Analgesic Combination Therapy Shows Promise for Acute Pain

The evolution of acute pain therapy has prominently included several combinations of analgesics, including paracetamol and codeine, paracetamol and oxycodone, ibuprofen and codeine, and several others. The promise of these combinations is well-known, but so, too, are the potential for adverse events and the lack of definitive late-stage clinical evidence of effectiveness beyond what is seen with monotherapy.

A recent study in The Journal of Headache and Pain examined the analgesic efficacy and safety of previously untested combinations of dexketoprofen trometamol and tramadol hydrochloride given as four different fixed combinations and as single components in comparison to placebo for patients experiencing moderate to severe acute pain following tooth extraction. The study found evidence that adding tramadol to dexketoprofen resulted in greater peak pain relief and greater pain relief over the longer term, particularly at times longer than six hours.

The study was a randomized, double-blind, double-dummy, parallel-group, placebo-controlled, single-dose trial in 606 healthy male and female patients aged 18 to 70 years who were scheduled for outpatient surgical removal of the one or more third molars under local anesthesia. The study included both ibuprofen 400 mg as active control as well as a placebo control. Following treatment administration, patients were requested to make multiple assessments of pain intensity and pain relief (PAR) over a period of 24 hours.

According to the study authors, all combinations were significantly better than placebo. “Dexketoprofen trometamol 25 mg combined with tramadol hydrochloride 75 mg provided good all-round analgesia, with rapid onset and long duration in a model of moderate to severe pain,” the researchers noted.

The highest percentage of responders (72 %) was achieved in the dexketoprofen trometamol 25 mg plus tramadol hydrochloride 75 mg group (numbers-needed-to-treat [NNT] 1.6, 95% confidence interval 1.3 to 2.1). Addition of tramadol to dexketoprofen resulted in greater peak pain relief and greater pain relief over the longer term, particularly at times longer than six hours (median duration of 8.1 h).

Adverse events were assessed throughout the study and included those typical of analgesic medications and tramadol in particular, including vomiting (3.4%), nausea (2.3%), and dizziness (1.8%).

The study authors note, “The particular combination of dexketoprofen trometamol 25 mg plus tramadol hydrochloride 75 mg delivered rapid initial pain relief, low (good) NNT for at least 50% max [total pain relief] over six hours, long duration, and a small proportion of patients remedicating. The NNT of 1.6 and the eight hours before 50% of patients remedicated were comparable to or better than most other oral treatments for acute postoperative pain… This is important because new rare but serious adverse events are less likely than, say, with a new chemical. But efficacy, tolerability, and safety need to be tested in more trials and more patients, perhaps especially in multiple dose studies that capture more information than a single dose efficacy study can do.”

The authors caution that although the study included a large sample of patients, the fact that the group receiving each combination of different analgesics at different dosages means that “extrapolation to clinical practice should not be undertaken.” But the researchers believe that the combination bears further investigation.