Editor's Note: The editors at Veterinary Forum recognize that Prozac is not approved for use in animals at this time. However, our magazine is a forum for presenting ideas and opinions, and for sharing the experiences of our readers with the veterinary community at large. We hope that the information contained in this article will further the understanding of the use, or non-use, of the products and procedures mentioned. This magazine, its staff and its advisors do not endorse die information in any manner.

Prozac (fluoxetine) has received a great deal of attention this past year for its use in the treatment of pet dermatological and behavioral disorders. Anafranil (clomipramine) and Zoloft (sertraline) are products with a similar spectrum of activity, although they have been viewed with less fanfare.

My first and main experience with Prozac was and is using it clinically for obsessive-compulsive disorders (OCDs). OCDs exhibit stereotypic, repetitive and constant behavior which performs no function. I have read articles and heard colleagues say that Prozac is ineffective, unscientific, risky, with unnamed side effects and worse. While some veterinarians remain skeptical, others have explored the beneficial uses of Prozac and others want to discuss new uses for the drug.

Most dermatologists and behaviorists have criticized it. My fellow dermoids have said it is too expensive, it takes too long to be effective or have given some other argument. Some behaviorists have been known to growl at the very mention of the drug. One argument is that it is too simplistic; that behavioral modification is fundamentally forgotten.

One reminder: Prozac and its cousins, such as Anafranil and Zoloft, while revolutionizing certain previously untreatable disorders, are often only a component in an overall therapeutic plan. The purpose of this article is to examine the conditions in which I believe psychopharmacologics can be effective and to review my clinical observations.

History

I first became aware of the use of selective serotonin re-uptake inhibitors (SSRI) drugs prior to the introduction of Prozac in 1988. At the time, a study at the National Institutes of Health by Dr Judith Rapoport first proposed that acral lick dermatitis (ALD, lick granuloma) was an animal model for obsessive-compulsive disorders (OCDs) such as trichotillomania. Her first work was with Anafranil. I met with her, she explained the use of Prozac and Anafranil, and I set out to prove their efficacy in acral lick dermatitis (ALD) and to find other OCDs and potential uses for SSRIs in dogs. While Dr. Rapoport was kind enough to instruct me, she also worked with Dr. Nick Dodman of Tufts, whose work on behavior, unbeknownst to either of us, seemed to parallel mine in dermatology. (See "Pharmacological Treatment Of Behavioral Problems In Cats," by N.H. Dodman, DVM, Veterinary Forum, April 1995, pages 62-71.)

In 1990, Shoulberg described the use of Prozac in ALD and Rapoport published papers in non-veterinary journals on Prozac, Anafranil and Zoloft. However, the first veterinary publication did not mention the use of Prozac for various conditions until 1994. The resulting enormous response on the part of colleagues, the public and the press was totally unpredictable.

Pharmacology

Prozac, Anafranil and Zoloft are selective serotonin re-uptake inhibitors (SSRIs) in a class known as heterocyclic antagonists. The elevated levels of serotonin are primarily found in the brain, leading many to believe that the primary lesions for the following described disorders are in the brain.

My original interest as a dermatologist in this class of drugs was due to their close molecular relationship to antihistamines. In fact, Prozac is chemically quite similar to diphenhydramine (Benadryl). In reality, they could not be more dissimilar. The negative effects of antihistamines, (i.e., dry mouth, sedation and urinary retention) are not found with fluoxetine use. Although many of their cousins (tricyclic antidepressants) do have multiple effects which are considered undesirable, it is my belief that the absence of sedation (as well as a lack of other side effects) has been the key point in the popularity of SSRIs.

Dosage

Fluoxetine and clomipramine are entirely water soluble, which is convenient in creating dose aliquots for smaller pets. The usual minimum effective dosage is (for side effects see text):

* The dosage levels can be exceeded dramatically and should be in cases where efficacy has not been enabled at the lower dose. In these cases, one can change to a different drug or raise the dosage. One spinner required fluoxetine at 5 mg/kg before a clinical response was noted.

** Amitriptyline is not considered to be anti-obsessional, which is critical to most psychodermatological needs.

Time Of Onset

The onset of efficacy in the 65 cases on which I am reporting was separated into two populations. One took 16.14 days on average while the other had a much quicker effect, with an average of 5.2 days. This is quite similar to humans. However, unlike in humans where the half life of Prozac is three days, it is only one day in dogs.

Side Effects

The most pleasant surprise with using these drugs was the relative absence of serious side effects. Unlike in humans, where aggression, homicide and suicide stories are rumored, there is virtually no serious abnormal behavioral side effect. In fact, these drugs are my choice for cases involving abnormal aggression.

Most owners described their pets as "mellow" while on the drug. Lethargy was cited in 26.2% of the cases while 18.5% actually showed signs of being hyperactive. On a scale of one to five, the owners rated their lethargic dogs an average of 3.2, with the hyperactive ones only 2.16. My observation was that lethargy was a more serious complaint.

Increased thirst (polydipsea) was noted in 16.9%, which the owners graded at 3.6, which indicates that it was moderate. 4.5% of dogs had diarrhea, which was a grade 4, perhaps because of the general dislike for this complication. The effect on the appetite was most interesting and somewhat surprising. While 24.6% of those dogs studied had a decreased appetite, (average grade 2.6) which goes along with the human data, there was a surprising 21.5% increase in appetite (average grade 2.4) with one pet actually exhibiting coprophagy, which I have listed as a potential indication for Prozac usage.

No animals required hospitalization as a result of the use of any of these drugs.

Clinical Indications

The following chart lists the many potential uses for these drugs - many of the uses have been tried successfully. Of those where SSRI therapy is unsuccessful, additional options are available. First, switch to a similar drug; if Prozac fails try Anafranil or Zoloft. Second, increase the dosage. I have found that many of my most serious cases - spinners and tail mutilation disorders - can handle much higher doses than previously reported. Elavil (amitriptyline) has been generally ineffective at therapeutic levels, up to three times greater than recommended.

The Case Study

Of the 65 cases, 31 had psychogenic pruritus, 14 had lick granulomas (i.e., acral lick dermatitis [ALD]), six were tail mutilation disorders, six had separation anxiety and eight had behavioral problems.

I will describe the clinical indications for use of serotonin re-uptake inhibitors in animals, with case reports for illustrative purposes. Examples of these reports will include tail and other mutilation disorders, psychogenic pruritus (as best exemplified in appropriately treated hyposensitization failures) and certain behavioral disorders.

Note: It is beyond the scope of this article to discuss the range of causes and treatments for the many diseases which I will describe. My success is in large part due to the products and methods that I use, which will vary from one veterinarian to another.

Lick Granulomas
(Acral Lick Dermatitis/ALD)

ALD is a common lesion affecting many breeds of dogs. It is usually believed to be associated with an instigating allergic reaction. It is proposed as an animal model for obsessive-compulsive disorders (OCDs).

Attention-requiring breeds like Golden and Labrador Retrievers seem to be disproportionately predisposed to these lesions. What cannot be explained is why the location of the lesions are so common on the top of the front extremities.

At the Animal Dermatology Clinics of Palm Springs, Calif., and Potomac, Md., I employ the following standard protocol:

Antibiotics. Cephalexin (10 mg/kg/BID) is usually my preference, but if the infection is deep enough, I start with Baytril as well. These are given until hair begins to re-grow, which may be as long as six months, but rarely less than two months.

Special Bathing. Preferably an allergic dog is bathed daily. It is mandatory for the lesion to be bathed daily with a Benzoyl peroxide formulation, allowing the suds to sit for at least 10 minutes before rinsing.

A good topical antibacterial can then be applied. I prefer an acetic/boric acid-containing product.

Prozac. Remember the lag phase of two to three weeks. Use for at least five weeks. Restrictive devices such as Elizabethan collars can usually be removed in two to three weeks.

Ivermectin. Treat as you would for scabies (.1-.15 mL per 10 pounds, given every seven to 10 days). Remember this is an extra-label use, which must be explained to clients. Collies and collie crosses can never use this drug.

Omega 3/6 fatty acid caps. The Omega 3 fatty acids reduce inflammation associated with itching. Whenever using these products (whose Omega 3 source must be fish oil to be effective), one must supplement Vitamin E and preferably C since they are depleted more rapidly.

An appropriate work-up is always necessary. If the case is unresponsive to therapy, exceptionally severe or large in size, then an X-ray may be necessary to check for underlying bone involvement. Skin scrapes for Demodex, cultures for dermatophytes, fungi and bacteria and biopsies are also important to rule out diagnoses such as tumors.

Of 14 cases, 10 were treated successfully (Grade 5) for a 71.4% success rate. This success rate, which was based upon regrowth of hair whenever possible, greatly exceeds any previously reported. My population consisted of four Golden Retrievers, a Doberman, Springer, German Shorthaired Pointer, Scotty, Spinone, Gordon Setter and a Sheltie. An interesting finding was the overrepresentation of males: there were 11 males and three females. Eight were on allergy vaccines determined by testing; at least five were on Elizabethan collars, all of which were removed before the mandatory re-exam in three weeks. Three stopped the drug for various reasons before completing the five-week protocol and alternative therapy was instituted.

The owners' responses were that all of the subjects seemed less obsessed by their lesions. One said it decreased barking, another said the ALD was better but not the aggression, a second behavioral diagnosis.

Psychogenic Pruritus

I define this as itching that is unresponsive to an appropriate therapeutic plan in the hands of a specialist. My work-up includes eliminating food, inhalant, insect, ecto- and endoparasite allergies as well as contact allergies. I also rule out pyoderma, other nonspecific causes such as cancer, liver disease and other organ malfunctions, cutaneous yeast and other disorders. A carefully timed trial using drugs, shampoo therapy and a food elimination trial is utilized to see if and when the itching stops, is reduced or returns. This allows a process of narrowing down the diagnosis by utilizing a combination of diagnostic tests and the response to a clinical trial. I then respond to each patient's individual needs.

Most cases in this category were considered to be suffering from inhalant allergy and were not responding to appropriate therapy, which included an allergy vaccine. An allergy vaccine created from the results of an allergy test (ELISA or intradermal skin testing) is considered to be effective in only 60-80% of cases nationwide. The remaining 20-40% are considered vaccine failures; it is mainly this population that I chose to study.

The gait control theory of pruritus illustrates the possible reason why psychopharmacologics are effective. It states that the pruritic threshold is lowered as a result of stress. This conforms with the theory of summation of effect, in which the sum of forces which may trigger an allergic/pruritic reaction may be added together. The issue of stress in pruritic/allergic pets has never been previously addressed as one of the contributors for summation of effect. Stress is known to be a major contributor to allergy in mall, notably in patients suffering from asthma. My standard protocol for a pruritic clog involves:

1. Fatty acid caps (as in the ALD chart).

    

2. A daily hypoallergenic shampoo (call be less frequent depending on the patient). I prefer one without dyes or fragrances but that contains nutrients and conditioners. This is contrary to conventional wisdom, but consider the tact that the dog's haircoat is nothing but a dust mop, and the pollen that it is allergic to is covering it. It is a fundamental of allergy treatment to avoid the source of die allergy. Thus, the necessity of frequent bathing.

    

3. Antihistamines, which have infrequently been effective by themselves, although they have been effective in reducing the need for corticosteroids (prednisone).

    

4. Corticosteroids. They have been effective for me when used judiciously - no more than every other clay.

    

5. Diet. Feed a premium packaged hypoallergenic diet to reduce the possibility of summation of effect causing a lowering of the patient's pruritic threshold.

Of the 3l cases observed, five were Golden Retrievers with two Shitzu, Miniature Poodles, Bichon Frise and Yorkshire Terriers. There was a slight overabundance of females (18) to males (13). All but four were allergy tested and on a vaccine. One was tested but did not have an inhalant allergy. Complications varied in these cases with 32.3% suffering from pyoderma, 9.7% from each of three disorders - hot spots, tail mutilation disorder and self-mutilation; 12.9% suffered from ALD; and 19.35% had a diagnosable behavioral disorder.

Prozac was the only drug used in addition to my standard therapy in the above cases. The results were equivocal with the average response of 2.5. One case has been on Prozac how for several years at a reduced frequency close (two times weekly).

The owners' assessments included comments such as: "Still itching, but less intense. More mellow - sleeping and resting more. Reduced hyperactivity. Lost interest in food. increased appetite (including coprophagy). Took his mind off licking." One case that was lethargic at a low dose actually became more energetic at a higher dose.

The most important finding was that 54.8% of the cases had a decreased dependence on prednisone. Of the five dogs that were either not tested or tested negative for allergies, three improved. Interestingly, the one clog that tested negative for inhalant allergies had a remarkable response.

These results indicated that Prozac, when used alone, was ineffective iii treating allergy tested, allergic dogs. It was, however, effective as a component of overall therapy. I continue to use it in a minority of cases during the peak of allergy season when clogs are suffering most. Perhaps a close adjustment might increase its efficacy in those cases in which there is an ineffective response.

Tail Mutilation Disorder
(Including Spinners)

Tail mutilation disorders (TMD) as a result of dermato/behavioral disorders were previously undescribed. I propose that one form of them is actually quite similar to ALDs on the tail, with a far worse prognosis than the traditional ALD case. My diagnostic plan rules out the following: anal sac disease, peripheral paresthesia as a result of an improper tail dock, intestinal parasites, ectoparasites (including fleas, scabies and Demodex), potential causes of infection, inhalant, food or contact allergy, osteomyclitis and some type of tumor or granuloma.

My first case using fluoxetine for other than ALDs was a 3-year-old Bichon Frise that was presented to me as a second opinion to avoid a recommended tail amputation. He had been on an E-collar for several months. My thought was that if he was after his tail and we amputated it, what would prevent him from attacking the remaining tissue? After a thorough and comprehensive work-up, he was placed on Prozac. We were able to remove the E-collar in seven days, stopped the drug in less than the prescribed five weeks and I never needed to use any other drug. He is bright-eyed and bushy-tailed today.

Of the five other cases, all were on some contraption to keep them away from their tails, and in all cases we were able to remove them at some close. Four of the six dogs were clinically cured, one of which had an ALD at another location that completely resolved, whereas the tail lesion improved but still requires treatment. Two of the six are still on Prozac.

Separation Anxiety/Fear

Anxiety is a state of chronic apprehension in which fear is a major component. Intimidating circumstances, such as being left alone or visiting the veterinarian; inanimate cues, such as thunderstorms and loud noises; and animate cues, such as other dogs, cats or people, usually contribute. No matter what the cause, a common biochemical pathway seems to be involved. Based on this principle, a drug could theoretically satisfy this biochemical need. I propose that SSRI drugs, such as Prozac, are acceptable. The following case will help illustrate this point.

Smoky, a five-year-old male castrated Weimeraner was presented to me in a desperate situation. The owners had to move to a new house, which they shared with people who owned cats. They both took jobs and their preschool child started school. When left alone, Smoky was barking all day, destroying property and when crated was doing damage to himself and the crate. The whole gamut of intimidating circumstances (being left alone), inanimate factors (being in an unfamiliar place) and animate factors (cats) were involved. Previous treatment involved sedative drugs to which he was gradually developing a tolerance. He was showing a personality change and becoming aggressive. The owners were cited for a noise violation and warned by a judge to cure or remove the animal from the premises. Prozac was effective in this patient in two weeks. After five weeks, a failure to return for a reexam led to the discontinuation of the drug and a reoccurrence of the behavior in less than one week. Reinstituting the drug afforded 95% recovery. Subsequent attempts to wean the drug have failed.

In the six cases that I reported five recovered totally with single drug therapy and no behavior modification other than what was attempted prior to a visit to me. The sixth case also suffered from psychogenic pruritus, which did resolve. All of these cases have required long4erm therapy with an SSRI drug.

The use of fluoxetine as a sole drug treatment for separation anxiety cases appears to be an acceptable, if not recommended, therapy. Behaviorists have argued that behavioral modification is important in these cases; however, behavior modification was not used in my cases in order to directly observe the effects of the drug. This was done at a time when Prozac usage for anything other than ALD or TMD cases was unknown.

Behavioral Disorders

These cases represent a broad group of behavioral disorders such as aggression, fly biting, territorial behavior and inappropriate urination; I am reporting on one to three of each. For lack of a better category, I placed one fly-biter in this category. Only one dog, a Kerry Blue Terrier, spayed female, exhibited an increase of aggression while on fluoxetine, and this was induced by the irritation of being handled during grooming.

Behavioral cases as described always require appropriate examination prior to the use of psychopharmacologics. For example, inappropriate urination requires a systemic work-up; anxiety and aggression in an older dog can be a result of a variety of possibilities, including deafness.

One argument supporting the use of fluoxetine is that it does not interfere with cognitive function. The animal can still effectively receive behavior-modifying training. The same argument is more difficult to make when using sedatives such as Phenobarbital or diazepam.

One case was a Jack Russell Terrier - owned by a very kind woman who herself was on Prozac - that displayed a dominant form of aggression toward males. It was not difficult to demonstrate in my exam room. He is now on an adjusted higher dose and doing much better, according to the owner. This finding could not be appreciated during my exam.

The fly-biter was a male, Doberman-Rottweiler mix who periodically would bite at the air as if at imaginary insects flying around. He was described as hysterical by the owners after two weeks on fluoxetine. They complained that he also totally lost his appetite, clung to them and demanded constant attention. Any beneficial effects of the drug were clouded. I changed the prescription to another SSRI and lost contact.

A castrated male Miniature Poodle was suffering from inappropriate urination. It started gradually as an adult with marking all over the house. The owners were greatly distressed and referred to me by family friends. He was worked-up by other veterinarians and myself for possible causes, including bladder and kidney problems. After about two weeks on fluoxetine, he discontinued his in-house marking.

Discussion

ALDs and a subset of TMDs, as well as psychogenic pruritus cases, appear to be OCDs. If we observe the symptoms of these patients, then we see their responses to SSRI drugs. When a stereotypic, repetitive disorder without a function is resolved when using a drug that is known to resolve OCD problems, then the disorder can and should be considered an OCD.

The finding of other OCDs in pets is not surprising. Dr. Rapoport sent Dr. Dodman, myself and others in search of them. This area of psychopharmacology in the treatment of behavioral disorders should be one of the most exciting disciplines at the onset of the 21st century. The use of fluoxetine by general practitioners remains controversial. Behaviorists and dermatologists promote an exhaustive work-up, yet it seems that even when indicated, they choose to avoid Prozac and use less effective, less expensive drugs.

The biggest drawback and source of complaint is the cost. The average per-day cost for a 40 lb. dog is $2.00. It is understandable for the owner of a very large dog to be critical of the cost, although I have treated a 100 kg Great Dane and many 100 lb. dogs. Perhaps at the level of referral specialist, my clients are already prepared for an economic investment, but $5.00 a day for a 100 lb. Dog ($1,825 annually) is a lot of post-tax dollars over the course of one year. Other drugs, however, can also be expensive, for example Baytril, which is used in many of my cases. Ultimately it is the client's decision.

Amitriptyline, which is available in generic form, has been used as an inexpensive substitute despite the fact that many experts do not believe it to be anti-obsessional. Its failure to be effective has led more than one expert to negatively pre-judge other psychopharmacologics. A 100 kg ALD Great Dane on 120 mg of fluoxetine is attempting to switch over to amitriptyline due to cost. It has failed at dosages as high as 500 mg as of this writing.

SSRI drugs have no place in the treatment of allergy cases, except those in which a vaccine has not been adequately effective, and then only as a component to traditional therapy. Although related to antihistamines, they are absolutely not effective as such. Dermatologists have a good point, at least in terms of arguing that fluoxetine use is improper for the average allergy case.

The philosophical arguments are just that. We are not toying with a healthy dog's psyche. We are not sedating or throwing hormones such as Depo-provera, causing the feedback system to go awry. These were the only other known acceptable drug therapies for the syndromes mentioned in this article used up to this point, other than behavior modification. However, there was no national controversy about the use or abuse of tranquilizers, sedatives or hormones.

Perhaps there is a statement that could be made about society being too busy to institute more holistic, if not time-consuming, therapy Acupuncture has been an acceptable alternative in some cases of ALD, although the patient needs to visit the doctor at least weekly for eight to 10 weeks. My clients are given alternatives; invariably they select the convenience of a pill. If they need it and it is appropriate, then let them have the Prozac, Anafranil or Zoloft.

References

1. Melman, S.A. Psychogenic Dermatoses. Skin Disease of Dogs and Cats: A Guide for Pet Owners and Professionals, 1994, DermaPet, Potomac, MD 20854

    

2. Melman, S.A. Psychogenic Dermatoses. DVM, March 1994.

    

3. Melman, S.A. A Tail of (Tale) Mutilation. AVSAB Newsletter, July, 1995.

    

4. Melman, S.A. Diagnostic Clinical Trial for the Pruritic Animal in "Skin Deep," VPN, July, August and September, 1995, p. 18.

    

5. Rapoport, J. Drug Treatment of Canine Acral Lick. Arch Gen Psychiatry 1992; 49:517-521.

    

6. Dodman, N. Pharmacological Treatment Of Behavioral Problems In Cats, Veterinary Forum, April 1995, pgs. 62-67.

    

7. Hunthausen, W. and Landsberg, G. Pet Behavior Problems: A Practitioners Guide. American Animal Hospital Association, 1995.

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