Medication - Selegiline (Anipryl Rx)


l-deprenyl (Anipryl Rx)

We have received several questions about the use of l-deprenyl (Anipryl Rx) recently. This medication was approved this year for the treatment of uncomplicated pituitary dependent hyperadrenocorticism (Cushing's disease). In clinical trials this medication was effective about 80% of the time in controlling this disorder but clinical improvement may take one to two months. Since there are fewer reported side effects reported for l-deprenyl than for mitotane (Lysodren Rx) there is a strong interest in its use.

As is the case with many new drugs, there are new problems relating to its use. Perhaps the most perplexing to vets is the lack of a really good way to monitor the success of treatment. Only a small percentage of dogs will show improvement in the traditional laboratory tests used to monitor Cushing's disease after treatment with Anipryl. This takes some getting used to after years of carefully monitoring the effects of Lysodren due to fears of toxicity. At present, improvement in clinical signs appears to be the best way to monitor the use. This leaves a little uncertainty that will make some vets and perhaps even some owners uncomfortable.

The other problem with Anipryl is that it is meant to be used in uncomplicated cases of hyperadrenocorticism due to the need to reduce cortisol levels quickly if diabetes or other complications are present. This is frustrating to vets and owners who would really like to use a safer medication in these circumstances. As time goes on protocols for use in some complicated situations may be developed. Until then there are going to continue to be many cases in which Anipryl use isn't going to be the treatment of choice.

Mike Richards, DVM

Selegiline (Anipryl Rx)

Question: Dear Dr Richards,

First of all - THANKS for doing what you do! This is a truly valuable service and I find it so helpful (along with my vet's advice of course).

I don't know if you remember, it's been awhile, but I have a lhasa named Paris, 12 years young, who was diagnosed around Chrismas with a pituitary tumor and Cushing's. She did not do well on the first med we tried and she almost died; now she's on Selegiline. She's doing so well! I'm being lulled into a false sense that maybe she was misdiagnosed because she IS doing well. I had read several places that Anapryl doesn't work well....

I guess my question is, do you think she is improving? Is that possible? I know the tumor isn't going to go away, and I'm ecstatic that she's doing well, but I'm afraid I'm in denial about the possiblity that she's really OK.

Thank you so much! Roxanne

Answer: Roxanne-

Selegiline (Anipryl Rx) is a medication that seems to have veterinary endocrinologists choosing up sides and issuing lots of strong opinions. I have a couple of textbooks that suggest it shouldn't be used at all and a couple more that think it will help a lot. The most recent information, pretty much the only study not funded by the companies that produce selegiline, is that it works really well in about 20% of dogs, OK in another 20% and doesn't work well at all for the remaining 60%, when treating hyperadrenocorticism (Cushing's disease). In the dogs in which it worked, it did appear to slow or arrest the growth of the pituitary tumor, so that was a strong incentive to consider use, especially in the subset of dogs with the tumor type it appears to work best for which was identified by MRI exam.

There is another complicating factor with the use of selegiline. It is also used to treat canine cognitive dysfunction and it is highly likely that many patients with Cushing's disease also have canine cognitive dysfunction, since the diseases are most common in the same age groups. So some of the perceived improvement is potentially due to a concurrent problem.

There really isn't a good way, other than observation of clinical signs, to tell if selegiline is working well. Since people do want to get results, there is always the potential for a placebo effect in these evaluations. Most veterinarians feel that a dog with laboratory evidence of Cushing's disease but no clinical signs does not require treatment, though --- so when looking at the use of selegiline from this perspective it seems reasonable to try it and to continue to use it as long as it does appear to be controlling the clinical signs of the disease. If it stops appearing to work, that would be the time to worry.

Mike Richards, DVM 10/9/2000

Hyperadrenocorticism and selegiline (Anipryl Rx)

Question: Dr Mike, just skimmed the September digest and noted with some fear that your described hyperadrinocorticism is a 'serious' condition. 'Sweetie' is/has been treated with Anypril for what was diagnosed as 'pituitary dependant' hyperadrinocorticism. I wrote to you a a couple of occassions re: dosage etc. I monitor her carefully but did not know the condition was considered 'serious'. Would you please claify for me ? She has been on medication for several months but I have not had a follow on blood test - and probably should have.

Answer: Bruce-

If it is not controlled hyperadrenocorticism causes a lot of problems that can become serious, including an increased susceptibility to bladder infections, skin infections, diabetes, heart disease, respiratory disease, seizures and a number of other conditions. Due to the association between pituitary brain tumors and hyperadrenocorticism, it may be fatal even in treated patients, since the treatment does not do anything for the presence of the tumor. So these are the reasons that the condition is considered to be serious.

It is very early in the understanding of how selegiline (Anipryl Rx) works, but there is some chance that it may decrease the rate of groth of some pituitary cancers from overstimulation by the hypothalamus.

On the other hand, the first independent study of selegiline that I know of, by Dr. Peterson, suggests that it is only helpful in about 40% of dogs and only highly successful in 20% (small sample size -- 10 dogs). This is lower than the reported rate of success from the manufacturer's studies but due to the relative safety of this treatment, it still seems reasonable to me to use it until it doesn't seem to be working, based on an increase in clinical signs such as increased drinking and urinating, panting, weakness, hair loss, concurrent diabetes or increased susceptibilty to infection.

It is hard to monitor the success of selegiline with blood tests, so there probably isn't any problem with not having that done. It would be a good idea to have periodic evaluations by your vet to ensure that there are not clinical signs that are suggestive of the need to re-evaluate treatment, though.

Hope this helps some.

Mike Richards, DVM 9/14/2000

Selegiline (Anipryl Rx)

Question: Doctor, I have been treating 'Sweetie', a 14 yr.old Shelty mix, for Cushings Disease for approx. 60 days. She is approx. 23 kg. and have been giving 15 mg. Anipryl daily. Diagnosis was made using low dose Dex suppression followed by ACTH. The Dex suppression was not positive and ACTH was "high normal"

Symptoms were: fur not regrowing after clipping, high water consumption and heavy panting in cool weather. Her fur started to re-grow after two weeks of medication and water consumption went down but she still pants quite a bit even in the house when it is cool. She prefers to lay on the tile floor. One large place (length of my hand and 1/2 the width) on her side the fur has not re-grown. My vet says stay the course with the Anipryl for a month or more and bring her back. Her health in general is great. What additional recomendations would you make if any.


Answer: Bruce-

The recommended dosage for selegiline (Anipryl Rx) is 1mg/kg for a starting dose. If there is no improvement, or insufficient improvement, in clinical signs within 60 days then the recommendation is to change the dosage to 2 mg/kg.

If Sweetie is 23 kg, she is being underdosed currently, based on the recommended dosing. If she is 23 lbs, she is being dosed in between the lower and higher dosage recommendations but there is still room to increase the dosage to about 20mg and to stay within the guidelines.

I would recommend trying a higher dosage before trying an alternative approach to treating the Cushing's disease, since you are getting at least a partial response. This is probably what your vet is planning on. I can see why your vet is tempted to stay at a lower dosage with the amount of improvement you have seen so far, though. But there is room for increasing the dosage safely to try to resolve the remaining clinical signs.

Mike Richards, DVM 4/6/2000

Anipryl for Cushing's Disease

Q: Dr. Richards,

Thank you for your response to my first E-mail.

I took Ruby back to the Veternarians office on Friday. I was concerned that she was loosing more weight. She weighed in at 4.6lbs. She has lost almost .5lb in a month. Very skinny.

I took your E-mail with me.

The Veternarian performed many tests:

He performed a pre-ansthestic test. It came back on the low side of normal. Doesn't this test give information on how the kidneys and the liver are functioning? If she has a liver shunt wouldn't you expect to have an abnormal test result?

Re-tested her ammonia level, within the acceptable range.

Since this Vet has the cababilities to perform the ACTH test in house I request that it be redone. I am not sure of the unit measurements, but her base level was 10. Too high I was told. After the administration of the Cortsol it was 25. Also too high. Therefore, he concluded she had Cushing's disease. Does this sound correct?

He also ran a urine test. He found no sugar, but he called it dilute. He said this was common for a dog with Cushing's disease.

I was reading that HAC is usually caused by an underlying benign and often microscopic tumor in the pitutary gland which secretes excessive quanitites of ACTH. Would it make sense to go ahead and test for Hypothyroidism since the thyroid hormone is under the control of the pituitary gland? I also read that with Hypothyroidism the hair is easily pulled out by the root. Ruby's hair pulls out very easily when I give her medication. If it is Hypothyroidism what types of medications do they have available? Will she put on weight eventually? Is it common for a dog to get Cushing's disease if they have Hypothroidism? What kind of life span with these two diseases could be expected?

This last month we placed Ruby on Science Diet K/D, since we thought she may have a Liver shunt. Now she has lost .5lbs. Her ammonia levels are normal. Should we wait until we have the results to the Bile Acid Response test before placing her back on Eukanuba?

We place Ruby on Anipryl for Cushing's Disease. He said it was safer than the other medications available. What is your thought? Should we use a more aggressive medication?

Thanks again, Heidi

A: Heidi-

The lab values you report for cortisol (pre ACTH stimulation level of 10 and post ACTH stimulation level 25 are indicative of hyperadrenocorticism (Cushing's disease). At this time, I prefer to start with l-deprenyl (Anipryl Rx) in cases of uncomplicated hyperadrenocorticism, too. Some of the clinical history that was in your original letter is not typical of hyperadrenocorticism but there are a lot of variations in the observed clinical signs with this disease. Most dogs have increased drinking, increased urinating, increased appetites, pendulous appearance to their abdomen, hair loss, thinning of the skin and sometimes itchy skin sores. Not all dogs exhibit all symptoms and some have different or even no symptoms.

It is not unusual for dogs with hyperadrenocorticism to also have hypothyroidism. It is a little difficult to interpret thyroid tests until the hyperadrenocorticism is under control but if you wish to do testing for this it would be best to use the free T4 by equilibrium dialysis and canine TSH levels to evaluate the possibility that hypothyroidism is present.

The continued weight loss is worrisome. Dogs usually don't lose much weight on k/d as it is not calorie restricted, just protein and phosphorous restricted. There wasn't much in the labwork to indicate other problems except the mild elevation in BUN (which is associated with kidney disorders) and the dilute urine --- which could be from hyperadrenocorticism or could be from an inability of the kidneys to concentrate urine. I would probably be tempted to retest the blood, at least the values related to kidney function -- BUN, creatinine, phosphorous, potassium and total protein levels. Often, it is necessary just to run a whole blood panel to get these tests, since most of the "mini" panels leave at least one out.

It is unusual for a liver shunt to be initially diagnosed in a dog that is Ruby's age. Not impossible, as I know of at least one older dog we diagnosed in our practice but it just seems like signs usually show up much earlier. So I guess with the lab work I would be comfortable not worrying about that possibility too much.

Hope this helps.

Mike Richards, DVM 5/3/99


Q: Tonight must be my night. My dog, a 6 y.o. Lab/Ret mix was recently diagnosed with pituitary-dependent Cushing's Disease in May 1997. One question I have is I do not understand why when he weighs 96 pounds and is given 2.5 mgs. of Cortisone he has an allergic reaction. Because he is so sensitive to so many drugs and has chronic colitis in addition, he was started on 45 mgs. of Anipryl. His specific gravity in the beginning was 10.07. After being on the Anipryl for one month, his specific gravity increased to 10.11 but then after the next month it went down to 10.7 again. He was therefore increased too 90 mgs daily. Unfortunately his specific gravity is hovering around 10.08 and he has little to no hair regrowth. What I do not understand is when he is taking 45 mgs. of Anipryl he is like my old playful....water intake decreases...his appetite has decreased, etc and he is not urinating for long periods of time. Because his specific gravity did not come up to at least 10.15, my Vet wants to start Lysodren. I feel like if I do this, I will be taking so much away from my dog. It's like he has his life back. I have heard so many horror stories about Lysodren that I'm scared to death of what will happen. I just hope that either you may be able to help me or direct me to someone/someplace that might be able to.

Thank you for your time. Linda

A: Linda-

I am under the impression that Anipryl (Rx) does not always change the laboratory values much and that it is best to evaluate its effectiveness based on clinical signs rather than lab testing, as is normally done with other medications used to treat Cushing's disease. I think it would be a good idea to ask your vet to call the manufacturer of Anipryl and ask their technical support vets about this. If your vet is a member of the Veterinary Information Network there is information in the database on monitoring dogs on Anipryl but none of it directly addresses the use of specific gravity as a monitoring tool. I have not used Anipryl, nor purchased it, so there is a chance that your vet is following a protocol included in the package labeling that I am not aware of.

Sorry I can't be more help.

Mike Richards, DVM

Anipryl for Cushing's

Q: Dr. Mike My 8 year old dog Ebony was diognosed with Cushings 1 month ago.He has had his daily doses of Mitotane and is on therapy now.(1/2 tab.500mg twice a week.) I'm unhappy that this drug kills off the adrenal gland.I fear that he might get Addisons disease.

There is a new drug in Canada called ANIPRYL that sounds so much better.( Do you know of this drug or anyone that has used it? Do vet Schools use it in studies? I wonder why the FDA has not approved it here yet? It sounds full of promise for not only cushings but cognitive dysfuction. I don't want to think that Ebony only has 2 years. Do you know why they give that figure and what happens at the end of that period? Anipryl effects the problem, Pituatary dependent, rather than adrenal gland. Can you help with ANY information? Thanks for your time.

A: The use of l-deprenyl (Anipryl Rx) is under investigation in the U.S. for treatment of Cushing's disease. There is a good article on this in a recent Clinics of North America, "Adrenal Disease" -- I am not sure of the exact issue but it was very recent.

Dr. Dave Bruyette has been involved in much of the study of this medication in the United States. I think that he would be willing to talk with your vet about use of this medication. I will try to locate contact information for you if I can.

Mike Richards, DVM


Michael Richards, D.V.M. co-owns a small animal general veterinary practice in rural tidewater Virginia. Dr. Richards graduated from Iowa State University's College of Veterinary Medicine in 1979, and has been in private practice ever since. Dr. Richards has been the director of the PetCare Forum...