Journal Scan: Is tramadol the new placebo?

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Journal Scan: Is tramadol the new placebo?

A recent study challenges the use of tramadol for canine osteoarthritis.
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Jul 05, 2018

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A placebo has no therapeutic action. However, the improvement in clinical signs (or development of side effects) associated with the administration of a placebo—the placebo effect—is a well-known phenomenon that affects human patients and caregivers alike. Physicians and veterinarians are not immune to its effects. Too easily, the improvement exhibited by a few patients can seemingly prove the efficacy of a treatment and promote further use in other patients. To avoid this bias, clinicians rely on evidence-based medicine and the use of placebo-controlled clinical trials to ascertain whether the effects of a medication are indeed beneficial.

In the last 10 to 15 years, tramadol has been widely used to control pain despite a lack of scientific evidence to support its use. Pharmacologically, dogs are known to produce insufficient amounts of the metabolite of tramadol that is responsible for analgesia, and the bioavailability of this metabolite drops significantly within one week of regular use. Clinically, few studies have been performed evaluating the efficacy of tramadol in veterinary species. That is, at least, until February of this year when a clinical trial was published that examined whether or not tramadol is effective for the management of pain associated with canine osteoarthritis.

What they did

Forty dogs with radiographically confirmed osteoarthritis of the elbow or stifle were included in a randomized, blinded, placebo-controlled, crossover study. All dogs received each of the following treatment regimens for 10 days, with at least a week of washout between treatment periods:

  • Tramadol: 5 mg/kg every 8 hours (morning, midday and night)

  • Carprofen: 2.2 mg/kg every 12 hours (morning and night, with a placebo midday)

  • Placebo: lactose powder every 8 hours

The dogs received these treatment regimens in random order, and all medications appeared identical.

To evaluate treatment response, force-plate analysis and pain scoring (using the Canine Brief Pain Inventory) were performed before each treatment period (baseline) and on the last day of each treatment regimen. A force plate measured vertical impact (VI) and peak vertical force (PVF) to measure the arthritic limb’s weight-bearing ability. To calculate the pain score, the owner assessed the severity of the dog’s pain and the degree to which pain interfered with daily activities.

What they found

Thirty-five dogs completed the study. Force-plate readings (VI and PVF) improved significantly from the baseline while the dogs received carprofen but not while they received tramadol or the placebo. The extent of the improvement seen with carprofen was also significantly greater than that seen with tramadol or the placebo.

Based on a reduction in pain scores, significantly more dogs improved while taking carprofen (42%) than while taking tramadol (24%) or the placebo (21%). There was no significant difference in pain scores between the tramadol and the placebo regimens.

Take-home message

In this study, the effects of tramadol were similar to the placebo. Although some patients may improve while taking a placebo, the improvement cannot be attributed to its action. For a medication to be considered effective, it must produce a significant benefit as compared to the placebo. In this study, carprofen proved therapeutic for the pain and dysfunction of canine osteoarthritis, whereas tramadol did not.

So, if an arthritic patient improves while taking tramadol, is it just the placebo effect? The results of this study suggest that it is.

Link to abstract: https://avmajournals.avma.org/doi/10.2460/javma.252.4.427

Budsberg SC, Torres BT, Kleine SA, et al. Lack of effectiveness of tramadol hydrochloride for the treatment of pain and joint dysfunction in dogs with chronic osteoarthritis. J Am Vet Med Assoc. 2018 Feb 15;252(4):427-432.

Dr. Amy Van Gels practiced companion-animal medicine for seven years before becoming a freelance medical writer and editor. Drawing on her practical experience, she creates clinically relevant articles for veterinarians and their staff, training documents for sales teams, and educational materials for pet owners. Dr. Van Gels is passionate about relaying accurate medical information to everyone who impacts patient care, at every level of medical knowledge.

tramadol efficacy

I have responded to a similar article printed in June 2018. I would be interested in a study using NSAID + placebo, NSAID alone and NSAID + tramadol, as we find in our practice that adding tramadol to our analgesic cocktails often aids in pain management.

Orange apples

When Tramadol was first introduced into vet med as the not so new wonder drug for pain in the early 2000's, it was described as an add-on drug to the clinicians choice of NSAID. This study was Tramadol vs Carprofen. The study needed is Carprofen+NSAID vs Carprofen alone vs Carprofen+placebo. Also the dose of Tramadol used in the study has come into question as of late. There are those pain gurus that suggest the dose should be at minimum 6 mg/kg.

Tramadol vs Placebo

The most interesting thing to me about this study is that 24% of dogs improved with placebo, when tested with an objective measurement (strike plate). That kind of placebo effect can be partially explained in people, simply because they know they're taking part in a test. But, how do we explain that degree of objective improvement in dogs?
Deborah Cottrell DVM