Most of our common cold medicines don’t work

We still don’t have a cure for the common cold. In your local pharmacy, though, you can find many shelves filled with products that claim to treat the symptoms.

Well, it turns out that one of the most widely used ingredients, long believed to be effective at treating congestion, doesn’t work at all. The ingredient, phenylephrine, has been in use for decades, and it’s in many common cold medicines that are taken by millions of people each year, including Nyquil Severe, Sudafed PE, Robitussin CF, Tylenol Cold & Flu and others.

It turns out that phenylephrine was never properly studied for effectiveness. How can this be? It’s FDA approved, which usually means it has to be safe and effective, right? Not exactly, as I explain below.

As for phenylephrine: well, the studies have finally been done, and last month an FDA panel unanimously concluded, after reviewing the results, that phenylephrine is “useless and no better than a placebo.” It probably won’t cause you any harm, but it won’t have any effect on your stuffy nose.

To understand how this happened—and why it might be true of many other FDA-approved remedies that you can buy at the pharmacy—you have to know about how the FDA approval process has changed over the years. Pharmacists Randy Hatton and Leslie Hendeles, who worked for years trying to get phenylephrine properly reviewed, explained in a recent New York Times editorial that when the FDA was originally created, way back in 1938, it was only required to ensure that drugs were safe.

At the time, that was tremendous progress. Prior to 1938, drug manufacturers could claim pretty much whatever they wanted to.

But it wasn’t under 24 years later, in 1962, that Congress required the FDA to show that drugs were also effective. Therefore the thousands of drugs approved prior to 1962 were mostly safe, but they might not actually treat the disease they were intended to treat. After 1962, the FDA created a process to check those previously approved drugs, but they’ve never had enough staff or funding to check most of them. So phenylephrine was never properly reviewed, until now.

What’s next for phenylephrine? The FDA might ban it from the market, but that will take time, and it might not happen, because the FDA doesn’t have to follow the advice of its panels, although it usually does. Meanwhile, you can still buy cold remedies with phenylephrine, and they still claim to treat congestion.

And don’t even get me started on other treatments that are not only ineffective but that aren’t even subject to review by the FDA, such as homeopathic remedies. These include Zicam, which claims in large print on the front of its packaging that it “shortens colds.” It doesn’t, and Zicam’s manufacturer doesn’t even have to prove it, because it’s homeopathic. If you zoom way in one of the labels on the Zicam website, you’ll find the disclaimer that “Claims [are] based on traditional homeopathic practice, not medical evidence. Not FDA evaluated.” On some of the packages, I couldn’t even find the small print.

(Aside: Congress protected homeopathic preparations from FDA scrutiny way back in 1938, thanks to a homeopath who was also a U.S. Senator, and who helped write the original FDA legislation.)

I wrote about Zicam and other ineffective cold remedies in 2014 (”The Top Five Cold Remedies that Do Not Work”), and that advice still holds. Now we can add another one to the list.

We simply don’t have any drugs that work particularly well for the common cold, despite the many claims you can find online and on the labels of so-called cold remedies. The best thing you can do is just drink warm liquids such as tea or lemon-infused water, stay home and get plenty of rest.

Sniffle. It's allergy season again. Do those shots work?

Ah, spring is in the air. The flowers are blooming and the trees are bursting into leaf.

For many of us, this time of year means one thing: allergies. The price of going outside for any length of time is sneezing and itchy eyes that last for many hours, even after we return indoors. Rather than going out and enjoying the warm air and colorful vegetation, we close the doors and windows and stock up on antihistamines and eye drops. Studies show that 20–40% of people in the U.S. have allergies.

Your local pharmacy has shelf after shelf of allergy treatments, ranging from mildly effective (Zyrtec and its equivalents) to laughably ineffective (anything homeopathic). But even the best pills have side effects, and they only serve to suppress the symptoms. As one study put it:

"Patients struggle to alleviate their misery, frequently self-adjusting their treatment regimen of over-the-counter and prescription medications because of lack of efficacy, deterioration of efficacy, lack of 24-hour relief, and bothersome side effects."

Isn't there a way to tell your body to just stop it already? After all, pollen is not a pathogen. Our misery is caused by our own immune system's over-reaction: it ramps up in response to the foreign particles (pollen) in our eyes and airways and creates a histamine reaction, which is simply not necessary.

None of the over-the-counter pills prevent this reaction, but they can dampen it–hence the term "antihistamine." However, what if there were a way to tell your body to simply chill out and ignore the pollen?

Well, maybe. You can get allergy shots. This is a surprisingly simple procedure: your doctor takes a small, diluted amount of the allergen (pollen, cat dander, etc.) and injects it into your arm. Over the course of many months, your doctor will very gradually increase the amount being injected. You have to go for the shots every week, and continue them for several years.

The question is, do they work? The answer is a qualified yes.

NIH and the Agency for Healthcare Research and Quality (AHRQ) have put together a long explainer of the evidence for and against allergy shots, which you can find at PubMed Health. The NIH study looked at 74 clinical studies of allergy shots. To save you some time, I'll cut to the chase: the evidence is quite good that shots work. Or, as the AHRQ study put it,

"we found high grade evidence that subcutaneous immunotherapy reduces rhinitis/rhinoconjunctivitis symptoms."

This might seem like pseudoscience, but it's not: what's happening is that your immune system is being de-sensitized to the allergen. It doesn't work for everyone, but in many people, this gradual de-sensitization trains their immune system not to react so badly. It's not necessarily permanent, either: after stopping the shots, allergies might re-appear after a few years.

So if you're looking out your window at the beautiful spring weather with a box of tissues by your side, maybe you have a way out. Talk to your doctor or visit the AAAAI site to find an allergy specialist. Don't expect miracles or a quick fix, but allergy shots are the best we've got, for now.

Legalized pot is already saving $165 million per year in medical costs

This news will give anti-marijuana crusaders fits.

A new study in the journal Health Affairs looked in great detail at prescription drug usage in U.S. states that have legalized medical marijuana. Researchers Ashley Bradford and David Bradford collected Medicare data for the period 2010-2013 to answer two questions: are patients choosing marijuana instead of prescription drugs for conditions that marijuana might treat, and what has been the overall effect on Medicare spending?

The bottom line: in 2013 alone, when 17 states had legalized medical marijuana, Medicare saved over $165 million. A simple extrapolation suggests that if all states legalize marijuana, annual savings could be triple that amount, $500 million. (Obviously this extrapolation is over-simplified: it depends on the actual populations of those 17 states, and it only considers Medicare. Commercial healthcare plans may save far more.)

The authors, a father-daughter team at the University of Georgia, looked at over 87 million prescriptions from the Medicare Part D database, focusing only on conditions where marijuana "might serve as an alternative treatment." These fall into nine specific categories for which at least some evidence suggests marijuana could help: anxiety, depression, glaucoma, nausea, pain, psychosis, seizures, sleep disorders and spasticity. The best clinical evidence of marijuana's benefits, according to the study, is for pain, for which the clinical evidence is "moderate"; most of the other conditions have evidence rated as low or very low.

Prescriptions fell for 8 out of 9 categories, with the biggest drop occurring for pain medication: in states with medical marijuana laws, physicians gave out 3645 fewer pain prescriptions per doctor, a difference that is highly statistically significant. Or, in raw numbers, the annual number of daily doses (in 2010-2013) per doctor in states without medical marijuana laws was 31,810. In states with medical marijuana, the number dropped to 28,165. That's an 11.5% drop. Depression and seizures both showed very significant reductions in prescriptions as well.

Prescriptions rose for only one condition: glaucoma. This too was expected–as the article explains,

"Clinical evidence is very strong that while marijuana sharply reduces intraocular pressure, the effect lasts only about an hour. As a result, new patients who seek glaucoma treatment after learning about the potential benefits of marijuana are likely to receive a prescription for an FDA-approved drug."

In an interview posted on the University of Georgia website, study co-author David Bradford states that they also wanted to know if medical marijuana laws were just a backdoor way to allow recreational marijuana use, or if people were really using it as medicine. He continues:

"What our evidence is suggesting is that ... there is a significant amount of actual clinical use at work here."

As of today, 24 states have medical marijuana laws on the books. This new study suggests that legalizing marijuana in all states would save hundreds of millions of dollars in Medicare costs, and even more money for people not covered by Medicare–not to mention the savings from no longer wasting law enforcement resources prosecuting marijuana use.

Opponents of legalization have argued since the 1930's that marijuana is a "gateway drug" that will lead to more serious drug abuse and that it increases criminal behavior, without (as Bradford and Bradford point out) any good evidence proving these links. This new study now provides a strong financial argument for legalization: legalizing marijuana, at least for medical use, will yield substantial savings for our health care system.

Get your wolfsbane here! Cures headaches, only $16 a bottle

Homeopathic drugs contain some pretty strange ingredients. These drugs (or perhaps I should call them potions) come in ordinary-looking packages, apparently designed to look just like real medicine, but they are not. Inside the bottles are concoctions of a wide variety of plant extracts and other substances, almost none of them effective for what’s written on the package.

This week I was browing the headache remedies at CVS, and I encountered a treatment I hadn’t seen before: Nova Headache Complex. It’s an expensive homeopathic remedy, advertised at $16.29 for a 50-ml bottle.

Because homeopaths and their treaments are unregulated, Nova can sell this stuff without having to prove that it has any effect at all on headaches. We can thank Congress for that: ever since 1938, when a homeopathic member of Congress passed the first law protecting them, homeopathic manufacturers have been allowed to forgo any testing to show that their products are safe and effective. And who decides what is homeopathic? The homeopaths themselves.

So: what does Nova’s Headache Complex contain? According to the package, it contains Aconitum Napellus 12X, Bryonia 12X, Cactus Grandiflorus 4X, Chelidonium Majus 6X, Cimicifuga Racemosa 6X, Sanguinaria Canadensis 6X, Spigelis Anthelmia 6X, Thuja Occidentalis 6X. Let's look at just the first of these.

Wolfsbane flowers

Aconitum napellus is a lovely flowering plant, commonly known as monk’s hood or wolfsbane. If that sounds ominous, it should: wolfsbane contains several highly poisonous compounds. It's listed at #3 in the top 10 deadliest plants at Zitbits, which explains:

"When ingested, an intense burning feeling in the limbs and abdomen is immediately felt. In large doses, death can occur in as little as 2-6 hours. Only 20ml of pseudaconitine is needed to kill an adult human. Its name comes the mythology that it was thought to keep away werewolves, hence ‘wolfsbane’."

Wolfsbane has been used as a poison for thousands of years, going back to Roman times. Many young readers will remember it as the main ingredient in a deadly potion in the Harry Potter books. Coincidentally, exactly one year ago, a gardener in England died after accidentally brushing against some wolfsbane flowers.

Yikes! How can they sell this stuff? Well, luckily for consumers, the 12X refers to an extreme dilution, in this instance equal to 10 raised to the 12th power, or 1 part in 1 trillion. The only reason people don’t die when they take Nova's Headache Complex is that there’s essentially no wolfsbane in it.

Fortunately, most homeopathic “drugs” don’t contain any measurable amount of their active ingredients. That’s because homeopaths think that the more you dilute a substance–even to the point where not a single molecule remains–the more potent it is. This laughably foolish notion flies in the face of modern chemistry, biology, and physics, but homeopaths believe it anyway.

What about the other ingredients? All of them are plant extracts, several of them also poisonous (including black cohosh and bloodroot). To avoid extending this discussion for many more pages, suffice it to say that none of these plants have been shown scientifically to cure headaches.

Nova Headache Complex does contain one real ingredient: 20% alcohol. That’s quite a lot, much stronger than beer or wine. Slate.com's Yvette d'Entremont demonstrated on YouTube how one can easily get drunk from a few bottles of these homeopathic products. (She used CVS's homeopathic constipation cure, which fortunately has no effect at all on constipation.) This revelation prompted NBC4 in Los Angeles to investigate why CVS was selling alcohol to minors.

Back to our headache "cure": fortunately, over-the-counter medicines such as ibuprofen, aspirin, and acetaminophen work very well for most people. If none of these work for you, drinking an alcohol solution laced with wolfsbane (or, to be more accurate, laced with nothing) won’t help either.

The FDA is currently considering whether or not to modernize its regulation of homeopathic remedies. They’ve held a hearing and solicited public comments. Interesting, the Federal Trade Commission weighed in, arguing that the FDA's current lax rules “may harm consumers and create confusion for advertisers.” I’m skeptical that the FDA will step in any time soon, but one can always hope.

Meanwhile, CVS will sell you wolfsbane for headache pain, but I hope that none of the bottles contain the deadly poisons listed on the label. If nothing else, at least you get a shot of overpriced alcohol.

The first therapeutic cancer vaccine

Time for some good news. This past week, the FDA approved the first-ever vaccine to treat cancer. The treatment is called Provenge, developed by a small company named Dendreon , and it’s designed for advanced prostate cancer. The idea of developing a vaccine to treat cancer has been around for a long time, but never before has a treatment made it all the way to the clinic. This is very good news, especially if it heralds many more new vaccine-like cancer treatments.

So what is Provenge? Unlike most vaccines, it’s not a simple shot. A typical vaccine contains some form of the infectious agent, usually a virus or a bacterium, which we administer as a shot (or a jab, as our friends in the UK put it). The virus is usually either dead or modified so that it cannot cause disease, but enough of it remains to “train” your immune system. The immune system reacts to the dead virus and, though the amazing mechanism of acquired immunity, is then primed to attack and eliminate a live virus (or bacterium) if it ever shows up again.

A cancer vaccine is not nearly so simple. Unfortunately, we can't just grind up a bit of cancerous tissue, treat it somehow, and then inject it. The reason this new treatment is called a vaccine is that, like conventional vaccines, it trains a person’s immune system to recognize and attack the unwanted invaders – in this case, the cancerous cells. But this presents a big problem, because cancer cells are the body’s own cells. How do we get the immune system to attack them without triggering a much broader, possibly damaging, autoimmune response? As Bruce Goldman explained in a 2002 article, the trick is to find some feature on the surface of cancer cells that marks them as abnormal, and then to get the immune system to target that feature (or antigen).

Luckily, because cancer cells have gone haywire, they tend to have lots of abnormal surface features. But every cancer tends to be a little bit different, which means that these antigens are different in each patient. That means that the vaccine has to be customized for each patient, an exquisitely difficult process. Cancer vaccines use another cell type, called dendritic cells, to create a vaccine that is customized for each patient: first a bit of the patient’s tumor has be collected, and then grown with dendritic cells, and then re-injected, which alerts the immune system to attack just the tumor cells. This is the process used in Provenge.

(Note that Provenge is the first therapeutic vaccine because it is used to treat cancer. There is already a preventive cancer vaccine available: Gardasil, which prevents some types of cervical cancer. But that’s another topic.)

Three years ago, the FDA rejected Dendreon’s first application, asking for more evidence that it worked. The company then conducted a new placebo-controlled, double-blind trial and found that Provenge (sipuleucel-T) extended patients' median survival time by 4.1 months. That might not sound like much, but for men with advanced prostate cancer, it’s better than anything else available. And this is only the additional survival time. Five years ago, Dendreon reported on an earlier study in which “34 percent of patients receiving Provenge were alive at 36 months compared to 11 percent of patients receiving placebo.” In that earlier study, median survival time increased by 4.5 months, essentially the same result as the newer study.

One disappointing part of the recent news is the price: Dendreon announced that it will charge $93,000 per patient. That’s an awful lot of money, and it’s not clear yet if insurance will cover this. No doubt desperate patients will be glad to pay for the few extra months of life. In fact, Dendreon said that its price is based on the assumption that people will pay $23,000 per extra month of life, based on the cost of other cancer drugs. We can only hope the price will drop dramatically as the company improves its manufacturing process, but (unfortunately) lower production costs don’t always get passed on to patients.

These are not miraculous results: Provenge is not a cure. And unlike conventional vaccines, it doesn’t prevent the disease; instead, it treats people who are already sick. But it’s a different type of treatment, and we can be optimistic that this opens the door for many improvements in cancer vaccines, not just for prostate cancer but for many other types of cancer. Trials are already under way for several other types of cancer, and the future looks very encouraging.

Pfizer wants you to make a New Year’s resolution

“80% of you will fail to quit smoking with Chantix. “ That’s what the ad should say, but it doesn’t. Instead, it shows a smiling woman who “quit smoking with Chantix and support in June ’07” and it promises “with Chantix you can smoke during the first week of treatment.” Nowhere does it say how likely you are to quit smoking.

This is from a very large, full-page ad that’s been running for weeks, almost every day, in the Washington Post and other newspapers. The top 1/3 of the page is the “sell,” and the rest of the page contains the required safety information, which tells you some of the problems, including hostility, depression, suicidal thoughts or actions, and nausea. Naturally, the top of the page is in a larger font with a colorful picture.

Why is Pfizer (Chantix’s manufacturer) running these ads now? Well, quitting smoking is a very popular New Year’s resolution. It’s on many top-10 lists, even one from the U.S. government. Pfizer is trying to grab smokers’ attention now, so they’ll ask their doctors for a prescription, which I have no doubt they’ll get. These direct-to-consumer ads work, big time, and the drug makers know it. The U.S. should never have allowed drug makers to advertise directly to consumers – and Congress should re-institute laws prohibiting these ads.

Crestor gets an undeserved boost from the FDA

The FDA planted a big, wet sloppy kiss on AstraZeneca this week. An FDA scientist told reporters that the benefits of Crestor, a cholesterol-lowering drug, outweighed the risks even for otherwise healthy people. Essentially, millions of healthy people with normal cholesterol levels could find themselves taking Crestor, if they listen to this anonymous FDA scientist and to Crestor’s manufacturer, AstraZeneca. This new recommendation was widely reported on Friday, appearing in the Wall St. Journal, in a widely carried AP report, and in a more skeptical Reuters report.

The new report isn’t based on anything new, though. It’s based on a study published a year ago – a seriously flawed study that I dissected at length on this blog in November 2008. The FDA took a year to review this study and then said yep, we agree. I should mention that the 2008 study has one condition before recommending Crestor: that the patients should have elevated levels of C-reactive protein (CRP). I described in earlier blog post the problems with this recommendation – including the fact that they study’s leader has a patent on the CRP diagnostic test.

Does it matter that, as I explained a year ago, the study was funded by AstraZeneca? How about the fact that this huge study found only a tiny benefit? That’s right: the benefit is so small that you’d have to treat 95 patients for 2 years in order to prevent one heart attack. As I wrote last year, and as others have pointed out, when the number needed (NN) to treat is over 50, the result is probably just statistical noise. Or to put it another way, if you take Crestor for 2 years, you have about a 1% chance of getting any benefit. Compare that to, say, taking vitamin C to treat scurvy, where the NN is about 1. With any decent drug, if you take it, you should have a very high likelihood of benefit.

We know who’s going to benefit here: AstraZeneca. Does it matter to them that there is a significantly higher risk of diabetes in people who take Crestor? There was also a higher number of deaths in the placebo group caused by gastrointestinal disorders, but the FDA dismissed this number because it didn’t reach statistical significance. (Kudos to the WSJ and Reuters reporters for highlighting these problems.) And no one besides me (see my Nov 2008 blog post) seems to have noticed some of the other problems with the study, such as the fact that the placebo group contained an excess in the number of patients with conditions that raise the risk of heart disease.

Does it matter that, as the FDA reported in 2005, “Rhabdomyolysis (serious muscle damage) has been reported in patients taking Crestor as well as other statin drugs.” Or that, as the same report said, “Kidney failure of various types has also been reported in patients treated with Crestor as well as other statins”?

So who the heck are these FDA scientists? After considerable searching, I found the lengthy FDA report here. It’s a “briefing document” for a FDA advisory committee that will meet on Dec. 15. It basically reviews the study in great detail and simply repeats the study results. What became clear to me once I downloaded the document, though, was that it was written by AstraZeneca! [Note: thanks to the first commenter on this blog, I also found the separate FDA-sponsored document - see comments.]

The reports from the AP, Reuters, and the WSJ I cited above mention an anonymous FDA reviewer, but apparently this “reviewer” did not want to be named on the record. It's too bad none of the reporters revealed the name of this anonymous FDA scientist, but the roster of the FDA panel reviewing Crestor is here.

It’s a shame that the FDA’s own scientists can’t take a more critical look at the evidence. Look for AstraZeneca stock to go up next week. Let me close with a video from Stephen Colbert, who had a great skeptical spoof of this last year on his show. Skip forward to about the 2-minute mark in this video to see the Crestor segment.

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As Stephen says in the video, "this is a great breakthrough in the battle to find things to prescribe to people who don't need them".

Nice.