Greedy and Ghostly Scientists

Story one: Zachary Stowe, psychiatrist at Emory University becomes Charles Nemeroff, Jr. Read all about it the Carlat Psychiatry Blog and University Diaries. And check out the WSJ Health Blog as well. The gist is that Stowe apparently did not report all of his external income from his many pharmaceutical industry gigs. Better yet, he was a frequent speaker for GlaxoSmithKline, which had the gall to cancel two of his commercial talks. He then wanted GSK to pay him even though he wasn't going to give the speeches. Read the relevant emails toward the bottom of this document. After reading about Stowe, refresh your memory about Golden Goblet Lifetime Achievement Award Winner, former Chair of Psychiatry at Emory University: Charles Nemeroff. Is there something in the water at Emory? Or is that just how we roll in modern academic psychiatry? Stowe is hereby nominated for a coveted Golden Goblet for his string of emails in which he attempted to shake down GlaxoSmithKline. Sometimes I think that the only thing worse than drug companies are the narcissistic academics who they employ as "key opinion leaders." Not all key opinion leaders are jerks; some are probably even able to reasonably balance their industry cash with being good scientists. But Stowe didn't really portray himself as Mr. Nice Guy in his string of soon to be infamous emails.

Oh, and this little gem:

"Especially disturbing is an email between employees at GSK and a public relations (PR) firm that the GSK hired. The email was titled “For your review/Paxil Breast Milk Press Release” and states:

"[P]lease review the attached press release and forward me any comments/edits.
As you may know, Dr. Stowe is on board for publicity efforts and NAME
REDACTED and I are coordinating time to meet with him next week to arm him
with the key messages for this announcement, which is slated for early February.
We are sending the release for your review at the same time in efforts to secure
distribution on Emory letterhead (as you know, would provide further credibility
to data for the media)."

In his testimony, Dr. Stowe confirmed that the press release was written by the PR
firm and concerned his research on Paxil and its presence in breast milk. He also
explained that placing the press release on Emory letterhead, as opposed to GSK letterhead, would make the data more credible to the public."

If I have this straight, Stowe was willing to place a press release written by a PR firm hired by GSK on official university letterhead to enhance its credibility. Apparently he wasn't concerned about his own credibility. Read the full document of Senator Charles Grassley's investigation of Dr. Stowe.

Part 2: Enter the Ghostwriters

One snippet, then go to Bloomberg for the rest:

Ensuring that medical journal articles presented Zyprexa study results in a positive light was one way for Lilly to reach its sales goal, company officials said in its plan, according to the documents. To do that, Lilly officials hired ghostwriters to prepare submissions to journals such as Progress in Neurology and Psychiatry, according to the unsealed documents. “The paper for the Progress in Neurology and Psychiatry supplement has been completed and sent to the journal for peer review,” Kerrie Mitchell, an employee of the public relations agency Cohn & Wolfe, wrote in a Feb. 23, 2001, e-mail to Michael Sale, a Lilly marketing official. The message was among the unsealed files. “We ‘ghost’ wrote this article and then worked with author Dr. Haddad to work up the final copy,” Mitchell said in the e- mail. Eric Litchfield, a spokesman for Cohn & Wolfe, didn’t immediately return a call requesting comment.

The Bloomberg story is based on a recently released set of internal Lilly documents. That's right -- more Zyprexa documents are on the loose. And the first round of documents provided some good stuff (1, 2, 3), so I can't wait to see what kind of chicanery will be revealed by the latest round. In one sense, it's not exactly news that Lilly ghostwrote Zyprexa papers. We all know that ghostwriting is rampant. How else do key opinion leaders get their names on dozens of papers per year when they are also flying around the country pimping drugs, holding administrative meetings, and doing all sorts of other tasks? But it's nice to have it officially documented that Lilly was playing the ghostwriting game with Zyprexa.

Seroquel Becomes Zyprexa, Part 2. But With More Sex.

I had a big post on Abilify ready to go for today, but I'll sit on it for a few days because Seroquel is the new Zyprexa, and that is the big news of the week. Well, that and Forest getting probed for allegedly marketing Celexa and Lexapro off-label for depression in kids. But more on that later. In the meantime, check out Jim Edwards' nice piece on the emerging scandal.

Back to the 'Quel. First off, a big-time round of applause for Philip Dawdy at Furious Seasons. He's been covering the unfolding Seroquel mess like a hawk, which is exactly what he did during the days of the Zyprexa documents scandal, which is still costing the admittedly criminal corporation of Lilly billions. According to legal documents, Wayne Macfadden, former U.S. Medical Director for Seroquel, admits to being engaged in sexual relationships with a British researcher at the Institute of Psychiatry (IOP) who participated in Seroquel research. Incredibly, Macfadden was also apparently entangled in a sexual relationship with a ghostwriter who wrote up results of Seroquel studies. The attorneys who are suing AstraZeneca claim that: "The IOP researcher suggested that Macfadden would punish her if she even looked at studies that were favorable to Seroquel's competitors." Better yet, Macfadden was alleged to have "promised sexual favors in exchange for intelliegence on AstraZeneca's competitors." It would seem a relevant conflict of interest to note that one was engaged in sexual relations with the Seroquel Medical Director, wouldn't it? I don't typically care about people's sex lives and am in favor of respecting people's privacy. Except when it is potentially related to poor science and/or poor care of patients.

So that's a little weird. And then... according to the Wall Street Journal, internal documents from AstraZeneca suggest that AZ hid concerns that the drug caused diabetes. Gee, that sounds like a page from the Zyprexa playbook. AZ sales reps were instructed to inform physicians that there was no causal link between Seroquel and diabetes. However, according to the WSJ, "In a 2000 position paper about the safety of Seroquel sent to Dutch regulatory authorities, an AstraZeneca doctor named Wayne Geller wrote that there was a relationship between the drug and diabetes. 'There is reasonable evidence to suggest that Seroquel therapy can cause impaired glucose regulation including diabetes melliutus in certain individuals,' Dr. Geller wrote." Expect a few more stories to appear in the mainstream press followed by AZ doling out decent chunks of change to settle lawsuits. This may kill Seroquel's chances of FDA approval for depression, generalized anxiety disorder, and the common cold (OK, I made that one up). Let's hope the documents make their way to the internet so that bloggers such as myself and Philip Dawdy can dig through and go into more depth than the mainstream press. Just like we did with Zyprexa (1, 2, 3).

Can we call this the Sex-o-quel scandal or is that too cheesy?

By the way, Furious Seasons is currently running a fundraiser. I will be making my donation today, and you should do the same if you are in favor of mental health journalism that breaks important stories and is bold enough to cover a wide variety of important issues, regardless of their level of controversy.

Zyprexa: Lilly Admits Guilt, But Also Blame Physicians

In February 2007, I wrote a post in which I described evidence that Lilly's antipsychotic olanzapine (Zyprexa) was marketed off-label for dementia. The evidence I discussed was based on documents generously and bravely hosted at Furious Seasons. At the time, I was careful to avoid labeling the practices as illegal -- they were definitely unethical but I couldn't really say for sure what if a law was broken. However, a law firm known to represent Lilly was regularly visiting my website at the time, which made me think that Lilly was seriously concerned about legal troubles. I suppose they had good reason to be worried.

I can now officially say that the off-label marketing of Zyprexa for dementia was criminal. Lilly just admitted to committing a crime in the off-label marketing of the drug for dementia and settled legal charges for a cool $1.4 billion. And there are more cases still on the books.

For a really interesting take on this situation, listen to New York Times reporter Gardiner Harris. You can find his talk embedded in the New York Times story from January 14, 2009, which is linked here. The plea agreement in the latest case is available here.

It is important to remember that pimping Zyprexa for dementia is far from a victimless crime. Antipsychotics, including Zyprexa, have been linked to an increased rate of death in elderly patients and have also been shown to be of little to no more benefit than a placebo in reducing dementia-related symptoms (1, 2). For a disturbing account of the widespread inappropriate use of such medications, read this post and weep.

This is truly a case where lust for profits likely led to the early demise of who-knows-how-many patients. And we're just talking about dementia, not the other cases where Lilly went berzerk with marketing Zyprexa (1, 2).

Blame the Physicians Too: While much of the blame for the overuse of antipsychotics in the elderly can be placed on corporations such as Lilly, it is also true that Lilly does not directly administer the drugs. Physicians need to understand that prescribing drugs which have been found to offer little benefit but are linked to killing patients -- how is that legitimately practicing medicine? First, do no harm?? Yes, I know that dementia is a hell of a difficult condition to handle. But does that mean we should be doling out ineffective and potentially deadly treatments to "manage" persons with dementia. Yes, reps from Lilly (and likely others) wined and dined physicians, "educating" them about the benefits of Zyprexa and other antipsychotics. That's their job -- to positively spin their products. No different than a used car salesperson except that drug reps are typically much better looking.

Doctors need to use critical thinking skills -- you don't just listen to a drug rep or skim a drug-company provided journal article reprint then jump on the Zyprexa bandwagon. How about learning how to evaluate evidence so that junky marketing disguised as science does not persuade you to write inappropriate scripts? Yes, we can be outraged that Lilly and others pimp ineffective and dangerous treatments, but the physicians are the most important link. If they cannot be better educated to understand clinical trial results, and cannot take time to critically review the scientific literature, then this pattern will repeat itself over and over again. It takes tricky pharmaceutical marketing in combination with an audience that is unwilling to think critically for this type of tragedy to occur. And occur again, it will.

Unfortunately, the published scientific literature is quite biased, as negative studies tend to vanish rather than grace the pages of our journals. But it's still a much better idea for prescribers to actually read journals and critically examine their findings, as opposed to relying on marketing alone. Better yet would be for research data on medications (negative and positive) to be available for all to see.

Big Drugs, Small Brains?

I've read on and off about brain shrinkage being linked to antipsychotics. I have not paid a lot of attention to research on the topic but kept it on my mental backburner. And now Furious Seasons notes that Nancy Andreasen is reporting that her research shows antipsychotics are strongly linked to brains getting smaller. The longer one takes these drugs, the smaller the brain. Does anyone want to set up a YouTube "This is your brain on drugs" video?

Interestingly, a group of researchers has claimed that olanzapine (Zyprexa) has "neuroprotective" qualities; it's good for your brain. Um, color me skeptical. Their research was based on rats, whereas Andreasen's work is on humans. Andreasen's latest work is not yet published, making it difficult to judge the quality of the findings. But research on monkeys exposed to antipsychotics found that:

In conclusion, chronic exposure of non-human primates to antipsychotics was associated with reduced brain volume.

I am not a neuroscientist, but if both sets of findings were accurate, then we'd have people taking antipsychotics who have smaller but better brains. The more neuroscientifically inclined may wish to comment on this possibility, because it seems a little odd to me.

Atypical Antipsychotics for All, Oregon Chapter

Oh boy. Here we go again. A study published online ahead of print at the Journal of Clinical Psychiatry notes that among Oregon Medicaid patients who received a prescription for an atypical antipsychotic:

• 52% had a depression diagnosis
• 34% had an anxiety diagnosis
• 15% had a PTSD diagnosis

But only 15% had a schizophrenia diagnosis and 27% had a bipolar diagnosis. So... the majority of atypical scripts were written off-label. Seroquel was the most frequently prescribed atypical, followed by Zyprexa, then Risperdal.

Doses less than what are typically given to treat schizhophrenia or bipolar disorder (subtherapeutic dosing) were quite common. As in 86% of Seroquel scripts were subtherapeutic, 59% of of Risperdal scripts, and 48% of Zyprexa prescriptions. Wait, am I calling for higher doses of these drugs? That doesn't sound like me at all, right? Don't worry, I haven't lost my mind (I think).

Here's the deal. The authors suspect that a lot of these low-dose prescriptions are being written to manage agitation and as sleep aids. The authors note that there are likely less expensive/more effective medications for such conditions. Not to sound too cavalier, but one could also recommend behavioral treatment to help with sleep as well. Nah, that's crazy talk -- not enough money to be made in that.

Primary care docs were more likely than psychiatrists to dish out low-dose antipsychotics. I guess that the Viva Zyprexa marketing blitz was a success after all. Thanks to Daniel Hartung and collagues for their study, which provides another insight into the wonderful world of atypical antipsychotics as a treatment for everything imaginable. Sorry to beat a dead horse with my zillionth post about the topic of atypicals, but isn't this getting just a teeny bit out of control?


Daniel M Hartung, Jennifer P Wisdom, David A Pollack, Ann M Hamer, Dean G Haxby, Luke Middleton, Bentson H McFarland (2008). Patterns of atypical antipsychotic subtherapeutic dosing among Oregon Medicaid patients Journal of Clinical Psychiatry DOI: ej07m03658

SSRI Doesn't Work? Try Zyprexa

...So said Lilly sales reps who pushed the drug in Alaska. I did a little reading on the topic from the new Zyprexa document set from the recent Alaska case, but was scooped by Furious Seasons, where it was written that:

Lilly was using cases of patients--apparently with bipolar disorder, likely type 2--who ran into problems on SSRIs such as agitation to create a scenario for selling doctors on using Zyprexa in these patients.

Snippets from sales call notes are then added to strongly support this assertion. Well worth a read. Especially the clincher that involves the old-fashioned trick of bribing docs with candy to get them to write Zyprexa scripts. If I get a little spare time, I hope to wrangle through the new Zyprexa docs and spread the word about whatever horrors lie therein.

Zyprexa Marketing: We Don't Need No Stinkin' Diagnosis and Hiding Risks

From an excellent piece at Bloomberg:

"The doctor's thinking that he does not see a schizophrenic or bipolar patient,'' [Zyprexa brand manager] Bandick said in a December 2000 internal e- mail to the marketing department. "But he probably does see patients with symptoms of behavior, mood and thought disturbances,'' he wrote. "Even if the doctor does not have diagnosis, he should treat anyway.''

Adding more fuel to the fire I discussed in February 2007:

The document discussed in this post is called the “Zyprexa Primary Care Presentation”. It appears to be a transcript of a speech Mike Bandick, the Zyprexa Brand Manager, gave at the Eli Lilly National Sales Meeting on March 13, 2001.

It is important to note that Zyprexa is only FDA-approved for use in schizophrenia and bipolar disorder. The document appears to indicate that Bandick was encouraging salespeople to market Zyprexa for treating more than just these two conditions.

Bandick said:

We intend, quite simply, to redefine the way PCPs treat mood, thought and behavioral disturbances. We will continue to focus on symptoms and behaviors that PCPs see every day.

Later he said, referencing Zyprexa:

Broad symptom efficacy in mood, thought, and behavioral disturbances.

It seems curious that Lilly states they did not market Zyprexa for off-label purposes, yet the term “Mood, thought, and behavioral disturbances” seems a fair amount broader than schizophrenia and bipolar disorder. In addition, schizophrenia and bipolar disorder (especially bipolar I, which is the much more severe form of bipolar in comparison to bipolar II) are uncommon disorders. It is highly unlikely that primary care physicians would see patients with such conditions “every day.” However, it is certainly possible that a PCP may run across individuals who are manifesting much less severe “disturbances”, and it may well have been that it was this group, the patients who exhibited mild “mood, thought, or behavioral” symptoms, for whom Zyprexa was being marketed.

But don't worry -- Lilly will tell you that they don't promote off-label. Do keep in mind that I'm not singling out Lilly, as this kind of thing seems to be par for the course.

As for risks of Zyprexa, well, according to Bloomberg...

Lilly added a warning to its packaging in October 2007 saying that more than half of patients in 13 studies gained an average of 12 pounds after taking the drug for less than a year. It said Zyprexa was more associated with higher blood sugar levels, a risk factor for diabetes, than similar medications.

Before the October 2007 label change, Lilly didn't instruct its sales force to say Zyprexa's diabetes rates were higher, former marketing director David Noesges said in a January deposition.

"We will NOT proactively address the diabetes concern,'' the Zyprexa sales force was advised in 2002, the documents show. "The competition wins if we are distracted into talking about diabetes."

The Bloomberg article is a must-read.

In the Name of Science and Charity

Philip Dawdy at Furious Seasons has noted that Eli Lilly released a short report in which they describe the funding they provided to a variety of organizations. All in the name of science and charity, of course. Beneficiaries of Lilly's largess include:

• The American Psychiatric Association
• Massachusetts General Hospital's Psychiatry Department
• National Alliance for the Mentally Ill
  
• Medscape
• American Academy of Child and Adolescent Psychiatry
• Center for Medical Knowledge
• Continuing Medical Education, LLC
  
• Institute for Continuing Healthcare Education
• Johns Hopkins University School of Medicine
• Postgraduate Institute for Medicine
• University of California -- Irvine

These were just some of the big recipients. The report itself is well worth checking out. One will note that Lilly is kindly funding a lot of "education" about fibromyalgia just as they try to move Cymbalta for all things pain-related. The amount of "education" regarding bipolar disorder is also instructive. Um, Viva Zyprexa?

Read some of the details at Furious Seasons and read Lilly's report as well. To Lilly's credit, at least they are making an attempt at disclosure; their industry colleagues are more than welcome to follow suit. Remember that the figures from Lilly's report are from the first quarter of 2008 only.

Vioxx Goes The Way Of Zyprexa

An interesting website (www.vioxxdocuments.com) provides a trove of documents related to controversies surrounding Vioxx. Some of them are hot items, containing statements like this:

The much broader issues, which surfaced at the American College of Rheumatology meetings, were most disturbing and involve suppression of data by Merck and a consistent pattern of intimidation of investigators by Merck staff...

Zyprexa documents, Vioxx documents, Neurontin documents, what's next? If there are any bored researchers, journalists, or bloggers out there, start reading!

Hat Tip: PharmaGossip.

Zyprexa and Key Opinion Leaders

Since the Zyprexa trial is ongoing in Alaska, I thought I should return to the wonderful world of Zyprexa. I encourage readers to follow the Zyprexa coverage at Furious Seasons, Pharmalot, and PharmaGossip. Today, I will discuss the link between key opinion leaders and the marketing of Zyprexa. To preface, a coveted Golden Goblet Nomination could be handed out to several individuals based on their involvement in Zyprexa marketing...

In March 2000, Zyprexa received FDA approval for treatment of manic episodes. One document laid out the multipronged marketing maneuvers that Lilly utilized to move Zyprexa shortly after its approval. Some of the details of this document have been well-covered in a terrific piece of investigative journalism at Furious Seasons. This post will provide some coverage of the link between Zyprexa and the key opinion leaders who helped popularize the drug across the nation.

Once approved for bipolar disorder, Lilly utilized several tactics to market Zyprexa for bipolar disorder, including a satellite conference beamed to about 6000 physicians, and 8000 treatment team members in 1000 facilities. The faculty providing this educational service included many of the big names in academic psychiatry, including Paul Keck, Jan Fawcett, Hagop Akiskal, and Alan Schatzberg.

Alan Schatzberg, you say? Yes, the same Alan Schatzberg who is set to become president of the American Psychiatric Association. Some have been less than pleased with his election as APA president, considering his background as a physician-marketer, a key opinion leader with large conflicts of interest. The same Alan Schatzberg who has been involved in marketing passing itself off as continuing medical education.

Lilly also bankrolled dinner meetings, anticipated to draw 150-400 physicians per sitting. Dr. Schatzberg was also listed as a speaker for such dinners. One mental health service provider was impressed enough with receiving such excellent medical education that you can find it on his CV.

In the document outlining Zypexa's big marketing launch, Paul Keck's name appears in the following contexts:

• Satellite symposium provider
• Trainer of "local speakers." I believe this means he would train local physicians in various markets to then discuss Zyprexa with their colleagues.
• Faculty for bipolar weekend symposia
• Faculty for audio conferences
  
• Faculty for a satellite CME workshop
• Faculty for "dissemination of Bipolar information to 30,000 customers"
• Faculty on a "closed symposium" resulting in a CME newsletter and a CME audiotape, both of which were mailed to 30,000 individuals
• Author of two journal supplement articles

Paul Keck was also a member of a task force chartered by the American Psychiatric Association that served to revise the organization's guidelines to provide a more favorable view of atypical antipsychotics (including Zyprexa) in the treatment of bipolar disorder. No conflict of interest there, eh?

Keck said in a 2002 interview that:

"Often," Keck said, "patients with bipolar disorder require complex treatment regimens to manage all phases of their illness, creating a compliance challenge for patients and a management challenge for clinicians. These studies suggest that physicians may be able to use olanzapine as a foundation to simplify patients’ treatment regimens, and the combination of olanzapine and fluoxetine could be an effective treatment choice

It is likely that Keck was not performing all of his "educational" functions for Lilly in exchange for lollipops. He was likely receiving a healthy dose of cold, hard cash. Yet in the article, nothing is written about his financial links to Lilly. Keck has also appeared in press releases saying nice things about Symbyax (fluoxetine/olanzapine combination).

To be fair, Keck has also stumped for Pfizer's Geodon in press releases. Oh, and he also said nice things about Abilify in a press release. I suppose that if one is going to be a true key opinion leader, a real mover and shaker, one should be prepared to say nice things about whatever new drug is released, since each new drug naturally represents an "important" treatment option. Keck, like Alan Schatzberg and Charles Nemeroff, is also currently listed as a member of the clinical advisory board for Neuroscience CME, a for-profit entity awash in drug industry money. Dr. Daniel Carlat has previously written that the "educational" content produced by this organization is biased, and I find that easy to believe. It's not hard to find examples of poorly done industry-funded CME. In fact, you might be interested in reading about a CME activity in which Nemeroff seems to have pulled data out of thin air.

In sum, the usual fun and games were in play when Zyprexa was initially being pushed for bipolar disorder. Some of the biggest names in psychiatry left their fingerprints all over the marketing of Zyprexa and one of these key opinion leaders recently won the presidential election for the American Psychiatric Association. I suppose, then, that American psychiatrists are generally either unaware of conflicts of interest or don't care about them.

The beautiful thing about being a key opinion leader is that one's name recognition is huge. Among psychiatrists, I bet that Schatzberg's name is better known than that of Bill Clinton, since Schatzberg's byline appears on journal supplements and CME so frequently. That can't hurt when running for president of the national professional organization. I will be very interested to see how Schatzberg handles questions about conflicts of interest and drug industry influence on his profession. Don't be expecting any major efforts at reform in the near future.

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.

The Slap Heard 'Round the World: Atypical Antipsychotics for Alzheimer's

Atypical antipsychotics just got slapped hard. A new study in the Archives of General Psychiatry delivered sizable blow to these medications by finding that they yielded no clinical benefit over "watchful waiting" (placebo) in treating dementia, while all atypical antipsychotics studies were associated with higher costs.

Olanzapine (Zyprexa) did particularly poorly. Patients taking Zyprexa had higher costs, yet their activities of daily living (personal care, doing chores, household activities, etc.) score was significantly worse than patients taking placebo. Patients taking risperidone (Risperdal) and quetiapine (Seroquel) also scored worse than patients receiving placebo on this measure, though Zyprexa patients had the lowest overall scores. In addition, Zyprexa patients were rated as significantly more dependent by their caregivers than patients taking placebo. Here's what the authors said:

The secondary finding that patients taking olanzapine scored worse on the activities of daily living measure than patients treated with watchful waiting most likely represents the greater level or combination of sedation, gait disturbances, and behaviorally inhibiting adverse effects with this drug.

Ouch. You may recall that this class of medications was marketed off-label for dementia. For example, see a prior post, complete with links to documentaton of how Lilly pushed Zyprexa for dementia/Alzheimer's. Let's not forget that antipsychotic meds are linked to that teeny little side effect known as death in older patients with dementia as well.

Let's see if I have this straight: A large number of dementia patients are placed on expensive drugs that have scant evidence of efficacy, and are linked to an increased rate of death. Uh, does this strike anybody else as W-R-O-N-G?

What Do Academics Say? Surely, academic psychiatrists are aware of the fact that atypical antipsychotics are poorly supported in treating dementia. After all, they are highly educated, objective scientists and they will pass along the objective evidence to the world. That's why they write things like this in the journal Current Psychiatry:

SGAs [atypical antipsychotics] remain the first therapeutic option for psychosis and agitation in Alzheimer’s patients.

Phew, good thing people can turn to objective, unbiased scientists for a realistic appraisal of the research literature, right? I think a Golden Goblet nomination can safely be issued to the authors of the above piece in Current Psychiatry -- you really should read my earlier post on the topic -- the article is mind-bogglingly bad.

Lilly Updates Label: A Little Too Late

The good news is that Lilly has updated its warnings for Zyprexa (olanzapine) and Symbyax (olanzapine/fluoxetine combo). Here's a bit from the PR release:

Specifically, the changes include new warnings for weight gain and hyperlipidemia (elevation of triglycerides and cholesterol) and updated information in the warning for hyperglycemia (elevated blood sugar), including additional language on a greater association of increases in glucose levels with olanzapine than with some other atypical antipsychotics.

Here's the tragicomic part:

"Today's communication is part of Lilly's historical and ongoing commitment to inform doctors and patients about updated prescribing information," said Sara Corya, M.D., global medical director, Lilly.

AND

"Lilly continues to recommend that clinicians consult expert guidelines for treating people with antipsychotics, particularly the monitoring of lipids and blood glucose, regardless of the medication prescribed," Dr. Corya said. "Over the last several years, the company has been actively informing healthcare professionals about these recommendations."

Yes, Lilly is all about honestly sharing information. Please read my prior post on the incredible shifting Zyprexa glucose data here. Read a whale of a great post from Furious Seasons on how Lilly tried to play weight gain on Zyprexa off as a benefit of treatment (!) here. Interesting questions about Lilly's handling of the glucose discussion can also be seen here. If you have some time to burn, look through the above posts, then tell me Lilly has a "historical and ongoing commitment" to sharing data openly and honestly.

As for the expert guidelines, yeah -- great idea! Like TMAP -- read my postabout how the research supporting said guidelines for treating bipolar disorder is flimsy at best, yet these "expert guidelines" are oft-cited as a great example of the good that comes from expert guidelines. Oh, and did I mention that the "expert guidelines" are often authored with the help of industry?

Here's the bad news. Really bad news. Philip Dawdy has posted an interview with the mother of a man who took Zyprexa, apparently piled on the pounds, and then allegedly died of "profound hyperglycemia." It is a sad, sad story and well worth your time to read it.

While you're there, look around the Furious Seasons blog and ask yourself, "Is there anywhere else where I can find this type of mental health coverage?" I bet you'll say no. If you want continuing coverage of these issues, I suggest that you contribute whatever you can to Philip Dawdy, author of Furious Seasons.

The Zyprexa Whitewash

Furious Seasons has another tidbit from the Zyprexa documents. It involves the terms "diabetes" and "whitewash." You can read the internal Lilly document yourself at Furious Seasons and decide for yourself.

If you've been living in a cave for the past 10 months or so, here are some other features regarding the infamous Zyprexa documents:

• Zyprexa: Off-Label Promotion?
• Demented Marketing of Zyprexa?
• Zyprexa: The New Mood Stabilizer and Downplaying Risks
• Zyprexa: Off-Label Marketing Part 2

And then there is Abilify. Read Brandweek NRX's piece here. Oh, and Seroquel? Read here and here. The lawsuits will keep coming, and there will be large payouts. I'm not a fan of suing the pants off everyone, but if there is no other way to fight off-label marketing and other dubious promotion tactics, then so be it.

Zyprexa for Youth: What Marketing Plans?

As reported on Bloomberg, Pharmalot and Furious Seasons, an FDA official has overruled FDA reviewers to put Zyprexa on track for approval for treating adolescent schizophrenia and bipolar disorder.

Lilly claims it has no plans for a major marketing campaign. Yet given the glut of atypical antipsychotics, their frequent use among kids already, and the concerns associated with Zyprexa's side effects, Lilly will have to market aggressively in order to win scripts. Bloomberg also reported that Abilify and Seroquel may win FDA approval for the youth market before long and with Risperdal going generic soon, Lilly will either have to market their drug like hell (i.e., Operation Restore Confidence Part Two?) or accept a minor piece of the market. But perhaps they don't care - maybe the studies were just an attempt to generate good publicity and to extend the patent for six months, which was estimated to be worth a billion dollars in itself.

Zyprexa for Teen Bipolar

Zyprexa for teen mania is great, except for the Fat Camp Factor -- from the study abstract:

The mean baseline-to-endpoint weight change was significantly greater for patients receiving olanzapine relative to patients receiving placebo (3.7 kg versus 0.3 kg), and the incidence of treatment-emergent weight gain 7% of baseline was higher for olanzapine-treated patients (41.9% versus 1.9%)

The drug did appear to be much more effective than placebo according to the abstract, but I'll have to read the article before I can weigh in on efficacy more confidently. Gaining 7% of your body weight in three weeks? Um, that ain't good. Gimme a D, Gimme an I, Gimme an A (can you see where I'm going here -- diabetes, anyone?)...

Maybe these kids should have been drinking diet soda -- that will save them from weight gain, at least that's what Lilly might tell them. There were 13 "authors" on the study -- apparently being good at recruiting patients counts as authorship, since there is no way that 13 people made a legit contribution to the study outside if recruitment is left out.

More at Furious Seasons.

Zyprexa: No Longer The Gold Standard?

Decision Resources has now reported that Zyprexa is no longer the market leader in schizophrenia. In March, I noted that the same company proclaimed boldly that Zyprexa was the "gold standard" in treating schizophrenia and would remain so until 2015. So in a matter of months, the same company has gone from labeling Zyprexa as the gold standard for treating schizophrenia to indicating that Zyprexa is an also-ran. The rather quick about-face of Decision Resources makes me wonder about the credibility of its reports.

According to the latest report, concerns about side effects have hurt Zyprexa's market share. Nah, really?

Hat Tip: Furious Seasons, a blog that has been absolutely ablaze with great material.

You REALLY Don't Wanna Publish That, Right?

Due to a lot of hits on a post from March over the past few days, I am providing a link to it since it is apparently becoming a hot commodity. The post is about Zyprexa, and the email of one Lilly employee in which different ways to suppress the study's results were discussed. Naughty. Very naughty.

And Lilly is painting David Egilman as the bad guy for his role in disseminating the now-infamous Zyprexa documents? Gimme a friggin' break! Oh, and did I mention the aforementioned post is based on one of those documents?

Atypical Antipsychotics Down Under

Furious Seasons has a roundup of the latest regarding atypicals in Australia. How about a substantial number of deaths related to their use? Add in a substantial number of patients complaining of other side effects and, for good measure, how about Lilly facing legal action over Zyprexa? Crikey.

Guilt By Association

Over at Drug Wonks is a recent post by Robert Goldberg that would be funny if it weren't so insulting. I have previously discussed how Drug Wonks appears to be a part of the drug industry PR machine. The latest is at least the second swipe that the Drug Wonks have taken at Carlat. It would appear that Carlat is guilty of guilt by association according to Goldberg's reasoning. Carlat was previously guilty of the heinous sin of criticizing the drug industry.

Carlat has linked to the AHRP in his list of sites labeled "Great Pharma Information". This induced a rant from Goldberg in which he called the folks at AHRP "whack jobs." I have likewise linked the AHRP on my blogroll, so I suppose I am equally guilty. Goldberg is also hot under the collar about Carlat linking to Prescription Access Litigation. Those greedy lawyers linked to PAL are just suing drugmakers to line their own pockets, or at least that's the Goldberg argument. The problem is that it has taken litigation to unearth the infamous Zyprexa documents, which have suggested strongly that Lilly's marketing of Zyprexa was waaaaaaay out of line (1, 2, 3 ). Are the lawyers set to make out like bandits in these lawsuits? Sure. But how else are corporations to be held accountable for pushing drugs for inappropriate uses or masking side effects of their products?

And more from Goldberg...

Let Carlat ally himself with anti-science extremists and tort lawyers. In the wake of the SSRI-suicide debacle I will put my trust in the so-called pharma-academic complex any day

Oh, Goldberg is apparently in the SSRI's are never linked to suicidality camp? Not sure, but it looks that way. He may want to refresh his knowledge on such matters here or here. Oh, but I guess that actually looking at the data from clinical trials and noting that it indicates SSRIs are related to a greater incidence of suicidal acts than placebo makes me a "whack job." That's for y'all to decide, I suppose.