Generic drugs for the treatment of heart disease are as effective as their brand-name counterparts, according to a study published today in the Journal of the American Medical Assn.
The study was aimed at addressing the common perception that generic versions of such drugs as beta-blockers, diuretics, calcium-channel blockers, antiplatelet agents, statins, ACE inhibitors and alpha-blockers are somehow different than brand-name drugs. Generic drugs are often much cheaper and insurers sometimes pay only for generic brands. Researchers at Harvard Medical School and Brigham and Women's Hospital examined 47 studies on the effectiveness of various cardiovascular medications. The majority of the studies found generic and brand-name drugs are equivalent. The researchers also looked at editorials and opinion pieces on the issue of brand-name-versus-generic and found more than half expressed a negative view of the interchangeability of the drugs.
Why would doctors prescribe expensive brand-name drugs when the evidence doesn't warrant it? One possibility, the authors of the paper say, is that financial relationships with brand-name pharmaceutical companies influence their opinions and prescribing practices.
The 14 names are so familiar they raise few eyebrows when prescribed -- even when prescribed for uses not approved by the Food and Drug Administration. But perhaps they should.
Among prescription drugs, those medications' effectiveness and safety in off-label treatment are most in need of evaluation, a team of health experts has announced. The drugs are being prescribed, if not willy-nilly, at least without enough proof that they can help -- and not harm, the experts contend.
In a report published in the December issue of Pharmacotherapy, the researchers at the University of Illinois-Chicago, Stanford University and elsewhere explain their selection of the above drugs as the ones most deserving of further study. They considered how often the drugs were prescribed off-label without much evidence, the potential safety problems and the costs.
Of note is the fact that many drugs used off-label are antipsychotics or antidepressants (six on the list are being used to treat bipolar disorder). The researchers expound a bit on that in a press release, which includes a chart of the drugs' approved and nonapproved uses. (For more information about the drugs themselves, try the FDA site or the somewhat more accessible drugs.com.)
Doctors can prescribe whatever they think might help a patient, regardless of whether it's been proven to work. And they do -- especially when they lack good, approved options. But the practice isn't without risks and potential conflicts, hence an increasing effort to get a handle on the issue.
This list could be the beginning.
-- Tami Dennis
Photo: Effexor, approved to treat depression, is among the drugs increasingly used to treat conditions for which they're not approved (in this case, bipolar disorder).
The number of U.S. children taking medications for chronic diseases is growing, with some interesting gender differences.
Researchers had already established that chronic conditions are on the rise among the not-yet-adult set, but how those conditions are being treated ... that has been less well understood. Now we have a clearer picture.
Using prescription claim data for 2002 to 2005, researchers at Express Scripts, St. Louis University and Kansas Health Institute evaluated the use of drugs to treat hypertension, high cholesterol, Type 2 diabetes, depression, ADD/ADHD and asthma in insured children ages 5 to 19.
The use of all medications rose, but the use of drugs to treat Type 2 diabetes soared. The rate of growth for drugs to treat these conditions:
Hypertension: 1.8%
High cholesterol: 15%
Diabetes: 103.3%
Depression: 1.8%
ADD/ADHD: 40.4%
Asthma: 46.5%
The researchers spent some time theorizing about the reason teenage girls had such a greater use of diabetes drugs than did boys -- 146.6% growth compared with 38.7%. Obesity is a primary contributor to diabetes, and yet obesity rates didn't account for the discrepancy. As the researchers pointed out, boys have had higher rates of the condition in recent years, as well as higher growth in those rates.
Possible reasons, they said, included the use of the diabetes drug metformin to treat polycystic ovary syndrome and metabolic syndrome, as well as the higher rate of doctor visits by teenage girls compared with teenage boys.
But then girls also had higher growth in the use of antidepressants and medications for ADD/ADHD.
Referring to the overall findings, lead author Emily R. Cox said in a news release:
"These trends are worrisome given that many of these therapies are treating conditions with modifiable risk factors and if not addressed, many of these children will carry these chronic conditions into adulthood."
The study was published in the November issue of the journal Pediatrics.
-- Tami Dennis
Photo: Chronic conditions among kids are more common than they used to be. Here, kids play during recess at Elizabeth Hudson Elementary School in Long Beach.
Two new studies highlight the importance of communication between doctors and patients -- and not just one-sided communication.
In one study, researchers from Yale University found that people 65 and older are quite capable of weighing the pros and cons of their medications, thank you very much. And if allowed to do so, they just might make choices that work well for them.
As the researchers point out, with age can come the development of chronic conditions requiring ongoing, sometimes conflicting, treatment. Adjusting the corresponding medications becomes, therefore, considerably more problematic.
In interviewing people taking five or more medications, the researchers found that study participants initially considered only individual treatment goals, such as reducing their cholesterol or lowering their blood pressure. But when pushed to consider the various ramifications of such treatments, the participants considered broader goals, such as longer life or symptom relief.
Said study author Dr. Terri Fried in a news release:
"Their prioritization of these outcomes revealed what was most important to them, and they chose the treatment option that would mazimize the likelihood of their most desired outcome."
In the second study, from the University of Pennsylvania, people taking the blood thinner warfarin were less likely to suffer a serious bleeding problem if they received both written and verbal instructions on how to do so safely.
The drug, commonly known as Coumadin, can reduce the risk of heart attacks and strokes but can be difficult to manage properly.
Said lead author Dr. Joshua P. Metlay in a news release:
"While we do not know the specific mechanism linking the medication instructions to reduce bleeding risk, it is likely that improved communication about medications leads to increased drug adherence and earlier recognition of medication side effects."
That research was published in the Journal of General Internal Medicine.
And although the placebo debate may be moot in these specific studies (related: What placebos say about the doctor-patient relationship), the new research suggests that many patients may benefit from more, not less, information.
At least one in five prescriptions that doctors write is for a drug to be used for purposes or in ways different from those approved by the FDA. In 2001, that added up to 150 million prescriptions. And with such a large market up for grabs, it should be no surprise that drug manufacturers are keen to find ways to work around legal restrictions against the promotion of prescription drugs for such "off-label" purposes.
A new study out today in PLoS Medicine (dated Oct. 28) details the creative ways in which drug companies conduct "stealth marketing" campaigns that encourage physicians to prescribe a medication for "off-label" use, but do so within the narrow confines of the law.
Though there's nothing illegal about a physician prescribing medications for uses that FDA has not approved as safe and effective, it is illegal for companies to tout them in advertising and public promotion. It can cost a company caught in the act big-time: Several years ago, Warner-Lambert, a subsidiary of Pfizer, was forced to pay $430 million in civil and criminal fines for marketing the anti-epilepsy drug Neurontin as a drug for psychiatric diseases.
The authors suggest that physicians are no less immune to "buzz" advertising strategies than the rest of us are. So, at professional meetings and educational seminars that physicians must attend to keep their licenses up to date, drug companies with a new drug to sell or an old drug to revive often stir interest in a drug's "off-label" uses by sponsoring the presentation of small, preliminary studies. Though the studies would likely not pass muster in a medical journal, doctors still hear of evidence that a medication they already prescribe for an approved purpose may treat other disorders too. And that evidence often comes from a researcher who has won lucrative funding -- and sometimes speakers' fees -- from the company that makes the drug in question.
In some cases, a drug company may foster wider use of a drug through this kind of stealth marketing than if it were to take the ordinary route to broad acceptance by doctors and patients -- seeking approval for the "indication" from the FDA. Asking FDA's blessing requires the performance of costly and time-consuming clinical trials, which sometimes don't yield impressive results. By comparison, creating "buzz" is inexpensive.
"Pharmaceutical marketing has distorted the discourse on off-label marketing and encouraged the unmonitored, potentially dangerous use of drugs by patients for whom risks and benefits are unknown," write authors Dr. Adriane Fugh-Berman of Georgetown University and Dr. Douglas Melnick, a preventive physician based in North Hollywood. One study has found that three-quarters of off-label prescriptions are written without a shred of scientific evidence supporting the drug's effectiveness for the purpose.
Fugh-Berman is the force behind a pharmaceutical-industry watchdog website, http://www.pharmedout.org/. Melnick worked in the pharmaceutical industry as a physician in the firm's medical affairs department, supporting marketing efforts.
The authors suggest that FDA regulators should expend more effort enforcing -- and perhaps extending -- restrictions of off-label marketing than is currently the case. They suggest that physicians, who often find themselves on the receiving end of such campaigns, could be offered rewards for reporting off-label marketing.
Doctors want to make their patients feel better. Got it. And sometimes a treatment that doesn't actually help -- a placebo -- will make patients feel better. Got that too. But ...
A study published today in the British Medical Journal found that many rheumatologists and internists in the U.S. seem to have few qualms about prescribing placebos to their patients. The study, based on a not-huge survey of 679 physicians, found that half prescribed placebos regularly. About 62% saw the practice as A-OK.
That's not to say that none of the placebo treatments did anything whatsoever, just that the treatments -- such as vitamins, over-the-counter painkillers, sedatives and antibiotics -- didn't actually treat the condition for which they were prescribed. (That's what we need -- more prescribing of unnecessary antibiotics.)
Said the authors in the abstract's conclusion:
Prescribing placebo treatments seems to be common and is viewed as ethically permissible among the surveyed U.S. internists and rheumatologists.... Physicians might not be fully transparent with their patients about the use of placebos and might have mixed motivations for recommending such treatments.
The practice itself is increasingly coming out of the shadows, its powers and potential discussed more openly among physicians. As an L.A. Times story published earlier this year points out: "For decades, research physicians have furrowed their brows at the mysterious powers of a treatment known in many medical circles as Obecalp." (That's "placebo" spelled backward.)
That story, "Doling out the placebo effect," notes:
Physicians' growing belief in the connection between mental and physical health has caused many to acknowledge that sometimes patients can be made to feel better, and even get better, simply because their doctor did something to help them.
Maybe.
But if the doctor-patient relationship is gradually eroding, as some contend, might it erode further as patients start to wake up to the use of placebos? Wonder what the placebo treatment for that is....
The United States can probably kiss goodbye to the arrival of Sanofi-Aventis' anti-obesity rimonabant (Acomplia). The European Medicines Agency, which assesses the safety of drugs after they have been released, has recommended that marketing authorization of Acomplia be suspended across the European Union.
The drug has been available in Europe since 2006, although it is not yet available in the U.S. In 2007, the Food and Drug Administration denied approval of Acomplia in the U.S., citing safety concerns.
In a release, the European Medicines Agency said it had concluded that "the benefits of Acomplia no longer outweigh its risks" and that studies not available at the time of the drug's approval, as well as experiences of patients who'd taken the drug since then, indicated "an approximate doubling of the risk of psychiatric disorders in obese or overweight patients taking Acomplia compared to those taking a placebo."
Warnings about these side effects had always accompanied the drug, and last year the agency acted to counter-indicate prescription to anyone suffering from depression (the principal side effect) and to warn doctors that the drug should be discontinued if the patient developed depression.
But the extent of the effects appeared higher after more studies were examined, the agency said. At the same time, the weight loss experienced by users in the real world was less than the studies had suggested because people don't tend to take the drug for very long.
The European Medicines Agency's announcement is a recommendation. Next, the European Union will decide what to do on the matter. But it doesn't look good for the drug, according to several news reports: In a Bloomberg News article, an analyst called this the "death knell for the drug."
Acomplia acts kind of like an anti-marijuana: It blocks a receptor in the brain that is activated by THC, the main active ingredient in the plant. (Just as THC stimulates the appetite, Acomplia does the opposite--suppresses it.) That receptor is present in many different regions of the brain and other parts of the body.
Earlier this month, another drug based on the anti-THC principle went south. Merck's experimental drug taranabant was abandoned by the company after Phase 3 studies showed that though it helped people lose weight it had too many side effects.
-- Rosie Mestel
* UPDATE: They come, they go, they come, they go. Also in the news right now: reports of a new promising anti-obesity drug, tesofensine, in the journal the Lancet. (Because that journal won't let you read for free, check it out instead at WebMD.) "Normally the drugs now on the market give you at best a weight loss of 5 kilograms [11 pounds] with diet and exercise," says study author Dr. Arne Astrup of the University of Copenhagen in the WebMD article. "In this study we doubled that weight loss."
But let's wait before we get too excited. The WebMD article also quotes Thomas Wadden, director of the University of Pennsylvania School of Medicine Center for Weight and Eating Disorders, as saying larger studies are needed, in spite of the promising results. Wadden cites blood pressure side effects as troubling, "as was the finding that study participants treated with tesofensine reported more anger, hostility and confusion than participants in the placebo arm of the study."
Businesses across the globe are flocking to the Internet in search of customers wanting to surf, chat, post and connect with products and the people who use them. But what $275 billion industry doesn't want to brave cyberspace for fear that its denizens may say something hurtful about that industry's products?
Big Pharma, says BrandWeek, a publication that reports on developments in the advertising and marketing industries. In an article in this week's issue, BrandWeek reports the world's prescription drug makers are wary of creating highly interactive websites because they fear that disgruntled consumers will use them to complain about side effects, interactions, prices and other matters that might not cast a positive glow on their offerings.
Mainly, it's a battle that pits the drug companies' marketing departments and their forward-leaning "digital" marketing strategists on the one hand, and the fogies in the legal and regulatory departments on the other, says BrandWeek. The fogies -- who have until now carried the day -- have argued that consumers will hop on the websites created around prescription drug products and post complaints. Their posts, in turn, could attract the attention of personal injury attorneys, regulators, investigative committees and critics.
The digital strategists -- who BrandWeek believes may soon pull ahead in the game -- are arguing that the drug companies are missing a big chance to foster brand loyalty among those who use their drugs, and that, properly managed, websites can handle the criticism that consumers may direct at them. Transparency is the watchword of these marketers, says BrandWeek editor Todd Wasserman, and drug companies are being urged to take a bigger dose.
BrandWeek cites the consumer-drug giant Johnson&Johnson as an example of a company that has boldly adopted a more sophisticated and interactive Web presence in spite of those concerns. J&J's website www.childrenwithdiabetes.com is reported to get 10,000 vistors a day, and though the company patrols the site for posters giving inaccurate information or reporting "adverse events," its Web managers are said not to censor visitors.
But for an industry that still takes criticism for advertising directly to consumers, jumping into the World Wide Web with both feet may feel like riding the tiger for drug makers, says Wasserman. "It's sort of like trying to market cigarettes -- your hands are so tied. There are so many things you can't do."
Everybody is worried about the rising cost of prescription drugs, but conventional wisdom would probably say that older people worry more.
Not so, says a new survey by Medco, a pharmacy benefit manager.
"According to the new national survey 'Feeling the Health Care Pinch,' nearly 70 percent of adults aged 25-34 claim the economic downturn of the last 12 months has made it somewhat or significantly more difficult to pay for health care expenses. Ironically, among people over 55 -- pre-retiree and retiree aged consumers whom many often think of as struggling to pay for health care -- more than half said the downturn in the economy has not impacted their ability to pay for health care at all. Overall, three out of four people are concerned about the cost of health care," the news release says.
A couple of things might be going on with young adults. First, problems like diabetes and heart disease are hitting younger people these days, connected to the growing rates of overweight and obesity among younger Americans, so more of them are taking prescription drugs than in the past. And second, young people are hit with economic hard times when they may still be paying off college loans and beginning to set up independent lives with their own rent, mortgages or car payments.
Older prescription drug users are more savvy about asking their physicians for cheaper, generic versions of drugs, and to use mail order pharmacies to save money, according to the survey.
So it seems that everyone is worried, and youth itself doesn't necessarily let people off the hook.
The search for anti-obesity drugs got a setback with Merck's announcement Thursday that the company has ended obesity research on its experimental drug taranabant. According to a statement from the company, though phase three results showed it did help people lose weight, it also had too many side effects. Here's the company's Oct. 2 statement.
Taranabant is a chemical that blocks a receptor in the brain that is activated by THC, the main psychoactive ingredient in marijuana. (Readers may be aware that partaking of marijuana stimulates the appetite; conversely, blocking the brain receptor through which this effect occurs might be expected to have an anti-munchie effect.) But the receptor blocked by taranabant is widely distributed in the brain and presumably involved in a variety of brain processes. Plus it's also found in certain other tissues of the body, including fat cells and the adrenal, thyroid and pituitary glands. So it's not surprising the drug would have other effects unrelated to appetite.
According to an article in the Wall Street Journal, "The company said Thursday that both effectiveness and side effects are dependent on dose levels, with higher doses producing greater effectiveness but more adverse events. Essentially, Merck wasn't able to find a dose level that adequately minimizes risk while helping people lose weight to a significant degree."
This isn't the first anti-obesity drug developed that acts on cannabinoid receptors. Another, Sanofi-Aventis' rimonabant (Accomplia), is available in some countries in Europe but hasn't received FDA approval in the U.S.; in 2007 an FDA advisory committee recommended against approval because of side effect concerns.
Score one for the consumer. The U.S. Food and Drug Administration today published its first list of drugs that are on the market and being used by consumers but are under review for potential safety issues.
The list, which will be updated quarterly, was part of the FDA Amendments Act, signed into law one year ago. The law requires that the FDA inform the public each quarter of new safety information or potential signals of serious risk based on the agency's review of adverse event reports.
The FDA explains the list: "The appearance of a drug on this list does not mean that FDA has concluded that the drug has the listed risk, or that FDA has identified a causal relationship between the drug and the listed risk. It is on the list only because FDA has identified a potential safety issue."
Dr. Janet Woodcock, direct of the FDA's Center for Drug Evaluation and Research added:
"My message to patients is this: Don't stop taking your medicine. If your doctor has prescribed a drug that appears on this list, you should continue taking it unless your doctor advises you differently."
The list contains 20 drugs along with the potential safety issue of each drug. Today's report includes the antidepressant Cymbalta and links to urinary retention; the multiple sclerosis drug Tysabri and reports of melanoma skin cancer, and the drug Revlimid for multiple myeloma that is linked to a life-threatening skin condition called Stevens Johnson Syndrome.
The list comes in response to complaints by the public and physicians that they aren't being told soon enough of potential safety problems reported to the FDA. Sometimes pre-marketing clinical trials do not produce evidence of a safety problem and it is only when the drug is in wide use that a problem emerges. The list will not be a comprehensive summary of all the drugs the FDA may be working on. Each new quarterly report will contain new listings; the lists will not be cumulative. You can read about the program at the FDA's website and see the current list of potentially unsafe drugs.
Tami Dennis, who takes the word "skeptic" to previously uncharted territory, is editor of The Times' Health section. She's adamant that pitches promoting awareness days, weeks or months are, by their nature, non-stories. And, because she's an adult, she refuses to use words like "veggies," "tummy" and "yummy."
Rosie Mestel, Health section deputy editor, studied genetics before abandoning flies, fungi and DNA for health/medical writing. Her hero is the biologist Ernst Haeckel, whose jellyfish paintings inspired snazzy chandeliers. Her favorite toast-spread is Marmite, a British delicacy made of yeast extract. Her least-favorite word is "millenniums."
Melissa Healy is a staff writer for the Health section reporting from Washington D.C. Healy's a veteran of The Times' National staff, having covered the Pentagon, Congress, poverty and social welfare, the environment, and the White House before shifting to Health in 2003. She writes frequently about mental health and human behavior, about federal health policy, prescription medication and ethics in medicine. More wonk than wellness freak, Healy chooses to believe in the health benefits of coffee and wine, and considers water a better work-out medium than beverage.
After a brief stint as a sports writer, Shari Roan turned to health journalism and has covered the topic for The Times for 18 years. She is the author of three books and the mother of two daughters, both teenagers who refer to her as a "health freak." She likes to jog, watch baseball and is very happy that dark chocolate contains some health benefit.
Jeannine Stein writes about fitness, sports medicine and obesity for the Health section. She’s a gym rat from way back and never met an elliptical trainer she didn’t like. Well, maybe one or two. She tempers exercise with a steady diet of reality television because she believes it’s all about balance.
Generic drugs for the treatment of heart disease are as effective as their brand-name counterparts, according to a study published today in the Journal of the American Medical Assn.
Two new studies highlight the importance of communication between doctors and patients -- and not just one-sided communication.
