The search for the perfect impotence drug won't end soon

Taking Viagra, Levitra or Cialis improves erectile function. That much we now know. Again.

What we still don't know is which medication works best.

At the request of the American College of Physicians, the Agency for Healthcare Research and Quality, part of the U.S. Department of Health and Human Services, set out to assess the impotence drugs' effectiveness and their risk of side effects. Doctors apparently like to have as clear a picture as possible before prescribing the drugs to patients.

The report, released today, distills evidence from 126 randomized controlled trials of the drugs technically known as oral phosphodiesterase type 5 inhibitors. But only four trials compared sildenafil (Viagra), vardenafil (Levitra) and tadalafil (Cialis) against each other, making cut-and-dried conclusions difficult.

Researchers have a pretty good idea of the drugs' benefits. And of their risks -- most common are headaches, flushing, dyspepsia (indigestion -- here's an explainer from MedicineNet) and rhinitis (inflammation of the nose's inner lining -- and another explainer). They just can't tell doctors which one should be prescribed. 
 
But the report does offer one-place-shopping for information on dose-response effect of the individual drugs (higher doses tended to get better results), plus less-conclusive assessments of injections, suppositories, topical treatments, hormones and drugs prescribed off-label. The researchers also tried to evaluate the usefulness of routine blood tests in identifying (and thus, treating) hormonal disorders. The limited amount of data made this problematic.

For most men, and their doctors, the report largely means: If you're looking for a thorough comparative summary of the data on these drugs, now you have one.

Of note, the big three drugs tended to work fairly well across the board. That is, they helped men regardless of the cause of erectile dysfunction. (Here's a primer on causes, courtesy of the Urology Channel.)

And men tended to prefer tadalafil (Cialis) over its cousins, partly because the drug's effects last longer.

The researchers wrote: "There is still insufficient information regarding the effectiveness and safety related to the use of different treatment modalities in various clinical subgroups of patients (e.g. diabetes, cardiovascular disease). Furthermore, there is insufficient data with regard to long-term adverse effects of oral ED medications that have been used by millions of users for over a decade."

Translation: We need more data, especially about how the drugs might affect men with diabetes and heart disease. And long-term data -- we definitely need more of that.

-- Tami Dennis

Photo: Viagra has been often discussed, but not often compared -- clinically speaking -- to its cousins Levitra and Cialis.

Credit: AFP / Getty Images

Brain drugs won't go away, so best give them some thought

If pills can make us better mentally -- and it seems clear they can -- it's time to answer the question of whether we should let them. 

For some people, the question is already moot. In the April 27 issue of the New Yorker, writer Margaret Talbot explores the issue of brain medications in "Brain Gain: The underground world of 'neuroenhancing' drugs."

She writes: "In recent years Adderall and Ritalin, another stimulant, have been adopted as cognitive enhancers: drugs that high-functioning, overcommitted people take to become higher-functioning and more overcommitted."

She tells her story in some part through a recent Harvard graduate named Alex. He makes a compelling case for what can be accomplished with a little help.

Some neuroscientists and ethicists have already answered the bigger question among themselves. Says a recent blog post from Times staff writer Melissa Healy: "Pop a smart pill? Why not, says a group of neuroethicists"

-- Tami Dennis

Photo: Ritalin -- the little helper for people with attention deficit hyperactivity disorder and overworked, over-stressed students -- is going mainstream.

Credit: Keith Beaty/Toronto Star/ZUMA Press

Birth-control shot linked to weight gain

The birth-control shot, a popular contraceptive choice among teenagers, causes significant weight gain and an increase in body fat, according to a study published in the current issue of the American Journal of Obstetrics & Gynecology.

The shot is comprised of the drug depot medroxyprogesterone acetate, or DMPA, which is administered once every three months to halt ovulation. The contraceptive, also known by the brand name Depo-Provera, is used by about 2 million American women, including 400,000 teenagers. Its advantages are the infrequent administration along with the fact that it's inexpensive and has a low failure rate.

But the study, by Dr. Abbey Berenson and her colleagues at the University of Texas Medical Branch, found that women who used the contraceptive gained an average of 11 pounds and increased their body fat by 3.4% over three years. After the women switched to a non-hormonal contraceptive they began to slowly lose the weight and fat they gained. But women who switched to oral contraceptives after the shots gained an average of four more pounds over the next two years. The study included 703 women. Overall, the DMPA users were more than twice as likely as women using non-hormonal birth control to become obese over the next three years. The researchers are now conducting follow-up studies to determine which subset of women is most likely to gain weight on DMPA. Preliminary data from this study show that about 25% of women on the medication experience significant and potentially dangerous body composition changes.

Berenson says researchers aren't sure why DMPA seems to cause weight gain. No connections were found between the drug and caloric intake, fat consumption or amount of exercise. But, she said: "Women and their doctors should factor in this new data when choosing the most appropriate birth control method. One concern is DMPA's link to increased abdominal fat, a known component of metabolic syndrome, which increases the risk of cardiovascular disease, stroke and diabetes."

The birth-control shot is a staple of many public health clinics that serve low-income and teenage women. Though preventing unintended pregnancy is a worthy objective, public health officials also might want to ponder whether the potential advantages of this contraceptive outweigh its potential contribution to the nation's growing obesity rate and the many diseases linked to obesity.

-- Shari Roan

Photo credit: Los Angeles Times

Antidepressant labels to carry new warning of life-threatening side effect

The FDA has ordered a wide range of antidepressants to carry new warnings of an unusual but potentially deadly side effect seen most often in the first few weeks of treatment or when a patient increases dosages. The labels of two classes of new-generation medications for depression -- selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) must now notify patients that malignant neuroleptic syndrome has been linked to the use of these drugs.

Among the drug companies ordered to revise their labels to alert patients of the danger were those making Celexa, Cymbalta, Effexor, Lexapro, Paxil, Pexeva, Pristiq, Prozac, Venlafaxine and Zoloft. The orders were dated Feb. 4, but disseminated this morning in a public notice of FDA actions.

In malignant neuroleptic syndrome, patients experience muscle rigidity, extreme variations in body temperature and wild fluctuations of heart rate and blood pressure -- all signs of malfunction in the body's autonomic nervous system, which regulates involuntary body functions. Malignant neuroleptic syndrome has been associated with older antipsychotic medication such as haloperidol, lithium salts and risperidone. But the widespread use of SSRI and SNRI antidepressants has made this syndrome a more common and visible affliction.

With one in 10 Americans taking prescription antidepressants, medicines such as Zoloft, Prozac and Effexor are currently the most commonly prescribed class of drugs in the United States, just ahead of high-blood pressure medicine, according to the Centers for Disease Control. And SSRIs and SNRIs have become by far the most common types of antidepressant dispensed by pharmacies, driving a tripling of prescriptions since 1988.

Malignant neuroleptic syndrome is a rare but extremely dangerous condition that results in death in, by some estimates, 10% to 20% of cases. Until recently, it was so uncommon it was unlikely to be recognized in many emergency departments. But the widespread use of SSRIs and SNRI antidepressants had made this bizarre syndrome a more common affliction seen in emergency departments.

A Food and Drug Administration spokeswoman said this afternoon that she had not been notified of the labeling change and was unaware of what led to it. Watch this space.

-- Melissa Healy

Generic heart drugs are just as good

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.

For more information about the bioequivalency of generic versus brand-name drugs, see this article from Consumer Reports as well as free reports called CR's Best Buy Drugs.

-- Shari Roan

Photo credit: Anne Cusack / Los Angeles Times

These 14 drugs need more study -- and soon, researchers say

Seroquel. Warfarin. Lexapro. Risperdal. Singulair. Wellbutrin. Zoloft. Effexor. Celebrex. Prinivil. Cymbalta. Desyrel. Zyprexa. Procrit.

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.

Off-label prescribing, they know and we know, is rampant. (See When there's little proof a prescription drug will work.) And a recent study pointed out some of the ways in which drug manufacturers encourage doctors to do this. (See Tricks help drug makers sell prescription meds for uses not approved by FDA.)

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).

Credit: Joe Raedle / Getty Images

More U.S. kids being treated for chronic diseases

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.

Credit: Rick Loomis / Los Angeles Times

Maybe patients should be in on those drug talks

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."

That research was published in the October issue of the Journal of the American Geriatrics Society.

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.

-- Tami Dennis

Photo credit: Ken Hively / Los Angeles Times

Tricks help drug makers sell prescription meds for uses not approved by FDA

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. 

-- Melissa Healy

What placebos say about the doctor-patient relationship

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 survey is garnering considerable attention.

From the Chicago Tribune: Mind over body: Half of doctors in U.S. use placebos, survey finds

From the New York Times: Half of doctors routinely prescribe placebos

From the Associated Press: Survey: Half of U.S. doctors use placebo 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....

-- Tami Dennis