Journal Scan: Is tramadol the new placebo?
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.
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.