonists have undesirable adverse effects. Memantine, however, is a noncompetitive, low-affinity NMDA receptor antagonist that acts selectively at NMDA receptors in the brain and retina. Memantine is available as memantine hydrochloride^a and is approved by the US FDA for treatment of Alzheimer's disease in people. Memantine is clinically well tolerated,⁹ and case reports^10,11 describe that memantine can be used to control treatment-resistant obsessive-compulsive disorders in people. To the authors' knowledge, this is the first report of the use of memantine to treat a compulsive disorder in a dog. The authors of the present report believe that memantine worked in this case because of its antiobsessional properties, as reported for people.^10,11

A seizure disorder could not be completely ruled out in the dog described in the present report, and memantine is known to have an ambivalent influence on seizure disorders. In some reports,^12,13 memantine has been reported to promote seizures, but it has also been described as having distinct antiepileptic properties.^14–16

It was not possible in the dog described in the present report to precisely distinguish the effects of behavior modification from the effects of the various medications that were given. However, the improvement was believed to mainly be a result of the medications because the owner had a busy work schedule and was not able to implement many of the behavioral recommendations. The dramatic improvement seen in this dog suggests that the combination of fluoxetine with an NMDA receptor antagonist might be an option for dogs with otherwise treatment-resistant compulsive disorders. However, it seems likely that memantine will not be helpful for all cases of CCD because different compulsive behaviors may have different underlying pathophysiologic causes. Because of its effects on seizure disorders, memantine might be especially helpful in cases of CCD with a partial seizure component, if its anticonvulsant effects prevail.

Memantine is not yet available in a generic version in the United States, and the brand name version may not be affordable for the typical owner. Dextromethorphan, which has already been proven to help in the treatment of repetitive behavior in animals,^6,7 was an affordable and effective alternative in this dog.