Furious Seasons

I Am On The Radio

For the last week, I have been obliquely referring to something afoot. That something is a taping I did for ABC Radio National on Monday afternoon for its "All In The Mind" program. Radio National is Australia's NPR/BBC. I talked with the host, Natasha Mitchell, for about 45 minutes on Zyprexa, the Zyprexa documents, Eli Lilly, the lack of effective mental health advocacy in America and my rather conflicted status as a journalist/blogger/advocate. I'll get edited down to six or seven minutes. The program runs 30 minutes and will also include an appearance by a woman with schizophrenia and a spokesperson for Eli Lilly (Australia).

I can't thank Mitchell enough for paying attention to this important issue. I continue to be confused as to why the major media in this country--aside from Slate.com--have walked away from this story just cuz' the Times broke it first. Wimps.

The show airs at 5 p.m. PST Thursday evening. Not sure about a live Internet feed, but a podcast version will be available for downloading from their website. I'll provide links tomorrow for those of you interested in listening to my blither-blather. BTW, the show apparently has a fair number of listeners in the US via podcast.

I reckon Eli Lilly's lawyers will be listening. After all, they have been reading this site a few times a day for the last month or so. Which is cool. I want transparency around matters Zyprexa, so I have no trouble being fly-specked in return.

Evidence Of Evidence-Based Problems

John Grohol, one of several psychologists manning the Psych Central blog, has an utterly brilliant post banging on peer-reviewed research in light of a study of biases reported in cancer research funded by Big Pharma.

"Some people believe that 'evidence-based medicine' is the answer. That if doctors simply followed what the evidence showed for a given illness or condition, some of these issues would disappear. The problem, as we are seeing, is that you can’t always trust the “evidence,” even when it appears in peer-reviewed journals (not to mention the negative evidence which never appears anywhere)."

And so on. It's great stuff and CL Psych has also gone off on the same topic.

I agree with Grohol that researchers and certain elements of human nature are a big part of the fix we are in with evidence base and treatments in the psych world. One of these days, peer-reviewed research will mean something again in the psych world. These days, it doesn't mean shit to me.

AHRP On The FDA Commish, The Saddest Fight And Cymbalta

One of the pleasures of the mental health blogging world has been the appearance of AHRP's Vera Sharav on the scene in recent months. She's interested in more than mental health, of course, and here she is going absolutely ripshit on the FDA Commissioner, who will be appearing before Congress later today.

"Last week, at a meeting of the Center for Medicine and the Public Interest, Dr. von Eschenbach demonstrated the depth of the cultural malaise at the FDA when he defended direct to consumer advertising of prescription drugs as a First Amendment right, but denied First Amendment right to his own drug safety staff experts! Dr. von Eschenbach said that he won't tolerate whistleblowers who go outside the agency just because they disagree with a final outcome."

Meanwhile, here's one of the saddest bits of bloggery I have seen. A mother trying to keep her daughter from walking into traffic. Her daughter, once thoughts to be bipolar because of wild wild mood swings, seems to have an organic brain malformation. Further consults with neurosurgeons are pending.

And, CL Psych is pounding on one of the studies used to approve Cymbalta for generalized anxiety disorder. It will be interesting to see what kind of response this drug has among patients with anxiety in the real clinical world.

Different Depressions, A Correction Question And Celexa

A reader posted a comment yesterday challenging a post I did referring to the STAR*D study. I don't completely understand the reader's point and the comment was left with a fake email. My policy here is to correct errors of fact and clarify matters of interpretation, so it'd be great if whomever could email me directly and we'll work it out. Your identity will be kept confidential.

I do agree with the commenter that all depressions are different and so are peoples' reactions to treatments.

Speaking of which, I ran into a friend of mine last night. She'd been having a round of depression and got put on Celexa a few weeks ago. She'd never been on anti-depressant before. She told me that for a week and a half after starting Celexa at 20 mgs. she felt very panicked, too panicked to leave her apartment. Plus some other side effects. She'd never had panic attacks before. She said the drug has been working OK for her for the last week and the side effects were mostly gone. I told her to just keep an eye on things and to contact her doctor ASAP if anything came up. I also stressed that if she felt the need to come off the med, then she absolutely had to talk with her doc about how to do that instead of just goign off and doing it herself. That almost always has bad outcomes.

It sure was weird to hear about such a reaction to Celexa--Prozac, Paxil, Zoloft, Effexor and, lately, Cymbalta are generally the suspects in bad reaction to anti-depressants land. Wellbutrin and Lexapro, too, to a lesser degree. Any Celexa stories people wish to share? I'll post the good, the bad and the indifferent.

I Love Celebrity Gossip!!!

OK, no I don't. But there's a bit more info on the Britney Spears situation. From TMZ.com, the most-trusted news source on Earth, comes a report that Spears' erratic behavior isn't being driven by booze and drugs--darn!!!--but is instead a function of either post-partum depression or bipolar disorder. I am so not surprised by this.

I wonder what Tom Cruise will make of this. Maybe TMZ.com can find out what couch he'll be bouncing on next.

Inevitably, some readers will wonder if Spears is taking meds that are turning her all goofy as well. No news on that front.

(Hat tip: Celebrity Baby Blog. I cannot believe I just credited a celebrity baby blog. Bizarre as it might sound, it's one of the most popular blogs on the Internets.)

Serotonin Syndrome? It's In The Times

It's taken me a long time to get my brain around the serotonin syndrome business. Not because I didn't believe it was possible, but because I really hadn't had time to look into it journalistically and one of my psych sources told me that the whole thing was a bunch of whoeey. It's whooey no more.

There is a good article on it in today's New York Times, penned by Jane Brody, a longtime health reporter at the paper who has been very kind to SSRIs over the years. I am pleased by the increasing skepticism that I am seeing from da' paper of record on where we stand in terms of the outcomes of the psychopharmacological revolution. I wish the rest of the media would get off its lazy duffs and start doing some reporting on these matters.

Here's a little tale of my own evolution as a journalist on these matters. From about 1999 to 2004, anything I wrote about mental illness, which was little at that point, operated on the journalistic consensus that, gosh darn, meds are always good, people just need to take them for the rest of their lives, so we just need to make systems of care more affordable, people need to get diagnosed, we just need to stick with the evidence base, and "the stigma" must be eliminated. That'll fix everything. I thought this in a professional manner even though my own outcomes as a patient on three different meds was poor (and that should've told me something) because, as someone who wrote for the general public, I worried about scaring people off their meds and didn't want to be perceived as a loon by readers. (You just don't want the angry phone calls from readers and sources telling you that you are way off-base for saying that SSRIs suck.) Speaking a different truth into a full-blown consensus coming from the other direction is a very difficult thing to do as a reporter and it's even harder for editors to let you do so.

But, in 2004 in an article where I wrote about the suicide of Cynthia Doyon, I took a little swing at the prevailing orthodoxy:

"My doctors would prefer that I take some hard-core meds as a preventative measure against future bouts of depression and mania. But I've been down that path before, with mixed results. In 15 years of downing psychotropic meds, they've never held off depression or mania for more than nine months. So what's my incentive to take the most potent of psychiatric medications--the risperdals, zyprexas, and various selective serotonin reuptake inhibitors (SSRIs--Prozac and its progeny) that psychiatrists push? Those pills are like neutron bombs: You're still standing, but your feelings and healthy range of emotional response to the world are dead. No, thank you."

That was it--one little graf in a 5,000-word article. Let's just say I heard from people over it. Later that year, however, I did a lot of reporting on the fates of schizophrenics in the public mental health system around Seattle. I kept running into patient after patient who took high doses of atypicals, but, contrary to the side-effect-free-and-more-efficacious hype, were showing obvious signs of EPS and tardive dyskinesia. This isn't supposed to be going on, I thought, and it made me press some more over the next year. Professionals denied to my face that these effects were present yet they obviously were. When I asked why patients were still seeing "breakthrough" symptoms if the atypicals were so good, I was met with cold stares. And, then, the CATIE study came out, pretty much confirming everything I'd picked up on.

I wish some others in the media would start taking a hard look at where we are these days. They would be surprised.

A Small Note

No posts overnight. My Monday was exhausting and I am drained. But it was for a good cause. Which I'll get into soon enough. More later.

Sanity On Bipolar Disorder In Kids, Redux

A post from earlier this month on the Bipolar Child paradigm has generated an interesting exchange between a staffer for the Child and Adolescent Bipolar Foundation--who's speaking for herself, but being honest about her affiliation, which I appreciate--and a long-time reader, former CABF devotee and mother of a once-bipolar child. She's also added some thoughts on her own blog. Go the original post to read the comments in their entirety. Here's a sample from the CABF person:

"There have been many studies of bipolar disorder in both children and adults. Research bears out that it is a brain illness with a genetic component."

Are you referring to the "age-appropriate" puppets studies allegedly establishing bipolar disorder in kids? I wish some researchers would use some age-appropriate puppets with me. But, seriously, there is no question in my, um, brain that mental illness and the brain and genes are intertwined. The degree to which that offers clinical meaning to patients and doctors is pretty limited, however. Researchers, for example, push out study after study claiming this gene or that gene (or is that gene over here?) as the locus of bipolar disorder, so I am not so inclined to put as much faith in the genetic component of all of this. As well, such talk is often just a way to ignore the psychological and environmental underpinnings of "abnormal psychology."

Then:

"If a child was acting out because he had another brain illness, say,a tumor, would you say 'oh, well, science isn't quite where I want it to be when it comes to a cure. I should just spank my child until he stops misbehaving?' What if the child was completely debilitated by the illness? Or, would you use the best methods available to treat the tumor and thank god people know way more about these illnesses than they did 5, 10, 20 years ago?"

Perhaps, we ought to start spanking the parents. Joking aside, I am not convinced that we know so much more about these illnesses than we did 20 years ago. We think we do, researchers insist that we do, and so on, but that really hasn't trickled down to the average patient much less the average pharma company. The research base for most meds was hammered out in the 1950s and 1960s and many meds--even "new" ones--are little more than re-engineered molecules from that era and the 1980s. I've been in this game 20 years myself and, I hate to say this, but the fate of the average schizophrenic, bipolar or depressive simply has not changed much at all. So we are dragging children into all of this for what reason? Or, after such knowledge what forgiveness? as TS Elliott once put it.

BTW, I truly appreciate the CABF commenter stopping by. We ought to be having an open honest debate about what's going on around the Bipolar Child paradigm, even if the disagreements prove to be very strong. And we all ought to remember Rebecca Riley.

BTW #2, a reader recently noticed how much I have stressed the disconnect between kids these days and physical activities as compared with my generation, and asked what the hell kind of activities I was involved in as a kiddo, or if I were just romanticizing my childhood. From the age of four to eleven, I was involved in the following activities which often overlapped: competitive swimming, competitive diving, baseball, football, basketball, hockey, figure skating, music lessons, horses, dirt clod fights, grass sliding. In other words, I was busy all the damn time. This didn't make me a perfect child, but it sure kept me from being sucked into the world o' meds at a young age. And my family was far from well-off. These kinds of activities were once available to even poor folks. Why they aren't anymore is both beyond me and a tragedy.

Cymbalta Approved For Anxiety, Harvard Prof Disapproves Of The FDA

Cymbalta, Eli Lilly's blockbuster anti-depressant, was today approved by the FDA as a treatment for Generalized Anxiety Disorder (GAD), the company announced in a press release. The drug is also approved for peripheral neuropathic pain. I cannot wait for the "Where does anxiety hurt?" TV ads. Perhaps it will feature a cat instead of the "Where does depression hurt?" ad's dog.

In other news, Marcia Angell, Harvard Medical School lecturer, has an op-ed in today's Boston Globe banging on the FDA:

"As part of the emphasis on speed, the FDA often approves brand-name drugs on the basis of less evidence than in the past. In these cases, approval may be contingent on companies conducting further safety studies after the drugs are on the market. But the companies usually don't honor that commitment. Of the roughly 1,200 such studies outstanding -- some for years -- over 70 percent haven't been started.

"The FDA is strangely silent about this inexcusable dereliction. When questioned, it weakly protests that it doesn't have the authority to compel the research. In fact, it has enormous leverage, since it can withdraw drugs from the market.

"The FDA also refuses to release unfavorable research results in its possession without the sponsoring company's permission. Here again, it contends not to have the authority to do so, but providing evidence of side-effects or negative results would seem to be an integral part of its job. It's no wonder that serious safety concerns about drugs such as Vioxx, Paxil, and Zyprexa have emerged very late in the day -- years after they were in widespread use."

Yeah, that's kind of a problem.

On Britney Spears And My Friend

The blog Dooce--a very popular parenting/mom blog--had some intelligent things to say about the whole Britney Spears spectacle and something revealing to say about herself involving Risperdal. Why am I bringing this up here? Several people have written to me to suggest that Britney is on a ton of psych meds and that they are the source of her erratic behavior. I don't know, but it sure is possible. Then again, maybe not. Like Dooce, I find this media absorption with her slow-running meltdown--she shaved her head recently, very badly, and pictures have shown up--to be disgusting. Whatever you feel about Spears, she deserves a little more respect, and as la Dooce points out, so do her children:

"I am surprised that no one has brought this up yet, that no one in the media who is hounding her has taken a step back to consider that she might be on the brink of something disastrous, tragic for both her and her children. I can honestly say that if I had filed for divorce from my husband within the first year of Leta’s life that there is no way I would be alive today. If cameras had been following me around during those awful months you would have seen me throwing full gallon milk jugs at Jon’s head. You would have watched as I slammed the front door so hard that it fell off of its hinges, or the countless number of times I called Jon at the office just so that I could hang up on him. Maybe you would have seen me through the window as I stood in front of the medicine cabinet in the kitchen trying to figure out whether or not I had the nerve to take an entire bottle of Risperdal."

Wow. I cannot imagine downing a bottle of Risperdal. And I am glad the author didn't go there, as she's a pretty good writer and such. Likely a good mom as well.

As does she, I think Spears is going through some very weird postpartum psychological reaction. I watched something vaguely similar play out with a former housemate of mine a few years ago, minus the photogs and the shaved head. My friend, who'd always been a bit squirrely, came unglued about three months after her daughter was born. After a year of increasingly erratic behavior, including kicking her partner out of the house, while taking anti-depressants (of course, it was Paxil she took), her family tried to get her to check herself into a psych unit one weekend. She wouldn't budge. So I got the call.

I am no fan of psych units and have never been in one as a patient, but have visited them as a reporter many times, so it took a lot for me even to walk over to her apartment. It was apparent to me that she was pretty wound up and manic-y. Worse than I'd ever seen her. I suggested that the assembled family members go get coffee for an hour because they were saying all the usual well-meaning "we love you, we'll do anything to help you" stuff that is just damn oppressive to someone in my friend's shape. They left. It was a weekend and she needed an evaluation right away, I determined. Within 15 minutes, I had convinced her to go to a nearby ER.

"So what's your diagnosis, smart ass?" she asked me.

"I'm putting my money on bipolar. You're pretty erratic but not psychotic."

So she went to the hospital, spent 10 days there and was diagnosed as schizophrenic. I disagreed with the dx, but kept my trap shut. My friend began taking Risperdal, returned to work, and was fired within two weeks. She went off Risperdal and continued to fall apart over the following year. She went back on Paxil briefly--why I will never figure out--and lost another job. She split with her partner for good, which was likely the worst thing she could've done. The guy had been a rock and had taken over all the parenting chores. He took the baby with him. When she called me one night to complain about this, I told her that if she fought him on the custody, then I would testify against her in court.

"Go to hell, you fat fucking faggot!" she yelled at me. I am neither fat nor gay, but she'd become mean to all her friends that way. Like the others, I've drifted away from her. She won't do anything about her condition--we've talked about the whole "why don't you take Lithium or something for a year and let's see where you are at" thing--and it's just way too tough and way too sad to be around. She's a smart 30-something with two masters degrees, but when she gets going it's like being around an abusive drunk.

She stopped by my apartment with her daughter and her ex-partner a few weeks ago. Within minutes, it was clear to me that things have gotten worse. She has some money from her first marriage and had been spending it wildly--$17,000 in one month on furnishings for her new apartment in a very schmancy building and clothes. She insisted to me that strange men were following her around the building. And so on.

She is one of the few cases I have ever been around that I have completely given up on. What hope I have is reserved for her daughter. My friend is lost and no one really knows why. There isn't shit anyone can do about it either. But something sure as hell happened after she gave birth, just like something happened to Britney.

Weekend Links

As usual, there's been a ton of good stuff in my little universe of reading this past week, which I haven't gotten around to linking to. I hereby rectify this situation:

The Last Psychiatrist tackles the question of how many drinks are in a bottle of wine. He says four, in general. I say three, all the time. In addition, since wine is one of my great obsessions in life, I want to point out for everyone's benefit that California ain't the only state vinting fine wine in this country. The Pacific Northwest is rapidly overtaking California when it comes to pumping out excellent Bordeaux-style blends, Syrahs and white wines, especially Vioginiers. But wait, you ask, doesn't it rain in the PAC NW? How can you grow anything there aside from moss? Just drive across the Cascades and it's like you are in Napa. OK, I'll shut up now.

The AHRP Blog goes ripshit on the FDA's new warnings for ADD/ADHD drugs and the "Gilberg affair." Fascinating.

Spanglemonkey considers some "bad ideas."

The excellent Shrink Rap gets into why some docs don't like Xanax. I agree with the reasoning, but I've always found it odd that docs bash on benzos while being perfectly willing to hand out atypicals for long-term use for the same basic complaints. I find that troubling in light of the huge side effects of these drugs, their feeble long-term performance and emerging accounts of the addictive potential of at least one of the atypicals (Seroquel).

A commenter on the Paxil Progress forum says that the chemical imbalance theory is officially bye-bye. Nonsense. I think it will stick around as long as people believe in, oh I don't know, virgin births and supply-side economics.

Have a nice weekend.

The Zyprexa Chronicles: Fear Of Linkage

One of the oddest situations I have seen in the blogosphere has cropped up around this blog of late. Other blogs fear linking to my site, especially to posts on the Zyprexa documents, I have learned through communicating with some fellow mental health bloggers. No names.

The deal is that everyone seems to be buffaloed by the federal court order earlier this month relating to the Zyprexa documents and that linking to my posts creates a scenario wherein people think they could get jammed up by Judge Weinstein and Eli Lilly's legal beagles for disseminating the documents. Weinstein's ruling clearly states that if you aren't specifically named in the injunction, then you can do as you please both with the documents and with linkage. Lilly won't be very happy but as long as you ain't speaking untruths about the Zyprexa situation, then the company cannot monkey with you. It just wants you to think that it can.

Correct me if I am wrong, but isn't the whole point of blogs and the Web 2.0 about going around traditional media outlets that ignore important issues and pointing out the flaws of major corporations with whom you might disagree?

Seroquel And Bad Dreams

I love Google alerts. Yesterday, it pointed me to the blog of someone who is having some interesting dreams kicked off by Seroquel:

"It is very interesting and kind of spooky because I have very weird & unusual dreams. Sometimes they are very dark, haunting dreams/nightmares that I find disturbing to think about when I'm awake. Last night, for example, I dreamed that two of the little punks that live in my neighborhood were terrorizing my cats: they would tempt them with food to catch them and one would hold them while the other hit them with a baseball bat. I woke up crying and shaking."

I had some horrid dreams on Seroquel, even though I almost never have true nightmares. Once, I woke up screaming my head off at 6 a.m. from a bad dream and couldn't remember what was in my mind. I'd never woken from a dream that way before in my life. A month or so later, I stopped taking Seroquel for good after other bad reactions cropped up. I haven't had a bad dream of which I am conscious since then.

So much for Seroquel being great for sleep. Actually, the drug made me do all sorts of weird things in my sleep. There were days I would go into work with a big scratch across my forehead--this happened several times--apparently from clawing at myself in my sleep. Kind of odd to have to say "Oh, my cat musta done that" at work. The drug also made my muscles, especially in my back and shoulder super-tight and I would wake up and feel the way I imagine old folks feel. Not good.

The final straw was one day when, after an editorial meeting, my then editor took me aside to say that I had been talking to myself during the meeting. "I was what?" I had never done anything of the sort before in my life.

"Your lips were moving. It looked like you were muttering to yourself."

I saw my doctor soon after and we both knew what that meant--the early signs of tardive dyskinesia. I'd been on the the drug for a little over a year at that point, and at a low dose, and that was that. It had showed me signs of being bad voodoo before, but between the dreams and the lip movements, a line had been crossed.

"I think you need to stop taking that," said my doctor.

"I already stopped three days ago."

And this is the stuff they want to give to four-year-olds?

Environment As An Anti-Depressant

Last year, I linked to a study done by Steve Ilardi, a psychologist at the University of Kansas, and his argument that depression can effectively be treated through getting people outside in the sun, moving about, paying attention to "environment" and so on.

There's a new article on the doc in the university's paper:

"Ilardi proposes that depression rates are increasing in part because of the psychologically harmful effects of our modern lifestyle. He also said that although many people believe antidepressant medications like Zoloft, Paxil, Prozac and Wellbutrin are a cure for depression, there are many patients for whom these drugs simply don't work.

The study is based on the theory that the environment serves as a natural antidepressant and although depression in part may be caused by genetics, it is not necessarily part of the brain's evolutionary makeup.

It is possible that we don't have any antidepressant circuitry in the brain because we were always anti-depressed by our environment, Ilardi said.

He based his conclusion on numerous studies concerning the lack of depression in ancestral hunter-gatherer groups that live away from modern civilization."

While I don't buy this 100 percent, I am sure he's onto something. And if he's theory proves out, I fully expect Eli Lilly or GSK to patent sunshine. Or stone tools.

The Zyprexa Chronicles: Off-Label Fun With CL Psych

During my flurry of work on Zyprexa this week, I have neglected to point readers to the excellent work CL Psych has done the last few days on Zyprexa and Eli Lilly's possible off-label marketing of the drug for use in dementia. Did I say "possible?"

You read this and decide whether Lilly's claim that "Martha," like "Donna" another hypothetical patient, is actually a schizophrenic holds any water. (Hint: It doesn't. It's not even a good lie.)

In addition, he has two other great posts up on Lilly firing up the sales machine to go after the PCP market circa-2001 and how Lilly wanted to reshape how docs treat mood and feeling. I wonder what Lilly's mood is these days and how they are feeling.

I am far from done reporting on these documents. In fact, I will be speaking about them soon, very publicly. More on that later. (Note to faithful Eli Lilly readers: could you get your people to, like, actually return my requests for comment?)

In the meantime, does anyone have any thoughts as to why so many of the hypothetical patients Lilly uses in its PCP campaign are women? There's Martha with dementia. Then, there's Donna, Ashley, Andrea and Cindy all with mild non-psychotic bipolar disorder (aka, BP2). The only man who shows up in the docs I have looked at is "Mark," who is mildly manic.

So is what Lilly trying to say in these documents that Zyprexa is really mother's little helper? Don't laugh. In the 1960s and 1970s, women presenting to a PCP--or GP, as they used to be called--with similar agitation, racing thoughts and mild depression would be put on a benzodiazepine or somethign similar. But doctors determined that those were addictive and out of most doctors' war chests they came. Then came the SSRIs in the 1990s--and they didn't work so swell either. (And, yes, there are serious chemical dependency issues attached to them, along with akathesia, and so on.) And, then the Big Pharma companies want to replace all that joy with an antipsychotic. AstraZeneca has been pushing just as hard on this front with Seroquel as has Lilly with Zyprexa.

I simply cannot wait to see what revelations come out of the Seroquel trial in federal court in Florida. Or the documents.

The Zyprexa Chronicles: Begging Questions

I don't often use the term "scandal" on this site. It's one of those over-used terms in the media like "epidemic" and "public health problem" that has been watered-down over time. In fact, I've only used the term four times in 18 months--twice in reference to Jayson Blair!

But I think Eli Lilly's marketing of Zyprexa in the PCP market for bipolar disorder in 2002, weeks after caving into Japanese demands that the company change its label in that country to reflect diabetes concerns, counts as a scandal. And, a public health problem. Judging by the number of links my earlier post is already getting, I suspect I am not alone in my thinking. And thanks for the links.

I have long-suspected--seriously, since 2005--that there was a very good reason Lilly has settled thousands of lawsuits against them over the drug's safety and the company's marketing, as well as injuries suffered by people who took the drug, because look at how Lilly handled all the Prozac lawsuits: it settled very few of them and, if I recall, didn't lose at trial. Prozac settlements amounted to about $50 million by 2000. Lilly was represented by a very talented, never-say-die group of lawyers at Pepper Hamilton.

Total Zyprexa settlements to date: $1.2 billion. Same law firm defending Lilly. That tells you something. These are not people who fold their hand unless there's a very good reason.

The media in this country and the UK have completely fallen down on the job in reporting this scandal, assuming it to be a short-lived story. The New York Times is an obvious exception--hell, Alex Berenson got the party started--and Slate.com has shown some interest, but the major media has been mostly silent. That's just stupid.

As I have noted before, I am leery of the Congressional investigations because they never seem to accomplish much. In this case, I think one is warranted and not simply about Zyprexa. How the entire class of atypicals has been marketed and how known side-effects have been downplayed is something that merits a very serious look-see. This whole nasty business also begs the question of where the hell was the FDA and why don't we have some kind of interconnected, global cooperative thingamajiggy wherein concerns in Japan about Zyprexa, say, would trigger substantive action in other countries in a timely fashion. It also begs the question of how these drugs were approved by the FDA in such a way that they could be marketed to people for long-term use who likely only needed them for a short time, if that. It also begs the question of why direct-to-consumer advertising--you know, Abilify ads on phone booths--could be undertaken for such aggressive medications.

It all begs a lot of questions.

The Zyprexa Chronicles: Marketing Zyprexa As The New Mood Stabilizer For Bipolar Disorder And Downplaying Diabetes And Weight Gain Concerns

This is an extremely lengthy post, one that requires use of the extended entry below, as well as numerous links to various Eli Lilly internal documents. Eli Lilly and the FDA were contacted repeatedly to answer questions. Neither replied.

Since mid-December, when the New York Times broke the news around accusations of alleged off-label marketing and alleged downplaying of risks associated with diabetes, weight gain and cardiac issues potentially connected with the use of Eli Lilly's Zyprexa, most of the resulting press attention, on and off-line, has focused on the drug's use in schizophrenia and dementia. In the latter condition, there have been accusations that Lilly marketed to drug off-label. The company has denied the accusations.

Little attention, however, has been focused on how Lilly targeted Zyprexa for use in bipolar disorder and how the company sought to change the medical treatment paradigm of patients with bipolar disorder by aggressively pushing doctors to use the drug, an antipsychotic, in mild cases of bipolar disorder, as opposed to cases of full-blown mania, and to use it as a long-term mood stabilizer along the lines of Lithium. This is not a minor matter. By some estimates, 50 percent of Zyprexa's $4.3 billion in sales comes from people taking the drug for bipolar disorder. The drug's use among these patients also potentially affects more patients, as bipolar disorder is estimated to affect from about six million to twelve million Americans. Schizophrenia is estimated to affect between two million to three million Americans.

As the company sought to turn Zyprexa into the "number one neuroscience drug in history," its strategy rested squarely in how much of the market for treating bipolar disorder it could carve off for Zyprexa. To do that, they cast Zyprexa as a long-term "mood stabilzer" far in advance of an FDA approval that would permit such language. Along the way, the company downplayed known risks associated with the drug.

CHASING BIPOLAR FROM THE START, WEIGHT GAIN CONCERNS

According to internal Lilly documents I have reviewed (and which I will link to throughout this post), the company aimed to go after this market more than a year in advance of Zyprexa's initial approval for schizophrenia in October 1996. In a document (3.9 MB) entitled (sic) "Zyprex--A Major Step Toward A Health Care solution For Psychosis" and dated July 20, 1995, "mania" is detailed as a new indication for the drug that the company planned to pursue in 1996 with "many" principle investigators at work on clinical research on the drug's use in mania (see page 43 of the lengthy document).

At the time, patients with bipolar disorder were commonly treated with a mood stabilizer such as Lithium, which had been approved for short and long-term maintenance use in the disorder since the 1970s. In some cases, an anti-depressant such as Lilly's Prozac would be added. Patients who experienced full-blown psychosis and were hospitalized were sometimes given an antipsychotic such as Mellaril, but only for short periods of time until the patient's condition stabilized. Some patients with mild symptoms of agitation, insomnia and racing thoughts might be given a small prescription of, say, Mellaril and be directed to take it for a few days only until their symptoms were properly knocked down. Mellaril is a "typical" or first-generation antipsychotic. Doctors were concerned that longer-term use of first-generation antipsychotics would lead to tardive dyskinesia and extrapyramidal symptoms and that such risks were not worth running when psychosis in bipolar mania tends to be short-lived and transient as compared with psychosis in schizophrenia.

Zyprexa was dogged by concerns of weight gain as far back as 1996 and Lilly's response, as it would be in later years, was to downplay concerns of weight gain. On October 1, 1996, Zyprexa was approved by the FDA for use in schizophrenia. The week before, it had been approved in Europe. Gary Tollefson, a Lilly official on its ironically-named "Heavyweight Team," conducted a conference call that day with several reporters to announce "the good news of the Zyprexa story." One reporter asked about initial reports of weight gain in some patients. Tollefson downplayed the concern, saying it was reported with all antipsychotics and that the patients were sometimes so underweight that the weight gain could be seen "in the majority of patients as being part of therapeutic recovery rather than an adverse event."

GOING AFTER LITHIUM, CHANGING THE PARADIGM

In a document (3.5 MB) from 1997, in which the company sought to "tee-up critical issues for the next 3-year planning cycle," company officials note that Lithium, an inexpensive generic product, was still the market leader in treating bipolar disorder. The company goes on to identify bipolar disorder as its number one goal for "disease state prioritization."

"Zyprexa will be the world's number one neuroscience drug in history," the document, authored by Tollefson, states in outlining the company's "strategic intent" for the drug. The company projected sales of $700 million for the drug in 1997, its first full year in the marketplace.

The company forecast that in the second half of 1998, Zyprexa would generate "'Depakote-like' uptake as a mood stabilizer," and already had a vision for its long-term use in treating bipolar disorder.

Both Lithium and Depakote were commonly referred to as mood stabilzers and were used in patients long-term. In Lithium's case, patients could well be on the medication for a lifetime (Depakote had only been used in bipolar disorder since the early-1990s.)

"To be a leader in the bipolar market, Zyprexa will need to be viewed as [a] true mood stabilizer (emphasis Lilly's). A true mood stabilizer will work in acute manic episodes without inducing depression, acute bipolar depression without inducing mania, and protect the patient from future episodes of mania or depression (emphasis mine)."

To "change the bipolar treatment paradigm" was seen as a major opportunity by the company, one that had "huge potential for (sic) increase in sales/value to Zyprexa and Lilly," according to the 1997 document. Weight gain was identified as one weakness of the drug, as was its cost relative to Lithium and Depakote. Zyprexa, at the time, cost on the order of ten times as much as a comparable dosage of Lithium.

As part of its bipolar marketing plans for Zyprexa, the company "planned/needed" bipolar disorder screening at the 1998 National Depression Screening Day, an activity sometimes carried out by the National Alliance for Mental Illness, as well as public relations programs aimed at journalists and grassroots media. In addition, the company hoped for an "Erasing the Stigma" partnership with the Rotary Club. The company planned to submit the drug for an acute mania indication with the FDA in 1998, according to the document. In 1999, the company hoped to have a celebrity spokesman on board.

"Zyprexa is a profound corporate opportunity," the document states. The company forecast as much as $1.1 billion in sales to bipolar disorder patients by the end of 2000.

"HIGH BLOOD SUGARS"

But in 1999, unsettling reports began to come in from clinicians. In a November 12, 1999letter (second part of letter here) from Albert Marrero, a staff psychiatrist with the Ventura County Behavioral Health Department, to Lilly's medical director, "high blood sugars" were cited as a problem.

"We have had eight patients out of possibly thirty-five patients on Zyprexa show up with high blood sugars," Marrero's letter states. "Two patients had to be hospitalized due to out of control diabetes....We have certainly never seen this with Haldol, Navane, Risperdal and others to this extent." It is not clear whether the patients were being treated for schizophrenia or bipolar disorder.

The drug was approved for short-term use in acute bipolar mania on March 17, 2000. Eli Lilly was prepared to change the paradigm.

THE ZYPREXA BIPOLAR LAUNCH

In March 2000, Lilly began a massive roll out of the drug for bipolar disorder. In a document from that month, the company detailed numerous marketing activities aimed at psychiatrists, according to the company document. A satellite symposium had been scheduled for February 23. Entitled "Clinical Management of the Bipolar Spectrum for the New Millennium," the program featured thought leaders in psychiatry such as Paul Keck, a psychiatrist at the University of Cincinnati School of Medicine, and was targeted at 6,000 doctors at 1,000 facilities and would also include 8,000 treatment team members such as nurses and social workers.

In addition, plans called for 15 bipolar dinner meetings, staged as continuing medical education events, and entitled "Restoring Balance: Long-Term Mood Stabilization in the Bipolar Patient." (Emphasis mine.) Anywhere from 150 to 400 psychiatrists were expected for each dinner. Lilly sales reps would attend as well, according to the document.

At the time, Zyprexa was not approved for long-term use.

It is not clear if such an event amounted to off-label marketing of Zyprexa for long-term maintenance use in bipolar disorder. Off-label marketing rules are murky and the FDA has not responded to repeated requests to clarify the matter. Neither has Eli Lilly. In general, companies can only market drugs to physicians for approved use. But doctors, paid by a company to speak for their product, have much more leeway to make broad statements about a drug's use, on or off-label, than do company sales reps, for example.

The company also planned to distribute a one-page "sell sheet" to 30,000 psychiatrists (that would be almost every psychiatrist in the US) and 95,000 pharmacists. In addition, Lilly planned to hold 30 regional "psychosis/bipolar weekend symposia" between April and November of 2000. Lilly also planned several other direct-to-physician initiatives between January and June 2000. The campaign aimed to "capitalize on reintegration, evolve private psych message to include depression data, neutralize weight gain." It consisted of a program called "dawn of a new era in treating schizophrenia and bipolar disorder."

The company had no indication for Zyprexa's use in depression.

In addition, Lilly planned to blast fax 30,000 psychiatrists every other month for three years with "schizophrenia, bipolar, elderly and health econ data," according to the document.

2001: BIPOLAR MAINTENANCE, LILLY DOWNPLAYS DOCTORS CONCERNS

In an "Integrated Product Plan" from January 18, 2001, it is clear that the company was pursuing indications for bipolar maintenance in the European Union and the US, according to a company document. In a separate document, the Zyprexa product team identifies "the Bipolar patient: mania, maintenance, depression" as one of its "2001 priorities."

Zyprexa was not approved for either depression or maintenance use in bipolar disorder at the time. It is not clear if the product team's priority for bipolar disorder translated into activities by Lilly's sales force in regard to long-term use of the drug. Lilly did not return repeated requests for comment.

But there was other troubling news afoot concerning perceptions about Zyprexa's side effects.

In April 2001 survey, 100 percent of psychiatrists surveyed believed that there was link between Zyprexa and diabetes and hyperglycemia. In this document, it is stated that the perception existed because some doctors were more selectively assessing their patients for diabetes and hyperglycemia if they are on Zyprexa, and, also, because more of their patients were on Zyprexa.

In a May 31, 2001 email, a company official reports on an FDA symposium called "Evaluating a Safety Signal in the Postmarketing Period: Hyperglycemia and the Atypical Antipsychotic Drugs." The symposium was led by Judith Racoosin, an FDA official. During a question and anser session, an audience member asked, "Where is the FDA headed with atypicals and diabetes?" according to the email.

"No decisions have been made" was Racoosin's reply.

A YEAR OF JAPANESE LABEL CHANGES

Lilly knew that a reckoning would soon be at hand for Zyprexa and concerns about hyperglycemia, weight gain and diabetes connected with its use. On January 30, 2002, the company's medical liaison in Texas emailed company officials to let them know of ongoing developments in that state's mental health system. Shelethea Dunning, the medical liaison, noted that Texas officials were hatching plans to have patients going onto Zyprexa go through baseline monitoring for glucose and weight, and to be continually monitored for changes. She explained that it was important for the company to do another presentation to researchers in charge of the state's so-called Texas Medical Algorithm Project, a highly-influential set of guidelines which was often used around the country as a tool for psychiatrists and other doctors in determining what medication to give to what patient. Dunning noted that TMAP researchers "are viewed as national leaders in mental health."

It is not clear what actions Lilly subsequently took. The company was soon faced with an even more serious challenge from abroad.

On April 15, 2002, Lilly learned that Japanese health officials would require a labeling change in that country. The label, according to a Lilly document, would instruct doctors not to use Zyprexa in patients with diabetes or in patients with a history of diabetes. The warning would also indicate that there was an increase in blood glucose for patients taking the drug. "Strongly disagrees" is what Lilly's assessment was of the Japanese decision.

"This does not change the status of Zyprexa as a safe, effective and cost effective agent in the US market," the internal document also states.

Lilly did not return a request for comment to clarify how the drug could be viewed as connected with diabetes in Japan but not in the US. The FDA did not return a request to clarify the same point and did not return a request to reveal what response the FDA undertook in light of the Japanese label change.

Within two months, Lilly showed just how much it disagreed with Japanese health officials.

"DONNA" AND LILLY'S MOVE INTO THE PCP MARKET

In June 2002, Lilly rolled out a new sales initiative for Zyprexa. The initiative was dubbed the "Zyprexa Limitless Team" and would create a primary care sales force targeting family practitioners, internists and other primary care physicians (PCPs) in an effort to sell them on using Zyprexa to treat patients in their practice who presented complaining of mixed mood symptoms such as agitation, insomnia and depression. The symptoms are considered hallmarks of bipolar disorder type 2 and cyclothymia, lighter forms of the disorder which stop far short of the psychoses and hospitalizations that are specific to bipolar disorder type 1 (or classic manic-depression).

The move into the PCP market was part of Lilly's long-held plan to reshape how bipolar disorder was treated. An estimated 50 percent of mental health care in America is delivered by PCPs, most commonly for depression. Typically, PCPs almost always refer patients with schizophrenia and bipolar disorder, key markets for Zyprexa, to psychiatrists much as PCPs refer patients with heart problems to cardiologists.

"Just as Prozac revolutionized the treatment of depression in the late 80s and throughout the 90s, so too will Zyprexa forever change the way primary care physicians view and treat bp disorder," the company states in a resource guide for sales reps. The company estimated bipolar disorder's prevalence in the American population at 6 percent. At the time, the National Institute of Mental Health estimated that the prevalence was a bit over 1 percent.

"We can change their paradigm," the document states. To do so, the company turned to "Donna," a hypothetical patient. It's customary in pharmaceutical sales to talk with doctors about hypothetical patient profiles and for the salesperson to work to convince the doctor that their product is what the doctor should be using on patients who meet that profile.

Donna, "a single mom in her mid-30s," was not even close to being a classic manic-depressive. She came into her doctor's office "seeming somewhat ill at ease. Her chief complaint is, 'I feel so anxious and irritable lately.' Today, she says she's been sleeping more than usual," continues the sales guide, "and has trouble concentrating at work and at home."

In a separate document from the campaign, sales reps are instructed to present Donna in such a way as to "make sure the kind of patient we are talking about today, [is] not the psychotic patient or severely ill patient, but the complicated mood patient."

The answer to Donna's problem was to be treated with Zyprexa, starting at a 5 mg. daily dose, roughly equivalent to 3 mgs. of Risperdal. "If her symptoms persist after one week, it is important to increase the dose to 10 mg--and you can feel comfortable doing so with Zyprexa's safety profile."

In the Donna script, the only safety issues addressed are those of other drugs and how Zyprexa compares favorably. The document states that older antipsychotics cause extrapyramidal symptoms--a truism--and that Zyprexa doesn't. In addition, the document states that Risperdal caused heightened prolactin levels in patients, but that Zyprexa did not.

"You will be able to assure Donna that Zyprexa is safe and that it will help to relieve the symptoms she is struggling with," the sales script states.

Nowhere in this Donna script is hyperglycemia or potential risks of diabetes mentioned, despite the fact that such risks were well-known at the time. As mentioned above, only six weeks earlier, the Japanese government had found such risks worthy of a serious label change for the drug.

"I would like you to get a patient like Donna started today," the script continues. "I will be back in a week to follow up."

In an undated "hyperglycemia/diabetes sell sheet implementation" document, the company notes, "Our goal and focus is on creating a market with Donna. The competition wins if we are distracted into talking about diabetes."

Nowhere does this Donna script instruct sales reps to communicate with PCPs about weight gain concerns. But the concerns were so prevalent among psychiatrists that a report from Lilly focus groups in March 2002 reported that psychiatrists saw a "100 percent association" between Zyprexa and weight gain.

In an undated document from the PCP campaign, sales reps are instructed in how to handle "frequent areas of concern" that might be brought up by some doctors. Reps were instructed to handle questions of weight gain by pointing out that "Zyprexa may cause an increase in appetite that can lead to weight gain....You can suggest that patients drink diet soda instead of regular soda or cut back on the amount of carbohydrates they eat."

Sales reps, in the same document, were instructed to handle diabetes concerns by stating that rates were comparable among all atypical antipsychotics. Not everyone believed the claim, however.

On Setpember 5, 2002, Lilly recived a letter from James Turnbull, an official at Frontier Health in Kingsport, Tenn. He explained to Lilly that 10 percent of their patients taking Zyprexa see changes in glucose, trigylcerides and cholesterol, as he had pointed out to the company in an earlier letter. Turnbull was not pleased with the company's reply, which I have not seen. "It just confirms the theory that there are lies, damn lies and statistics," he wrote.

As I reported last week, in October 2002 a Lilly medical writer exchanged emails with several company officials trying to "hammer out" how the company would characterize glucose production that arose in recent clinical studies of Zyprexa in the long-term treatment of bipolar disorder. The company was preparing submissions to the FDA to have the drug approved for maintenance use in bipolar disorder.

"John [Saunders] is ok with this explanation BUT has reservations about including it, because it operates on the assumption that olz [shorthand for olanzapine, Zyprexa's generic name] automatically increases glucose," [medical writer] Campbell writes in the email. "This may be a true assumption, but do we want to present this this way? Does inclusion of this explanation open us up to questions on glucose that we'd rather not bring up?"

In 2001, Zyprexa sales were approximately $3.3 billion. For 2002, the company reported sales of $4 billion, a 21 percent increase over the previous year, according to IMS Health.

AVOID REFERRING TO ZYPREXA AS MOOD STABILIZER

Double-digit sales gains were met with consternation by Lilly. In a 2003 "Brand Council" document (5 MB), the company describes its frustrations. The document is marked "for strategy and evaluation purposes." It called for hitting $6 billion in sales by 2006.

"Zyprexa obtains 'foundation of treatment' in bipolar in the US," the document states, but "only vs. AP's," meaning only in comparison with other atypical antipsychotics but not against mood stabilizers such as Lithium and Depakote. The company felt "significant" sales gains were possible in a "short time."

Still, the document states that Lilly should "avoid referring to Zyprexa as a mood stabilizer." The company expected a new indication for bipolar maintenance in early 2004.

On January 14, 2004, the FDA approved Zyprexa for use in bipolar maintenance. The company's press release cast the approval thus:

"Zyprexa is the first treatment in nearly 30 years to be recognized by the FDA as a treatment for both acute mania and maintenance treatment in bipolar disorder."

The other treatment approved for maintenance use was Lithium.

What's A Thought Leader In Psychiatry?

A reader left a fabulous question in response to an earlier post on Market Analyst Cognitive Disorder.

"'...according to thought-leading psychiatrists.' What is a thought-leading psychiatrist?"

The answer isn't especially precise, but the alleged thought leaders in the mental health world are MDs attached to the tony medical schools, who publish lots of papers on the glory of this or that new pharmacological treatment and, sometimes, also do prospective research on diagnoses, neurology and advanced treatments. People like Joe Calabrese at Case Western, Michael Thase at Pitt, Dan Casey at OHSU/VA, Lilly's Maurico Tohen, Ron Kessler at Harvard, Jeff Lieberman at Columbia, Fred Goodwin at George Washington University and so on. Generally, these are the kind of folks who when a study or editorial has their authorship credit on it, then docs in the field pay attention, as do the PR folks at pharma companies who can quote these folks and lend credibility to whatever snake oil they are hocking that day.

In general, I find their work to be uncreative. But that's for another day.

Market Analyst Cognitive Disorder

That's right. I have created a new DSM disorder. It is to be used in cases such as this:

"Decision Resources, Inc., one of the world's leading research and advisory firms focusing on pharmaceutical and healthcare issues, finds that AstraZeneca's Seroquel will overtake GlaxoSmithKline's Lamictal as the gold standard in the treatment of bipolar depression by 2010. According to the new DecisionBase report entitled Bipolar Depression: Turning Physician Insight into Projected Market Share, Seroquel's advantages over Lamictal include the more profound effect on depressive symptoms seen in short-term trials. The drug's efficacy on this measure differentiates it from other therapies, according to thought-leading psychiatrists, and the importance assigned to this measure by prescribing psychiatrists drives Seroquel's product score above Lamictal's."

OK, I had no idea Lamictal was a "gold standard" in treating bipolar depression. And, as rotten a drug as I believe Seroquel to be in anything other than short-term use, of course it outperforms Lamictal in short-term treatment situations: Lamictal takes about 8 weeks of up-tapering to achieve a therapeutic dose, whereas Seroquel can get there inside of a week.

Um, this bit of PR hype raises serious concerns on several levels and highlights a need for long-term treatment in this troubling disorder of market analyst cognition which afflicts tens of millions worldwide.

Brandon and the Bipolar Bear

I completely forgot that today's is President's Day, so my planned uber post for today is officially off until tomorrow.

In the meantime, a source tipped me to a couple of books to help the bipolar children recognize their bipolarness. The first is a book with a super cute cover, Brandon and the Bipolar Bear: A Story for Children with Bipolar Disorder. Um, since the disorder doesn't exactly exist in the DSM, the subtitle is a bit off. And, if more kids were behaving like the kiddo on the cover, then I am guessing the Bipolar Child mafia at Harvard would be out of business.

The next book is called My Bipolar Rollercoaster Feelings Book. The latter is some kind of mood chart dressed up as a rollercoaster. The Brandon book is apparently filled with a little boy talking with a bear, and getting useful information about his chemical imbalance and why he must take meds.

There is something of a book industry that has grown up around the Bipolar Child paradigm. Thank God, this paradigm isn't consensus yet. Given time, I am sure the veritas squad at Harvard will preppy that little obstacle to the ground.

Once again, let me link to Maria at Intueri's fabulous post of yesterday on her doctorly frustrations with the BP kiddo who-ha and quote her stepping through some of what actual child psych researchers are putting out there as symptoms, along with my snide commentary:

"Elated mood:

“...it can be very misleading to see a happy child laughing in the office in the context of a miserable history (e.g., school suspensions, family fights).” I used to laugh at adults all the time when I was a kid. I still do.

Grandiose delusions:

“A common presentation for bipolar children is to harass teachers about how to teach a class; this harassment is often so intense that teachers telephone parents, begging them to ask their children to desist.” I called it "constructive criticism."

“Another common grandiose manifestation in children as young as seven is to steal expensive items and be impervious to police officers who attempt to make them understand that what they have done is wrong and illegal.” OK, this is a problem.

“Common adolescent grandiose delusions include are that they will achieve a prominent profession (e.g., lawyer) even though they are failing at school, i.e., the belief that they can have a high attainment when they have failing school grades bypasses the laws of logic.” As I recall, Einstein wasn't such a whiz at math in school.

High activity level:

“Manic adolescents will wait until their parents are asleep and then go out 'partying'." Yes. And we go have sex and look at the stars and wonder at life's odd majesty. We often turn into far more creative and interesting adults than the future technocrats who were the good kids.

Pressured speech, racing thoughts:

“...children state that they are not able to get anything done because their thoughts keep interrupting.” OK. I can buy this one.

Hypersexuality:

“Children may masturbate frequently, initially openly, and then when told not to do it publicly will simply make frequent trips to the bathroom to continue the stimulation.” Oh geez.

“Adolescents develop romantic fantasies and delusions about teachers.” Um, you stare at a hot 20-something teacher for hours on end each day and you'd have to be declared "ill" for not having the odd teacher-related fantasy. And, if they medicate this one away, they will kill off an entire sub-genre of porn.

Risk taking:

“Interest in money appears in young children when they start their own businesses in school and when they begin to order multiple items, trips, and plane tickets.” Take it away, Maria.

"What?

"These criteria significantly overlap with the range of normal. Should every kid who is experiencing difficult social stressors never laugh? Can’t kids be obnoxious and tell off the teacher? Are kids “mentally ill” for possessing dreams and aspirations? Do kids who disobey their parents have a condition that is only treatable with medications? Is distractibility a marker of pathology?"

Moral of the story? Remember Rebecca Riley.

Up To Speed On Possible Off-Label Marketing Of Zyprexa, The Blakemore-Brown Case, What A Doc Thinks Of The Bipolar Child Paradigm And Newsweek

CL Psych yesterday posted an excellent item on how Lilly in 2001 appears to have engaged in suspicious marketing tactics for Zyprexa in illnesses other than schizophrenia and acute mania, for which it had indications at the time. It's great stuff. Go read it. I will be posting something of my own on Zyprexa in a few hours because, like Lilly's legal team at Pepper Hamilton, I work all-hours. Unlike Lilly's legal team, I do not bill at $400 an hour.

Lots of readers are checking out the transcript of the bizarre case of Lisa Blakemore-Brown and the British Psychological Service. The latter is trying to hound Blakemore-Brown out of business because she was insane enough to engage in skepticism and academic freedom. Word has it that the BPS is none too happy that I am hosting the transcript. Bummer, dude.

A lot of bloggers are writing about this case in England, so read about it here and here.

Maria, a psychiatric resident in the Seattle area who authors Intueri, has written a splendid post on the whole Bipolar Child nonsense and debate that is racing through the media and psychiatry. I am glad to see she finds the bipolar kiddos thing to be as dubious as I do and that, like me, she thinks it may well be making psych docs look like fools in the eyes of the public.

In addition, Newsweek's cover story this week is on men and depression. It's a very important subject, but since a newsweekly is tackling it I expect the article to be a big gloss (haven't had a chance to read it yet). I wonder if they'll go into how just how poorly anti-depressants--and by that I mean the SSRIs mostly--have performed in clinical trials and in long-term independent studies in the years since the same magazine lionized Prozac on its cover in 1990. To me, that's as big a problem as depression itself. We are working with weak technology people.

I wonder, too, if Lilly won't now churn out a variation on its "Depression Hurts" commercial just for men. Maybe they can get Walt "Clyde" Frazier and Keith Hernandez to star in it.

The Weirdness Of The Blakemore-Brown Case

I have briefly mentioned recently the very odd case surrounding Lisa Blakemore-Brown, a psychologist in the UK. She's been the object of what Americans would call a fitness-for-duty evaluation. Her supporters claim this is because she challenged a psych diagnosis and the jail sentences handed down to people based on that diagnosis. She's also been vocal in her views on the possible connection between vaccines and mental disorders such as autism. She is currently being looked into by the British Psychological Society, apparently as payback for her stands. Her supporters say she is a victim of academic stalking, or academic persecution as we might term it on these shores.

The BPS has been fairly mum on the case, preferring instead to jam up Blakemore-Brown in secret proceedings. Or a Star Chamber, as the classic term would have it.

I have obtained a copy of the transcript of a hearing the BPS held on the psychologist this past summer. It is fascinating reading--and very, very weird stuff. I have posted it on my site right here.

Friday Thanks, Friday Links

First, I want to thank readers for being incredibly kind to me this week--not that you haven't been before! But the last couple of weeks have been quite the test. So, thanks.

I also wanted to pass along some links to other interesting matters.

The Rebecca Riley case continues to generate loads of attention, as it should. CL Psych had a blistering post on this, so did AHRP, the always fabulous Jacob Sullum at Reason's Hit & Run wrote this up and so on. In fact if you search under the girl's name in Google News, you'll get well over a hundred cites. I hope all this attention leads us someplace sensible. It should also be a massive wake-up call to psych docs, the APA and those who are crafting the next edition of the DSM.

BTW Sullum's post has generated a massive string of comments. Worth skimming through.

CL Psych has also had a fabulous series of posts on SSRIs and suicide stats in teens. And speaking of SSRIs, I have long-meant to point readers to the fabulous CorePsych blog and the series of posts Charles Parker has been doing on ADHD/ADD drugs and so on.

I know there's much more out there and I will link to other things soon.

Documentary Matters And Such

The Zyprexa documents are now available on a German website. They are available as single .pdf documents or as one big old file. They are also available as searchable text. I haven't the faintest as to who did all that work, but good for them. Rob Wipond also continues to host them in Canada.

I am getting a number of tips from readers on all manner of things. Thanks. I appreciate it. It'd be great if you guys just emailed me directly instead of leaving things in comments (it's a bit easier for me to manage). Or do both, please.

In addition, there seems to be quite a bit of interest in this story in Australia. More on that later.

The Zyprexa Chronicles: Time For The Media And Others To Do Their Jobs

It probably comes as no comfort to Eli Lilly that yesterday Slate.com wrote up one of the Zyprexa documents, apparently downloaded from this here website. Go read their nice piece here. Many thanks to Slate.

This makes me wonder where the hell is the rest of the media on the Zyprexa story. The Times gets the documents first and busts out some great stories in December, does some folos and the rest of the major national media goes slinking away like babies because they were "beaten" on the story. Big deal. Only the Times of London has gotten on them since, although everyone has taken a little run at the story of the documents, the court ruling and Alex Berenson. "60 Minutes" was supposedly poking around the story as well, but I've heard nothing more about them. I know NPR has the documents, so does the Wall Street Journal. I bet that the Washington Post and Los Angeles Times have them as well. Silence has been the result.

Um, I think there are some editors, and maybe some reporters, who need to understand that the story here is bigger than they think. Or have they all forgotten about the many revelations around Prozac in the 90s, Paxil in the 90s and the 00s, and now Zyprexa? Are there some dots they are incapable of connecting? I'm a nobody but let me try to help.

Zyprexa is but one of class of drugs called atypical antipsychotics. The others are clozaril (which has killed people), Risperdal, Seroquel, Abilify and Geodon. (Serdolect never made it to market in this country because it ran into too many problems in the UK.) You know the news around Zyprexa. Risperdal's maker, Johnson & Johnson/Janssen, is currently tied up in court in Texas in a lawsuit brought by the state for allegations around the company using undo influence and potentially illegal schemes to get the state to use the drug. AstraZeneca, Seroquel's maker, is facing 10,000 lawsuits related to allegations of product liability. Bristol Myers-Squibb, Abilify's maker, recently settled a huge case with the feds for reasons that I still cannot fully figure out (gee, bet those documents are sealed too!). So this is a class of drugs with big problems and Big Pharma has behaved incredibly sleazily in promoting their use. BMS had ads for Abilify on phone booths in Seattle and Philadelphia recently--have you guys ever seen such a blatant attempt to mainstream such an obscure product? I think everyone has a clear idea of how Lilly handled Zyprexa.

And guess what guys? These drugs don't work too well either. There are at least two major long-term, independent studies that now establish this. Yet these same drugs are now being given to millions of children and teens, and many millions of more adults--and not just for schizophrenia, for which they were designed, but for very mild cases of bipolar disorder (as a sleeping aid no less), for combative kids, for depression, for anxiety and so on. I have previously detailed just how aggressively AZ is trialing Seroquel for everything under the sun, including among FOUR-YEAR-OLDS for this trumped-up bipolar disorder in kiddos.

If you guys in the media don't smell a story, then you need a fresh cup of coffee. I'll buy.

In addition, I am confused as to why the American Psychiatric Association, the American Medical Association, the American Psychological Association and their fellow organizations in the UK, Europe and Australia haven't issued even the most tepid of statements on the matter. What part of Hippocratic Oath and social responsibility don't you people get?

If the APA doesn't take up Zyprexa and the atypicals at its national convention in San Diego in June, then it is asleep at the switch.

I am just as frustrated with many of the so-called advocacy groups for the mentally ill. DBSA, NAMI, CABF. You guys have said nothing. Or are you busy cashing checks from Lilly? The only good actor among the mainline advocacy groups has been MHA (NMHA) which, last week, signed on as part of the legal challenge to the documents remaining sealed. Good for you guys. But you have still taken no public position on this matter.

It is time as well for the feds to step up to the plate. Earlier this week, David Graham, who seems to be the only brave person at the FDA, testified before a Congressional subcommittee on the fact that the FDA knew full well the problems with Zyprexa. It is time for Congress to press harder on this matter. It is time for the FDA to get off its butt and investigate Zyprexa, and itself while its having fun. The FTC should be looking into this matter as well, and so should the SEC.

It's time for everyone out there to wake up. And do their jobs.

A Bipolar Child Murdered: "We Work In Uncharted Waters"

WBUR-FM in Boston, the city's main NPR station, today took up the question of bipolar disorder in kids. Appearing on the program was Janet Wozniak, director of the Pediatric Bipolar Program at Massachusetts General Hospital (i.e., Harvard), who defends the diagnosis. I only listened to the first five minutes of the program. Wozniak defends the diagnosis and treatment, says the prevalence is 1 percent amongst kiddos, argues that people criticizing the diagnosis and treatment are "insulting to clinicians." Please. Consider yourself fucking insulted, Janet.

Could we find a better way to address all these over-stimulated, "wild" children? Calling them bipolar and medicating them is bad and, in my opinion, far worse than dx'ing and rx'ing adults and teens. Why? Because the little ones have no say in the matter and because this paradigm cannot be good for their long-term psychological development much less for their brains. More Little League, less Lexapro.

Here's a link to a streaming version of the program. Lots of smart comments on my earlier post on the Times article on the death of Rebecca Riley. Thanks. Keep 'em coming.

A Bipolar Child Murdered: It's In The Times

The New York Times has an article on the death, murder, unintentional over-dosing or whatever it turns out to be of four-year-old Rebecca Riley. Reporter Ben Carey smartly uses it as a wedge to talk about the debate within psychiatry about The Bipolar Child paradigm. Highlights:

"'Bipolar is absolutely being overdiagnosed in children, and the major downside is that people then think they have a solution and are not amenable to listening to alternatives,' which may not include drugs, said Dr. Gabrielle Carlson, a professor of psychiatry and pediatrics at Stony Brook University School of Medicine on Long Island.

Paraphrasing H. L. Mencken, Dr. Carlson added, 'Every serious problem has an easy solution that is usually wrong.'"

I love Mencken. And, one of the Harvard psych mafia offers this:

"Dr. Jean Frazier, director of child psychopharmacology at Cambridge Health Alliance and an associate professor at Harvard, said that up to three-quarters of children who exhibit bipolar symptoms become suicidal, and that it is important to treat the problem as early as possible.

"'We’re talking about a serious illness with high morbidity, and mortality,' Dr. Frazier said, 'and for some of these children the medications can be life-giving.'"

Or life-taking in the case of Rebecca Riley. Interestingly, Carey asserts rather strongly that this poor kiddo was on Seroquel--other press accounts had downplayed that drug--in addition to Depakote and clonodine and a host of OTC meds. It will be interesting to see where this story winds up.

BTW, I wonder if any of these Harvard muckety mucks can offer me a double-blind, placebo-controlled, peer-reviewed series of articles establishing the prophylaxis of psych meds being used in kids this young--forget about adults for the moment--and how they prevent suicide. Thank you.

The Last Psychiatrist On The Zyprexa Documents

So, The Last Psychiatrist stopped by the other day and left the following comment which, with the good doctor's permission, I am putting up as a standalone post because I am against Saltines.

"Hi. Thanks for collecting the documents. I would never have gone through them otherwise.

The most obvious thing of all is that the science is not represented, just politics. For example, a common theme is that zyprexa causes weight gain and diabetes, but clozaril causes it more. Ok--BUT IT'S NOT THROUGH THE SAME MECHANISM.

Here's an example: in the first document, "Alan Breier" correctly notes that 20% of patients actually lose weight on Zyprexa. Has it occurred to anyone that this might not be random, that there might be a reason those 20% lost weight and not gained weight, and a different 20% gained more than 20lbs for a very specific set of reasons? And that this might, to some extent, be predictable?

As a forensic guy obviously I understand the trial is about money and not truth, but it is absolutely amazing to me that all the scienticians and psychiatrists involved never bothered to discuss the MECHANISM and write some papers on it. All there are are imbecilic association studies. Does the public ever get to find out what they can do to prevent Zyprexa induced diabetes? Isn't that something, um, worth knowing?

In other words, it is as if the involved psychiatrists purposely hid the mechanisms, or didn't research the mechanisms, so that they could engage in a political discussion about "antipsychotic induced diabetes" rather than trying to figure out how to handle Zyprexa's diabetes vs. Risperdal's diabetes, etc.

It's as if they discovered Cheerios caused cancer and roasted turkey caused cancer, never bothered to find out why, and started saying, "it is well known that brown products cause cancer, but the makers of Saltines tried to hide this fact."

I read six--SIX--articles describing the various and different mechanisms by which various antipsychotics affect glucose homeostasis. None--NONE--were in psych journals. Only one was referenced BY a psych journal.

For this reason, Breier can write, "all antipsychotic drugs... are associated with weight gain; mechanism [sic] is not known" and believe he is telling the truth, but in fact be lying.

It's plausible deniability, by willful ignorance.

Sorry for the long rant. I'm going back to coffee."

I'm guessing you drink it black. I am also guessing that Dr. Alone often reduces medical students and residents to tears. Meanwhile, in this fabulous post he expounds on coffee and blood pressure in terms that a Seattleite like me must cheer.

The Zyprexa Chronicles: The Media's Job Is To Be "Reprehensible"

My my. There continues to be much commentary about the federal court ruling in the Zyprexa documents case and New York Times reporter Alex Berenson's role in the mash-up. Who woulda thought that this end of the story would have these kinds of legs?

Peter Rost offers some thoughts so well-wrought that I wish I'd penned them:

"According to the ruling, Mr. Berenson obtained the documents after he discussed ways to circumvent a protective order related to the documents. Mr. Berenson put one guy who had the documents in touch with a lawyer who simply issued a subpoena for the documents. Then the lawyer turned them over to Berenson. And this way they circumvented the protective order which applied only to the parties in the case.

Shocking? Of course Lilly is crying all the way to court.

Reality, in my humble opinion, is that this kind of trickery is exactly what any major legal defense firm practices on a daily basis. But the fact that a journalist makes an end-run around a court order, without apparently violating said order, shouldn't be very shocking.

Truth is that our legal system has long ago been subverted by very rich and very corrupt lawyers and our legal system simply can't keep up with their chickanery. That is the big problem, not the fact that a media company employs the same methods."

Then comes Center for Medicine in the Public Interest's co-founder Robert Goldberg, writing on the group's Drug Wonks blog in a post entitled "Media Schizophrenia Over Zyprexagate":

"Also note that 'co-conspirators' like MindFreedom and other web-based ax-grinders now claim that being in possession and posting of stolen documents is okay. And of course none of this is related to lawsuits contemplated by state AGs in Illinois, Vermont and elsewhere to sue Lilly regarding Zyprexa. (Nothing like going to the well again.)...

"This whole jihad is being driven by crackpots, money hungry state AGs and aided by a newspaper that is willing to sacrifice both national security and the truth to play to its shrinking readership."

If this were actually wonkish I might be interested in it, even though I disagree with the premise. The public gets informed about a problematic drug and Lilly's alleged behavior. Frankly, I could care less about how Berenson got the documents. He's a smart reporter who found a way--mixed metaphor ahead--to tie a bad court seal in knots. But the way some people are reacting, it's as if he took a Glock and stuck it at someone's head to get the documents. Please. There is no crime here.

As for Goldberg's other rhetorical gibes: Better an axe-grinder than an ass-grindee. Seriously, this putz's group makes much hay about being free-marketers and that there is too much regulation of pharma companies, but then pisses and moans when that other sine qua non of free markets--that would be "perfect" information so that markets can, like, clear at equilibrium, as we learned in Macroeconomics 101--shows up to the Big Pharma party.

And I suppose Goldberg will next attack David Graham, an FDA official, for testifying before Congress the other day about how the agency knew about Zyprexa's issues, but did little until its black box warning of 2004. But since Graham appeared as a private citizen instead of agency official, as the FDA's press office told me, the agency denied my request to interview Graham. (Insert Kafka reference here.)

Thanks to Rost, CL Psych, and PharmaGossip for linking to my thoughts on the court's ruling.

The Zyprexa Chronicles: Gottstein And Egilman

Two of the central figures in the Zyprexa documents case are Jim Gottstein and David Egilman. Gottstein is a lawyer in Alaska who does tons of pro bono work on behalf of psych patients, and Egilman is a doctor and professor at Brown University who is often an expert witness in product liability lawsuits against Big Pharma. I don't know much about Egilman beyond that, but Pharmalot has a good post on his background.

I won't replay who did what to get the documents to the public. Following yesterday's federal court ruling, however, both Gottstein and Egilman face potentially serious court-imposed sanctions. Egilman reportedly has a big shot law firm back East defending him for free. Gottstein, who is expected to appeal the ruling against him, has another lawyer in Anchorage helping him out. It is not clear what kind of sanctions Eli Lilly's lawyers will seek or what the judge in the case will impose. Gottstein could face a huge fine and face potential criminal proceedings.

He is a former psych patient--he calls himself an "escapee"--and has written about his experiences compellingly. A legal defense fund has been established to raise money for his defense:

"Jim Gottstein Legal Defense Fund c/o Dominick Riccio, Ph.D. 1036 Park Avenue, Suite 1B New York, NY 10028"

The Zyprexa Chronicles: Judge's Ruling On Zyprexa Documents Is Good, Bad And Ugly

As most of you know by now, yesterday US District Court Judge Jack Weinstein handed down his ruling in the Zyprexa documents case. It was a mixed decision--defending the rights of anyone who didn't illegally obtain the documents to publish them on a website, but backing Eli Lilly's claim that the court's seal had been illegally broken and that Lilly had been irreparably harmed, as well an enjoining innocent parties such as MindFreedom's David Oaks, who never laid a paw on the documents, from doing anything with them. And so on. A lot of legal analysis by people smarter than me is out there, so go here to see what wiser minds believe.

That said, I want to point out that I respect Judge Weinstein, who's enjoyed a storied career as a jurist and legal thinker. He was involved in Brown v. Board of Education and was the judge who basically created class action lawsuit procedures in his handling of the Agent Orange case back when. I think he made a good ruling in one respect, grossly screwed up in another, disrespected psych patients with some of his language, backed Eli Lilly in terms he shouldn't have--and, then, showed a complete lack of regard for how reporters operate in order to report the news to the public. Since I am a reporter, I have some thoughts about that, but will take them up in a moment.

The good bit was that the judge effectively declared that there was no way he could control the Internet and that any copies of the Zyprexa documents on the Web are not subject to his order (unless they were subject to his earlier injunction). Such as on this site.

"Prohibiting five of the internet’s millions of websites from posting the documents will not substantially lower the risk of harm posed to Lilly. Websites are primarily fora for speech. Limiting the fora available to would-be disseminators by such an infinitesimal percentage would be a fruitless exercise of the court’s equitable power....Mindful of the role of the internet as a major modern tool of free speech, in the exercise of discretion the court refrains from permanently enjoining websites based on the insubstantial evidence of risk of irreparable harm. Restrictions on speech, even in the context of content-neutrality, should be avoided if not essential to promoting an important government interest. No website is enjoined from disseminating documents."

Thanks, Your Honor. Much obliged.

But here's one bit of legal thinking that troubles me:

"The harm faced by Lilly is amplified by the fact that the protected documents which respondents seek to disseminate are segments of a large body of information, whose selective and out-of-context disclosure may lead to confusion in the patient community and undeserved reputational harm –– 'what appears damning may, in context after difficult proof, be shown to be neutral or even favorable to the defendant.'"

I am not sure what reputational harm the judge is talking about. As a reporter, I have had real live psychiatrists tell me that Zyprexa is the worst of all the atypical antipsychotics when it comes to bad effects on patients' bodies. They have also told me that Lilly has never squared up with them about that fact. In fact, to read these documents as a whole, it is clear that Lilly knew--and knows--full well that it enjoys a poor reputation amongst psychiatrists and other doctors for the way it markets its products, for how its sales reps will chase docs down the hall to get a sale (having been a pharma rep myself once, I smile at that one), and for how they responded without compassion when faced with news of untoward side effects of their drugs. It was blame the patient and blame the underlying illness, but don't blame the drug. I have read documents that indicate Lilly was congratulating itself internally for eventually improving its image somewhat amongst docs. They had marketing surveys to back this up as well.

So what reputation are you talking about, Judge Weinstein?

Second, as a patient myself, I am staggered that such a smart judge would write "out-of-context disclosure may lead to confusion in the patient community." What patient community would that be? People locked up in state hospitals, little kids being given Zyprexa, old ladies being given Zyprexa, high functioning bipolars being given Zyprexa? Apparently, the judge's notion of the patient community was shaped in the 1960s when President Lyndon Baines Johnson appointed him to the federal bench and anyone diagnosed with a mental illness was supposed to be locked away or coddled to death by their families or the state. For the most part, Your Honor, those days are long, long gone. And what would be the problem with patients having complete information about the drugs they take and how the company that makes said drugs has behaved, conducted research and marketed its products?

It's not clear to me that the Judge believes in a free market of ideas unless those ideas come from the utterances of either Big Pharma, the FDA or astroturfing groups such as NAMI. What is clear to me is that the patient community is going to hear a lot more about what's in these documents. Then they can make up their own minds. The truth is out there.

Finally, I take considerable umbrage at the Judge's characterization of New York Times reporter Alex Berenson. The Judge found that Berenson committed a "conspiracy" to get the documents into his hands, report on them and relay the news to the public. He also called Berenson's behavior "reprehensible." According to the Bloomberg wire service, Lucy Dalglish, executive director of Reporters Committee for Freedom of the Press, called the judge's order "troubling."

"'Any time you have a federal judge finding that a reporter participated in a conspiracy, that's a frightening notion,' she said."

More like maddening. So here's the deal: Berenson was not subject to any part of the Judge's seal on the Zyprexa documents and, though he apparently knew of the seal, he was not obligated to abide by it. Why? Because a federal judge is part of the government. The government is, last time I checked the First Amendment, not allowed to take any actions to abridge a free press. That means if someone wants to drop some documents on a reporter at the Times, the town Crier or me (oh, and it's happened), then the reporter's job is to get the documents and report the truth, regardless of what any branch of the government might think about it.

We are mad dogs like that. Give us some tasty documents--the Pentagon Papers, say--and off we go to tell the public what their government is up to, what Big Pharma is doing and so on. Sometimes, the public doesn't like what we dig up. Sometimes, the government doesn't either. Big Business never likes the results. Bummer. I can assure you that if the press took a month off, the public would be crying for us to come back in two days at twice the pay. The government probably would be, too. The way reporters work is a good deal for the public. We get paid like school teachers, think like lawyers and detectives, fight like Marines where necessary and write like...oh, nevermind.

If I had been in Berenson's shoes (and I have been with other sorts of documents), I would have done exactly the same thing.

In a way, I suppose I am.

Oh, a Times attorney, George Freeman, said:

"For the reasons set forth in our letter responding to Judge Weinstein’s invitation, we declined to testify voluntarily about our newsgathering methods. Unfortunately, that resulted in an opinion which vastly overstates Alex’s role in the release of the documents. We continue to believe that the articles we published were newsworthy and accurate, and we stand by them."

Newsworthy? yes. Accurate? Has anyone heard Eli Lilly dispute the facts in these documents?

Eli Lilly spokeswoman Marni Lemons told the paper:

"Our adversaries carefully selected the documents to tell a story that they wanted to tell. These cherry-picked documents in no way reflect the strategies or activities of Eli Lilly & Company. Lilly feels vindicated because the judge issued an injunction that prohibits future wrongdoing by those who took the law into their own hands."

Cherry-picked documents in no way reflect the strategies or activities of Eli Lilly? So, Ms. Lemons, what I reported on yesterday--that your company was talking about potentially downplaying glucose increases noted in studies used to approve Zyprexa for long-term use in bipolar disorder--was based on these documents and it sure looks to me like your employees were strategizing all over the Lilly email system. I contacted your press office on Monday and asked them to respond to several questions about that document. Your people never responded. I know I am a mere blogger these days, but since the Judge seems to be OK with Internet-based media, feel free to respond at any time. Maybe we can also talk about Traci Johnson.

The same goes for you people at the FDA. Stop telling me to file FOIAs in order to get basic public information that affects millions of people that should already be freely available on your website.

Don't worry. The patient community can handle the truth.

The Zyprexa Chronicles: FDA Staffer Calls For Scrutiny Of Zyprexa

From Reuters:

"WASHINGTON (Reuters) - Eli Lilly and Co.'s antipsychotic medication Zyprexa carries risks that call for closer safety monitoring by the U.S. Food and Drug Administration, an FDA whistleblower told Congress on Tuesday.

FDA scientist Dr. David Graham said there were concerns about weight gain from Zyprexa and diabetes. Other antipsychotic medications also warrant closer scrutiny, he added."

Graham is an FDA safety expert who, in 2004, essentially outed his own agency for shoddy work in alerting the public to problems with Vioxx. It is significant that he is stepping up on this matter. More later.

The Zyprexa Chronicles: Judge Rules For Lilly

This morning US District Court Judge Jack Weinstein ruled in favor of Eli Lilly's arguments for keeping the leaked Zyprexa documents under seal. His ruling affects those named in the recent injunction, namely MindFreedom, AHRP, various websites and a few individuals. The ruling does not apply to the press however. More later, once I've been able to read the 80-page ruling--churned out within 24 hours after Lilly filed its brief yesterday. That's lightning fast by court standards. TortsProf has a post up on this already, which includes some choice language the judge leveled at some of the central figures in this case:

"Berenson’s, Egilman’s, and Gottstein’s brazen flouting of this court’s protective order raises serious questions about their responsibility. The court, based on the evidence before it, is not satisfied that they can be counted on to return all copies of the documents they may have in their possession or control. Egilman and Gottstein are therefore being permanently enjoined as noted in Part IV.H.5, supra. Berenson is not being enjoined since no injunction against him has been sought by Lilly."

Oh my.

The Zyprexa Chronicles: Bipolar Disorder Studies And Glucose Increases, "This May Be A True Assumption"

On October 11, 2002, Giedra Campbell emailed a group of Eli Lilly officials to "hammer out" clinical summary issues around at least one study on the use of Zyprexa in maintenance of bipolar disorder, according to a copy of the document I have reviewed. Campbell is a medical writer with the company. Among others, she emailed John Saunders, a Lilly regulatory affairs official in England, Doug Williamson, a doctor who was part of the Zyprexa Bipolar Team, and Mauricio Tohen. Tohen is a professor of psychiatry at the Harvard University School of Medicine and, at the same time, a Lilly employee. In other posts, I have noted that he is the primary author of many of the papers in the clinical literature on Zyprexa and that he designs the studies, which are then performed by outside researchers. Tohen is also a major shareholder of Lilly stock.

Campbell's purpose was to work out how Lilly should phrase language used in reporting what appear to be two separate studies--one gauging Zyprexa's performance as a monotherapy in the maintenance of bipolar disorder, another detailing Zyprexa's efficacy in combination with a mood stabilzer such as Lithium. Some of the language involved how to phrase data on glucose increases in patients in a company-sponsored study.

"John [Saunders] is ok with this explanation BUT has reservations about including it, because it operates on the assumption that olz [shorthand for olanzapine, Zyprexa's generic name] automatically increases glucose," Campbell writes in the email. "This may be a true assumption, but do we want to present this this way? Does inclusion of this explanation open us up to questions on glucose that we'd rather not bring up?"

It is not clear what was the earlier language to which Campbell refers. Lilly officials did not return a request for comment.

The principle data she refers to in the the email involved 361 patients with bipolar disorder who were given Zyprexa for 12 months, or a maintenance period, according to the document. At the time, Zyprexa was only approved for treating acute mania in bipolar disorder, in addition to its approved uses in schizophrenia. The company had plans to have the drug approved for maintenance, or long-term use, in bipolar disorder, as well as having it approved for use in combination with either Lithium or Depakote in bipolar disorder, according to other company documents I have reviewed.

The 361 patient study was an important one for Lilly. It appears in Zyprexa's current package insert as demonstrating the clinical efficacy of the drug in the long-term treatment of bipolar disorder. It is common for pharmaceutical companies to highlight studies for which their product gained regulatory approval in the package insert. A spokeswoman for the FDA did not return repeated requests to clarify whether this was the study used to later approve Zyprexa for maintenance use, as occurred in January 2004. Lilly officials did not return a request to clarify this point.

Campbell, the Lilly medical writer, notes in her email that of the 361 patients (225 taking Zyprexa, 136 taking a placebo), only 66 completed the entire one year trial without a recurrence of a manic, mixed or depressive episode or did not discontinue for another reason. She tells Saunders that she'd rewritten the study's language to "try to soften the 'only 66 completers' language." Almost 24 percent of Zyprexa patients in the study completed versus 9.6 percent of placebo patients. It is not clear how many of the 53 Zyprexa patients who completed the study experienced no symptom recurrence. I am unable to find the 361-patient study in the clinical literature. Lilly officials did not return a request to provide a published citation for the study.

In addition, Campbell's email details that in a study--apparently separate from the 361-patient study--of patients taking Zyprexa plus a mood stabilizer, the patients who took Zyprexa had a mean increase in glucose while patients who received a mood stabilizer and a placebo had a mean decrease in glucose. The mood stabilizer plus Zyprexa study was important, too. In 2003, not long after Campbell's email, the FDA approved Zyprexa for use in combination with Lithium or valproate (Depakote) for the treatment of acute manic episodes associated with bipolar disorder.

Regarding the glucose data language, Campbell pointed out to Tohen, Williamson and Richard Risser that "John [Saunders] suggests that if we include it, we need to pass it by Patrizia to check it against the company line on this topic." "Patrizia" is a reference to Patrizia Cavazzoni, a leading researcher at Lilly and co-author with Mauricio Tohen of several Zyprexa studies. "Mauricio--how strongly do you feel about including an explanation here?"

"I would like to include the FU glycemia issue because it points to the reversibility of the event," Tohen responded in a subsequent email on October 16, according to a copy of the document I have reviewed. "FU" refers to a code for one of the studies.

"But surely we want patients to stay on OLZ long-term, so the reversibility of the event is not an advantage?" Williamson, the doctor on the Zyprexa Bipolar Team, wrote to Tohen and others later on October 16.

It is not clear where the study's intended destination was, although in the email she refers to a department called "Publishing" and that she had mere days to get the final document to the department. Lilly officials did not return a request for comment.

In January 2004, Zyprexa was approved for long-term maintenance of bipolar disorder. In a press release, the company stated that "Zyprexa is the first treatment in nearly 30 years to be recognized by the FDA as a treatment for both acute mania and maintenance treatment in bipolar disorder." The treatment that had been approved 30 years before was Lithium, the so-called gold standard in treating bipolar disorder.

Quoted in the company press release is Frederick Goodwin, a psychiatrist at George Washington University Medical School and the godfather of psychopharmacology. "It is good news that the FDA has
now approved Zyprexa as a new tool for physicians to use to delay relapse and prolong periods of stability and wellness." It is not clear if Goodwin was aware of the glucose data.

NOTE: Reporting is based upon Zyprexa document number ZY200540696, which is available on this site's Zyprexa documents page.

A Bipolar Child Murdered: Media Mostly Asks The Right Questions

The Boston-area media continues to pound on the murder of Rebecca Riley, a four-year-old who'd been diagnosed with bipolar disorder and ADHD and was overdosed on an ADHD drug. Her parents stand accused of murder, her psychiatrist has temporarily stopped practicing medicine and the state's social services department is under fire. Area editorialists are starting to write things like:

"The death of 4-year-old Rebecca Riley of Boston from an overdose of a drug used for hyperactivity raises all manner of difficult questions about the drugs used for children diagnosed with mental disorders."

And:

"The public is left to wonder, for starters, how a psychiatric doctor could have diagnosed a 28-month-old with attention deficit hyperactivity disorder and bipolar disorder."

More here. I wonder how psychiatrists who've pushed the ADHD in toddlers paradigm and bipolar disorder in children as young as two-years-old paradigm feel about all of this right now. I think the use of psych meds in children this young needs to be dramatically curtailed, reevaluated and, yes, stopped altogether. Is this the endgame of kids watching tons of TV and playing video games endlessly? Is this what happens when kids don't play sports or run in the woods?

This whole diagnose-medicate-blame-the-"illness"-for-bad-outcomes nonsense has got to stop. It's bad enough in adults and teens, but in kids it is a complete outrage. It is interesting to me, though, that when a child dies, the skeptical questions are asked. When an adult has awful results from taking Zyprexa, say, or Paxil, the media is largely silent.

The Zyprexa Chronicles: Lawyers File Arguments On Zyprexa Documents

Last week, several of the parties to a federal court order pertaining to the release of the Zyprexa documents offered US District Court Judge Jack Weinstein their final briefs. In each the parties argue that they've done nothing wrong and that the documents, now that they are essentially in the public domain, should remain publicly available. Highlights are posted below.

Writing for MindFreedom, the Alliance for Human Research Protection and others, Fred von Lohmann of the Electronic Frontier Foundation argues:

"Eli Lilly's request to suppress public discourse about this important public health issue cannot be squared with the First Amendment."

Ted Chabasinski, for MindFreedom, makes a public interest argument and then drops this:

"[F]or most institutionalized psychiatric patients, there is no choice whether to take such toxic drugs as Zyprexa. More is needed to protect these people than some words on a package insert that they will never see....One protection could be an aroused public opinion. Another is the necessity of criminal prosecutions of those drug company leaders who promote their products by lying about