Combining Meds for Fibromyalgia May Offer Added Benefits

Treating fibromyalgia with both pregabalin (Lyrica) and duloxetine (Cymbalta) is more effective that using either drug alone, according to a new study out of Canada.

Fibromyalgia is a chronic health condition characterized by widespread muscle pain, fatigue, memory problems, sleep disturbance and mood changes. If non-drug treatments such as exercise and avoiding triggers 

(which can include physical and psychological stress) don’t provide enough relief, medication may be prescribed. Common choices in the United States include pregabalin, duloxetine and milnacipran (Savella).

Often, doctors prescribe more than one medication at the same time, but until this study, little high-quality evidence existed to support a multi-drug approach to treating fibromyalgia.

The study, published in the July 2016 issue of Pain, was conducted by researchers at Queen’s University and University of Toronto. More than 30 patients rotated through four different six-week treatment periods. During one period they received pregabalin; during a second they received duloxetine; a third period combined the two drugs; in the fourth, the patients received only a placebo. During the study, neither the doctors nor the patients knew the order of the treatments.

The results showed “substantial and statistically significant superiority” of the combination treatment for global pain relief, functional improvement and overall quality of life.

“It really is the first study showing that people with fibromyalgia often do better on both drugs than just one,” says Daniel Clauw, MD, professor of anesthesiology, rheumatology and psychiatry at the University of Michigan in Ann Arbor. Dr. Clauw was not involved in the study.

The results were not entirely surprising to the researchers, who suspected the combination therapy would provide better pain relief.

“We did expect to see that the combination was superior to either monotherapy specifically for the reduction of pain,” says lead study author Ian Gilron, MD, director of clinical pain research at Queen’s University School of Medicine. “However, what was particularly impressive with these results was that … we also saw that the combination was superior to both monotherapies for other important outcomes such as physical function and quality of life.” (Physical function was assessed by the fibromyalgia impact questionnaire, and quality of life was assessed by the SF-36 survey.)

Many other chronic diseases are treated with a combination of drugs, notes Dr. Clauw. “We use combination therapy like this to treat nearly every chronic disease – hypertension, diabetes, congestive heart failure, cancer, etc. So it should not be surprising that this is the direction the pain field will go.”

Mechanisms and Side Effects

Duloxetine and pregabalin are thought to work in different ways. Therefore, in theory, they offer what’s known as an additive effect when taken together.

“We believe that the treatment outcomes were more favorable for the combination compared to each monotherapy because overall, there was a more additive effect for pain relief than there was for side effects,” says Dr. Gilron.

Duloxetine is a type of drug known as a serotonin-norepinephrine reuptake inhibitor (SNRI). It helps restore the balance of the neurotransmitters serotonin and norepinephrine in the brain. Pregabalin is an anticonvulsant. Experts aren’t certain how it works to relieve fibromyalgia symptoms.

The study found that duloxetine alone worked better than pregabalin alone for reducing pain intensity, but that pregabalin was “significantly superior” to duloxetine for sleep improvement.

Patients on the combination treatment experienced drowsiness more often than patients on duloxetine alone. But, Dr. Gilron notes, the vast majority of patients who reported moderate to severe drowsiness (27 percent of all patients) stayed in the trial. “Therefore, each of those patients might have considered this side effect worth tolerating in exchange for the other benefits provided by the treatment,” he says.

Says Dr. Clauw, “I think the fact that only a quarter of people have drowsiness is actually good – unless you’re one of those people, of course. But that means three-quarters did not.  I also think it is telling that people decided to keep taking the drugs, because if they thought that the benefit of the drug was not worth the side effects they likely would have dropped out of the study.”

Work with Your Doctor

Talk with your doctor about the right treatment approach for you. If your current medication is working well there may be no reason to make a change. If you’re not currently taking medication but need more relief, your doctor might start you on a single drug rather than combination therapy. “Some people get a lot of benefit from a single drug,” says Dr. Clauw.

But many don’t, says Don Goldenberg, MD, emeritus professor of medicine at Tufts University School of Medicine in Boston and adjunct faculty in the department of medicine and nursing at Oregon Health Sciences University. “Only about one-third of fibromyalgia patients will have a good response and not have significant adverse side effects to a single medication,” he says. For those patients, combination therapy may be the right approach.

Fibromyalgia medications work best when used along with non-drug treatment approaches, especially exercise, experts say. Acupuncture, meditative movement and cognitive behavioral therapy may also provide some benefit.

“All patients with fibromyalgia should use the non-drug therapies such as exercise and cognitive behavioral therapy,” says Dr. Clauw. “Most also need to take one or more medications as well. We have no way to predict in advance who will respond to what.”

Dr. Goldenberg also stresses the role of non-drug therapies. “Medications, either alone or in combination, work best when combined with non-pharmacologic management, including education, cognitive behavior therapy and exercise.”