Considering a New Med?
FDA-approval doesn’t mean “best in show”
by Alan Spanos, M.D., Chapel Hill, NC
Given all your different symptoms—pain, fatigue, disturbed sleep, brain fog, muscle stiffness, and GI upset—there are more than 100 medications to choose from. You are not limited to only those that are FDA-approved for fibromyalgia (pregabalin, duloxetine and Savella), so how do you narrow down the list? There are no clear-cut ways for doctors to predict how a drug will work for you, but you can participate in your own individual treatment trials to determine which meds work best.
Some of the comments in this article may confirm your gut feelings about new and existing medications. Hopefully as you read through the advice, it may help you fend off the urge, or pressure by others, to try every new drug the instant it hits the prescription market.
‛New’ Doesn’t Mean ‛Better’
We truly don’t know whether the new, patented fibromyalgia meds do better than the old, generic (and therefore much cheaper) ones. It’s important for fibromyalgia patients to understand that when the FDA labels a drug as being “indicated for fibromyalgia” that doesn’t mean it’s any better than others that have been around for years. It doesn’t mean it’s powerful. In fact, it may have only a marginal effect on a few patients. Based on that, it can still pass the FDA tests and get labeled “effective in fibromyalgia.”
Most drugs used for fibromyalgia are generic, i.e. they can be made cheaply by any number of manufacturers. But drug companies naturally want the FDA’s seal of approval on their own, new, patented product. To get this, they must present evidence that it’s “effective,” but it doesn’t have to be better than already-available medications.
Putting the FDA approval label into perspective, these medications only have to outperform a sugar pill, which is simply a placebo, and not by a wide margin. It only has to do slightly better than the sugar pill—enough to satisfy a statistician that the apparent benefit to the patients in the study was more than just the play of chance. Such a benefit might be minuscule in real terms, but it still earns the label “effective for treatment of fibromyalgia” in the FDA’s eyes.
The FDA’s definition of effective is probably not what this word means to you or most people. For instance, if a fabric cleaner was touted as “effective for removing fruit stains,” you would expect it to remove most fruit stains from most fabrics. But the three FDA-approved fibromyalgia medications don’t remove fibromyalgia symptoms from most people. At best, the studies show they reduce one or two symptoms a bit, for a while, in a minority of patients. Yes, a minority: much less than half the people treated get a benefit compared to placebo.
The drug company may trumpet the fact that its product is “effective in 50 percent of cases.” But this claim can be misleading to patients if the placebo did just as well for 35 percent, which means that only 15 percent (the difference between 50 and 35) actually did better taking the drug compared to the sugar pill, or maybe nothing at all. Fifteen percent means only one person in every seven gets a small benefit, and that defines “effectiveness.”
Big Responders
Despite these gloomy figures, a few people apparently do get a sizeable benefit from some drugs. In a large fibromyalgia patient survey, 10 to 15 percent indicated that one of the three FDA-approved medications helped them in a major way. Doctors would like to know more about these patients who report striking success. Unfortunately, these big-responders are not studied, so we don’t know if they share certain features that might predict greater success with a given medication.
Doubts about New Drug Trials
The drug trials that are sent to the FDA do not include people with severe fibromyalgia. People who have more than one diagnosis don’t get into the trial. And generally, patients must stop all their usual medications before starting the study. People with severe symptoms are virtually guaranteed not to enroll, because they rightly suspect they will feel a lot worse without their usual medications, especially if they are given the placebo! So in general, even the modest benefits claimed by the drug manufacturers have only been reported in people with rather mild symptoms.
In addition to screening out the severe cases of fibromyalgia during the selection process, there are major problems with bias in these studies. Any doctor who participates in such trials quickly discovers that they are riddled with opportunities to tilt the results in favor of the test drug. And since it is the drug’s manufacturers who carry out the studies, one can be very sure those opportunities were taken.
For the reasons above, Marcia Angell, M.D., the retired editor-in-chief of the prestigious New England Journal of Medicine, has written, “It is simply no longer possible to believe much of the clinical research that is published.” *
So What Should I Try?
If new drugs for fibromyalgia are over-sold, and if the older alternatives number several dozen, how can you or your doctor sort out what you should try? A common approach is to test just one drug from each chemically-defined group (or drug class), and if it doesn’t work, to ignore the others in the group. For instance, using this line of thinking, if you had tried amitriptyline and didn’t like it, then you would not try other members of the same “tricyclic antidepressant” group. Or, if gabapentin didn’t work, you would avoid pregabalin because they are chemically similar. Unfortunately, the facts about the various drugs don’t bear out this attempt to simplify things.
Quite frequently, a patient responds very well to one drug but not at all to other closely related ones. And the reverse is just as common. One drug in a class may cause really unpleasant side effects, while its relatives in the same class might not.
Examples of drugs that are chemically similar, but may have very different effects in some patients, include the “SSRIs” fluoxetine, sertraline, and paroxetine; the sleep enhancers zolpidem and eszopiclone; the benzodiazepines clonazepam, alprazolam, and lorazepam; and opioids like morphine, methadone, or oxycodone.
Your Own Clinical Trial
A better way to approach your drug treatment options may be to accept that you will have to try several different medications before finding one or two that help. I tell my patients that this is one area where you have to kiss a lot of frogs before one turns into a prince. The important thing is to try each medication properly. This involves using an adequate dose, for long enough to tell what it’s doing but no longer, and then move on to the next candidate. The most common mistake I see is to leave patients on a drug for months without properly establishing whether or not it helps.
The take-home message for fibromyalgia patients is that they shouldn’t get too cranked up about the latest wonder drug. There is no medication for fibromyalgia that benefits 50 percent of patients. So you could say that most meds the doctor can prescribe for you probably won’t work, just as most times you throw a dice, it won’t come up with a six. But if you throw several dice in quick succession, the chance that you’ll get a six with at least one of them is quite good.
To find out which medications work for you, try only one new drug at a time. The trial period may be as short as a day or as long as a month. The trial length depends on how long it takes for the drug to begin working, whether the dose has to be increased gradually to minimize side effects, and so on. For drugs that take weeks rather than days to assess, patients should keep notes in a symptom diary to help evaluate the medication’s impact.
Many patients want to try a number of different treatments for various symptoms: pain, fatigue, poor sleep, etc. Others quickly get tired of the process. They want to stop and settle on something, even though there might be better medications out there that they haven’t yet tried. Some may want to go home with a frog rather than hold out for a prince who may never show up. We should respect patients’ choices on this.
Dr. Alan Spanos has specialized in the treatment of difficult chronic pain including fibromyalgia and chronic fatigue syndrome/ME since 1986. He is trained in internal medicine, family practice, anesthesiology, acupuncture, clinical hypnosis, and myofascial pain. He has taught at several of the most prestigious medicals schools and hospitals nationwide. He recently retired from his practice in Chapel Hill, NC.
* The Truth About the Drug Companies: How They Deceive Us and What to Do About It , by Marcia Engell, M.D. Random House Trade Paperbacks. ISBN-10: 0375760946.