Zyprexa Play by Play

The New York Times has issued a play by play account of what has happened with those now famous Zyprexa documents. How the documents got released and by whom are contained therein.

In a manner more eloquent that I put it earlier...

On his TortsProf blog (snipurl.com/Torts), William G. Childs, an assistant professor at Western New England School of Law in Springfield, Mass., put it this way in a headline: “Judge Tries to Unring Bell Hanging Around Neck of Horse Already Out of Barn Being Carried on Ship That Has Sailed.”

Yeah, good point. Another ruling on access to said Zyprexa docs is expected on January 16th.

Breakin'

I'll likely be away from the blog for a few days. I also may take a few days to reply to emails and comments.

The Actonel Saga Continues

Dr. Aubrey Blumsohn continues his battle with Procter & Gamble. The short story is that Procter & Gamble appears to have cooked the data regarding its osteoporosis drug Actonel. Blumsohn was one of the authors on the Actonel work and when he made the audacious move to ask if he could see the data upon which his study was based, his request was rejected on multiple occasions. The documentation on his site is in-depth and if you have time to look around, I believe you will come to the conclusion, like Blumsohn did, that P & G indeed screwed with the data, which was one good reason for P & G to hide the data from the academics who are listed as the study authors.

Blumsohn is seeking to publicize the actual study data, yet P & G continues to play games. They are sticking with their line that the data are "proprietary," meaning that they want to stand by their apparently fraudulent analyses of the data and keep Blumsohn from re-analyzing the data for presentation and/or publication.

Please see his latest post and just dig around on his site for a while. You'll be amazed. If only all academics who were under the employ of drug companies kept such thorough documentation and were willing to take a stand.

Instead, we have many academics such as Graham Emslie, who openly admits that he withheld study data because it was negative to a sponsor. In a sense, I view Emslie somewhat positively for having the courage to say something. However, his remarks came after he sat on the negative data for years and there was no damage to be done since the sponsor, under intense pressure, appears to have released the previously suppressed data.

Australia Issues Slap on Wrist

A pharmaceutical trade group, Medicines Australia, has lightly punished some of its own.

The authority [Meedicines Australia] received 27 new complaints in 2005-06, with 11 found to be breaches and seven left unresolved. A third of the complaints were made by health care professionals, while a similar number were lodged by pharmaceutical companies about their competitors.

The allegations range from false advertising and claims about drug effectiveness to lavish entertainment of doctors.

The authority fined the pharmaceutical industry a total of $260,000 and ordered several companies to withdraw advertising from magazines.

Baxter Healthcare was banned from taking doctors on any more "educational" cruises.

Source.

Here's a quote from the Medicines Australia report:

In discussing the education provided at the function, the Committee expressed concern that no formal invitation had been provided for the meeting nor any formal agenda, which would have added weight to the justification that the primary purpose of the evening meeting was educational. Members considered it unfortunate that in the absence of any formal invitation or agenda, Baxter had had to ask several doctors, including the presenter, to provide testimonials to the Committee. This did not reflect well upon the industry.

Yeah, kinda hard to be eduational when it is apparent that there was no plan to educate prior to the event. If you went to class on a boat in which there was no planned agenda to teach you anything, that may actually be considered less than educational!

Just the Zyprexa Facts, Ma'am

Not the lies from the blogosphere (like this and this) and the New York Times. Taking a page directly from Wal-Mart, Lilly has now set up a website called Zyprexafacts.com. This strikes me as a bit of a desperate PR move by Lilly.

What’s on the site?

Well, on a few occasions, it makes statements like: “Illnesses that affect the brain, such as schizophrenia and bipolar disorder, are thought to be caused by certain chemicals in the brain being out of balance.” Please. There may well be brain issues in people with various “mental illnesses,” but this whole ‘chemical imbalance’ thing is 95% marketing, 5% science. Find a serious scientist who will step up to the mic and tell us about the definitive chemical imbalance that causes bipolar, schizophrenia, or much of anything else in the mental disorder world.

Check THIS out:

News reports claim that Lilly encouraged doctors to prescribe Zyprexa to children and elderly populations for non-approved uses. Is this true?

Lilly is committed to following the highest ethical standards and to promoting our medications only for approved uses.

However, it is important that the public understands physicians can and do prescribe medications outside the labeled uses. We believe that the final word on treatment and medication choices is well-placed in the hands of treating physicians who are best qualified to make the most informed decisions in prescribing medications for their patients.

It is important for doctors to be aware of information about medications, so they have the best available clinical data to help them make informed decisions when choosing a treatment for patients.

The statement that the final word on treatment rests with treating physicians is used repeatedly on the site. Obviously physicians write the prescriptions, but Lilly is helping to make doctors “aware of information” about medications (i.e., Zyprexa) to help them make “informed decisions” in prescribing medications (i.e., Zyprexa) for their patients (who may or may not have bipolar or schizophrenia).

You really should check out their Zyprexafacts site. It’s a laugh a minute. Remember that Lilly was able to push Prozac through the FDA based on the most meager evidence imaginable (Please see Breggin’s Talking Back to Prozac or Healy’s Let Them Eat Prozac – some of you might be having a cow that I’m citing Breggin, but his bit on how Prozac was approved is spot on), yet Lilly described Prozac as having an unprecedented amount of empirical support. We're not dealing with a company that has a history of honesty about its meds.

One more thing. Healy has also uncovered evidence suggesting that Zyprexa may be associated with suicidality. Perhaps Lilly can cover that on their website next.

Hat Tip: HealthCareVox.

Check Out the Health Wonk Review...

... and much more at Health Care Renewal. The HW Review has links to a number of interesting posts from various healthcare blogs.

There is also a great post regarding the head of the Massachusettes Biotechnology Council who has been convicted of obstructing justice, yet continues to serve in his executive role.

Also check out the post regarding William McGuire, the incredibly rich former CEO of United Health. I'll quote the snippet that made me want to wretch:

She says his income gives him extra credibility in health-policy debates because it shows his success. 'He needs to be compensated appropriately so that his business model has believability in the market,' says Ms. Mundinger [board member of United Health], who is dean of the nursing school at Columbia University.

Yeah, people wouldn't take McGuire seriously if he was not stocking away hundreds of millions in salary and stock options. These people live in a world so different than 99.5% of the population that we can't possibly understand them, and they, likewise, can't possibly understand us. Which would be fine, except that it is these detached from reality New Rockefeller Health Care Executive Robber Barons along with the legislators in their pockets who are determining the policies and costs of health care that affect everybody. Scared?

Metabolic Syndrome and SSRIs

A recent study (Raeder et al., Dec 2006, Journal of Clinical Psychiatry) indicated that SSRIs were associated with abnominal obesity and elevated cholesterol levels. There was a nonsignificant trend indicating that SSRIs may be associated with increased incidence of diabetes.

Which SSRIs? Citalopram (Celexa) was not associated with any of the risk factors studies, while paroxetine (Paxil) made out quite poorly. Due to a lack of large numbers of subjects on fluoxetine (Prozac), fluvoxamine (Luvox) or sertraline (Zoloft), people on these drugs were treated as one group, which was associated with increased abdominal obesity and elevated cholesterol.

Antipsychotics: Unsurprisingly, antipsychotic use was also associated with obesity and other health problems.

The authors suggest that SSRI-treated patients be monitored closely for the metabolic syndrome, which is a major risk factor for heart disease and diabetes. Sounds like a good idea.

My View on SSRIs: I’m not saying that SSRIs absolutely don’t work – they work a little bit better than a placebo. And placebo works pretty well, so you’re prescribing a nice-sized placebo effect with an SSRI.

Yet the cost is an elevated risk for suicide as well as potentially the risk for metabolic syndrome (though some research has indicated that SSRIs may actually improve metabolic health). The sexual side effects are also notable for many. The long-term outcomes with SSRIs appear poor.

One Drug For Another...

A recent study (Tiihonene et al., Am J Psychiatry 2007) compared aripiprazole (Abilify), methylphenidate (Ritalin) and placebo in the treatment of amphetamine addiction.

Here are the study results (quoting from the abstract):

Patients allocated to aripiprazole had significantly more amphetamine-positive urine samples than patients in the placebo group (odds ratio=3.77, 95% CI=1.55-9.18), whereas patients who received methylphenidate had significantly fewer amphetamine-positive urine samples than patients who had received placebo (odds ratio=0.46, 95% CI=0.26-0.81).

My problem with the abstract: The abstract concludes with a positive statement about methylphenidate, but says nothing about the drastic ineffectiveness of aripiprazole. I’ve not read the article, so I cannot say anything about what its actual text. I can say, however, that when a drug is related to drastically worse outcomes than placebo, as was the case for Abilify, then I think a statement should be put into the abstract’s conclusion about this finding. This is related to one of psychiatry’s big problems – focus on the positive (sometimes in a distorted manner), and ignore the negative. I’ll have to get the full text and look further.

Abilify’s performance: Why would people taking Abilify be so much more likely to use amphetamines compared to people taking placebo? Well, if I’m big into amphetamines and somebody puts me on a drug that includes sedation, akasthisia (extreme agitation), tremor, restlessness, and potential extrapyramidal symptoms (movement disorder) as side effects, I can see how someone who likes amphetamines might be tempted to jump back into the amphetamine habit.

Methylphenidate’s performance: Using a minor stimulant such as Ritalin makes some sense in that you’re following the same logic as replacing heroin with methadone. Replace a more dangerous habit with a less dangerous one. Ritalin might help some folks get the stimulant effect they’re looking for without the dangers of (meth)amphetamine use. However, there’s no free ride – there are likely some issues with long-term use of methylphenidate as well, though I’d rather be a regular Ritalin user than a so-called “Meth Head.”

One Quote Says It All

Dr. Graham Emslie, who has participated in a number of psychiatric drug trials for children, appeared in a brief interview clip on an Austin TV station’s investigation into SSRI use among children. Emslie was contracted by GlaxoSmithKline as an investigator in a study examining the effects of paroxetine (Paxil) on child/adolescent depression. As such, he was aware that data showed that Paxil was no more effective than a placebo, but (and here’s the killer quote):

I couldn’t talk about it because it was proprietary.

In other words, Emslie had an agreement with GSK that he would not share their trial data without GSK's permission, even when it showed that Paxil was no more effective than a placebo and related to poorer safety outcomes than placebo. This is what I have been beating the drum about repeatedly…

Of note, on his webpage, it is stated that Emslie "is known internationally for his work in the treatment of pediatric depression." Perhaps he should also be known as an academic who is willing to suppress results unfavorable to his corporate sponsors. Of course, Emslie should not be singled out; at least he had the courage to be interviewed. There are many other who have agreed to keep unfavorable data hidden.

Academics have increasingly become puppets of the drug industry. If you can’t share the negative results of your study, you are acting as a puppet. A well-paid puppet, but a puppet nonetheless. Science supposedly involves the disclosure of all of your data. Especially in the case of medicine, when scientific data are buried, people suffer and die needlessly. If anyone wants a good example of why industry and academia need to get out of their shared bed, this is it.

Thanks to AHRP for the link to the video and thanks to K-EYE TV in Austin, TX for running the story. Direct link to the video here.

SSRIs and the Zyprexa Docs

The AHRP blog is smoking hot with posts on SSRIs and the latest developments regarding the Zyprexa documents, which Lilly is still desperately trying to control.

There are links to several YouTube videos on SSRIs. I’ll be watching them in the near future – they sound tantalizing.

Roll on over to the AHRP site and check it out for yourself.

PharmedOut

On occasion, lawsuits bring great good to the people. PharmedOut is one such example. At this new site, you can see such jewels as:

• The Zyprexa drug rep video.
  
• Links to abstracts and articles on how the drug industry influences prescribing practices.
• A nice list of links to excellent websites covering said topics

Justice Alert: This program was funded as part of the settlement between Warner-Lambert (a division of Pfizer) and the attorneys general of all states and Washington DC. What settlement? The one regarding the blatantly misleading advertising for Neurontin.

If you are a blogger or journalist, please see if you can give PharmedOut a spot of coverage.

One of Those Feel-Good Stories

The Guardian has a neat story today about people with schizophrenia and depression who appear to benefit from playing soccer (football).

An Italian psychiatrist is obtaining startling results with patients suffering from schizophrenia and depression by enlisting them in a competitive football team. Mauro Raffaeli trains his players, many of whom cannot work and are on psychiatric medication, twice a week on a pitch on the outskirts of Rome.

Of the 80 who have passed through the ranks since the team formed in 1993, over half have cut down their drug intake, but more importantly, more than half have returned to work. "Drugs you can often never get rid of, but reintegrating into society is as important," he said.

Obviously, this is not tightly controlled research. But it does back my intuitive sense and observations as well as some research (the research is only relevant to people with depression) indicating that physical activity is good for one’s mental health. In this case, I think the combination of physical activity with teamwork helps to provide a sense of meaning – hey, I’m part of a team! People are counting on me. Et cetera.

I’m all for more creative interventions for schizophrenia and/or depression. The drugs and psychotherapy that are currently provided are unfortunately not getting the job done, so it’s nice to see someone trying something unconventional that is likely to not result in many adverse effects.

Check it out at the Guardian.

The Creativity Crisis Continues

I’ve mentioned this theme earlier. PharmaGossip and Merrill Goozner, among others have been banging this drum for much longer than I. The problem is that, on one hand pharmaceutical companies bemoan the allegedly huge costs of research and development. On the other hand, there have been a lack of innovative developments.

For example, the FDA has now approved Invega as a treatment for schizophrenia. The active ingredient?

“Although the drug contains an active substance never before approved by the FDA, that substance is an active metabolite of an old drug, the atypical antipsychotic Risperdal (risperidone), which is marketed for treating schizophrenia.”

Who developed Invega? Janssen, which also developed and markets Risperdal. Not coincidentally, Risperdal will soon be going off-patent. So, as generic competition swoops in, Janssen wants to keep its patients on its high-cost med, which, of course, is now switching from Risperdal to Invega.

Are there likely to be clinical advantages for Invega over Risperdal? Nope. It’s too similar to Risperdal to expect any notable differences. So, scientifically, it would have of course made better sense to develop something different, but this ain’t about science or benefiting patients…

Post Spree Blues

After going on a binge of posts yesterday, I've got a several more pressing issues to tackle today. So I refer y'all to the PharmaMarketing Blog and to Health Care Renewal, two sites where things have been moving and shaking with very interesting topics.

In addition, don't shirk your duty to vote for the Best of 2006 Medical Blog Awards, especially the best new medical blog award!

Zyprexa: $500 Million in Lawsuits

Lilly has agreed to shell out a half billion dollars to settle legal claims brought by those who claimed to be harmed by Zyprexa. There are 1200 more claims that will head to court in April, so the $$ to be paid out will nearly certainly increase. To nobody's surprise, Lilly has described the lawsuits as "baseless." Just like the last batch of "baseless" lawsuits that were settled for $700 million, I'm sure!

Source.

Selling Zyprexa

PharmaGossip has a great link to a video, purportedly of a Lilly drug rep discussing how he sold Zyprexa to docs. You should check out the full video, but I’ll provide two rough quotes from the video below:

1. Just drink a glass of water before a meal and another glass after the meal. That will counteract the weight gain with Zyprexa.

2. Statistics are like prisoners – torture them long enough and they’ll tell you whatever you want to hear.

NASW and Janssen: Strange Bedfellows

The National Association of Social Workers is coming under some serious heat from a group of its members. Why? Here’s the letter from the opposition group.

“On October 6, 2006, the National Association of Social Workers (NASW) sent to its Specialty Practice Sections on mental health and private practice an emailed “Invitation to Join The National Adherence Initiative for Schizophrenia.” An article in the November issue of NASW News also announces and describes the initiative.

The brief text in the email asked social workers to consider enrolling “in a nationwide data collection effort.” It stated: “Partial adherence is a significant problem in the treatment of schizophrenia … and can affect up to 75% of patients.” It invited participants to “identify up to 10 clients with schizophrenia that you feel are at risk for partial adherence.”

The last line of the text informed that this initiative “is sponsored by Janssen, L.P. in partnership with NASW.” The pharmaceutical company Janssen, a subsidiary of Johnson & Johnson, markets Risperdal (risperidone), an antipsychotic drug that grossed $2.3 billion in US sales in 2005. Social workers who enrolled received a packet from Janssen, with the “study instrument,” that spoke of nothing but the importance of drug treatment adherence for schizophrenia.”

Say what? Oh, it gets even more juicy.

“Treatment compliance is an old issue in schizophrenia care. Everyone in this field knows that antipsychotic drugs’ unpleasant effects make them extremely undesirable to patients. The Janssen initiative closely follows the government-sponsored CATIE studies’ findings that three quarters of patients on atypical antipsychotics such as Janssen’s Risperdal—falsely touted for a decade as vast improvements over older drugs—stop taking their prescribed medication because of “inefficacy, intolerable adverse effects, or other reasons.”

The study instrument mailed to social workers consists of eight “yes/no” questions, each describing a “deficit” in patients that would put them “at risk” of “partial adherence.” In our view, no information not already well known from dozens of previous studies on adherence to neuroleptic treatment, including the $45 million CATIE studies on nearly 1,500 patients, is likely to come from this Janssen-NASW study. The adherence initiative repeats that “partial adherence” is a significant problem in the treatment of schizophrenia—but the more significant problem lies rather with the drugs’ now well established ineffectiveness and adverse effects.

Why would Janssen be doing this? Pay close attention…

“Janssen’s exclusive patent to market oral risperidone will expire in 2007, and the company stands to lose significant revenue as cheaper generic versions come to market. Janssen is therefore now emphasizing the long-acting injectable version of risperidone, which it markets as Risperdal Consta—on which it still holds patent for several more years (and which sells for more than the oral version). The history of antipsychotic drug use shows that one notion, and one notion only, has ever justified using long acting injectable antipsychotics: adherence (compliance). In this light must Janssen’s “adherence initiative” be more fully appreciated.”

It appears that Janssen initiated contact with NASW on this matter and they allegedly made a contribution to the NASW foundation in return for this collaboration.

What was Janssen going to do with this information? I don’t know, but I’ll speculate they wanted to get patients to try out a Janssen product like Risperdal Consta or Invega (their “new” antipsychotic that is essentially a clone of Risperdal). I don’t know what the next steps will be – hopefully the social workers will respect patient confidentiality and not just start handing out names and contact information to “researchers.”

To summarize: Janssen gets a wild hair and contacts NASW, which agrees to participate in this “research” campaign to “help” patients, possibly in exchange for a donation from Janssen. There is little scientific knowledge to be gained from such a study, but Janssen gets to push its Risperdal Consta and/or Invega on what could be a large group of patients. Unfortunately, I’ve not been able to track down the full text of the email, but I’ll work on it and I’ll follow up the story as it develops.

Thanks to Writhe Safely for covering the story. Note that her site is not for those who are offended notably by profanity.

I NEED my Quell, Man!

Over at Furious Seasons, there is a great post about the possibility that for some, Seroquel might be addictive. Apparently, prison inmates are crushing and snorting Seroquel, or "Quell" as it's known in the clink. Ironic, given that Seroquel is being investigated as a treatment for addiction.

There have been a couple of documented cases of significant problems resulting from Seroquel withdrawal. Of note, there is very little research on any symptoms that may emerge as a result of discontinuing antipsychotic medication, especially for atypical antipsychotics. If nobody bothers to study the topic, then how would we ever know if "Quell" and perhaps some of its brethren cause nasty withdrawal effects? Of course, there's no money to be made by studying something as unsexy as withdrawal effects, so it probably won't be done.

There's much more over at Furious Seasons.

Newspeak Update:

There is yet another article in the New York Times on Zyprexa today. It is not flattering. To make a long and sad story short, a patient gained a lot of weight on Zyprexa (80 pounds over five years) and died of a heart attack. Granted, who knows if the Zyprexa was responsible for the weight gain and subsequent death, but it raises suspicions.

The part of the article I’ll focus on is the language used by Lilly in its response. As I’ve alluded to in a prior post, Lilly has trotted out Newspeak, or Maximum PR, to defend its drug. One of their statements regarding the latest incident was “Zyprexa is a lifesaving drug.”

Does Zyprexa save lives? As a class of drugs, atypical antipsychotics, of which Zyprexa is a member relate to a higher death rate compared to placebo for elderly patients with dementia. In schizophrenia, compared to clozapine, Zyprexa is associated with more suicide attempts. I am not familiar with any research showing that Zyprexa relates to fewer suicide attempts than any other treatment or less suicide than a placebo. Please inform me of any studies to the contrary – I could have missed something.

Enough about suicide. We know that Zyprexa can cause diabetes and we know that diabetes is not good for one’s health and life expectancy. Now, the clincher from the New York Times story today: “[Lilly’s] own clinical trials show the drug causes 16 percent of the patients who take Zyprexa to gain more than 66 pounds after a year.”

Yeah, that’s a lifesaver.

Hat Tip: Furious Seasons.

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THE MEDICAL BLOG AWARDS OF 2006!

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