A study has found a combination of the pain drugs pregabalin and duloxetine to be more effective than monotherapy in relieving fibromyalgia pain. The findings, published in Pain, provide support for combination therapy, which is commonly used in this patient population despite a lack of strong evidence for the practice, the investigators wrote. They noted that previous trials have tended to examine pain reduction using monotherapy.
The investigators conducted a single-center, randomized controlled trial comparing the effectiveness of pregabalin (Lyrica, Pfizer) and duloxetine (Cymbalta, Lilly) with that of each drug individually, as well as with placebo (Pain2016;157:1532-1540). They recruited 41 patients with fibromyalgia (age range, 18-70 years) between April 2011 and September 2014. All the patients had experienced daily pain of 4 or higher on a scale of 0 to 10 for at least three months before recruitment. In addition to study medications, the participants were given previously prescribed analgesics, including acetaminophen, nonsteroidal anti-inflammatory drugs and opioids.
Patients were randomly assigned to one of 24 possible medication sequences over four six-week periods. The target daily dosage ceiling was 450 mg of pregabalin and 120 mg of duloxetine. Each period was broken down as follows: days 1 to 24, escalation toward the ceiling dose; days 25 to 31, stable dosing at the ceiling dose for the given treatment; days 32 to 41, dose taper; and day 42, complete washout. Participants who chose to withdraw from a study treatment due to adverse events or other causes were offered the chance to receive the next treatment after taper and washout of their current treatment. The primary outcome measure was “average pain intensity over the past 24 hours,” rated at 0 through 10 on a numeric rating scale each morning and averaged over seven days at the ceiling dose.
Although the original study design called for 49 patients, an interim analysis determined that the results could be considered reliable using only 41 participants, 39 of whom were finally included in the efficacy analysis. The average pain rating (mean ± SEM) at ceiling dose was 3.7±0.3 for combination therapy, compared with 5.1±0.3 for placebo (P<0.001) and 5.0±0.3 for pregabalin alone (P<0.001). The average pain rating for combination therapy was also lower than for duloxetine alone; however, this finding was not statistically significant (P=0.09).
Moreover, in terms of global pain relief, a secondary outcome measure, 67.7% of patients reported moderate or greater pain relief from combination therapy, compared with 38.5% for pregabalin (P=0.02) and 41.7% for duloxetine (P=0.03).
Ian Gilron, MD, director of clinical pain research at Queen’s University in Kingston, Ontario, who led the study, said the findings validate other studies that found this drug combination to be effective for nonfibromyalgia pain.
“As with other areas of clinical research, it is always important to replicate study results in other trials conducted in different regions of the world and with different research teams so as to provide an even more robust estimate of treatment effects,” Dr. Gilron said. “However, since we know that this combination is already being tried by many patients with fibromyalgia, this study provides evidence that this is a reasonable combination for health care providers to try in cases where patients are getting only partial relief with one of these drugs.”
This study provides hope for fibromyalgia patients, most of whom receive “very poor care,” said Chad Boomershine, MD, PhD, medical director of Boomershine Wellness Centers, scientifically based rheumatology clinics specializing in personalized care for patients with fibromyalgia, chronic fatigue syndrome and gout.
“Studies have consistently shown that treatment of fibromyalgia with monotherapy typically only results in a 25% to 30% improvement on average, with some patients not having any improvement,” Dr. Boomershine said. “Until better treatments are found, combination treatment is a reasonable and, per this study and others, safe option that may significantly improve symptoms over monotherapy.”
Dr. Boomershine added that as other studies have demonstrated the efficacy of different combination therapies, crossover studies comparing the efficacy and tolerability of different combination therapy options would be “very interesting.”
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