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What are the Benefits of Long-Term NSAIDs?

A look at the research.


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Originally published in the July 2015 issue of Veterinary Practice News. Loved this article and want to see more like it? Then subscribe today!

Many experts are unflagging proponents of long-term nonsteroidal anti-inflammatory drugs to control arthritis pain, and for them the reasons are as plain as the limp in an arthritic dog’s leg.

Arthritis pain is a big barrier to wellness in the eyes of B. Duncan X. Lascelles, BSc, BVSc, Dipl. ECVS, Dipl. ACVS.

“The main thing is that controlling the pain allows a number of improvements to take place,” said Dr. Lascelles, Ph.D., CertVA, DSAS (ST), a professor of surgery and pain management at North Carolina State University College of Veterinary Medicine.

And Lascelles sees qNASIDs as one of the best ways to control pain, enabling muscle to be built back up, which gives an animal greater control of the joints, resulting in further decrease in pain.

Use of NSAIDs also allows central sensitization, which contributes to the pain state, to lessen or reverse. If a pet’s pain oscillates, he said, going from better to worse, that oscillation doesn’t allow for slow, progressive long-term improvements.

Julie Meadows, DVM, agreed. She is associate clinical professor for Community Practice (primary care) at the Small Animal Community Practice Veterinary Medical Teaching Hospital at the University of California, Davis.

Effective pain relief is the top benefit Dr. Meadows cited for using NSAIDs.

“The combined anti-inflammatory and analgesic effects of NSAIDs allow ongoing activity which perpetuates muscle mass and helps the joints share the load of the animal's weight,” Meadows said. “As pain progresses, disuse atrophy accelerates the overall decline of the animal's mobility.”

Jennifer F. Johnson, VMD, CVPP, owner of Stoney Creek Veterinary Hospital in Morton, Pa., is another proponent of long-term NSAID use.

“From a pain-management perspective, I believe that my patients that are on chronic, daily NSAID use fare much better than the patients whose owners try to chase pain by giving NSAIDs as needed, or on tough days,” Dr. Johnson said.

It’s difficult for clients to judge definitively how much pain their pet is in, which makes it impossible to accurately dose the pain with an NSAID "as needed," Johnson said.

“When you think about the pain pathway and what happens in the spinal cord during chronic pain, it is easy to see that a chronic situation can turn into a situation where we have maladaptive pain,” Johnson said. “There are actually changes in the expressions of genes during maladaptive pain situations. We need to do everything we can to keep the pain at a minimum and this is where chronic NSAID use in arthritis should be our first line.”

After two or three weeks at the label-recommended dose, the dose can be adjusted downward to minimize the medication needed to keep the pain under control and prevent maladaptive pain conditions, or persistent pain that tends to be out of proportion to actual tissue damage, she added. 

Osteoarthritis

With osteoarthritis, a common cause of pain in pets, the cause of the inflammatory process cannot be reversed, so some biomechanical issue leads to what Johnson described as a vicious cycle: joint inflammation, leading to cartilage degeneration, leading to bone remodeling, leading to expression of inflammatory mediators in the joint, leading to the process repeating all over again. 

“We can use the NSAID to help to break this cycle,” Johnson said. “We cannot change the conformation of a dysplastic hip, but we can control the inflammatory process.”

Robin Downing, DVM, Dipl. American Academy of Pain Management, Dipl. American College of Veterinary Sports Medicine and Rehabilitation, said NSAIDs are a cornerstone for managing the inflammatory pain of osteoarthritis.

“They are very effective for that component of the OA patient’s pain,” said Dr. Downing, hospital director at Windsor Veterinary Clinic P.C. in Windsor, Colo., and owner of The Downing Center for Animal Pain Management LLC. “Therefore, the benefit is that the NSAIDs help us to break the pain cycle and provide the animal with the opportunity to be more functional and therefore more active.”

Risks

There’s a fear among practitioners and pet owners that the longer NSAIDs are used, the risk of something bad happening increases, said NCSU’s Lascelles. 

But he and a colleague examined extensive data to come up with some insights on this thinking.

“We found that was not true, there was no association between the longer you give a non-steroidal and the risk of side effects,” Lascelles said. “As far as we can tell, we don’t find any relationship between those two things — length of non- steroidal use and incidence of side effects.”

Most side effects that do occur appear within two to four weeks, he said.

In a paper on this topic from 2010, “Risk-Benefit decision making in the long-term use of NSAIDs for canine osteoarthritis,” Lascelles fleshes out the wrong-headed notion.

“Often, the clinical approach to a young or middle-aged dog with OA-associated pain is to avoid the use of NSAIDs,” the paper states. “The rationale often quoted for this approach is that the practitioner wants to ‘save the use of NSAIDs for later, and not have a dog on NSAIDs for the whole of its life.’ This is a flawed and rather naive approach.”

Based on evidence Meadows of  U.C. Davis has seen, the negative effects occur on hepatic and renal function and gastrointestinal bleeding, and they can occur early on after the medication is prescribed.

“Anecdotally, most practitioners will know that G.I. effects are rare with the newer NSAIDs, however use should be discontinued if intermittent G.I. signs are present,” Meadows said. “I screen for urine specific gravity and abnormal blood renal/hepatic parameters before use in animals over the age of 8 and every six months if the patient is being administered them daily or every other day.”

Good to Know

Side-effects, if they occur, vary from pet to pet, said Johnson, with Stoney Creek Veterinary Hospital.

“I think the thing to remember about long-term use in dogs is that each dog is an individual and that the likelihood of an adverse event with an NSAID is subject to that individual dog,” Johnson said.

Most G.I. adverse events will occur in the acute (first two-week) phase, and if a dog initially tolerates the NSAID and does not have any G.I. issues it is unlikely to develop G.I. issues chronically, she added.

“The other good thing to remember is that using an NSAID chronically does not increase the chance of developing adverse events with the liver [and] kidneys,” Johnson said. “For example, if a dog is on an NSAID for six months and another dog is on an NSAID for three years, this does not mean that the dog on it for three years has a six times greater risk of developing organic disease from the NSAID. The adverse events that we see seem to be individual events.”

Another thing to keep in mind about long-term NSAID use is that if one NSAID stops working then another may work better, Johnson said. 

“Initially, this is a good bet,” she said. “There are individual variations in how one's body responds to drugs, so after a wash out period, it is reasonable to try a different NSAID if the first one does not work well.” 

She recommends this in the acute phase of treatment. 

“However, if you have used an NSAID chronically and it worked well, then all of a sudden it does not seem to work anymore, you should assume that you are seeing some maladaptive pain situation – that we have now reached spinal cord wind-up, and you need to add additional pain management to the NSAID to continue to offer relief,” Johnson said.  

Lascelles said by taking away the pain the whole body improves. And the longer the pain it taken away, the more progressive the improvements, to the point that often the non-steroidal drug can be removed from the treatment plan, he said. 

“This is a tool,” Lascelles said. “It’s a very effective tool and we just need to use it in the most effective way.” 

An Expert’s Take on Pain Control

What do most general practitioners assume about long-term NSAID use for arthritis that they shouldn’t?

That question was put to Robin Downing, DVM, Dipl. American Academy of Pain Management, Dipl. American College of Veterinary Sports Medicine and Rehabilitation, hospital director at Windsor Veterinary Clinic P.C. in Windsor, Colo., and owner of The Downing Center for Animal Pain Management LLC.

Here’s what she had to say:

General practitioners need to belong to the International Veterinary Academy of Pain Management. If they are not a part of IVAPM, they do not have access to the very most up-to-date information about pain and pain management. 

The IVAPM offers a credential called the “certified veterinary pain practitioner,” which enables practitioners to enhance their understanding and expertise in chronic pain management.

Too many veterinarians rely only on NSAIDs for managing the pain of osteoarthritis, and the fact is that, as stand-alone agents, NSAIDs are inadequate. A similar misconception is that having several NSAIDs on the shelf means a practice is providing multi-modal pain care. Nope!* Chronically painful patients must have neuromodulation as a part of their pain care, and this means a tool like gabapentin – there is no other tool for this purpose than gabapentin. 

“Gabapentin is an essential part of every pain case I deal with in my pain management/rehabilitation specialty referral practice,” Downing said. 

“Unfortunately, most practitioners are utilizing gabapentin doses that are completely inadequate, and then conclude that it doesn’t work. I am working on a retrospective study right now on the use of gabapentin for chronic pain in dogs and cats in order to provide useful dosing.”

General practitioners need to be more open to referring to providers who possess expertise they do not that would be beneficial to the patient. 

These providers would include rehabilitation diplomates or practitioners, medical acupuncturists, etc. Alternately, training is available in the various relevant disciplines.

FDA Primer on Veterinary NSAIDs

The U.S. Food and Drug Administration addresses the use of non-steroidal anti-inflammatory drugs in companion animal medicine, and notes that approved veterinary NSAIDs are used to control the pain and inflammation associated with osteoarthritis in dogs and horses.

Some veterinary NSAIDs are also approved for the control of postoperative pain in dogs and cats.

Potential risks are associated with the use of NSAIDs, and the FDA warns veterinarians and pet owners to be aware of the following:

  • All dogs and cats should undergo a history and physical examination before beginning NSAIDs.
  • Appropriate blood and urine tests should first be performed to establish baseline data, and then periodically during administration of any NSAID.
  • Common side effects include vomiting, diarrhea, appetite loss and lethargy;
  • Veterinary NSAIDs may be associated with gastrointestinal ulcers/perforations and liver and kidney toxicity.
  • Serious side effects associated with the use of NSAIDs can occur with or without warning and can result in death.
  • Use with other anti-inflammatory drugs, such as corticosteroids, should be avoided.
  • Patients at greatest risk for kidney problems are those that are dehydrated, are on diuretic treatment, or have pre-existing kidney, heart or liver problems.
  • NSAIDs can cause stomach or intestinal bleeding.
  • Risks associated with NSAIDs are detailed on the package inserts and client information sheets that accompany all veterinary NSAIDs dispensed to clients. 
  • A Client Information Sheet should always be given to the client with each NSAID prescription. 

Veterinary NSAID List

These are commonly used nonsteroidal anti-inflammatory drugs, their indications, recommended dosage and comments from the Association of Veterinary Anaesthetists, the American College of Veterinary Anesthesiologists and Pfizer Animal Health.

 

Drug

Approved indication(s)

Dose

Comments

Carprofen, Rimadyl (Pfizer)

Pain and inflammation associated with osteoarthritis; pain associated with soft-tissue or orthopedic surgery

4.4 mg kg-1 PO, once daily 2.2 mg kg-1 PO, twice daily 4.4 mg kg-1 SC

Safety not evaluated in dogs <6 weeks of age

Deracoxib, Deramaxx (Novartis)

Pain and inflammation associated with osteoarthritis; postoperative pain and inflammation associated with orthopedic surgery

Osteoarthritis: 1–2 mg kg-1 PO once daily Postoperative: 3–4 mg kg-1 PO once daily (7 day limit)

 

Safety not evaluated in dogs <4 months of age

Firocoxib Previcox (Merial)

Pain and inflammation associated with osteoarthritis; pain associated with soft-tissue surgery and orthopedic surgery

 

5 mg kg-1 PO, once daily

 

Use of this product at doses above the recommended 5 mg kg)1 in puppies <7 months of age has been associated with serious adverse reactions including death

 

Mavacoxib, Trocoxil (Pfizer Animal Health) Non-USA

Pain and inflammation associated with degenerative joint disease in cases where continuous treatment exceeding one month is indicated

2 mg kg-1 PO Days 1, 14, 30 days then once monthly

 

Do not exceed 6.5 months duration of continuous therapy

 

Meloxicam, Metacam (Boehringer Ingelheim)

 

Pain and inflammation associated with osteoarthritis

 

0.2 mg kg-1 PO (Injectable SC/IV) on day 1, then 0.1 mg kg-1 PO once daily

 

Safety not evaluated in dogs <6 months of age

 

Phenylbutazone (various manufacturers)

 

Relief of inflammatory conditions associated with the musculoskeletal system

 

3 mg kg-1 (max 800 mg per 24 hours) PO every 8 hours. Maintain the lowest dose capable of producing the desired clinical response

No age related safety information reported

 

Robenacoxib, Onsior (Novartis Animal Health) – non-USA

 

Treatment of pain and inflammation associated with acute musculoskeletal disorders; treatment of pain and inflammation associated with orthopedic or soft tissue surgery

 

1 mg kg-1 PO once daily

 

Do not administer with food. The safety has not been evaluated in dogs <2.5 kg (5.5 lbs.) or, < 3 months of age

 

Tepoxalin, ZubrinTM (Schering-Plough)

 

Pain and inflammation associated with osteoarthritis

 

10 or 20 mg kg-1 on day 1, then 10 mg kg-1 once daily

 

Safety not evaluated in

dogs < 6 mos of age

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