Terra Sigillata

I know that many of you have seen this article by Matthew Perronne since it was picked up by the majority of AP outlets this morning:

Two drugmakers spent hundreds of millions of dollars last year to raise awareness of a murky illness, helping boost sales of pills recently approved as treatments and drowning out unresolved questions — including whether it’s a real disease at all.

Key components of the industry-funded buzz over the pain-and-fatigue ailment fibromyalgia are grants — more than $6 million donated by drugmakers Eli Lilly and Pfizer in the first three quarters of 2008 — to nonprofit groups for medical conferences and educational campaigns, an Associated Press analysis found.

That’s more than they gave for more accepted ailments such as diabetes and Alzheimer’s. Among grants tied to specific diseases, fibromyalgia ranked third for each company, behind only cancer and AIDS for Pfizer and cancer and depression for Lilly.

The physician credited as lead author of the fibromyalgia diagnostic guidelines in 1990, Dr Frederick Wolfe, is now one of the disorder’s most vocal skeptics:

“I think the purpose of most pharmaceutical company efforts is to do a little disease-mongering and to have people use their drugs.”

Wolfe is now with the National Data Bank for Rheumatic Disorders in Wichita, KS.

The best definition I could find for fibromyalagia comes from NIH’s National Institute of Arthritis and Musculoskeletal Disorders (NIAMS):

Fibromyalgia syndrome is a common and chronic disorder characterized by widespread muscle pain, fatigue, and multiple tender points. The word fibromyalgia comes from the Latin term for fibrous tissue (fibro) and the Greek ones for muscle (myo) and pain (algia). Tender points are specific places on the body – on the neck, shoulders, back, hips, and upper and lower extremities – where people with fibromyalgia feel pain in response to slight pressure. . .

. . .Fibromyalgia is a syndrome rather than a disease. Unlike a disease, which is a medical condition with a specific cause or causes and recognizable signs and symptoms, a syndrome is a collection of signs, symptoms, and medical problems that tend to occur together but are not related to a specific, identifiable cause.

Let me state for first time visitors that I am not a physician. Therefore, I lack the specialized knowledge or clinical experience needed to weigh in as to whether fibromyalgia is a disease or disorder or syndrome that is responsive to pharmacotherapy. My unscientific survey of physicians in my community (not rheumatologists) are that people with fibromyalgia are considered hypochondriacs or have depression, arthritis, or sleep disorders that can be treated based upon those defined disorders with clear diagnostic criteria.

Whatever the case, and I encourage clinical colleagues to weigh in down in the comments, I am a strong proponent of the relief of human suffering. However, where I am dismayed is when drug companies begin to support programs that Dr Wolfe describes as “disease-mongering” for the sake of generating drug sales.

Comments

  1. #1 Prometheus
    February 9, 2009

    I have discussed this issue with half a dozen MDs from a liability perspective and they seem to be on the same page as Wolfe.

    Duloxetine has a very strange history and a large outlay associated with its development and approval.

    I am starting to see it advertised as a treatment for men suffering from “Nerve Pain” in sportsman’s magazines which gives me the creeps.

    That the symptom profile used to advertise Duloxetine treatment resembles nothing so much as this:
    http://panexa.com/

    I am inclined to be extremely suspicious.

  2. #2 Jim
    February 9, 2009

    [...] people with fibromyalgia are considered hypochondriacs or have depression, arthritis, or sleep disorders that can be treated based upon those defined disorders with clear diagnostic criteria.

    That’s consistent with western medicine’s tendency to treat the symptom(s), nevermind the actual problem, when confronted with something it doesn’t already understand.

    The presumption is: there’s nothing we don’t already know about/understand [in human illnesses] so if someone presents a set of symptoms that don’t appear to make sense, well, it certainly can’t be anything previously unknown or inadequately studied so it must be “in their head”. This is, naturally, occasionally true but it is not true often enough to be applied universally.

    We continue to discover new plant and animal species on this planet, when one might rightfully believe there’s no place left that modern humans have not been (above water). Why would it be so difficult to accept that there are valid non-healthy conditions in humans whose cause(s) have yet to be described in medical terms?

    Being mysterious does not equal imagined. You’d think we’d have figured that out by now, the generalization having been proven unusable so many times already.

  3. #3 anon
    February 9, 2009

    “The presumption is: there’s nothing we don’t already know about/understand [in human illnesses] so if someone presents a set of symptoms that don’t appear to make sense, well, it certainly can’t be anything previously unknown or inadequately studied so it must be “in their head”.”

    Jim. Your presumption that real (it’s not ‘western’) medicine holds such an assumption is utterly utterly false. Everybody involved in real medicine is quite aware that our knowledge of human biology is incomplete. You need a quack to find certitude about disease processes.

    The problem with a symptom cluster like what is described as Fibromyalgia is that the symptoms are not specific and are quite common. So plenty of people can, purely by chance, have a symptom cluster, caused by who knows what, that sounds like fibro.

    It’s not a case of doubting the sincerity of the patients’ complaints. It’s just doubting that the complaints are all caused by the same underlying chronic disorder.

  4. #4 Oliver
    February 10, 2009

    @anon

    You say
    “The problem with a symptom cluster like what is described as Fibromyalgia is that the symptoms are not specific and are quite common. So plenty of people can, purely by chance, have a symptom cluster, caused by who knows what, that sounds like fibro.

    It’s not a case of doubting the sincerity of the patients’ complaints. It’s just doubting that the complaints are all caused by the same underlying chronic disorder.”

    True. But as usual, absence of evidence is not evidence of absence. The same points, namely unspecific and common symptoms, are true for a wide variety of diseases many of which we DO know specific causes for, even though we have to delve a bit deeper sometimes. Unfortunately, diagnosis is treated more and more like something that every given general practitioner is a profound expert in, with laboratory medicine being degraded to “give me the numbers I ordered and shut up”. Pick your next best MD and ask him if ferritin is a reliable marker of iron deficiency anemia. He’ll likely say yes, even though it is only reliable if it is low, not if it is normal or high. Low ferritin means that the patient lacks iron. Normal ferritin, however, doesn’t mean that the iron gets to where it is needed. If you look at Wikipedia, a lot of medical articles are dominated by practicing MDs. And a lot of them are on the scientific level that said MDs were educated at 10, 20 years ago, which sometimes makes you wonder if CMEs are a humongous waste of time and money.

    While your statement is true that people might have the symptom cluster independently of the underlying cause, the question is whether that is any argument in the discussion at all. There’s plenty of situations in which we treat symptoms and not the underlying cause. And if we have no way of treating the underlying cause, I dare say that ensuring quality of life for the patient is as good a second best solution as there can be – if the cost/benefit ratio is sound. And this latter point should be the real question here. If the drugs help people lead a normal life which they would otherwise not be capable of AND doesn’t do any other harm, then on a general economic level it would be nonsense to waive the productivity of these people and on an ethical level it would be questionable to keep them suffering even though there is no need.

    Yes, it’s questionable to “invent” diseases. It’s equally questionable, however, to suggest people shouldn’t be offered treatment for their condition just because the condition is a syndrome not attributable at this point to a specific physiological process.

  5. #5 Kim
    February 10, 2009

    I know a couple of people diagnosed with fibromyalgia, and what kills me about it is that as far as I can tell from their stories, their doctors never took a thorough history. I’m no doctor, but if I was you can bet that anyone coming in with a history of pain for no apparent reason would be grilled pretty thoroughly, not just given the “you must be a crazy lady” diagnosis and sent off to the pain clinic.

  6. #6 chat
    February 11, 2009

    very good sites

  7. #7 anonmd
    February 12, 2009

    Since I see and treat this group of patients daily, a comment or 2 is in order.

    The symptoms of fibromyalgia represent the symptoms that the human body is capable of producing. Our bodies can only cause a certain limited number of symptoms (pain, numbness, tingling, aching, nausea, etc). So almost any generalized disease (Flu, Borrelia infection, HIV infection, thyroid disease) will cause a very similar list of symptoms. The syndrome of fibromyalgia “diagnostic criteria” appears to be a list of the symptoms a body is capable of producing, and is not specific for any disease.

    Patients complaining of fibromyalgia absolutely need to have a complete medical evaluation. Once. To look for diseases that cause the same list of symptoms.

    The “treatments” are non-specific. Prior to the appearance of pregabalin, the only treatments that were shown effective were daily exercise and low dose antidepressants. Almost no one with the diagnosis was willing to do this, because it meant exercising every day. (“its hard”). Pregabalin works fairly well for the symptom complex of fibromyalgia.

    Last comment regarding “western medicine” or “eastern medicin”–there is no such thing. There is only evidence based medicine or unproven treatments. If any “alternative medicine” can show in a placebo controlled trial that it works better than placebo, then it gets used. See Petasitis Hybridus for headaches (Neurology Dec 2004) and Co Enzyme Q10 (Neurology Dec 2004), and compare to the Ann Int Med Feb 10 2009 article on vitamins for cancer prevention (160,000 women x 8 years follow up, no change in cancer incidence).

  8. #8 juniorprof
    February 12, 2009

    Umm I think that there are two things going on here. 1) Pharma companies that would like to publicize more broadly a set of symptoms that can be fairly common in order to prescribe more drugs (bad). 2) a group of patients that have a real disease and suffer badly from it. I agree with anonmd above, pregabalin seems to work and so do antidepressants (which likely increase spinal norepi as a mechanism of analgesia. There are some clear human imaging and psychophysical studies out there that indicate that there are some specific pathologies in these patients. For instance, go to pubmed and put in bushnell and fibromyalgia. Check out the J Neurosci 2007 paper.

  9. #9 3+speckled
    February 13, 2009

    As a rheumatologist I can live with calling the fibromyalgia constellation of symptoms a syndrome rather than a disease because we don’t know of any cause so far. In fact, there are no widely accepted physiological markers, and certainly no diagnostic tests. Science may well figure it out, as they eventually did with “unexplained” menstrual pain and “stress” induced ulcer disease, but in the mean time we’ve got lots people with a debilitating group of symptoms that need taking care of, whatever term you want to use. My only real concern with the terminology debate is that replacing disease with syndrome is used by some to diminish the importance of the condition, something that helps no one.

    The pharmaceutical industry supports patient groups to increase sales. They hope too sensitize the population, not to get to the suffering patients, who have by and large seen a doctor, but to widen the field to every depressed, anxious or plain tired person who might have musculoskeletal complaints. It’s just more direct to consumer advertising.

  10. #10 Abel Pharmboy
    February 14, 2009

    @3+speckled – thanks for commenting because I was going to e-mail you before writing the post. Very, very good points about people actually suffering, no matter what you call it. I guess my question remains whether the drugs being pitched are of any good in a reasonable percentage of your patient population.

    Thanks so much for the insights and helping me understand an area where I am not particularly well-versed.

  11. #11 3+speckled
    February 15, 2009

    The drugs are not great but every little bit counts in this difficult to treat condition. The studies done to get approval show rather unimpressive results. For pregabalin, 43% of treated patients got 30% better, compared to 35% of controls. The patients that got better were generally taking 300-600mg of pregabalin and the study lasted only 13 weeks. In real life fibromyalgia patients tend to tolerate meds poorly. I start at fifty mg/day and feel lucky if I get anybody to 300mg/day. I have almost never gotten above 300mg for prolonged periods and how they did so in the study is beyond me. That said, a small number of patients do seem to do well despite failing many other meds, and in this condition, any success is a big deal. I do use pregabalin a lot for this reason. I have a lot less experience with duloxetine as it has only recently become available in Canada

  12. #12 Dan
    February 23, 2009

    The Unique Pain Of Fibromyalgia Syndrome

    The experience of pain appears to be a complex phenomenon with humans. The reason for the occurrence of pain can be physical, psychological, or a combination of both of these causes. And how one defines or describes the intensity of the pain they experience varies as much as the types of pain that exist. Although the origin may be the same from one person to another, the experience of pain is, in fact, a subjective emotional response to the sensation and perception of the pain itself.
    This is why the syndrome of Fibromyalgia is so difficult to define objectively and treat for health care providers, who are usually primary care physicians. Rheumatologists have said that Fibromyalgia Syndrome is the second most common musculoskeletal diagnosis after osteoporosis.
    Fibromyalgia is a very controversial syndrome. Some doubt it is as prevalent as others believe (3 to 6 percent of the population, some have determined). About 80 percent of the sufferers that are diagnosed with fibromyalgia are women. Furthermore, fibromyalgia is not a disease- it is a syndrome. A syndrome is what you call something that has multiple symptoms that occur together. A disease, however, is an actual dysfunction of one’s physiology in some manner.
    Fibromyalgia syndrome is considered a muscle condition that involves varying intensities of chronic pain for a prolonged period of time. As a result of this pain which is rather brutal with many sufferers, their physical function becomes limited. In addition, the location of the pain associated with fibromyalgia is determined by the health care provider according to at least 11 of 18 defined tender points at various locations on the human body.
    Regardless, fibromyalgia is misunderstood by the medical community overall. To further complicate the subject of fibromyalgia syndrome, some have suggested that the pharmaceutical companies that make the only two medications actually approved for the treatment of fibromyalgia, which are the drug giants Pfizer with their drug Lyrica, and Eli Lilly, the maker of Cymbalta, have conducted what is known as disease mongering.
    Disease mongering is when others expand the diagnostic criteria for a particular medical issue though various ways of informing the public of the potential undetected cases of such an issue through advertising, primarily.
    Also, another method of disease mongering is though the funding of various related associations and societies through educational grants to be the voice for those who conduct disease mongering with deliberate intent to increase the profit of their medications. There is evidence to support this claim- with more funds from these companies dedicated to advertising much more than grants.
    Yet it is clear that fibromyalgia syndrome exists, as there are so many diagnosed with this medical issue that share the same symptoms, which include other symptoms besides pain alone. And it often takes a great deal of time for a patient that has fibromyalgia to receive the correct diagnosis due to the absence of any objective diagnostic testing to assess this syndrome. The fibromyalgia patient often goes through numerous other diagnostic testing, such as blood work and X-Rays, as their doctor orders such tests to rule out other diseases and disorders that may be present with the symptoms expressed with fibromyalgia syndrome.
    Variables associated with those diagnosed with fibromyalgia syndrome include those patients with a history mental illness. They also tend to be overweight and live an inactive lifestyle, overall. Also, there seems to be an association with those diagnosed with fibromyalgia and these patients being in a state of low socioeconomic status.
    Also in over 50 percent of those diagnosed with fibromyalgia, the patients are experiencing mental stress, emotional distress, as well as some sort of family conflicts as well. In fact, this stress amplifies the symptoms of fibromyalgia if these emotions are expressing themselves in the fibromyalgia patient. Insomnia is associated with fibromyalgia as well. It appears that mean age of onset of Fibromyalgia is around 40 years old, yet fibromyalgia syndrome can occur at any age.
    Aside from systemic pain of varying degrees with the fibromyalgia patient, the patient experiences affective disorders typically. Since the symptoms of fibromyalgia also could indicate other disease states in 25 percent of the patients, usually X-Rays and blood work are examined to rule out other possible causes for the symptoms.
    The Journal of the American Medical Association gave these symptoms the name of Fibromyalgia in the mid 1980s, as well as this association publically acknowledging that it is a disabling illness
    There is evidence the cause is neurological. Upon examining the spinal fluid of a fibromyalgia patient, their serotonin levels are low, which is a neurotransmitter that has multiple emotional functions, as well as elevations of the neuro-chemical protein called substance P, which is the catalyst for pain. The patients also have elevated levels of what is called nerve growth factor (NGF). NGF is a protein molecule that, when elevated, is also associated with Alzeimer’s disease, and, believe it or not, one falling in love.
    Furthermore, some fibromyalgia patents have had their brains scanned for abnormalities that may be present, and their brains in fact have shown varying degrees of structural dysfunction with their brains due to fibromyalgia.
    So some suspect not only the cause may be some sort of central nervous system injury, but also there is evidence the syndrome is from some sort of viral infection, it has been reported.
    Treatment of the fibromyalgia patient includes not only the drugs mentioned earlier, but also other medications for pain, anxiety, and insomnia in particular. Lifestyle changes are recommended for the fibromyalgia patient, as well as many other treatment methods in order to relieve their discomfort. Physical exercise is appropriately recommended for the fibromyalgia patient as well.
    What is perhaps not recommended enough is cognitive or behavioral therapy for the fibromyalgia patient. There seems to be a strong association between fibromyalgia syndrome and psychogenic or psychophysiological causes for their symptoms.
    Or, perhaps the fibromyalgia patient is suffering from some sort of guilt for some reason that is amplifies the unfortunate syndrome they are forced to tolerate.
    Mea Culpa is Latin, meaning, ‘my fault’.
    Pain is a Latin word as well. Its meaning: a fine or penalty.
    Further research, however, is needed regarding this unfortunate syndrome experienced by so many others for no solid reason defined yet.
    ww.fmaware.org
    Dan Abshear