Friday, October 19, 2012

The Profusion of Fibromyalgia Therapies Studied

FibromyalgiaFibromyalgia syndrome (FMS) can be a difficult condition to characterize and treat, and only relatively recently have specific medications received regulatory approval for FMS. A new study provides a snapshot of the profusion of medications and nonpharmacologic therapies that patients with FMS typically receive in everyday practice; however, many of the 182 prescription medications and 17 nonpharmacologic treatments were not being used in accordance with best supporting research evidence.

In this study — appearing in the October 2012 issue of Pain Medicine — a team of researchers investigated the burden of illness and treatment patterns in 1,700 patients with fibromyalgia syndrome (FMS) [Robinson et al. 2012]. They also examined patient, physician, and care factors associated with the treatment choices of individuals receiving new prescriptions for FMS.

Data for the report came from baseline assessments gathered for a prospective observational study titled, “Real-World Examination of Fibromyalgia: Longitudinal Evaluation of Costs and Treatments (REFLECTIONS).” This included a physician survey, a patient visit form, and computer-assisted telephone interviews conducted from July 2008 through May 2010 in 58 care settings (including 91 participating physicians) in the United States and Puerto Rico.

Of the 1,700 patients included, most were female (94.6%) and white (82.9%), average age was about 50 years and mean duration of illness was 5.6 years. The average Fibromyalgia Impact Questionnaire (FIQ) total score was 54.4 (total score range 0–80), and Brief Pain Inventory (BPI) average pain severity level was moderate at 5.5 (range 0–10). On average, patients were overweight to moderately obese (mean body mass index 31.3; 95% CI, 26 to 37).

The burden of illness was high for study patients, incurring extensive annual health care use and numerous work limitations related to FMS. Most patients experienced clinically significant levels of disability, insomnia, depressive and anxiety symptoms, and cognitive problems. For example, patients reported an impaired ability to focus/concentrate, a reduced ability to recall information, word-finding difficulties, and decreased mental clarity.

Surprisingly, at baseline, patients were taking 182 different medications prescribed for their FMS. These included (in order of the 11 highest drugs or drug classes): duloxetine (in 26.8% of patients), nonsteroidal anti-inflammatory drugs (NSAIDs 26.6%), pregabalin (24.5%), opioids (24.2%), tramadol (15.3%), benzodiazepines (15.2%), selective serotonin reuptake inhibitors (SSRIs 13.1%), cyclobenzaprine (12.9%), nonbenzodiazepine sedative/hypnotics (12.9%), gabapentin (11.2%), milnacipran (8.9%), and many others.

Polypharmacy was prevalent: only 22% of patients were taking only one medication, most (78%) took an average of 2 to 4 (mean 2.58; 95% CI, 1 to 5) different medications concurrently. The type of current medications used was most strongly associated with patient medication history and medical specialty of the prescriber, with specialists tending to more often prescribe newly approved drugs.

All patients with FMS had used some form of nonpharmacologic therapies in the prior 12 months, and such therapies were newly prescribed for 61% of patients during the study baseline visit. Nonpharmacologic therapies consisted most commonly of rest, exercise, massage, counseling, and heat/cold modalities; although prayer/meditation and cognitive distraction approaches also were prominently noted. Hypnosis, biofeedback, energy healing (eg, Reiki), and acupuncture were noted relatively infrequently (in 1% to <9% of patients). Cognitive behavioral therapy had been used by only 4.5% of patients, despite good evidence for its efficacy; whereas, trigger-point injections, with less supportive evidence, had been administered to 27% of patients.

Clearly, there is an abundance of therapeutic approaches available for treating FMS, although only a few are approved specifically to treat the disorder and there is inadequate research evidence to support many of the others. The researchers conclude that the burden of illness is high for patients with FMS, and treatment patterns are highly variable. Most importantly, pharmacotherapies with the most evidence to support their use were not always the most frequently chosen and treatment guidelines were not always followed.

COMMENTARY: This cross-sectional snapshot of a large group of patients with FMS provides some interesting perspectives, especially on the noteworthy range of therapies that these persons are administered. Despite this array of polypharmacy and multimodal approaches, FMS remains a major diagnostic and clinical challenge.

Patient demographic factors in this study were typical of most populations with FMS; largely middle-aged white females, with persistently moderate pain levels, and overweight or moderately obese. We had commented in an earlier UPDATE [here] how excess body weight may incur many health problems and has been strongly associated with FMS, but causal relationships in this regard are unproven.

Among the many medications prescribed for this population of patients with FMS, only 3 are approved in the United States specifically for fibromyalgia: duloxetine (prescribed in 27% of patients, FDA-approved in July 2008), pregabalin (25% of patients, approved June 2007), and milnacipran (9% of patients, approved March 2009). Therefore, only a relatively modest proportion of all patients were receiving these FDA-approved medications; although, 2 of the 3 were newly introduced during data collection for this study by Robinson and colleagues.

The variety of medications prescribed for FMS, as discovered in this study, seems rather astounding, ranging from analgesics to antidepressants or anticonvulsants to psychotropic medications (eg, sedative/hypnotics and stimulants) to muscle relaxants. Small percentages of patients (<3%) were prescribed antipsychotics, antivirals, corticosteroids, lidocaine, a dopamine agonist, and nutritional supplements/vitamins.

At the same time, high-quality clinical evidence — ie, unbiased randomized controlled trials (RCTs) — strongly supporting most pharmacotherapies for FMS is inadequate, as shown in recent systematic reviews and meta-analyses by Häuser et al. [2009] and Roskell et al. [2011]. In these investigations, there were either too few RCTs of good quality for proper analysis, considerable heterogeneity across trials, and/or suboptimal effect sizes to reach truly definitive conclusions regarding specific medications. [How to interpret and critique systematic reviews and meta-analyses will be featured in the next article of our series on “Making Sense of Pain Research.”]

This present study by Robinson et al. [2012] was limited by its observational, cross-sectional nature and insufficient data to fully capture all factors that might have influenced treatment selections. Furthermore, a possible reporting bias must be considered, since the study was funded by Eli Lilly and Company, a manufacturer of select drugs used in FMS treatment, and 4 of the 8 authors were either employees or otherwise subsidized by the company.

> Häuser W, Bernardy K, Üçeyler N, Sommer C. Treatment of Fibromyalgia Syndrome With Antidepressants. JAMA. 2009;301(2):198-209 [
article here].
> Robinson RL, Kroenke K, Mease P, et al. Burden of Illness and Treatment Patterns for Patients with Fibromyalgia. Pain Medicine. 2012;13:1366-1376 [
> Roskell NS, Beard SM, Zhao Y, Le TK. A Meta-Analysis of Pain Response in the Treatment of Fibromyalgia. Pain Practice. 2011;11(6): 516–527 [

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