The treatment of fibromyalgia syndrome appears to be entering something of a golden age. Recently, after years of struggling just to be taken seriously, fibromyalgia patients have witnessed the release of a series of medications indicated for the treatment of fibromyalgia syndrome. While it is true that these medications are far from perfect and aren’t effective for everyone, they have provided a strong sense of direction for researchers and raised hopes for more efficacious treatments in the future.

Currently, the most promising areas of research center around central nervous system neurotransmittors and the role they play in pain modulation. In the United States, the drugs currently approved for the treatment of fibromyalgia syndrome affect either the neurotransmitters, serotonin and norepinephrine (duloxetine, milnacipran), or gamma-aminobutyric acid (pregabalin). These are not the only neurotransmitters that are involved in pain modulation, however, leading researchers to look at the role that dopamine may play in the pathology of fibromyalgia syndrome, too.

In fact, there are several good reasons to think that dopamine may play a key role in the etiology and clinical presentation of fibromyalgia syndrome:

1. A link has been identified between fibromyalgia syndrome and an abnormality in a gene responsible for proper dopaminergic expression.⁽¹⁾ This genetic link suggests that altered dopaminergic pathways may be at least partially responsible for the symptoms of fibromyalgia syndrome.

2. Studies utilizing positron emission topography (PET) to map brain response have empirically shown that fibromyalgia patients exhibit decreased dopaminergic activity in response to painful stimuli when compared to control groups.⁽²⁾⁽³⁾ These fibromyalgia patients also perceived the painful stimuli to be more severe than did the control group. Since dopamine has been implicated in both pain modulation and processing, these studies suggest dopamine may be at least partially responsible for the widespread pain experienced by fibromyalgia patients.

3. Anecdotal evidence shows that low dopamine levels are associated with stiff, achy muscles, cognitive impairment, and difficulty focusing. These symptoms are familiar to most fibromyalgia patients.

These are among the factors that have lead researchers to conduct clinical trials on the dopaminergic agent, pramipexole, with intriguing results. Compared with the control group, patients in this study experienced gradual, significant improvement in measurements of pain, fatigue, function, and overall well-being, suggesting that dopaminergic agents may be of value in the treatment of fibromyalgia syndrome.⁽⁴⁾

While these results are encouraging, pramipexole is not yet approved for the treatment of fibromyalgia syndrome, and in the absence of an approved prescription product, some fibromyalgia patients have turned to natural alternatives (dietary changes, natural supplements). Foods thought to affect dopamine levels include almonds, bananas, avocados, lima beans, pumpkin seeds and sesame seeds. Unfortunately, despite anecdotal evidence reporting positive results, no controlled studies exist to verify the efficacy of these efforts.

Though research into the role of central nervous system neurotransmission in the expression of fibromyalgia syndrome appears to hold great promise, the medications currently available are only marginally effective and the need for better therapies is acute. As research progresses, dopaminergic agents such as pramipexole are likely to be added to the growing arsenal of approved agents, hopefully leading to greater relief for a growing number of fibromyalgia patients.

Learn more about fibromyalgia at: www.myalganex.com

1. Dan B, Hagit C, Lily N, Ebstein RP. An association between fibromyalgia and the dopamine D4 receptor exon III repeat polymorphism and relationship to novelty seeking personality traits. Molecular Psychiatry, 2004 9, 730–731. [↩]
2. Wood PB, Schweinhardt P, Jaeger E, Dagher A, Hakyemez H, Rabiner E, Bushnell MC, Chizh BA. Fibromyalgia patients show an abnormal dopamine response to pain. European Journal of Neuroscience, 2007 June;25(12):3576-3582. [↩]
3. Wood P, Patterson II J, Sunderland J, Tainter K, Glabus M, Lilien D. Reduced presynaptic dopamine activity in fibromyalgia syndrome demonstrated with positron emission tomography: a pilot study. The Journal of Pain, 8(1):51-58. [↩]
4. Holman AJ, Myers RR. A Randomized, Double-Blind, Placebo-Controlled Trial of Pramipexole, a Dopamine Agonist, in Patients With Fibromyalgia Receiving Concomitant Medications. Arthritis & Rheumatism, 2005 Aug;52(8):2495-2505. [↩]

Just as in 2007 with Lyrica and again in 2008 with Cymbalta, the fibromyalgia community is abuzz in anticipation of Savella, the third drug approved by the FDA for the treatment of fibromyalgia. That this news should garner such attention is not really surprising given the level of involvement and sophistication among fibromyalgia patients, but we should always remember to temper our expectations with a bit of sobriety. A little rational analysis can tell us a lot about how these drugs were developed, and what can be reasonably expected from them.

When Pfizer’s Lyrica was approved by the FDA in June of 2007 it became the first prescription medication indicated for the treatment of fibromyalgia. It’s approval represented not only a hope for better individual treatment, but also a kind of validation for the fibromyalgia community at large. After years of struggling just to be heard by the medical establishment, fibromyalgia sufferers were suddenly watching Big Pharma recognize fibromyalgia as a treatable condition.

Not surprisingly, the drug has been a big winner for Pfizer. Lyrica’s fibromyalgia sales have been brisk from the start and are expected to grow to $641 million by 2016. In light of these numbers, it is easy to understand Pfizer’s motivation in pursuing the FDA approval. They fails to explain, however, exactly what fibromyalgia patients can expect from Lyrica.

Despite the hype, the approval of Lyrica for fibromyalgia has offered little in the way of novel treatment for fibromyalgia. In fact, Lyrica already has been available in the U.S. (with a neuropathic pain indication) since 2005, and of course, doctors have always been free to prescribe for off-label uses.

So, if the drug was already available, what was gained by the FDA’s approval of Lyrica for fibromyalgia? For the fibromyalgia patient, there were two main benefits. The first was that insurance companies were more likely to include Lyrica in their formularies, and the patient was less likely to be required to pay out-of-pocket for the medication. The second was that some doctors (primarily those unfamiliar with treating fibromyalgia) became more comfortable with prescribing Lyrica for fibromyalgia.

These are not small matters, to be sure, but they aren’t exactly the breakthrough for which some fibromyalgia patients had hoped. In contrast, Pfizer got exactly what they desired: a regulatory license to directly market Lyrica to fibromyalgia patients.

All of the subsequent largesse was not lost on Eli Lily and Company, and in a manner similar to Pfizer, they pursued a fibromyalgia indication for one of their existing drugs (the anti-depressant, Cymbalta). Upon receiving Cymbalta’s approval in June of 2008, they poured millions of dollars into a direct marketing campaign and once again sales boomed.

Both of these approvals caused quite a stir, but both were really more about market positioning for the manufacturers than about breakthroughs in fibromyalgia treatment. This is not to say these medications are ineffective. Quite the opposite, they help a number of fibromyalgia patients live better lives. It is actually somewhat intuitive to surmise that a medication originally approved for neuropathic pain and a medication originally approved for depression would be helpful in the treatment of fibromyalgia, but neither of these medications offers a true breakthrough in treatment.

This summer, Forest Pharmaceuticals plans to release Savella, the third FDA approved fibromyalgia medication. Right away, we should recognize that Savella is different from Lyrica and Cymbalta in that it is actually a new molecular entity not previously approved by the FDA for any indication.

Savella, like Cymbalta, is an anti-depressant categorized as a Serotonin-Norepinephrine Reuptake Inhibitor (SNRI). That is to say, it’s mechanism of action is the same as that of Cymbalta. Savella does differ from Cymbalta in that it is more selective for norepinephrine, while Cymbalta is more selective for serotonin. This gives reason to believe that Savella may provide a valuable alternative to Cymbalta for some patients, but we should also be aware that Savella does not represent a radical step forward in treatment.

For clarity, it is informative to examine the manner in which the FDA handled the New Drug Application (NDA) for Savella. Every NDA is classified during the drug review process according to it’s perceived importance to society. According to the FDA, “Fast Track, Accelerated Approval, and Priority Review are approaches that are intended to make therapeutically important drugs available at an earlier time.”⁽¹⁾

Drugs for previously untreatable conditions or drugs with a novel mechanism of action would likely qualify for these high priority reviews. For instance, Lyrica, by virtue of being the first drug with a fibromyalgia indication, was given a Priority Review even though it was not a new molecular entity. Savella, however, was not reviewed under any of these priority classifications, but rather, under the Standard Review process which according to the FDA, “is applied to a drug that offers at most, only minor improvement over existing marketed therapies.”⁽¹⁾ [emphasis added]

Keeping things balanced and in perspective is important for fibromyalgia patients, so as summer approaches and the hype for Savella shifts into high gear, remember those words, minor improvement, and set your expectations accordingly.

Learn more about fibromyalgia at: www.myalganex.com

1. US Food & Drug Administration, “Fast Track, Accelerated Approval & Priority Review,” May, 2006, http://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/SpeedingAccesstoImportantNewTherapies/ucm128291.htm (March 20, 2009) [↩] [↩]