Atypical Antipsychotics for the Elderly: A Booming Business

A recent report in the St. Petersburg Times has indicated that between 20-26% of atypical antipsychotic prescriptions are for elderly people. The drugs are typically given in order to help calm patients. This is interesting because the data supporting their efficacy is very weak (1, 2, 3). While the article in the Times is interesting and discusses the problems with the drugs in terms of side effects, it, along with other media coverage with which I am familiar, is missing a major point: Atypical antipsychotics show minimal effects over the benefit given by a placebo. They are also linked to an increased risk of death. So you are increasing the odds of your patients dying, but you are, according to clinical trial research, providing minimal clinical benefit.

Here's a shocking snippet from the article:

Testifying at a congressional hearing, Dr. David Graham, a prominent FDA drug safety expert, was asked if he had issues with any medications already on the market.

"I would pay careful attention to antipsychotic medications. ... The problem with these drugs are that we know that they are being used extensively off-label in nursing homes to sedate elderly patients with dementia and other types of disorders. ...

"But the fact is, is that it increases mortality perhaps by 100 percent. It doubles mortality. So I did a back-of-the-envelope calculation on this and you have probably got 15,000 elderly people in nursing homes dying each year from the off-label use of antipsychotic medications. ...

"With every pill that gets dispensed in a nursing home, the drug company is laughing all the way to the bank."

Granted, this is a back of the envelope calculation that may be inaccurate. But nobody disputes that these medications are linked to increased odds of dying for the elderly, and someone needs to get the science writers to read the research (cited above) that these medications don't work very well. It is hard to think of a bigger scam -- works as well as a sugar pill but increases your odds of dying. The public outrage won't start until people in the media gets rid of headlines that read:

Dementia relief, with a huge side effect: The off-label use of some drugs is helping elderly patients, but may be killing thousands.

Again, the data do not support that these drugs are much more helpful than a placebo, making the headline misleading. Please incorporate the actual research findings regarding atypical antipsychotics into the story and let's try again...

Newer antipsychotic medications offer little to no benefit over placebo, and are killing thousands of elderly patients.

Doctors talk about the risk-benefit ratio with various treatments, which makes sense. When a class of drugs seems to have little benefit and a high cost, both financially and in terms of side effects (including death), shouldn't we try something else? The media create the outrage and then the change occurs. What about the academic experts who have participated in studying these drugs? They should be the most aware of the small at best benefits and the high side effect burden. Yet instead, some of them are churning out tripe such as the latest study pimping Abilify for dementia. If academics are asleep at the wheel, then it is up to the media to start the outrage. I generally like this St. Pete Times article, but if even the most skeptical writers are still claiming the drugs work, it is not a good sign.

But What Else Can Be Done? It is true that elderly patients with dementia can be difficult to manage and that giving them a chemical restraint such as Zyprexa may slow a person down. But how about the following crazy idea, again taken from the St. Pete Times piece...

There are other options, but they take time, money and effort.

At the Cobble Hill Health Center in Brooklyn, Dr. Louis Mudannayake decided to try to change the thinking at his 400-bed nursing home.

Ignoring naysayers and the doomsday predictions of senior nurses, 18 months ago he put together a team of pharmacists, social workers and recreational therapists to review every atypical prescription.

If a new roommate caused agitation, room assignments were changed. If a new aide was hit while dressing a patient, the aide was given special training on that patient's preferences and routine.

Though the nursing home's resources were initially stretched, Mudannayake said the quality of patients' lives improved. "Ultimately, I'm convinced financial expenditures will be diminished, because it's easier to manage a patient who is calm," he said.

Atypical use at Cobble Hill has been cut from about 25 percent of patients to about 10 percent, he said. Almost 40 percent of patients were taken off the drugs completely; 75 percent of those still on the drugs have had their dosage reduced.

"We instituted a cultural change. That's what's required to bring the numbers down," said Mudannayake, who said psychiatric hospitalizations did not increase as medication dropped.

"You'll always have doctors say there's nothing else to use but atypicals, and I agree there are a small minority of patients where you need to use these drugs. But not in the numbers we are using them."

I see, so you can do something else besides dole out Zyprexa and its siblings like candy. But it takes time, effort, and using one's training in mental health. You'd think that psychologists and/or other mental health professionals could easily be hired as consultants to devise such plans. Of course, it is a lot easier to just attempt to sedate chemically over and over again. But are we supposed to do what is easy, even if it is not in the best interest of the patient?

Shame, Shame, Shame. In my humble opinion, this phase atypical antipsychotic mania will be associated with gigantic shame on the psychiatric profession. Just wait a few years. The amazing part is how few "leading lights" within the field have stepped up to the plate and pointed out the problems associated with these medications. When they were first released, all sorts of "key opinion leaders" happily pushed them as a huge improvement over older antipsychotics in terms of treating schizophrenia. Turns out that was mostly hype. Then the atypicals for bipolar rush hit full force, again with the help of "key opinion leaders."

Without academics pimping these treatments well beyond what was scientifically justifiable, these medications would never have achieved such huge success, but now this rather dangerous group of medicines is used for virtually every psychiatric disorder under the sun. These uses include "bipolar disorder" in infants, ADHD, and dementia. Let's put the most vulnerable individuals on the riskiest treatments despite no clear evidence that they work particularly well. There is indeed some evidence for the efficacy of these medications in the short-term treatment of schizophrenia and bipolar disorder, and in a small number of trials, even some long-term evidence of efficacy. But their indiscriminant use across the board for virtually every condition brings great shame upon psychiatry as a profession, on Big Pharma for its slick marketing strategies (1, 2), and most especially upon academic psychiatry for its morally bankrupt role as a group of salespeople who have misrepresented scientific findings to help promote drugs (1, 2, 3, 4, 5, 6, 7, 8).

Update: I forgot to publicly tip my hat to Furious Seasons, where I first saw the link to St. Pete Times piece. Philip Dawdy also added some spot-on commentary, as is the norm at Furious Seasons.

Advertising as Education: CME Part Deux

I had the good fortune to read the Journal of Clinical Psychiatry supplement which featured Dr. Henry Nasrallah (the author) sneaking in some friendly messages about ziprasidone (Gedon), the antipsychotic from Pfizer that has been dwarfed by its competitors such as Zyprexa, Seroquel, and Risperdal. The piece discusses the findings of the CATIE study, which compared several newer antipsychotics to an older medication, perphenazine, and generally found that the newer and older drugs were of roughly equal effectiveness and that olanzapine had the worst safety profile. I thank an alert reader for passing the article along.

CME Overview: The good news is that physicians can read this article and take a quiz as part of the continuing medical education (CME) that helps them maintain their licenses. The bad news is that these articles are often thinly veiled advertisements for a product or a message that supports a product.

Highlights: It is stated that the difference favoring olanzapine (Zyprexa) over ziprasidone in terms of efficacy was not significant after a statistical adjustment (granted, this seems like a legitimate argument). It then mentions that olanzapine had the worst metabolic profile in terms of effects on weight, blood glucose, glycosylated hemoglobin, cholesterol, and triglycerides. It then states “In contrast, patients treated with ziprasidone had the best overall metabolic profile.” It places some numbers in a table regarding the metabolic effects of the various drugs in the CATIE study but provides not a single statistical analysis (or reference to an analysis on CATIE data) backing its assertion that it is significantly better than all other drugs in terms of metabolic profile.

The piece then turns to a secondary phase of the CATIE study, in which patients who discontinued their medications in the first phase of CATIE were assigned to other medications. It mentions olanzapine weight gain then mentions that patients on ziprasidone lost weight. It then discusses weight loss on ziprasidone again, then moves on to ziprasidone being associated with decreases in cholesterol and triglycerides, whereas olanzapine was associated with gains in both of these measures.

In case readers have been sleep-reading through this piece, it then moves to state that “except for clozapine, olanzapine clearly caused the heaviest burden of metabolic side effects. Ziprasidone, on the other hand, was consistently associated with the most benign side effect profile.”

Then, the piece moves to scare the reader about older antipsychotics and their risk of inducing extrapyramidal symptoms [EPS]. “The clinician must carefully decide whether the lower cost of the typical antipsychotic is worth the potential striatal neurotoxicity manifested by acute extrapyramidal side effects and long-term TD [tardive dyskinesia].” Of course, he must be assuming that atypical antipsychotics never or rarely induce EPS, which appears to be wrong and that all older medications induce EPS at the same rate as Haldol, which is likewise incorrect (1, 2).

Overall Message: The bottom line message of the piece is clear. Geodon is safe; Zyprexa is unsafe. Don’t use older meds because they’ll cause EPS – ziprasidone won’t. In fact, Geodon is the safest of the second generation antipsychotics.

Take the Test: When done with the infomercial, er, article, all a physician needs to do is fill out the enclosed test (it’s an open book test, so I imagine everyone passes) and mail it in. Physicians can even complete the test online. [this section was taken directly from an earlier post]

Ghostwriter Watch. Who wrote the article? You tell me – I’m confused. Here’s what is written in the article…

This article is derived from the planning teleconference “Evaluating the Evidence: Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and Beyond,” which was held on May 10, 2006, and was independently developed by the CME Institute of Physicians Postgraduate Press, Inc., and Health and Wellness Education Partners (HWeP) pursuant to an educational grant from Pfizer and addition support from HWP Publishing

Dr. Nasrallah is a consultant for, has received honoraria from, and been on the speakers/advisory boards for Abbott, AstraZeneca, Janssen, Pfizer, and Shire and has received grant/research support from AstraZeneca, Janssen, and Pfizer.

Content development and writing support for this article was provided in part by an independent writer contracted by HWeP: Martin Korn, M.D., a psychiatrist in private practice in New York.

I may be piecing this together wrong, but here goes… Pfizer writes a check to the CME Institute and HWeP. Nasrallah and a few other bigwigs engage in a conference call and are reimbursed (likely quite well) for their time. HWeP hires Martin Korn to write the piece, which then is reviewed, likely in a cursory manner at most, by Dr. Nasrallah. The piece is then reviewed by a member of the CME Advisory Board. These "reviews" appear to be consist of a race to grab the rubber stamp as quickly as possible.

I’m not sure if Pfizer provided the talking points directly to Dr. Korn, but it seems he got the message that Zyprexa and older meds should be slammed while Geodon should come across looking angelic. The CME Institute then stamps their approval and we call all be assured that doctors are being “educated” about the latest and greatest treatments in a purely objective fashion.

Please also feel free to read my earlier piece on CME. I recall seeing Dr. Korn's name on an earlier CME piece similar to this, but I can't seem to track it down.

Don't be confused -- I'm not defending Zyprexa. Geodon appears to be a safer drug than Zyprexa, but this quite thinly veiled advertisement that masquerades as independent education is ludicrous -- how does reading or watching commercials passing for "education" help physicians make better decisions for their patients?