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Back to Apoquel Article 9/8/16 note:

Dogs are the most genetically diverse animals on our planet - And diversity means unpredictability when it comes to the possible effects of drugs. Apoquel (oclacitinib) does indeed have the ability to enter the brain - And its human cousin, the medication tofacitinib/ (Xeljanz™), can change the personality of a mouse. Both drugs have a degree of overlap and "bleed-through" in the their targets. (ref) Or read that entire article here. So the range of effects of this group of drugs might be broader than we vets initially thought and it may be difficult to separate the physical from the psychological. Perhaps one of the many interleukin messengers these drugs interact with play a part in this. (ref)

When I wrote this article in early 2015, I asked for feedback from pet owners like you whose dogs were receiving Apoquel. That seemed to me to be the best way to get unbiased opinions as to the drug’s effectiveness and safety.

Over the time I have done that, I got occasional emails that mentioned changes in the pet’s mood and behavior that occurred subsequent to receiving the medication and stopped after it was discontinued. Most described their pets as being "more relaxed, "more playful" or "happier" while on Apoquel. But a few describe their pets using terms like "lethargic", "fearful", "clingy", "distressed" "confused" or "nervous".

I tended to discount those negative reports. I had learned over the years that your dog is so attuned to your emotions that it is extremely hard to sort out your anxieties from your pet’s anxieties. When you are anxious or worried, your dog will also be. The reverse is also true. But these emails continue to come. There were two more in my inbox this morning. I can not tell any of you if these are real or just perceived effects. Only time will tell.

Apoquel was designed to targets your pet’s immune system. To block the inflammatory cascade that is causing your dog to itch. That, at first consideration, appears a long way off from your dog’s brain and its mood. No psychological warnings are given on the product insert or its “sister” human medication Xeljanz.

Both those medications block the production of the the interlukin cytokines thought to be involved in skin inflammation in your dog, particularly the JAK1 family (eg IL-2, IL-4, IL6, IL-13 and IL-31) (ref) or joint inflammation in humans (eg Xeljanz, IL-6). There is overlap in which of the many interleukins these medications suppress.

But it is not far-fetched to question if Interleukin-6 (or perhaps another affected interleukin) could be involved in behavior and mood changes in your pet and if lowering IL6 levels might influence its mood. (ref1, ref2, ref3, ref4, ref5) Some medications given to humans and animals can not enter the brain. They are locked out by the blood-brain barrier. I do not know about oclacitinib (=Apoquel). But at least some "nibs" (like Pacritinib) can pass. Another research team suggested that lowering IL6 level has the ability to influence behavior and thought patterns. (ref)

But there are other possible explanations I need to mention: Perhaps it is only an illusion. Perhaps this effect is only present in a small genetic subset of dogs. Perhaps these dogs had developed mild prednisone-induced (iatrogenic) Cushing's disease and become dependent on their prednisone medications. Prednisone is known to affect mood and memory. (ref) Taking pets off or putting them back on prednisone medication might be to blame. I do not know - more importantly, I do not possess the advanced knowledge required to figure out something this complex.

I know your dog will experience substantial itching-relief on Apoquel. But among other things, I  would like to know more about how your dog behaves while on and off the medication. Here are some emails I received that deal with the subject. Read them at this link:





Since I wrote this article, several owners have told me that those changes gradually returned to normal as time went by on the medication.