Wednesday, November 7, 2007

Irrational Exuberance

Alan Greenspan, former Federal Reserve Chairman, used the phrase "irrational exuberance" to refer to a kind of overenthusiasm for the market during an economic boom; notably, he only used it once, and there was a worldwide plummet in stock prices following that speech, but I think it's an appropriate term to refer to something that I've thought about quite a bit.

I love the drug companies. I really do. We've come a long way in the past 50 years in terms of effective pharmacological treatments for illnesses across a broad spectrum because of dedicated scientists and researchers working to develop the next blockbuster drug. These companies really are doing the public a great service. Just to throw out an example, cholesterol-lowering statin drugs are estimated to have saved 83,000 lives in the last 20 years. Most people nowadays die of heart disease or cancer instead of typhoid and diphtheria, and the death rate due to coronary artery disease in the U.S. has dropped 25% since 1994.

The drug companies are providing a valuable service. And like any other service, we have to pay for it. I don't think that's wrong, really, because pharmaceutical research companies have to make money too. It's not a crime to want to make money, especially if you've invented or discovered something useful, whether it's a rubber O-ring that holds together mechanical parts better than existing joint fasteners or a tiny carbon-based compound that relieves migraines. Of course pharma is "in it for the money." They have to eat, too. If I didn't get paid to do my job, I'd quit. I sincerely doubt you can find anyone who's willing to work for free full-time, no matter what field we're talking about.

What I don't like is when they're being dishonest about it.

I don't mean dishonesty that they're trying to hide. I can't do anything if Lilly or Glaxo or Roche or whoever is committing tax fraud or exploiting weird financial loopholes to widen their profit margins, and while I do care about it, it's outside my area of expertise. I'll leaave that to the lawyers and the accountants to scrutinize. No, what drives me nuts is when pharma is talking about their latest product like it's the greatest invention since the wheel when in fact it's about as useful as most of the gadgets you see on late-night infomercials.

Usually this sort of thing comes up when a company is about to lose their patent on a drug, at which point they attempt to extend the life of their branded drug entity by rolling out products with new release mechanisms (Coreg vs. Coreg CR, for example) or "follow-on" drugs that are actually derivatives of the original drug molecule. The drug Celexa is a great example--Celexa's generic name is "citalopram." It's an antidepressant. Like many drugs, its structure is complex enough that the "mirror image" of that structure is not the same compound. Essentially, at least one set of chemical functional groups is "reversed" in its rotational arrangement in three-dimensional space. This is really kind of complicated, so here's a way better link to explain what I'm takling about:

Someone else can teach you organic chemistry.

Usually, the left-rotating and right-rotating compounds get designated as L (levo, or left) or D (dextro, or right) enantiomers of a substance. Sometimes the letter S is used, for the Latin word for left ("sinister").

Anyway, Celexa as a drug is a 50/50 mixture of both S-citalopram and R-citalopram. Some pharmaceutical chemists playing around in the lab figured out that the S-citalopram is the part that's doing the real work, so some time later they decided to develop a way to just synthesize the pure S-form (which is harder, incidentally) and marketed the new drug as "escitalopram." Say it aloud. Cute name, no?

Escitalopram is available in dosages that are half of what Celexa comes in--Celexa tablets come 10, 20, and 40 mg. Escitalopram tablets are 5, 10, and 20 mg. The theory is that by getting rid of that R-form and dosing the patient with only the pure S-form you end up with fewer side-effects or better efficacy. Sometimes that's true. Sometimes it isn't.

Escitalopram, for the curious, is the popular antidepressant Lexapro. By purifying the S-form from what chemists call the "racemic mixture" (the 50/50 mix of both forms), Forest Pharmaceuticals gets to call what they've cooked up a "new drug" and has an exclusive patent on their creation for about the next 20 years. Joy! Studies do suggest that Lexapro works a little better than Celexa, and that it's slightly better tolerated, but it's also pricier because it's currently brand-name-only: $80.31 for 30 tablets of the 10 mg strength vs $39.99 for the roughly equivalent generic citalopram 20 mg tablets. It might be worth the difference. It might not. The drug companies really want you to think it is, and they tell doctors that Lexapro is way, way better than Celexa, because it's about twice as expensive. They tell pharmacists that it's better, too, and occasionally bother to produce the graphs that prove it. And pharma is really big on phrases like "not equivalent" when they're comparing their new drugs or dosage forms to old drugs or dosage forms. They insist very strongly that the drugs are not the same, and woe to any pharmacist who dares suggest the older drug is just as good as the new one. Some patients will ultimately try both and like one or the other better. That's cool for them.

I don't appreciate pharma sending a rep into our store to talk about how Lexapro is so much better than generic citalopram that any effort to inform patients that yes, there are generic antidepressants that are cheaper (if you would like to save money) is tantamount to blasphemy. How dare you compare their superior product to the clearly inferior generic products on the market, even those that their company also makes! Their newest branded product is a bargain at ten times the price, even if it's only 5% better than the generic!

The Forest Pharmaceuticals rep who came into our store gave us the schpiel about Lexapro being awesome, but that bothered me a lot less than his pitch for Namenda. He vehemently expressed his opinion that Namenda was the coolest thing in the entire world because "the evidence is so strong for it. I always ask all the doctors who I talk to if they would want the opportunity to add Namenda to their drug regimen if they had Alzheimer's, and they always say, 'well, yes, I would.'"

Background. Namenda is a drug to treat Alzheimer's disease. Wait, I take that back. It's a drug to prevent Alzheimer's disease from getting worse. Wait, no, that's not really true either. It's a drug to make Alzheimer's disease get worse more slowly. That's about right.

The other big drug on the market for Alzheimer's management is called Aricept. You start a patient on Aricept as soon as you suspect they have Alzheimer's, because it works best in mild to moderate cases, but if you don't catch it for some reason, it can work in more severe cases. One study showed an improvement or stabilization of cognitive function in 63% of patients taking it (versus 39% on placebo, not terrible). It's worth a shot to put a patient on Aricept because it's about the best we can do right now.

However, the rep was trying to convince us that Aricept plus Namenda was vastly superior to Aricept alone, saying that there was a whole wealth of evidence available.

The information I've found suggests that the gains on cognitive function scales for treatment with Namenda are roughly a 5% absolute increase. OH MAN. We're still looking at only marginal improvement no matter how we approach drug therapy for Alzheimer's disease. This is totally worth spending an extra $1600 in prescription drug costs a year, considering that Aricept costs about $1700 a year by itself, excluding medical insurance. Behold the power of sarcasm.

Don't come to me and tell me how awesome your drug is unless you're prepared to prove it. And if your drug really isn't all that awesome, quit telling me how awesome it is. The FDA may have approved it because you demonstrated it was better than placebo with studies that showed statististical significance, but don't hype it up when we're talking about 5% absolute gains. I realize that it's the job of people who do marketing to get way more excited about their products than is rational, but this is medicine. That just won't do here.


Mike said...

Great post. One little quibble: D(+) and L(-) (for dextrorotary and levorotary) are designations that refer to the rotation of polarized light when passed through an optically active sample. R and S (for rectus and sinister) refer to the molecular structure of a chiral center and have no direct relation to D and L designations. For example, a chiral molecule could be both "D(+)" in optical activity and "S" in configuration. Nice blog so far, keep up the good work!

Abel PharmBoy said...

I'm assuming this is your first post so congratulations and welcome to the pharm blogosphere. I linked to you with this announcement.

By the way, I'd like to put up a "Pharmacy" category on my blogroll sidebar. If you have any experience with good blogs written by pharmacists or pharmacy students, please suggest them in my comment thread.

The Lil'est Naturist said...

I think I'm falling in love with your blog. =D