BOSTON, Massachusetts—A new meta-analysis in the Journal of Rheumatology¹ concludes that tramadol (Ultram®, Ortho-McNeil Pharmaceutical, Inc) may be a useful option for relieving moderate pain in osteoarthritis (OA) patients but that it is unlikely to be adequate in severe pain and that one in eight OA patients will stop taking the drug due to adverse events (AEs).

"In summary, there is gold-standard evidence that tramadol or tramadol/paracetamol decreases pain intensity, produces symptom relief, and improves function, but these benefits are small," conclude researchers led by M. Soledad Cepeda, MD, PhD, of the Tufts-New England Medical Center, in Boston. "Adverse events, although reversible and not life-threatening, often cause participants to stop taking the medication and limit the usefulness of tramadol or tramadol/parecetamol, unless slow titration regimens substantially reduce adverse events."

Tramadol number-to-treat: to show benefit (6), minor AEs (5), AEs (8)

The systematic review and meta-analysis was based on 11 randomized control trials that included 1019 participants who received tramadol or tramadol/paracetamol and 920 who received placebo or an active comparator.

Compared with osteoarthritis (OA) patients who received placebo, patients who received tramadol reported a 12% relative decrease in pain intensity; one of every six OA patients who took tramadol or tramadol/paracetamol showed at least moderate global improvement; and patients who took tramadol or tramadol/paracetamol had an 8.5% relative improvement in Western Ontario and McMaster University Osteoarthritis Index score.

The maximum decrease in pain intensity that could be expected with tramadol or with tramadol/paracetamol would not be greater than 12.5 units on a scale of 0 to 100, the researchers point out. "This decrease represents the smallest change that people can discern when pain is moderate; however, the same decrease would be unnoticed when pain is severe," they write.

One of every five participants who received tramadol or tramadol/paracetamol experienced minor AEs and one of every eight stopped taking the medication because of AEs, compared with participants who took placebo. AEs included nausea, constipation, dizziness, somnolence, itching, and headache.

Tramadol versus active comparators

In studies with active comparators, tramadol was "superior to weak opioids, similar to diclofenac, but inferior to paracetomol in regard to analgesia," the study authors conclude.

Patients who took tramadol had a higher incidence of opioid-related side effects than those who received either dihydrocodeine or dextropropoxyphene. Pentazocine, however, was less tolerated in patients than tramadol. Tramadol users also had a higher incidence of minor side effects than did diclofenac users, but one patient who took diclofenac experienced angioneurtic edema.

Is slow titration a solution?

Slowly titrating tramadol up to the therapeutic level greatly improves the risk/benefit ratio in OA. The study authors point out that tolerability may improve if tramadol is given via a slow titration regimen, such as 100 mg/day for 7 to 10 days, followed by 200 mg/day. "This approach halves the proportion of people who interrupt therapy because of adverse events," they write. They predict that slow titration would reduce the number of patients stopping tramadol because of AEs from 1 in 8 to 1 in 33.

"Tramadol has some opioid-like characteristics, and there is some debate as to how it should be classified," Dennis C. Turk, PhD, anesthesiologist at the University of Washington, in Seattle, told CIAOMed.

"It can have a very positive analgesic effect, but it does have some drawbacks of opioids, namely, constipation and risk of dependence," Dr. Turk cautioned. "The good news is that it doesn't have the cardiac effects we see with coxibs. It has to be used with caution in OA."

Reference

1. Cepeda MS, Camargo F, Zea C, et al. Tramadol for osteoarthritis: a systematic review and metaanalysis. J Rheumatol. 2007;34:543-555.