Alarmist Media Soundbites Annoy Pharmacy Student

Let it be known that there are few ideas that cannot be expressed in a more entertaining way by using AP-style headlines.

There's been a lot of talk about how common medication errors or overdoses occur in hospital settings, particularly in children. A good bit of this can be attributed to the recent heparin mix-up involving Dennis Quaid's children. This particular error, fortunately, caused no deaths, unlike some previous errors in Indiana a year or two ago. The Quaids have every right to be upset--and they have every right to campaign to make the issue more visible. Medication errors are serious business, and hospitals should do everything in their power to prevent them from happening.

That said, the issue is being way over-hyped by the media.

According to the first link, one in fifteen children admitted to a hospital--about 7.3%, or 540,000 children across the United States each year--is harmed by a medication error. These are the figures that are being pitched around by the media in multiple places.

But these figures are misleading and alarmist. What a shock! Here's the study they're citing.

Part of the issue is the definition of an adverse drug effect. According to the Washington Post:

More than half of the problems cited involved overdoses or allergic reactions to painkillers.

The "or" in that sentence complicates the issue, but here's a simple statistic. The two biggest classes of pain medication are NSAIDs like ibuprofen and opioids like morphine or codeine.

True opioid allergy is exceedingly rare. In fact, less than 1% of the population is estimated to be allergic to opioids. Likewise, only about 1% of the population is estimated to be allergic to NSAIDs (though NSAIDs may precipitate problems in some patients with asthma).

This means that if the numbers reported are accurate and 11 out of 100 children hospitalized experience an adverse effect, only one of those is truly allergic to the drug in question--and there's nothing that can be done about that, short of avoiding the drug. Unfortunately, patients without a history of an allergic reaction are not going to discover the allergy without being exposed to the drug. This seems largely unavoidable. So what about the other ten kids? If the Post is correct, all of them recieved some kind of overdose.

Let's take a look at the actual study:

Twenty-two percent of all adverse drug events were deemed preventable...ninety-seven percent of the identified adverse drug events resulted in mild, temporary harm. [emphasis mine]

Mild, temporary harm? What kind of harm?

The most common adverse drug events identified were pruritis [itching] and nausea, the most common medication classes causing adverse drug events were opioid analgesics and antibiotics

Huh.

Even patients not truly allergic to opioids may react with what is called a pseudoallergy. Where a true allergic reaction is a result of inappropriate overactivity of the immune system, pseudoallergy reactions are a result of sudden histamine release, causing flushing, itching, sweating, or hives. This is a well-documented side-effect of opioids. Is it totally preventable? Sure--by not giving opioids! Of course, this is why using the lowest effective dose of a drug is always a good idea--unlike true allergies, opioid pseudoallergies are dose-dependent, so higher doses increase the probability of a reaction. The good news is that antihistamines can be used to reverse the majority of these symptoms.

Antibiotics, conversely, wipe out friendly bacteria in the digestive tract, which is commonly accepted to be a cause of antibiotic-induced nausea and diarrhea. Other factors include the direct effect of the drug on the digestive tract, but decimating gut flora isn't doing anyone any favors. Some antibiotics are worse than others, but nausea is extremely common with antibiotic therapy--and, again, there's basically nothing that can be done about it.

At this point, the question should not be "how many children suffer adverse drug reactions?" This statistic is too simple to have any predictive power, especially when including mild or easily reversed side-effects that are extremely common (and predictable) or associated with the use of particular drugs. We should be more concerned with medication errors than minor adverse reactions. A patient getting a thousand-fold overdose of heparin is serious. A child getting a stomachache as a side-effect of antibiotics is not. So let's turn the statistics around--only 3% of adverse reactions were serious. A full 97% were mild and/or reversible. That sounds like good news to me!

I've come to expect that the media is going to spin everything they report to make it sound infinitely worse than it actually is--bad news sells. But the last thing we need is parents panicking about medication errors and being afraid to take their children to the hospital. Vigilance on the part of both parents and healthcare providers is good. Panic--and subsequent distrust--is not. Distrust of medical professionals is one of the main factors that turns patients to supporting woo.

And since I can't resist plugging my own profession, let's not forget that well-trained pharmacists are crucial players in reducing medication errors.

Please Understand Me--and Shut Up

This article has been making the rounds, in one form or another, for the past couple days. Naturally, most people get the beautifully condensed MSNBC version.

Let's go to the article for a quote:

“Patients aren’t sure how ill they really are, and neither is the clinician — sometimes dismissing their symptoms, sometimes overestimating them,” said Dr. Alexander Niculescu, III, a psychiatrist at the Indiana University School of Medicine in Indianapolis, who led the research published Tuesday by the journal Molecular Psychiatry. “Having an objective test for disease state, disease severity, and especially to measure response to treatment, would be a big step forward.”

Absolutely right. Granted, the test that's being discussed isn't actually anywhere near 100% accurate. Rather, it's about 60-70% at best. Plenty of room for false negatives--or false positives, though it would be irresponsible to diagnose an illness based on a single blood test with 60% accuracy.

The problem I have is that instead of cheering that we might finally have a good biomarker for a devastating mental illness, everyone is whining about ethical concerns. Let's think about this. An objective measure of bipolar disorder would not only allow for more accurate diagnosis, but it would give us better treatment benchmarks. It's easy to tell if a drug for hypertension is working; does it lower the patient's blood pressure by a significant amount when compared to a placebo? Evaluating the efficacy of treatments for bipolar disorder essentially comes down to asking patients "so how do you feel?" and hoping they're being totally honest. Is it any wonder why doing research regarding new treatments for the illness is so hard?

But no, nobody seems to be saying "this is amazing!" Instead, they're all complaining about how people with bipolar disorder are going to get discriminated against in hiring or rounded up and thrown into camps.

Let's start from the beginning. In the US, your health information is private. It is protected by federal law. Employers are not allowed to ask questions about any illnesses you may have, nor are health care providers allowed to disclose any information about your health to employers (or anyone else), including what medications you may be taking.

You might be wondering about urine screening for drug use when hiring new employees. Yes, the practice is legal, but laws vary from state to state. You could argue that this provides a foothold for pre-hire blood testing--except for the fact that most of the people whining about the blood testing procedure are saying that it's going to go beyond hiring. They're suggesting that landlords might blood test people before letting them sign leases, or banks might want people to submit blood before they'll hand out loans. You'll notice that none of these entities can legally conduct urine tests. Under current law, even if an employer were able to get a blood sample and test you for illness X or Y, you could sue them if they refused to hire you based on the results of the test--and you'd win.

Being mentally ill is a disability. Discriminating against people with disabilities in the workplace is illegal. It doesn't matter the disability is patently obvious (a person in a wheelchair) or totally invisible (bipolar disorder). As long as you're qualified for the job, that's all that matters--unless the employer wants to risk a huge lawsuit. This isn't likely to change any time soon. The ACLU would throw a fit, for starters.

The ability to definitively diagnose mental illnesses on the basis of a blood test is 99.9% good. Unless all the work of anti-discrimination proponents is suddenly reversed tomorrow, there's no reason to assume that this is going to create a problem. The only reason to think otherwise if you've watched Gattaca in the past week and it's cranked your paranoia setting up to 11.

Some Depressing News

A friend of mine sent me a link to an article yesterday, thinking it might be useful blog fodder. However, I didn't have the actual study in front of me--but thanks to The Frontal Cortex, now I do. If you ask me, Jonah has hit the nail on the head when he pointed out the biggest weakness in this study--all of the trials involved were, at most, eight weeks long.

For those unaware, this study was a meta-analysis. A meta-analysis involves doing no new research trials; instead, the results of a large number of old trials are compiled and analyzed using statistical methods. Results from fourty-seven trials were compiled for the meta-analysis; thirty-three of those were only six weeks long. Short trials are known to be less valuable in testing the efficacy of antidepressants; the longer the studies run, the farther apart the placebo and treatment groups usually get. For example, this study demonstrated that if you give patients escitalopram (an SSRI) for sixteen weeks and then switch half of them to placebo without them knowing about it, the placebo group will do significantly worse in terms of probability of relapse into depression.

It's interesting to see placebos compared to antidepressants. According to the PLoS study, placebos had about 80% of the therapeutic activity of SSRIs in the short term--that is, they were about "80% as good" in the six-to-eight week studies they analyzed. This is not actually all that surprising. For many depressed patients--or those with mental illness in general--the placebo effect is huge. Sometimes, the pro-active nature of seeking treatment is enough to bring depressed patients out of a slump, if only temporarily. Patients who feel as though they're finally doing something to fix themselves are likely to experience an emotional boost. And let's face it--not everyone on SSRIs is experiencing symptoms because they have low serotonin, one of the major neurotransmitters behind depression. Other diseases can cause patients to present with depression-like symptoms if they aren't properly ruled out before initiating treatment. That isn't likely the case with this study; before patients can participate in a drug trial for a new antidepressant, other causes of depressed mood must be ruled out.

The problem is that the mainstream media tends to get ahold of things like this and run amok making claims that "a new study proves antidepressants don't work," which is both incorrect and irresponsible. It's incorrect because all this meta-analysis (like many individual trials on the subject) suggests is that SSRIs must be taken long-term to have benefit, and that short-term reactions are largely attributable to placebo effects. There's a big difference between "antidepressants don't work" and "antidepressants have to be taken for months to see major improvement." The rate of relapse for patients switched abruptly to placebo is higher, even if the authors of the meta-analysis aren't convinced that antidepressants create "enough" improvement in the short term to be clinically significant.

To continue, this style of reporting is irresponsible because the everyman is a lot more likely to read a news article with a catchy headline than he is to seek out the original study and pore over the methods of the researchers, either because he has no idea where to look or because he hasn't taken enough statistics to have any idea what the hell these sciencey people are talking about. Which means that the everyman on antidepressants is going to take the words of some reporter at face value--perhaps higher than the words of his doctor, if enough reporters are all saying the same thing--and they're going to throw away their meds, decrying them as a useless waste of money. I've seen this happen before in clinical practice; many mentally ill patients take meds for a while, decide they don't need them any more (either because they "aren't working" or they "feel better"), pitch them, relapse, and start the whole vicious cycle over again.

Is there a tendency to "cover up" the results of clinical trials with negative outcomes? Sure. That's publication bias. But antidepressants aren't the only medications for which reporting bias is an issue--and just because some negative studies don't get published doesn't mean that the positive ones are automatically worthless. The negative studies don't necessarily get swept under the rug as part of some "grand pharma conspiracy." One negative study doesn't prove a drug is ineffective any more than one positive study proves that it is. If the overwhelming trend is positive or negative, then we can make judgments. But even trends can be misleading; you can connect the dots many different ways, depending on where the dots are and what kind of analysis you're doing. And that's one of the risks of meta-analysis studies. There's just as much room for spin there as anywhere else.

So don't throw out the Prozac. There's no such thing as an "official study" that proclaims antidepressants to be therapeutically useless. And any journalist who tells you otherwise is being sucked in by spin just as badly as the drug reps who are trying to push the products--they're just being spun in the opposite direction.