In an era where a lack of interest in sex is considered a treatable medical disorder, these are the pros and cons for patients seeking a pharmaceutical fix:
If you give the new female sexual desire drug Addyi (flibanserin) to 12 women, one will experience a modest improvement in her sex life, after factoring out the placebo effect.
But one of out of seven will experience drowsiness.
Give nine men with low libido the testosterone supplement Androgel and one will see increased sexual activity.
But one out of 14 will develop acne and one out of 33 will experience troubling emotional swings, such as impatience or anger.
In short, the drugs won't help most of the people who take them. And, in some cases, they are almost as likely to produce a side effect as a benefit.
Medicine's Secret
"It's the biggest secret in medicine," said , MD, of Yale University School of Medicine, who is one of the physicians who reviews 番茄社区app articles for scientific accuracy. "For the vast majority of the drugs out there, the chance that you as an individual are going to see a benefit is quite small."
There is another secret: Even these numbers are exaggerated because the dangers and benefits are determined in clinical trials, which are highly controlled and often don't reflect real-world experience.
Aggressive efforts by drug companies to turn a series of conditions of everyday life into medical disorders, often with carefully but vaguely worded definitions that capture large segments of the population, can result in more people taking -- and possibly being harmed by -- the drugs.
A 番茄社区app/Milwaukee Journal Sentinel investigation this year examined eight everyday conditions that became part of mainstream medicine over the past 20 years, including pre-diabetes, binge eating disorder, and intermittent explosive disorder.
Those eight conditions alone are purported to affect more than 180 million Americans, or the equivalent of 77% of the adult population.
The conditions are not life-threatening. Treatment benefits are often marginal, and in some cases dangerous.
For instance, women who take Addyi -- a daily medication -- are told to avoid alcohol because the mixture can cause them to pass out from a dramatic drop in blood pressure.
Testosterone supplements for men can increase the risk of blood clots and prostate cancer.
Consider just one measure of harms: reports of negative side effects filed with the FDA once the drugs are approved.
Since 2013, nearly 65,000 reports of serious side effects involving drugs used to treat five of the conditions have been reported to the FDA's database, according to a 番茄社区app/Journal Sentinel analysis. That includes 1,631 deaths.
, a health policy and ethics expert, said many patients would be surprised by the lack of benefit and likely would turn down treatment with drugs that were part of the analysis.
"Even when people take these drugs for weeks or months, the benefits are modest or small, and the harms are nearly of the same size," said Prasad, an assistant professor of medicine at Oregon Health & Science University.
Benefits vs Harms
To examine benefits and harms, Wilson, the Yale researcher, conducted a biostatistic analysis for 番茄社区app and the Milwaukee Journal Sentinel focusing on drugs used to treat lack of interest in sex among women, low testosterone in men, overactive bladder, and adult ADHD.
Wilson started with the number-needed-to-treat (NNT), a cornerstone of clinical decision-making, which is used to calculate benefit. NNT is typically balanced against number-needed-to-harm (NNH).
Vyvanse (lisdexamfetamine) is an amphetamine approved to treat two of the conditions: binge eating disorder and adult ADHD.
The NNT to achieve benefit in adult ADHD symptoms is 2.9, meaning nearly three people have to take the drug before one improves. Its treatment number for a reduction in the number of binge eating days per week is 2.3.
In the case of Vyvanse, the number needed to produce the harmful side effect of insomnia is 5, meaning for every five people who take it, one will get insomnia, after factoring out the placebo effect -- those in the control group who saw improvement simply by taking a sugar pill.
At the same time, Vyvanse and other stimulants carry a high risk of dependence and abuse. They can increase blood pressure and heart rate, as well as the risk of a heart attack or stroke.
Vyvanse has a retail price of $310 for a 30-day supply.
In an email, Clotilde Houze, a spokesperson for Shire, which markets Vyvanse, said the company stands behind the safety and effectiveness of the drug, which has been on the market since 2007. She said Vyvanse is not right for every patient with ADHD or binge eating disorder and that it is critically important that Vyvanse treatment be monitored by a doctor.
Another drug analyzed by Wilson is Toviaz (fesoterodine), which is used to treat overactive bladder. The condition once was known as incontinence, or leakage. But in the late 1990s, doctors with drug company financial ties gave it a new name and helped expand the definition.
For every 3.6 people who use it, one will have a reduction in incontinence, or leakage. For every 5.7 people who use it, one will have reduced urgency.
The drug's side effects include dry mouth (one out of every 3.6 people), and constipation (one out of 25).
It also has a retail price of $365 a month, or $4,300 a year.
Steven Danehy, a spokesman for Pfizer, the drug's maker, said Toviaz's safety and effectiveness has been well-established in clinical trials conducted before and after it got on the market.
"Each product label details accurate information approved by regulatory authorities on the benefits and risks to ensure that both prescribers and patients are fully informed," he said.
There are now are more than a dozen drugs and other treatments on the market aimed at overactive bladder. But experts in the field say the condition is best managed using non-drug approaches known as behavioral therapy, such as bladder training and pelvic muscle exercises.
But , a clinical professor of obstetrics and gynecology at George Washington University School of Medicine, said such an analysis can be misleading when it comes to conditions that rely on patients' self-reports, like low sexual desire or even depression, to say whether a specific treatment worked or did not.
For Addyi, for example, monthly satisfying sexual events are "a very strange metric," he said, as many outside factors can influence it. A husband being out of town, or angry, or uninterested can have a real impact on such a figure, he said. Satisfying sexual events are far "downstream" from feelings of desire.
Even the side effects can be over-represented, he said, as many come in the first few weeks of treatment and disappear over time. If a patient is still on the medication after eight weeks because it is working, he said, side effects have tapered off and the odds of desirable outcomes increase.
"I think we accept that flibanserin (Addyi) has imperfections, all drugs have them," he said. "At the moment, it's the best thing we've got," he said.'
The monthly retail cost of Addyi is $830 -- nearly $10,000 a year for a drug that will help one in 12 women.
Tracy Valorie, a spokesperson for Valeant Pharmaceuticals, which markets Addyi, said clinical trials showed that using Addyi led to a statistically significant increase in sexually satisfying events and an increase in sexual desire.
"The trials also consistently demonstrated an improvement in sexual desire and a reduction in associated distress," she said.
Controlled Trials vs Real World
Researchers say randomized controlled trials, by their nature, present a problem that most patients do not understand, and that doctors do not always consider.
For example, patients in clinical trials are selected to meet certain criteria and then are closely monitored for the duration of the study -- circumstances that don't match real-world clinical care.
What's more, the trials usually are of a much shorter duration than how long a person may actually be on a drug.
"It's Disney World versus the real world," said , a professor of medicine at the University of Toronto who studies drug safety. "The point is that, by design, industry-sponsored (trials) tend to make drugs appear more effective and safer than they are eventually found to be in practice because the (trials) milieu is often an artificial one."
Indeed, some of the clinical trials of the drugs excluded vast numbers of people:
- The trial that tested the effects of Androgel on sexual function in older men excluded those who were at higher risk for prostate cancer and cardiovascular problems and those with severe depression. The minimum age was 65.
- The trial of Vyvanse for adults with ADHD excluded those who were significantly underweight or severely obese; those with other significant mental disorders; those with certain heart conditions; those who abused drugs in the previous six months; women who were pregnant or breast-feeding; and those with high blood pressure.
-
In the Addyi trial, many groups of women were excluded and they also had to be in "a stable, monogamous, heterosexual relationship that is secure and communicative."
The 番茄社区app/Journal Sentinel review of the FDA data found that, since 2013, at least 20 people had serious medical complications attributed to Vyvanse while also being treated for high blood pressure.
A 52-year-old woman, for example, saw an increase in blood pressure and blood cholesterol after taking Vyvanse and Vasotec, a hypertension medicine.
In its trials, Androgel excluded those with depression.
At least 180 people being treated for depression reported problems attributed to Androgel, including a 52-year-old man who, after a "cerebrovascular accident," couldn't speak and had limited use of half his body, the 番茄社区app/Journal Sentinel review found.
The monthly retail cost for Androgel is $550, more than $6,000 a year.
All told, there were more than 12,000 cases where side effects from the drugs used to treat ADHD, binge eating disorder, premenstrual dysphoric disorder, low testosterone, and overactive bladder led to hospitalization.
An additional 1,000 cases were considered life-threatening.
The analysis of side effects includes only those cases that were reported by manufacturers or healthcare professionals. Even then, it was limited to only those cases where the drugs were considered the primary cause of the problem. Cases where they were a contributing factor were not included.
, of the University of Southern California, who champions the 'Slow Medicine' approach to clinical care, said that as a primary care doctor, many of the treatments "don't strike me as a worthwhile trade-off."
"Too often, patients get started on medications and don't experience any benefit, yet the medications are continued," Hochman said. "Or worse, they experience side effects that they do not realize are related to the medication and the net result is more harm than good."