Furious Seasons

Bristol Myers Squibb To Pay Feds $515 Million Settlement

Late yesterday, the Department of Justice announced a settlement with BMS of allegations involving a range of drugs the company makes and markets, including Abilify. The company is paying $515 million. The allegations involving Abilify were these:

"Second, the Government alleged that, from 2002 through the end of 2005, BMS knowingly promoted the sale and use of Abilify, an atypical antipsychotic drug, for pediatric use and to treat dementia-related psychosis, both “off-label” uses. The Food and Drug Administration has approved Abilify to treat adult schizophrenia and bi-polar disorder, but has not approved the use of Abilify for children and adolescents or for geriatric patients suffering from dementia-related psychosis. Indeed, the FDA has mandated that the package for Abilify carry a “black box” warning concerning its use in the treatment of dementia-related psychosis. Nonetheless, BMS directed its sales force to call on child psychiatrists and other pediatric specialists, and the sales force then urged physicians and others providers to prescribe Abilify for pediatric patients. BMS also created a specialized long term care sales force that called almost exclusively on nursing homes, where dementia-related psychosis is far more prevalent than schizophrenia or bipolar disorder."

Off-label marketing. Pushing an antipsychotic on kids and the elderly. So now two companies--Eli Lilly and BMS--have been busted for these kinds of activities. More are on the way, as various states allege similar types of activities in their lawsuits against AstraZeneca, maker of Seroquel, and Janssen/J&J, maker of Risperdal. Total industry payout from this and the Zyprexa settlements now comes to about $1.5 billion (not all of the $515 million settlement relates to Abilify).

Think about that when a doctor presses you or your child to take one of these drugs. Think about that when you read a website on bipolar disorder that acts as if these drugs have no problems. There's a reason these companies are settling these lawsuits.

More to come.

The Zyprexa Chronicles: Zyprexa On French TV

The French news program "Complement d'enquete" on the France 2 network had a piece on Zyprexa last week. The piece was mostly shot in the US. Because of a bad video feed, I haven't been able to assess what it says, but it includes an appearance by the mother of someone who died as a result of taking Zyprexa, the New York Times' Alex Berenson, and images of certain documents which the show may or may not have gotten from this site.

The web link is here. If you click on the "Voir ou revoir cette émission en intégralité" link on that page, the show will come up in a streaming version. The Zyprexa portion of it is the final third of the program.

Is there anyone out there who understands French who can watch it and tell me what's going on?

UPDATE: We now have a loose account of the Zyprexa portion of the program.

"I watched the Zyprexa part -- they have Alex talking about Eli Lilly sitting on proof of Zyprexa-driven hyperglycemia and diabetes while actively marketing off-label uses, they have a mother who lost her son who was on Zyprexa, they have a mother whose bipolar daughter gained a lot of weight and developed hyperglycemia, they have the doc who blew the whistle. Then they go to Eli Lilly and ask the PR guy, Does Zyprexa cause diabetes, and he says, Love to answer that but I know that in France it's illegal to advertise drugs on TV, and I don't want to get fined for this interview if I talk about how a particular drug works. They don't seem to believe he's being completely honest with them on this point. Then they go back and talk about how much money Eli Lilly has been making on Zyprexa and how (interview with Yale doc) studies indicate that it's no more effective than older medicines, but has more dangerous side effects.

"At the end of the show, btw, they have a French psychiatrist on, and since they've covered an involuntary commitment center and a family-run outpatient care, they ask him for his views on dangerous crazy people. He says there's no way for a medical professional to predict this or that person is dangerous to others because they have a mental disorder. He also says that he wants to make it clear there is no link between mental disorders and violent behavior (presumably in comparison with the general population)."

Thanks MvB.

The Bipolar Child: 60 Minutes Takes On Riley Case

Just a brief note to let you all know that CBS' "60 Minutes" will take on the case of Rebecca Riley this Sunday. Riley was a four-year-old who was diagnosed with bipolar disorder and ADHD who was either drugged to death by her parents last year, as prosecutors allege, or was diagnosed to death, as some observers allege. The show ought to be interesting and if my intell is correct includes an interview with at least one psychiatrist who is critical of the bipolar child diagnosis. Harvard psych prof Joe Biederman will also make an appearance. Set your Tivos.

From an advance piece, Riley's jailed mom says, "Maybe she was just hyper for her age."

I'll have more on this on Monday morning. Those of you who see it on the East Coast, feel free to shoot me your thoughts Sunday evening, as the program doesn't air out here until 10 p.m. EDT.

About When I Start I Get A Worried Mind

The fall has hit with a vengeance in Seattle this year. It's pouring tonight, leaves are falling on the ground, the Mariners' season is almost over, and the big light change has begun. It's about this time of year when I start get a worried mind over myself. For most of my life, depression has stalked me this time of year (OK, last fall was pretty pain free), right up through early November. So far, no sign of the dragon, but I know it's waiting for me. For the first time since 1988, I will be doing battle without whatever advantage meds conferred upon me. We'll see how that works out.

I'm kind of glum, too. A couple of days ago, I had to kick a friend out of my life. Someone I thought I knew, but apparently did not. It's always bracing to run into that realization about someone you like, whose company you generally enjoy--and it's not the good kind of bracing. I haven't had to do that with someone in years, and it doesn't feel so grand. More like pouring rain, dark skies, baseball ending for the year, leaves that haven't changed color being blown to the ground, and someone plunging into the unknown of the future with one less friend. That's harder to do as you get older because new friends are hard to find--even harder in Seattle where people are already beginning their annual hibernation.

I hope there's less rain where you are.

FDA Lax On Clinical Trials Safety

This is so not a surprise: the agency has few inspectors, inspects few test sites and often after trials are complete. And so on.

A report is due from HHS's Inspector General later tdoay. The New York Times has this advance piece, in which no less than Art Caplan offers:

"'In many ways, rats and mice get greater protection as research subjects in the United States than do humans,' said Arthur L. Caplan, chairman of the department of medical ethics at the University of Pennsylvania."

I wonder why the feds have such a hard time understanding that regular old citizens--you know the ones who pay the freight around here--expect the agency to have a tense relationship with the companies it's supposed to regulate. But then this an agency that is set to approve Zyprexa for use in teens even though the drug has killed over 1,000 Americans.

More on this later.

Blowback!

Recently, I linked to an op-ed by Chris Lane in the New York Times in which Lane criticized just how loose psychiatry has become in diagnosing kids with social anxiety disorder and medicating them, adding that the whole thing is driven by Big Pharma's vast influence and so on. Now some defenders of the faith in the psych world are attacking Lane's assertions on the letters page of the paper. One of the attackers is Ronald Pies, a professor of psychiatry at the SUNY Upstate Medical Center. He writes, in part:

"[T]here is no credible evidence to support Mr. Lane’s implication that S.S.R.I. antidepressants are linked with increased risk of suicide in children prescribed these medications for social anxiety. The Food and Drug Administration’s initial concerns stemmed from studies in children with major depression, not anxiety disorders, and the latest evidence has not supported a strong link between S.S.R.I.’s and risk of suicide."

I'm not sure how strong Lane's implication was in his original piece (you read it and decide for yourself), but Pies' point is absurd. Trying to excuse away suicidality caused by SSRIs by saying it only affects kids treated for depression is missing the point that when you give some a medication and they become suicidal on it, but they weren't suicidal before then it would hardly matter what condition was being treated. I'm surprised that someone of Pies' standing would offer such childish rhetoric, especially since he must well know that SSRIs have caused suicidality in all kinds of conditions.

I am not immune from such silly attacks either. Everyone Needs Therapy has this to say about yours truly:

"We've got Furious Seasons who raves (as in disses) certain psychopharmaceuticals. I'm telling you now, if you're taking one of them, don't stop just because you heard it on the blogosphere! Please! If you bother with this, read my comment."

I'm not sure what inspired this since most of my 'dissing of meds is based on actual studies of the meds and real world reports. What's more, I've never advocated that anyone go off meds. I'm just trying to introduce some much needed transparency into the mental health world, as are various reporters including the New York Times. By ENT's logic, one shouldn't read the Times when it offers some tough assessments of Zyprexa, say. But I'm not surprised that my motivation gets misread. ENT's far more malicious handling of Bipolar Blast is offensive.

It's a pity, but whatever. If we cannot have free and open debate and information in the mental health world, then I guess the public will remain in the dark about just how skewed the "education" and "peer-reviewed" studies used to get them on meds forever actually is. Or that some meds have killed thousands of patients.

Yes, let's cover that sort of thing up, shall we?

The Zyprexa Chronicles: Teen Bipolar Zyprexa Study Authors' Many Pharma Ties

As I noted earlier today, a new study of Zyprexa use in teens was just published. I've just reviewed the full paper and will have more thoughts in a bit. Until then, take a look at the disclosure statement for the study authors at the end of the paper:

"Drs. Tohen and Kryzhanovskaya are employees and shareholders with Eli Lilly. Dr. Carlson reports affiliations with Eli Lilly, Otsuka, Shire, Janssen, Bristol-Myers Squibb, Sanofi-Aventis, Cephalon, and NIMH. Dr. DelBello has served as a consultant and has received research support from Eli Lilly; she has received research support from and served as a consultant and speaker for AstraZeneca; she has served as a consultant for and received research support from Johnson and Johnson and Pfizer; she has served as a speaker for GlaxoSmithKline, and she has received research support from Shire. Dr. Wozniak has served as a consultant for Pfizer and Shire Pharmaceuticals; she has received research funding from Eli Lilly and NIMH; and she has served on the speaker's bureaus of Eli Lilly and Janssen; her spouse has served on the speaker's bureaus of Cephalon, Sanofi Aventis, Sepracor, GlaxoSmithKline, and Takeda; he has served on the advisory boards of Pfizer, GlaxoSmithKline, Sepracor, SchwarzPharma, Takeda, and Boehringer-Ingelheim; and he has received research support from Pfizer, GlaxoSmithKline, UCB Pharma, Boehringer-Ingelheim, and Schwarz-Pharma. Dr. Kowatch has received research support from Bristol-Myers Squibb, Stanley Research Foundation, NIMH, and NICHD; he has served as a consultant/advisory board member for Creative Educational Concepts, Child and Adolescent Bipolar Foundation, and Abbott; he has served as Editor of Current Psychiatry; and he has served on the speaker's bureaus of AstraZeneca and Abbott. Dr. Wagner has received research support from NIMH; and she has served as a consultant and advisory board member for Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Forest Laboratories, Janssen, Novartis, Otsuka, Pfizer, Sanofi Aventis, and Solvay. Dr. Findling has received research support, acted as a consultant, and/or served on a speaker’s bureau for Abbott, AstraZeneca, Bristol-Myers Squibb, Celltech Medeva, Cypress Biosciences, Forest, GlaxoSmithKline, Johnson and Johnson, Eli Lilly, New River, Novartis, Otsuka, Pfizer, Sanofi-Aventis, Sepracore, Shire, Solvay, Supernus Pharmaceuticals, and Wyeth. Drs. Lin, RobertsonPlouch, and Xu are employed by Eli Lilly. Dr. Dittmann is an employee and shareholder with Eli Lilly. Dr. Biederman has received research support from and has served as a speaker or advisory board member for Shire, Eli Lilly, Pfizer, McNeil Abbott, Bristol-Myers Squibb, New River Pharmaceuticals, Cephalon, Janssen, Novartis, UCB Pharma, AstraZeneca, Forest Laboratories, GlaxoSmithKline, and Neurosearch; he has also received research support from the Stanley Medical Institute, Lilly Foundation, Prechter Foundation, NIMH, NICHD, and NIDA. Sponsored by Eli Lilly and Company."

Fascinating, eh? Why isn't the study author simply listed as Eli Lilly?

The Zyprexa Chronicles: Zyprexa Good For Teens, Packs On The Pounds In Short-Term Trial

Late last night, a study touting the use of Zyprexa in teens aged 13 to 17 years with bipolar disorder hit the web. It's published in the October issue of the American Journal of Psychiatry. The study was lead-authored by Mauricio Tohen, the Harvard psychiatry professor who simultaneously works for Eli Lilly. One of the other authors is Joe Biederman, a Harvard psych prof and one of the chief proponents of the bipolar child paradigm. Also listed is Janet Wozniak of Harvard. But here the study subjects are teens where the disorder faces little debate as to its existence.

And here's the quick news: in a 3-week study of acutely manic or mixed state teens, Zyprexa outperformed placebo. It also made the teens gain an average of about eight pounds during that three weeks. By the numbers, 44.8 percent of manic teens taking Zyprexa improved versus 18.5 percent of subject giving placebo who were experiencing mania (35.2 percent versus 11.1 percent for the mixed groups). I haven't seen the full study yet. But eight pounds on average out of 107 teens who got Zyprexa in the study is a hell of a lot. We all know what large weight gains mean.

So, too, does the AJP apparently and in the same issue of the journal published an editorial by Jon McClellan of the University of Washington, who is a critic of the Harvard bipolar child extremists. A sample:

"[T]he study by Tohen et al. also adds to the growing literature documenting serious metabolic consequences of the agent. The long-term consequences of obesity, dyslipidemia, and insulin resistance—and the risk of diabetes and cardiovascular disease—raise serious questions over the risk-benefit ratio of olanzapine as a first-line treatment in juveniles."

No kidding. I'll have more about this later today.

I've previously written about Tohen here and here, Wozniak here, Biederman here and McClellan here.

Atypical Nation: Abilify TV Ad Targets Women

I've just viewed the Abilify TV ad online and BMS is clearly marketing the drug at women. From the sound of symptoms they describe, it sounds like an ad for a bipolar disorder 2 treatment. You can view the ad here (just be patient and let the screen flip several images at you and then you should be able to click on a little banner to watch the ad). If anyone can get that puppy into YouTube form, send it over and I'll post it. Or would my readers at BMS prefer to just send me an mpg?

Here's the reaction of one reader who viewed the TV ad recently:

"It basically goes like this: attractive, 20-something woman is walking through a path in the woods on a gloomy day, looking sad, and passes by family and friends who look at her from the side of the path. They look sad too, as if there's nothing they can do to help her. Meanwhile, the soothing announcer asks if you feel sad, etc. Then, the announcer lets you know that Abilify is the answer to your problems. The woman walks out of the woods, and has a friend with her on the path. Then the disclaimers start. And continue. And continue. What's amazing is that the disclaimer actually lasts longer than the ad. And my boyfriend pointed out that death is mentioned no less than 3 times. "Take home message--Abilify might kill you, but at least you'll be popular."

Well, who doesn't want to be popular?

The Zyprexa Chronicles: Zyprexa Set For Teen Approval

And just in time for the new school year.

Pharmalot has news that an FDA official has overturned objections of colleagues, who recommended not approving a new indication for Zyprexa, and set the drug on its way for almost-certain approval by the agency for use in pediatric cases. It's not clear to me exactly what age range that means, but we'll see when the FDA's approval comes.

Go read Pharmalot for a good rundown of many issues in this case, including news that the drug fattened up almost half the patients in a short period of time. What's also interesting to me is that the approval trials were done in Russia. Several FDA officials noted internally that Lilly's ease ay rounding up research subjects in Russia struck them as suspicious.

I find it galling that given just how much is now known about injuries caused by this drug--known to anyone with eyes that can read--that the FDA would feel comfy approving the drug. Or that one official would overturn the recommendations of colleagues. Perhaps the agency is trying to drum up business for the its adverse events reporting unit. Whatever.

Once the drug is approved, it ought to be interesting to see how Lilly handles marketing the drug to doctors and how it counteracts the drug's negative press (not to mention a growing set of accusations in lawsuits filed against the company by nine states), especially since docs have steered away from prescribing the drug in adults.

From Bloomberg:

"'These medications may help some patients, but I'm worried FDA approval may lead to rampant prescription writing,' said Steven Klotz, a child psychiatrist in Harrisburg, Pennsylvania. 'I don't want drug reps telling pediatricians every adolescent that throws a tantrum is bipolar and should get antipsychotics.'"

You can vote on whether you think Zyprexa should be approved for teens over at Pharmalot.

Oprah On Bipolar Disorder, Part 2

After mulling it over for a day, I've come around to the idea that Oprah, who featured bipolar disorder and several examples of the same on her program on Monday, is out to paint bipolars as inherently violent and dangerous. I've not seen a lot of data on this point. Most of the research on violence and mental illness has been done on schizophrenia and shows a risk that is not particularly elevated above the general population.

I wrote about the program here yesterday.

But this is Oprah and she gets to do what she wants, data or no data. Why Kay Redfield Jamison, who appeared on the program and should be acutely aware of this issue, didn't peep in protest is beyond me. She appeared to be on the program to lend some medical authenticity to the affair and get a major plug for one of her books, which have been strong sellers for years and have had major media plugs aplenty. Jamison is an odd case--she's a professor of psychiatry, works in private practice as a psychologist, has oodles of money and privilege, and yet I have never heard her speak up on behalf of her brothers and sisters when they are getting kicked around by the media. There literally hundreds of thousands, if not millions, of positive stories around people with bipolar disorder, and she stands aside and let's the talk show queen get away with painting the rest of us who work very hard on these matters with the problems and bad outcomes of three other people, two of them Hollywood actors and one a convicted murderer.

If Jamison cannot start standing up when she makes her many media appearances, then perhaps it is time for her to stand down.

On its blog, the Treatment Advocacy Center complained that, Oprah didn't get into what the group sees as the benefits of outpatient commitment. I'm not sure where outpatient commitment would even apply to the two actors and Kay Redfield Jamison, and I am not convinced at all, based on what the program showed, that Andrea Petrosky was non-compliant with treatment in a way that outpatient commitment would be called for. As I noted yesterday, I think her case is clearly one of bad doctoring, misdiagnosis and bad medicine, and major screw-ups by Andrea and her husband. The woman should've been in a psych unit, plain and simple, not staying home with her child.

Although one commenter who apparently knows the couple insisted that the husband is a good man--and I don't question that--I still think he dropped the ball the night before his wife killed his son. Andrea slashes herself up with a knife and the husband doesn't move heaven and earth to get her to a hospital for an evaluation? If he did, I've encountered no evidence of this. Cutting like that, especially when it's a new behavior for the person, is a major alarm bell, and should be addressed immediately, in particular if the person has been unwell for a time as was the case here. Sadly, Petrosky could've been headed off at the pass. If someone knows differently about how things played out, please let me know.

The other thing that sticks with me is that something weird seems to be going on in Virginia. Cho at Virginia Tech, a young man in Fairfax gunning down cops last year, and the Petrosky case. I know the state has a troubled mental health system, and that a lot of individual factors are present in each case. But something more than random seems to be at work here, and I am not sure it's just a matter of commitment laws and access to medical care. Anyone have any thoughts on this?

And, yes, like many readers, I am sick and tired of Hollywood actors being the go-to bipolar examples on shows such as these. They are poor proxies for the reality the rest of us live with. But have no fear: I hear that Sinnead O'Connor is coming out as bipolar on Oprah next week. I'm so happy. The Irish singer and the rest of us have so much in common.

Abilify Ad On CNN

I heard from a reader who's seen ads for Abilify, an atypical antipsychotic, on CNN. If anyone has seen this ad, I'd appreciate it if you could shoot me a description of the ad and what condition it was being aimed at, as well as what time of day you saw the ad. I've seen some fairly weird ads in my life for some fairly weird products, but never an ad for an antipsychotic on TV. It stuns me that BMS would even need to advertise the drug on TV and it tells me a lot about where we are as a culture just as the Abilify phone booth ads did earlier this year.

We live in weird times.

Second Anniversary

Today marks the second anniversary of this blog and this post is the 1,000th post on the blog. My friend and sometime contributor Puckett has written a half-dozen or so posts. The rest are mine. That works out to about an average of 2 posts a day, allowing for weekends, holidays and a few days of slackerness here and there (hey, I've had a day job much of the time!). More surprising to me is that this blog is at 4,100-plus comments, or about four comments per post (although most of them have come in 2007). I thank you all for your interest in what I write. It's humbling in ways I don't have words for.

In other news, I'll soon have an announcement about the future of this site.

Oprah On Bipolar Disorder

Talk show queen Oprah Winfrey did a program on bipolar disorder yesterday. Her show is the number one talk show in the US--it's viewed by 46 million viewers a week here--and is also broadcast in 134 countries. I was not able to catch the program when it aired on the West Coast, as I was working on some freelance articles. I did see the promos for the program, so I got an idea of where they were heading and have reviewed a copy of what looks to be the air script.

I'm a bit busy with outside work to do a full walk-thru of the show (I'm actually writing this at about 10 p.m.), but I'll get to that later today. Oprah's show has too prominent a place in our culture--or should I say in world culture?--to ignore the program and what it did well and what it did poorly, and so on.

I know many of you saw the show, so I hope you'll pass along your thoughts in comments or by email.

Most viewers will likely cling to one segment (of four) involving a woman from Virginia only identified as Andrea--Petrosky to go by a very odd report in a Roanoke paper in advance of the show--who killed her son in 2005. She blames bipolar disorder, which she was later diagnosed with in prison, but a jury found her guilty of murder and she's in jail for 42 years. It's not clear to me if her appearance on Oprah's show was an attempt to begin a campaign for re-sentencing--likely to a psych facility--but reportedly she appeared without consulting her attorneys. Having dealt with the whole convicted murder and media dynamic before in a professional capacity, I can tell you that convicts don't talk unless they want something. But, then I am a natural skeptic, and am perhaps being a bit tough here. Still, Oprah failed to offer an answer to that inherent question--and anyone in the media knows that when a convicted murderer chooses to speak publicly then that issue has to be addressed.

What jumps out at me: her friends describe her as being a bit screwy most of her life, and as a super mom; Petrosky had been diagnosed with depression by a doctor; she had a bad reaction to an unidentified anti-depressant, which made her manic; the night before killing her son, she slashed herself with a knife repeatedly; her husband apparently did nothing (that alone is stunning to me) to get her immediate medical help; then, she strangled her son, after reportedly hearing voices.

The newspaper I referenced above identified her as having bipolar disorder 2. I was not aware that delusions and psychosis were one of BP 2's criteria (OK, they aren't and the paper cites her lawyer as an expert on the subject. Weird). But whatever the case, her case is a dropped ball times ten. And I'll come back to that later today.

Until then, I'd appreciate your thoughts.

Seattle Suicide Bridge May Get Barrier, Adobe Execs Could Care Less

I noted last week that the Seattle Times had written about the Aurora Bridge, Seattle's version on the Golden Gate Bridge. My article on the Aurora Bridge problem came out in Seattle magazine this week. Here's a link to the online version. Not sure if my piece is better than the Times', but it's got some fabulous pictures taken by Brian Smale. You'll have to buy the print version if you want the pics.

My very real hope is that the Washington State Legislature will cough up the $5 million needed to put a barrier on the bridge to prevent people from hurtling to the ground below (instead of a narrow slip of water) where they've rattled the local neighborhood for years. Now, with new businesses in the area, they are traumatizing high tech workers at Adobe and Impinj, offices for which are next to the bridge.

Once, in Portland, I happened upon a jumper soon after he'd hit the pavement. It was not a pretty sight, and has stayed with me ever since. I can understand why the neighbors and workers end up being rattled by what they see.

When I reported the article, officials at both Adobe and Impinj did not return requests for comment. In Adobe's case, someone connected with the company told me they considered it too controversial to comment upon. What a bunch of fools--irresponsible ones at that who apparently could care less about the welfare of their employees. If i could exist without using Adobe's pdf and Flash, then I would show them how I feel about their silence.

By comparison, Seattle police and union officials had no problem going on the record asking that something be done because cops are basically sick of putting themselves at risk of being pulled off the bridge while trying to talk down would-be jumpers. I guess we know who the adults are in this situation.

In addition, I have to compliment a small group of local citizens going by the handle of Seattle FRIENDS, who've done much to press local officials to do something about this situation. Here's the group's website. It's one of those rare moments when you see a bunch of citizens get together and force change without the stench of politics in the air.

From last week's posting on this, I know some will criticize the barrier as little more than an attempt to assuage the feelings of glossy high tech workers when the problem has been going on for 76 years and the money can be used for other purposes. Let me put it like this: let's say there's a highway with a corner where four or five people die in car crashes each year and have for years. One day, a developer builds a new tract of homes in the area and builds a park where children play near the corner. After a few more crashes and deaths and children shaken by seeing headless torsos and such, the parents press the local government to put up a stop sign at the corner. The crashes stop, the deaths stop, the kids continue to play in the park. This is kind of like that.

And if you cannot understand that, then I cannot help you.

Suicide Rates As A Public Relations Tool

That's the headline on this op-ed in the Boston Globe yesterday. Penned by Alison Bass, a former medical writer for the paper, it's like I could've written it myself. She rips apart the recent Gibbons paper in the Asmerican Journal of Psychiatry which had all manner of illogic in it and which I and others have ripped apart endlessly. Bass asks why some docs insist on pressing the SSRI-Rx-drop-causes-suicide hypothesis the way some folks believe in virgin birth.

"Who stands to benefit from the latest alarm about an apparent upturn in youth suicide rates? The sharp drop in the sale of SSRIs since 2004 has put a big dent in their manufacturers' bottom line. These companies have an enormous stake in reversing the current FDA warnings. That might explain why Pfizer (the maker of Zoloft) contributed $30,000 to cover the cost of collecting data for the American Journal of Psychiatry study, which was also funded by the National Institute of Mental Health. It's also worth noting that the two lead authors of the paper have disclosed financial conflicts of interest: Columbia professor of psychiatry Dr. John Mann has been a paid consultant to at least two SSRI makers, Pfizer and GlaxoSmithKline (the maker of Paxil), and Robert Gibbons has served as an expert witness for Wyeth Pharmaceuticals (the maker of Effexor, another SSRI)."

A couple of errors in Bass' copy, however. Effexor is not an SSRI. It's an SNRI, or serotonin-norepinephrine reuptake inhibitor. She also claims that 2005 suicide data is not available yet. In fact, the figures recently became available, as I noted recently, and while they are preliminary, such numbers don't undergo much revision when they become final--and they sure serve to bolster the argument of those who, like me, believe that anti-depressant prescription rates are not tightly linked to suicide rates. The evidence is simply more mixed than some in the psych world would have you believe.

But I sure agree with the thrust of Bass' op-ed. As I've stated before, the Gibbons paper's flaws much be addressed promptly by the AJP. Unless the journal happens to believe in virgin birth. (Via The Trouble With Spikol.)

Atypical Nation: Arkansas Plans Suit Against Eli Lilly, AstraZeneca And Janssen

Late last week, Arkansas' Attorney General, Dustin McDaniel, informed legislators that his office is on the verge of suing the makers of Zyprexa, Seroquel, and Risperdal over off-label marketing schemes involving the use of their drugs in the state's Medicaid program. The lawsuit has not been filed yet, so specific accusations will have to wait an expected three to four weeks, according to this report in the Arkansas Democrat Gazette. If it follows the pattern of nine other states which have sued Lilly, most prominently, and the other companies, then it should relate to use of the drug in schizophrenia, bipolar disorder, dementia, depression, ADHD and include accusations of drug safety violations. The suit would also likely include accusations surrounding use of the drugs in children. Pharmalot has some thoughts here.

From the article:

"McDaniel told reporters after the meeting that researchers have known since the 1950 s that anti-psychotic drugs had serious side effects, including weight gain, hypoglycemia and Type II diabetes.

“'What [the three companies] did was intentionally hide that and downplayed the efficacy of alternatives,' he said.

"McDaniel said the companies engaged in a 'marketing scheme that was very effective to where a drug that was never approved by the [federal Food and Drug Administration] for children... the elderly... or run of the mill behavioral disorders like depression, all of a sudden was touted to America’s doctors, Arkansas ’ doctors, as a miracle drug. So, a child that has [attention deficit disorder] is taking a drug that was never authorized for that child, causing serious complications... that could last a lifetime.'"

Arkansas was mulling joining an expected multi-state lawsuit against the companies, but decided to go it alone. Apparently, the AG felt his smaller state would get lost in the shuffle as much larger states joined forces to go after the three principle makers of atypical antipsychotics.

The state plans to use its anti-fraud statutes against the companies. Reportedly, the state has spent $200 million on the three drugs over the past eight years and could collect as much as $600 million in damages. It's difficult to estimate how much the companies could be liable for in a multi-state action, but it's safe to say that, counting in the other states lawsuits, that the three companies could be on the hook for from $25 billion to $50 billion. That's my own estimate.

If the companies were to settle their claims, the payout would be perhaps half of that amount. It is not clear what effect this would have on the companies' stock prices.

Eli Lilly has already settled approximately 30,000 suits against it brought in three separate class action lawsuits for about $1.3 billion. To date, suits against Janssen/J&J and AstraZeneca have not resulted in any awards or settlements, but cases against the companies are ongoing in state and federal courts. At last report, one lawsuit against Lilly over accusations involving Zyprexa was set to go to trial in federal court in New York in October.

As I reported last week, Zyprexa and Risperdal have been linked to the deaths of 2,098 people, according to the FDA's adverse events database. The two drugs have also been linked to 7,145 reported non-fatal adverse events. The FDA's adverse events database is considered by experts to represent only a fraction of adverse events related to a drug in a particular year. Numbers for Seroquel were not available.

More on this story as it develops.

More Evidence That Anti-Depressants Are Bad For Bipolar Disorder

As I noted in March, the recently-completed STEP-BD study found that anti-depressants were virtually useless in treating bipolar depression. In fact, a placebo beat the meds. Now, comes another paper from STEP-BD showing that anti-depressants are ineffectual for depression in bipolar disorder.

This time out, researchers measured the effect of using anti-depressants in patients with co-occurring manic and depressive episodes, or mixed states. Results:

"In bipolar depression accompanied by manic symptoms, antidepressants do not hasten time to recovery relative to treatment with mood stabilizers alone, and treatment with antidepressants may lead to greater manic symptom severity. These findings are consistent with those from the STEP-BD randomized trial for pure bipolar depression, in which adjunctive antidepressants did not yield higher recovery rates than did mood stabilizer monotherapy."

No surprise there. An editorial in the same issue of the American Journal of Psychiatry noted:

"[T]his article adds to the growing evidence that in the setting of adequate therapeutic mood stabilizer prescription, the addition of antidepressants appears to provide little additional benefit for depressed bipolar patients but may impart a risk of switching to mania."

So why is it that doctors continue to prescribe anti-depressants for bipolar disorder? Don't they read research articles? Anti-depressants have been handed out like candy to bipolars since the late-1980s and now it makes you wonder just how much of this was the result of possible off-label marketing of the drugs--which remain unapproved for use in bipolar disorder--especially in light of the damage they've caused bipolars. I have to count myself as one of those unlucky many.

I remember going to my psych doc several times in the mid-1990s, complaining of increased rather than lessened depression while on Lithium and a host of anti-depressants, and also complaining about a feeling of agitation on the meds. He assured me each time that research showed that anti-depressants worked for bipolar disorder--and so each time I accepted his decision to either dramatically up my dose of Prozac or switch to Paxil or Zoloft. And, then, came the awful suicidality which I contended with for well over a year. Fun times.

So what are doctors to do when faced with a patient with bipolar disorder with strong depressive symptoms? A subject for another day.

Thinking Blogger Award

Psych Central kindly gave me a thinking blogger award the other day and now I am supposed to mention five blogs in return. When this went on six months ago or so, we ended up with a rotating list of the usual suspects. So I am going to avoid adding to the fame and glory of Psych Central, CL Psych, Mind Hacks and the like, and focus on some lesser known blogs that generally don't get enough attention (yes, there are more than five of those!)

Soulful Sepulcher
One of the most gut-wrenching reads on the 'Net, the author regularly details the life of her psychotic daughter and her struggles in dealing with this as a mother.

Beyond Blue
Spiritually-based, it shows that there's more than one way to slaughter depression.

The Last Psychiatrist
This is simply one of the best medical blogs in existence. The author is funny, outrageous and likes rum. 'Nuff said.

Intueri
The blog of a psychiatry resident who is soon to land a fellowship back East, it's a great entre into the mind of a young doctor who genuinely struggles with many of the key issues in mental health care. Too bad so many veteran docs struggle much less.

AHRP Blog
Vera Sharav, AHRP's leader, was on the witness stand before Judge Jack Weinstein last January. She was a central figure in the Zyprexa documents case and under questioning from one of Lilly's lawyers proceeded to say in open court that Lilly had covered up evidence that Zyprexa injured patients. She said, "I consider that a major crime and to continue to conceal these facts from the public is I think really not in the public interest. This is a safety issue." The lawyer moved to strike her comments from the record. The judge declined. Her blog is just as gutsy as her performance that day.

Now, these folks are all supposed to list five blogs that make them think.

Medicating Shy Kids

An op-ed in yesterday's New York Times goes after the medicating--or is it over-medicating--of shyness in kids. It's a good overview of how fairly normal human emotions that have been around for thousands of years are now considered a mental illness and suitable for Paxil and Zoloft, some of the spookiest psych meds on the market. The author, Christopher Lane, also goes after how all-capturing diagnostic criteria have become over the last generation. That's a concern I share--not only with social anxiety disorder but with bipolar disorder.

Here's a bit from the piece:

"The recent book “Nurturing the Shy Child: Practical Help for Raising Confident and Socially Skilled Kids and Teens,” insists, “Don’t be afraid to try medication.” “When an S.S.R.I. is properly prescribed and monitored, medication can be very helpful,” say the authors, two psychologists. This book says it is a sign of social anxiety disorder if a child complains about or tries to avoid asking the teacher a question or getting up from his or her desk to sharpen a pencil.

"Clearly, there is a need to reconsider the diagnostic standards. A team of mental health experts has recently gathered to oversee a new edition of The Diagnostic and Statistical Manual, and this time they should make sure to carefully distinguish normal — even healthy — shyness from social anxiety disorder. They should also remove shyness from the lists of symptoms of avoidant personality disorder and schizoid personality disorder. With so much else to worry about, psychiatry would be wise to give up its fixation on a childhood trait as ordinary as shyness."

Speaking of the DSM, I head through the rumor mill that Scientific American is about to run a piece with documentation establishing that the so-called revolutionary DSM-III of 1980 was deeply controlled by pharma companies. If anyone sees the article, please pass it along.

Exercise As Good As Anti-Depressants

At least that's what this new study claims, not that it's news to anyone that exercise is good for depression. Which makes you wonder why they needed to do this study in the first place. It's 2007 and docs still need someone to go out an quantify that exercise is good for people who feel down? Please. Then again, we are talking about psychiatrists, the branch of medicine that almost never even weighs their patients or takes their blood pressure. Which would kind of be a good idea given some of the wacky meds out there these days.

One thing struck me as odd about this study: they used Zoloft as their anti-depressant. Is that shit even prescribed anymore? I cannot think of the last time I heard of anyone taking it. Or maybe it's a Seattle thing.

I also find it fairly dubious that Zoloft could fix the depression in 47 percent of the patients in a 16-week trial. That number strikes me as oddly high. Exercise worked for 45 percent of patients.

Hm, exercise or taking a pill that's well-known the strip away human character? Such a hard choice.

Off Meds Update #3, And Thanks

A few of you have recently written to ask how things are going now that I've been off Lamictal, the last psych med I was taking, for two months. Thanks for even asking. I'm a bit tired, so my thoughts will be brief and badly-formed.

Once I got past 10 days or so of withdrawal hell from Lamictal in late July, things have gone quite well. Except my back went out, likely in response to coming off meds after 18 years of having a whole bunch of juju in my central nervous system. I was in agony from back pain and spent the better part of a week on the couch. When I wrote, I was in screaming pain. This happens when you don't have health insurance. But I was able to do some very improvised self-care and eventually worked the tightness and knots out of most of my back.

Now, I feel great. Better than well, as the classic "how does Prozac make you feel" line goes from Kramer's Listening to Prozac. The deep irony of me telling you all this during this week is that it is this week that marks my 18th Anniversary as someone with bipolar disorder. I like irony. A lot.

I'll have further reflections on this in the near future. For the moment, I want to stress that my circumstances are fairly unique and I've put myself in a position where I have few major stressors in my life right now. It's way, way too early to say if I am one of those bipolars who gets to make it to the other side, so I am trying to remain humble about the whole process and see what happens. And, yes, this was partly my doctor's idea. We are conducting an experiment with an N=1. And that's the only sample size that matters.

More later. I deserve a beer and I'm going to go have one.

In addition, I truly want to thank my readers for making yesterday the heaviest day of hits on this site since the glory days of the Zyprexa scandal. Perhaps even heavier, but I didn't have a proper stats counter on my site then. It was also the heaviest day of reader comments since February. Which is cool.

Pills, Booze And Chantix

As I noted yesterday, a Dallas musician wound up being shot to death after having a bad reaction to a combination of Chantix, a smoking cessation cum anti-depressant made by Pfizer, and some booze. He apparently tried to break into a neighbor's house while spun up on the pills and booze. The neighbor had a gun and shot him dead.

We all know of bad reactions to psych meds stories--and, yes, I count Chantix as a psych med--but this kind of tragedy could have been avoided. I generally avoid talking about how people should take meds and live and so on, but here's one iron-clad principle: If you are starting a med (especially if you are a first timer), going off a med or changing a dosage, you must be very careful about how much you drink and should only drink under controlled circumstances until you know what you can handle. Psych meds can do very tricky and tragic things to the human brain and force all manner of untoward human behaviors. I've seen this firsthand many, many times, especially with anti-depressants for some reason. It's sad.

Be careful out there.

If readers have any Chantix stories, pass 'em along. It's still a new drug and we need to start getting a picture of how folks who are trying to quit smoking are doing on this pill.

Senate Passes Mental Health Parity

I'm late with this: on Monday, the Senate passed mental health parity legislation. It was approved unanimously, which is stunning to me given all the years that members of the GOP fought the bill. The bill moves onto the House which already has enough co-sponsors for the bill, 270, to pass the legislation.

Perhaps one day the treatments and care covered by this landmark legislation will work as smoothly. I'm not holding my breath.

Statements were issued by MHA, and NAMI.

The American Psychiatric Association's president, Carolyn Robinowitz, offered this: "We know firsthand that treatment works."

Perhaps she missed my reporting yesterday on the 6,000-plus deaths reportedly caused by several psych meds. The American Psychological Association had nothing to say about the bill's passage.

Chantix Tied To Musician's Death

OK, this is a sad, weird story. A Dallas musician and his girlfriend decide to quit smoking and begin taking Chantix, made by Pfizer, which is approved by the FDA for smoking cessation. A few days later, the musician goes out for some drinks and comes home completely off his nut, something the girlfriend says she'd not seen in him before. She says she'd never seen him be a crazy drunk either. Anyhow, musician ends up hammering on the door of a neighbor late at night and the neighbor responds by shooting a gun, fearing that someone is breaking into his home. The musician died. The girlfriend blames Chantix.

It's not clear to me how similar the drug is to an SSRI, but if it's anything like them, then I'd blame the drug too. Or the drug-alcohol interaction.

Apparently, a fair number of people have run into problems on this newish drug. Goes to show you that quitting smoking can be as dangerous as smoking, I suppose.

Worse Than Vioxx: Zyprexa, Risperdal, Clozaril, And Paxil Killed Thousands Of Americans

Last week, there was much media coverage of a large jump in adverse events reports and deaths due to the use--and, perhaps, misuse--or prescription drugs. Most of the coverage cited the general trend, noted how many thousands of deaths occurred among users of opiate painkillers, and moved along. I wrote about the study here, but at the time had not obtained the entire paper. I have rectified that situation.

What the media failed to report is that Zyprexa, Risperdal, and Clozaril, three atypical antipsychotics, and Paxil, an SSRI anti-depressant, were tied to the deaths of 6,225 Americans from 1998 to 2005. These numbers are shocking and far outpace estimates I've run into previously. That this data was not reported by the media is inexcusable, given the millions of Americans--and others around the world--who take these four drugs.

The numbers come from a study in the Archives of Internal Medicine and are based upon reports in the FDA's adverse events database. There are limits to the numbers from this study. I'll get to those in a bit. The study may be accessed here.

Since news broke around Zyprexa last year and accusations that its maker, Eli Lilly, had downplayed and covered up known injuries caused by the drug, the media has not provided an accounting of how many people died as a result of taking the drug. For my part, I downplayed the numbers I ran across in press accounts and in the Zyprexa documents. I didn't want to cast false aspersions.

But, now, I can say this: Eli Lilly, your drug killed 1,005 Americans. And, Janssen/J&J: your drug killed 1,093 Americans. GSK and makers of generic Paxil: you guys make a drug that killed 850 Americans. As for Novartis, makers of Clozaril, and whomever makes its generic form: you asshats killed 3,277 Americans. The doctors who prescribed these drugs are just as responsible, ethically if not legally.

And I have a question for you guys: How's it feel?

Excepting Paxil, each of these drugs killed more people than Vioxx, which claimed 932 lives, according to the study. Vioxx was pulled from the market in 2004, following intense publicity around its association with heart attacks. Some estimates of deaths related to Vioxx go as high as 55,000 deaths, but I don't know how solid those numbers are.

Zyprexa, Risperdal, Clozaril, and Paxil are all still on the market in the US. Zyprexa and Risperdal account for about $8 billion in sales each year. Why are these drugs still available? Partly because the FDA allows them to remain on-sale, partly because researchers continue to go to bat for these drugs, and partly because the media has failed to adequately police these issues (the New York Times gets a pass from this criticism).

Back in 2004, America's media spilled ink all over the street about Vioxx. Good, decent, hard-working Americans taking that drug for arthritis and other pains were having heart attacks and dying out of the blue. That wasn't right--any editor could understand that--and the media responded appropriately.

So why is it that the New York Times was virtually alone in reporting on Lilly's attempts to downplay problems with Zyprexa and accusations that it marketed the drug off-label? The documents were in the hands of NPR, the Wall Street Journal, and the Washington Post--and yet these media giants remained largely silent. Wimps.

I know some far-flung reporters are trying to now play catch up. Good for them. Just a note for you guys: Zyprexa and Risperdal aren't just so-called "crazy people" drugs, or for schizophrenia and chronic mania, if you prefer. They were actively pushed by their makers for use in lighter forms of bipolar disorder, depression, and dementia--hardly the crazy folks the media seems to have been willing to blow off as unimportant somehow, at least in comparison with the solid citizens being wounded by Vioxx. And, these drugs were actively pushed for long-term use, not just a day or two here and there. Most outrageously, Risperdal, a drug associated with over 1,000 deaths, is used in children--and the FDA approved its use. In the case of child bipolar disorder, Risperdal is being used in children when psychiatrists cannot even agree upon whether the diagnosis exists and if using atypicals is an appropriate response.

Something is deeply wrong with this picture and its time for this rotten situation to be cleared up. That means it's time for the FDA, Congress and the media to do their jobs. And it's time for the doctors who prescribe these drugs to wake up and recognize that you are endangering your patients.

What I find puzzling is that I've been told by numerous practitioners that no one prescribes Clozaril anymore due to known problems with the drug. But the Archives report also contains data on non-fatal adverse events and breaks them out by year between 1998 and 2005. There were more adverse events reports for Clozaril in 2005 than there were in 1998. I've been told that Paxil scripts are way down too, but in 2005 there were over twice as many adverse events reports for the anti-depressant as in 1998. Some of this can be explained by the argument that the adverse events reporting system is still fairly new, that reporting is voluntary, that other factors may explain the events (for example, multiple drugs in the same patient) and that the boost in events reports in the last few years can be explained by lawyers pushing clients to file reports with the FDA. Maybe.

Keep in mind that if lawyers were really pushing their clients to file adverse events reports willy-nilly, then there would be approximately 30,000 or more adverse events reports in the FDA system for Zyprexa alone--one for each plaintiff in lawsuits already settled by Lilly. According to the study, there are only 4,110 adverse events reports on file for Zyprexa. By comparison, 8,698 adverse events reports were filed for Vioxx.

Why aren't there 30,000 or so events reports for Zyprexa, for example? Likely because plaintiffs who settled claims against Lilly signed a confidentiality agreement and are reportedly muzzled from speaking to the press about their experiences and probably also believe that they cannot make reports to the FDA. That's some breathtaking legal advocacy by Lilly's outside attorneys and some bizarre work on the bench by US District Court Judge Jack Weinstein.

As for adverse events as a whole, several psych meds had more than 500 adverse events reports between 1998 and 2005. In order and using brand names:

Paxil--8,945
Clozaril--7,665
Zyprexa--4,110
Effexor--4,049
Zoloft--3,781
Neurontin--3,215
Risperidone--3,035
Lamictal--2,317
Depakote--2,158
Tegretol--1,944
Cymbalta--1,053

Some of the Depakote, Tegretol and Lamictal events could be as a result of their use in epilepsy. Cymbalta's reports would be based on less than two years of patient experience since the drug was approved in 2004.

I'm not trying to ignore the rest of the world, but I simply don't have access to many numbers concerning these drugs in other countries, except for the 399 deaths recently reported among Australians who were given atypical antipsychotics.

In closing, I want to cycle back to a post I did over a year ago. In it, I groused that a thought leader in the medical community had told me that Zyprexa's use was, on the whole, therapeutic for patients. I wonder if he's even read the Archives study.

09-18-2007 Media Madness

I've been remiss on doing roundups the last week or so. Here are just a few things I've found interesting in the last few days:

CL Psych notes that Decision Resources was for Zyprexa as the gold standard in treating schizophrenia before they reported it was losing market share. He notes further problems with the Gibbons SSRI-suicide paper--um, like not running statistical tests. The AJP and APA are going to address the problems with this paper, right? And, in a classic moment, catches his favorite researcher Charles Nemeroff, saying serotonin plays a role in depression and, then, saying it doesn't. What I want to know is which of those statements was ghost written for him by a pharma company.

Pharmalot gets an Rx tracking firm to run the numbers on anti-depressants around 2004. Once again, no drop in scripts in 2004.

The Last Psychiatrist has some interesting thoughts on the 2004 suicide data and the attention it received.

Soulful Sepulcher on moms loving their kids and more Munchausen Syndrome by Proxy nonsense that's resulting in the British government planning to take a young mother-to-be's baby away from her because she's a rape victim who used to be a cutter. Liz Spikol calls it a human rights violation. I agree.

John Grohol also takes a peek at the Gibbons paper and is amazed at how such a sloppy bit of work could've cleared review hurdles at AJP. The Boston Globe notes that whatever the data shows you cannot tie the '04 suicides to the FDA black box warning. Grohol also has a great piece on abuse allegations at a state hospital in Delaware. State hospitals are as bad as jails for this kind of thing.

Chris Iris has a post at Psych Central on these "tell us all about you and win an award" contests from Big Pharma and advocacy groups. He wonders if he would win were he honest and wrote about how hopeless he feels, at times, with bipolar disorder.

Speaking of Big Pharma feel-good awards, Lilly is looking for nominations for its "Welcome Back" depression awards.

I wanted to note that I appreciate the huge surge in readers the last week or so. People seem to be very interested in the Zyprexa documents. I wonder what the sudden interest is about.

Stopping Bridge Jumpers

Yesterday's Seattle Times had a fine article on attempts to get a suicide barrier erected on the Aurora Bridge, one of the very worst suicide bridges in the world. The article was on A-1, very unusual for an article talking about suicide in an American daily newspaper. On the order of 300 people have leaped to their deaths from the bridge since it opened in 1932 (four suicides a year is the estimated average, but last year it was nine). Many citizens in the Fremont neighborhood of Seattle, where the bridge is mostly situated, have banded together to demand that the State of Washington put up a barrier to stop the jumpers.

And it's not necessarily because of concern for the jumpers (although that is part of the story), but because the half-mile-long bridge is mostly over land and, in recent years, an increasing number of jumpers have not leaped into the Lake Washington Ship Canal 170 feet below, but instead have hit dry land and parked cars. In the past, neighbors put up with this situation, but because several high tech offices have opened in the vicinity of the bridge in recent years--namely, Adobe, Impinj, Getty Images and Google among them--we now have the situation in Seattle where innocent people are having to watch desperate people crash into Earth right in front of them. The bystanders wind up traumatized and so on.

Also, police officers I've spoken with are tired of having to talk down jumpers up on the bridge itself--this happens as much as three times a week--because they could easily end up getting pulled off the bridge themselves. It amazes me that that hasn't happened in the bridge's history.

I believe a barrier on the bridge would end this problem. But i'll have more to say about this sometime next week. You see, I've written an article for Seattle magazine about this bridge and it ought to be online then.

The Zyprexa Chronicles: Zyprexa Loses Market Share

According to Decision Resources, a market tracking firm, Risperdal and Seroquel have overtaken Zyprexa as the go-to antipsychotics in treating schizophrenia. I mostly pass along this news on a for-what-it's-worth-to-ya basis. I also found this quote from the press release interesting:

"'Zyprexa dominated the schizophrenia market just two years ago; however, recent focus on the drug's risk of weight gain and diabetes has changed physician perception of this agent,' said Sandra Chow, analyst at Decision Resources. 'With the launch of new formulations and line extensions over the next two years, such as AstraZeneca's Seroquel XR, Wyeth/Solvay Pharmaceutical's bifeprunox, Janssen's paliperidone depot, and Eli Lilly's olanzapine depot, as well as the expiration of Janssen's Risperdal patent protection in 2008, the landscape of schizophrenia is poised for even greater changes.'"

I guess doctors do read the New York Times and blogs after all. I'm kidding, of course.

But, seriously, what the analyst avoids saying is exactly what the schizophrenia market will chance into. Methinks, there is going to be even more bad news on that front and likely around Risperdal and Seroquel. Both the drugs and their makers are the objects of several lawsuits (one a class action), a Congressional investigation and I imagine the various states are poking as hard on how these drugs were marketed and sold to their state Medicaid programs as they are on Zyprexa. We just don't have the Risperdal or Seroquel documents in the public's hands.

Yet.

Not Hiring The Mentally Ill While Employing The Mentally Ill

The San Francisco Chronicle had an article yesterday on a program designed to get the mentally ill jobs. Good idea although it's hard to say how successful the program is right now, but I hope they are successful over time in changing the job market culture in San Francisco. Because if employers in diversity-embracing-ad-absurdum SF find it spooky to hire someone with schizophrenia or depression, as the article gets at, then the rest of the country has got to be worse. OK, I know it's worse.

Ironically, the writer carefully points out, many employers bugged by the prospect of hiring someone with depression or bipolar disorder likely already employ people with depression and bipolar disorder and so on.

"'If you have 100 employees, one of them is schizophrenic. And 15 will struggle at some point with depression,' [the program head] says."

Fine point. I know for a fact that there are major companies in the Seattle area that employ people with schizophrenia. And apparently there is now a Chuck E. Cheese in San Francisco that does as well.

"Michael recalls one client, diagnosed with schizophrenia, who felt a strong desire to work with children. Her illness, however, made it unlikely she'd be allowed such a position--as Michael says, her hair was a mess and she had a flat affect common to schizophrenics. Hire-Ability had zeroed in on Chuck E. Cheese as a potential employer, and Michael asked if there was any position that nobody else wanted.

"'Wearing the mouse costume,' he was told."

Soon Chuck E. Cheese had a happy mouse. Not only did the client end up working well with the kids, Michael says, her own state of mind improved dramatically.

As I've noted before, work is good. Or as the Chron's writer puts it:

"The line between work and therapy is thin. To be productive and self-sufficient is to build self-esteem and establish healthy habits. This isn't just a good idea, researchers are starting to note, it actually helps improve mental health."

That's so true that I think I'll leave it at that.

The AJP Must Immediately Address Suicide Study's Flaws

Over the weekend, I became even more troubled by the conclusion reached in a recently-published study which asserted that 2004's black box warning on anti-depressants had led to a decrease in prescriptions for those drugs and had also led to an uptick in suicides among youth. The study was published in the American Journal of Psychiatry, but since its appearance two weeks ago its central assertions have been challenged.

Last week, the New York Times reported that, in fact, prescription rates had not changed much in 2004 (that came the next year), so that calls into question this conclusion by the study's authors:

"SSRI prescriptions for children and adolescents decreased after U.S. and European regulatory agencies issued warnings about a possible suicide risk with antidepressant use in pediatric patients, and these decreases were associated with increases in suicide rates in children and adolescents."

What's more, the black box warning in the US was not applied to anti-depressants until Oct. 15, 2004, so it is difficult to believe that the warning could have affected suicide data for the entire year.

Further doubt is cast on the study's findings because preliminary suicide data for 2005 released last week show a 3 percent drop in suicides for that year--the first full year of the black box warning and a year in which anti-depressant prescriptions actually did drop. This would seem to be the opposite of what the study's authors argued.

This whole affair is an embarrassment for the AJP. Central flaws in a significant study were not caught by peer reviewers and the journal's editors. A flawed and fundamentally incorrect paper was published to wide media attention. Americans--and especially the parents of America's youth--are now in essence being told that down is up and up is down by the world's leading psychiatric journal.

This situation must be remedied by the journal and promptly. The politics and emotions around the SSRI-suicide debate are too intense and divisive to permit this paper to just sit out in the public realm and be regarded by some forces, especially policy making ones, as "evidence." It doesn't make sense for the journal to let whatever debate will erupt over this paper to take place six months from now in the letters section of the journal.

The journal either needs to ensure that a correction is promptly issued for this paper--and done so very publicly--or that the paper itself is retracted. I don't think that these kinds of discrepancies can be cleaned up in any other way. I have no idea what the journal is doing to address this situation, but I will try to find out.

Readers from the mental health world might want to make a point of writing to the journal directly.

In addition, I have to wonder why Robert Gibbons, the study's lead author and a very experienced statistician, could screw things up as badly as has been reported. It kind of makes you wonder how reliable his testimony as an expert witness for Wyeth, makers of Effexor, could have been.

For background, I have written about this matter here and here and have also written about the CDC and media's odd handling of the 2004 suicide data.

The Bipolar Child: "It Depends On What Side Of The Controversy You Are On"

Last Friday afternoon, KUOW-FM, Seattle's NPR affiliate, did a program on the bipolar child controversy and the explosion in diagnoses of the disorder in children. The station's guest was Jon McClellan, medical director of the Child Study and Treatment Center at Children’s Hospital and Regional Medical Center in Seattle. He's also an associate professor of psychiatry at the University of Washington and is one of the principal investigators of an ongoing NIMH-=funded study of the use of Lithium in children. Also, McClellan chaired a panel of the American Academy of Child and Adolescent Psychiatry that recently concluded there is no proof that children under 6 can be diagnosed with the disorder.

Of course, there are those in psychiatry who think researchers like McClellan are wrong. They were not on the program and it's not clear to me if KUOW tried to get any of the Harvard folks on the show--knowing KUOW, they tried. Anyhow, McClellan's appearance can be accessed here. Just download the .mp3 and off you go. McClellan has, of course, been quoted in the press lately casting doubt on the whole bipolar child business.

I've transcribed a bit of his interview to give you a sense of what he's saying. My transcription is a bit rough and has gaps, but here goes.

The interviewer asked why there was a 4,000 percent increase in bipolar disorder in kids and teens.

"It depends on what side of the controversy you are on....Many kids have periods where they are quite irritable and they don't want to go to bed at night and they brag....[Classically,] they never would've been called manic. That changed in the last decade. Those kids are now being called manic."

Why?

"Well, that's a good question. Probably because some fairly influential research centers nationally decided that was the proper way to apply the diagnosis."

McClellan is referring of course to the Harvard School of Medicine. He spends a lot of time going into the differences between ADHD and bipolar disorder. He's quite clear that what's driving the bp kids diagnosis is a very loose definition of what counts as mania--a hard or soft definition.

"Some of this is really a semantic argument....The disagreement is about if it's the same thing as the classic adult illness. The descriptions are not the same. Kids do not have that syndrome like adults do....I think you need the classic adult disorder in order to be characterized with that [having bipolar disorder]."

He goes onto discuss that long-term studies of kids with bipolar disorder have shown that they don't develop the full-blown disorder as adults. The interviewer asks, "Wouldn't that suggest to you they aren't the same diseases [child and adult bipolar]?"

"It would to me," says McClellan.

Anti-Depressants Prevent Schizophrenia?

From today's Sydney Morning Herald:

"ANTIDEPRESSANTS could prevent the onset of schizophrenia if prescribed before the first psychotic episode, a ground-breaking study by a Sydney researcher has found."

You can go read the rest. Most of you know that I am fairly dubious of all this prodrome identification talk going through psychiatry these days, especially as relates to the controversial PRIME study at Yale. So are some researchers.

But all the same, it's nice to see someone doing some research using less toxic agents than antipsychotics. Not that anti-depressants aren't plenty toxic on their own. Of course, this research would have to be replicated many times before it could become a line of treatment--and there are all manner of ethical questions about giving SSRIs to youngsters as well as how accurately doctors can identify psychosis before its first onset. But those are questions for another day.

Youth Suicide Rates Study Deemed Dubious

A statistician is casting doubt on last week's claims that an increase in youth suicides in 2004 over 2003 could be tied to a decrease in prescriptions for anti-depressants due to a black box warning placed on the drugs by the FDA in the final quarter of 2004. According to a report in today's New York Times:

"[S]uicide rates for Americans ages 19 and under rose 14 percent in 2004, the number of prescriptions for antidepressants in that group was basically unchanged and did not drop substantially, according to data from the study. Prescription rates for minors did fall sharply a year later, but the suicide rates for 2005 are not yet available from the Centers for Disease Control and Prevention.

"'There doesn’t seem to be any evidence of a statistically significant association between suicide rates and prescription rates provided in the paper' for the years after the F.D.A. warnings, said Thomas R. Ten Have, a professor of biostatistics at the University of Pennsylvania."

Actually, as I noted yesterday, preliminary 2005 suicide data just became available--it shows a decrease of about 3 percent that year--but, since it's preliminary, I can understand the reluctance of some to lean on it too hard. However, I've been following these stats for eight years and don't recall a later upward revision of more than one-tenth of 1 percent. Final 2005 data isn't due until next summer sometime.

All the same, I congratulate the paper's reporters, Alex Berenson and Ben Carey, for continuing to push on this important and controversial issue. And for the millionth time, let me point out that the data on suicides, suicidality and anti-depressant use is mixed.

A Fiddy Victory

Last week, I wrote of Robert Fiddaman's efforts to force a stealth ad for Paxil/Seroxat/Aropax off the website of an Australian counseling center. Looks like Fiddy won. Details here. See, folks, making noise about this stuff actually does work. Bruce Lee wins again.

Sally Satel On DSM-V

Sally Satel, a Washington D.C. psychiatrist and conservative policy wonk on mental health issues, had an op-ed in yesterday's New York Times. It's hard to tell what drove the paper to run an op-ed on the DSM right now. All the same, DSM-V is very much in the planning stages--it's due sometime in 2011--and there is a lot of controversy within the psych world over some diagnoses, especially early-onset bipolar disorder. Satel, who also writes for the Weekly Standard from time to time, takes up the bp kids business first:

"High on the agenda will be the controversial diagnosis of childhood bipolar disorder. Recent data show that office visits by children and adolescents treated for the condition jumped 40-fold from 1994 to 2003. We still don’t know how much of this increase represents long-overdue care of mentally ill youth and how much comes from facile labeling of youngsters who are merely irritable and moody.

"Part of the confusion stems from the lack of a discrete definition of juvenile bipolar illness in the diagnostic manual. But there is a deeper problem: despite the great progress being made in neuroscience, we still don’t have a clear picture of the brain mechanisms underlying bipolar illness--or most other mental illnesses."

I've been in the mental health world for almost 20 years and it is discouraging to me that doctors are still saying much the same things now that they were about the sources of mental illnesses back when--namely, that it's all driven by chemicals in the brain and we'll identify the central lesion through MRIs and PET scans any day now. It's 20 years later and there is still no concrete answer as to what is going on in peoples' brains. After a generation of waiting for "proof," I've lost my patience. When the docs can establish the root cause of bipolar disorder in children, for example, then I'll be a lot more sympathetic to listening to wonks talk about diagnostic criteria and treatments, especially when it comes to applying adult disorders to children.

Satel offers the usual explanation--the brain is very complex!--and moves onto the DSM and depression.

"Another may be what Dr. First calls the “unfortunate rigidity” that all-or-nothing diagnostic checklists and sharply bounded categories impose. In order for the condition of a patient to meet the definition of clinical depression, for example, he or she must have five out of nine symptoms. But does a patient with only four symptoms have a different disorder, or no disorder at all?"

I'm not quite sure I buy that there's that much diagnostic rigidity in the DSM-IV, aside from what insurance companies require or the official rigor of clinical trials. Satel offers no evidence that this situation is much of a problem.

But she has a solution.

"One way to improve the classification of mental illnesses would be to define certain pathologies along a continuum so that patients who are truly ill won’t fall short of qualifying for a diagnosis. Take major depression. The symptoms could be weighted so that suicidal preoccupation or immobilization, the most extreme and debilitating aspects, would get high scores, while loss of energy and interest for a short periods would get lower scores. Thus, a patient with few, but severe, symptoms would not be excluded.

"A more nuanced approach could also make a real difference for population surveys of mental illness and clinical trials, both of which tend to rely on rigid symptom checklists."

That's an interesting idea, but ultimately I don't think it would change much in practical terms. I cannot think of ever hearing of anything other than a few stray instances of a patient going to see a doctor, telling the doctor that they are suicidally ideating and unable to leave the house, say, and not have that patient walk away with a diagnosis of depression because they happened to be sleeping well and eating well at the same time. As these things go, depression is easy to diagnose, and schizophrenia is a bit harder although it's obvious much of the time (I've dealt with enough street folks over the years to say this). Bipolar disorder and ADHD are much trickier.

There has been much noise lately about whether depression is over or under diagnosed, and the World Health Organization and its allies last week launched a huge media push to convince the world that depression is tied to every ailment under the sun and that depression is under-diagnosed. It's hard to say who is right on this matter absent an objective standard, but whether over or under diagnosed, I am not sure that we have much better treatments for depression than we did 20 years ago. And some of the treatments we have can cause very serious problems--and I can say that with the same confidence that researchers assert that mental illnesses are the result of bad brain chemistry. So we are rushing to diagnose even more people and offer them even more problematic treatments for what reason?

To be clear, where someone is suicidal or practicing extreme isolation, then I am certain a diagnosis should be made. I'm not so certain of where the diagnosis and treatments will lead a particular person.

What I find amusing is that the Times' editorial pages chose to run an op-ed from Satel. She is very much a member of the forced outpatient commitment crowd--who all seem to be in the D.C. area for some reason--but at the same time is also the author of One Nation Under Therapy, a book examining the notion that talk therapy has damaged America's character. Interestingly, you never hear much from Satel about how medications have damaged America's bodies. And you won't read it on the editorial pages of the Times either, which seems to be run by a very hidebound bunch on medical matters (the news side of the paper is different). Satel is also in the forefront of the debate over tightening--or is it loosening?--commitment laws. I have written about her work previously. And yet here she seems to be arguing for more diagnosis and more treatment. Like I said, an odd choice and one I don't trust as much of an authority.

As for her proposal that mental illnesses be regarded as existing on a spectrum, that sounds to me like yet another call for softening diagnostic criteria a la subthreshold bipolar disorder. I am against that. I've watched the practical impact of an already softened bipolar disorder--bipolar 2--lead to too many patients getting screwed up on Seroquel, Risperdal and Zyprexa. But, then, I was one of those patients, so I am biased.

Also, I find it odd that, given the lack of objective diagnostic tests, that researchers and opinionators such as Satel don't also call for the DSM-V to include some kind of guidance for doctors on re-evaluating a patient's diagnosis every so often, especially with patients who are treatment compliant and making decent progress. I think there's plenty of evidence that the course of mental illnesses can abate over time and it makes sense that some recognition of that fact be carved into the DSM as well.

2005 Suicide Data Shows Decrease, SSRI Debate Might Follow

Remember that last week there was much news around 2004's suicide data, which showed an uptick, and how in the mind of many psych docs quoted in the press a black box warning added to anti-depressants in 2004 was to blame for the increase in suicides? Well, yesterday the National Center For Health Statistics (a branch of the CDC) released preliminary death data for 2005 (see Table B of report here).

The suicide rate dropped from 10.9 per 100,000 in 2004 to 10.6 per 100,000 in 2005, a decrease of about 3 percent--still unacceptably high. 2005 was the first full year of the black box warning of possible suicides and suicidal ideation, which technically only applied to ages 0 to 14 at the time (it's been expanded through 24 year olds more recently). The new data won't be broken out by age groups, genders and race until next summer, so for now it isn't possible to say how the 2004 and 2005 suicide data compared.

But something tells me that the less-use-of-SSRIs-causes-suicides argument heaved to by many in the psych field just took a beating. That may explain the press silence on this new data so far, since it would upset what many in the media, especially the Associated Press, gave voice to last week. In fact, in an AP article on the new data, reporter Mike Stobbe doesn't even mention the decrease in suicides while last week his colleague Greg Bluestein made it sound as if telling Americans SSRIs have problems lead to certain death. What amuses me greatly is that both reporters datelined their articles, which ran five days apart, Atlanta. That means they both likely work in the AP's Atlanta bureau, so for the AP not to mention the drop in suicides after the ink they expended last week strikes me as odd. Or really lazy.

I'm sure some other smart reporter will figure all of this out in the meantime and get a nice article out of it. Hopefully, he or she will understand that the evidence on SSRIs and suicide/suicidality is quite mixed and say so in print, regardless of how displeasing that argument might be for defenders of the SSRI faith and regardless of how much it annoys some advocates in the health care world who would prefer that complete information about the side effects and injuries sometimes caused by these drugs be kept from the public because the public cannot handle the truth.

Based on 2005's data, I'd say the public is doing just fine with the truth, however mixed it might be.

BTW, Psych Central has an interesting post on just how useful suicide hotlines are or aren't.

The Zyprexa Chronicles: Swedish Psychiatrist Bashes Zyprexa, Lilly And Colleagues

I am just going to let this speak for itself, from a Swedish account of a television appearance by Rolf Adolfsson, a professor of psychiatry at Umea University in Sweden. Make of it what you will.

“'There is nothing worse than seeing a young person 17-18 years with a weight gain of 40-50 kg, and no one does anything! What is Swedish psychiatry doing?'"

And:

“'I’ve seen so many complications, and I have met so many patients--that I completely choke. Are we so damned gullible, and it must be--there is only one thing--marketing.'"

And:

"When the reporter takes up the endocrine effects of the new neuroleptics, Professor Adolfsson says that they are extremely dangerous. He says: 'You die prematurely, 10-15 years.' And upon the surprised follow-up question from the reporter if he means that the pharmaceutical industry, with these new drugs, drives persons with schizophrenia to an early death, Dr. Adolfsson simply responds: 'Absolutely!'"

Oh, I doubt that it's only schizophrenics who've paid a price for taking Zyprexa.

"It is further revealed that the Professor has had a long relationship with Eli Lilly (10-15 years). He says: 'And I have discussed very much with them that you have to be trustworthy--this I maybe said 5-6 years ago--they must come out and say: This is a very dangerous thing with our drug, because people are gaining weight. And you must do these and these tests, and if we have this increase in weight so quickly, then you must switch to another drug.'"

During the program, the doctor asks, “Why doesn’t Swedish psychiatry react?" I guess it depends on whether or not you consider silence a reaction.

A Nice Surprise

Psych Central today handed out awards to the best bipolar blogs, 10 of them in fact. Some are blogs I'd never heard of, which is cool. Among the winners were The Trouble With Spikol, Crazy Tracy, a blog by some guy named John and several others. I came in at number two of the 10, a very nice surprise.

My favorite part is this: "Depending on your perspective, Philip Dawdy is either a whistleblowing hero or provocative conspiracy theorist."

Thanks to Psych Central.

Health Insurance Still Too Costly For 45 Million Americans

So the cost of health insurance went up only 6.1 percent this year, the lowest increase in years. But 45 million or so Americans cannot afford health insurance or do not get coverage through their employers or governmental programs. Here's why:

"Since 2001, the cost of premiums has gone up 78 percent, far outpacing a 19 percent increase in wages and 17 percent jump in inflation, according to a survey released Tuesday by the Kaiser Family Foundation, a health care research group that annually tracks the cost of health insurance.

"This year, the cost of premiums paid by workers and their employers was up 6.1 percent, while wages rose an average of 3.7 percent and inflation went up 2.6 percent, the survey said. Kaiser estimates that between 1 million and 2 million people join the ranks of the uninsured every year."

I joined those ranks this year, losing my health insurance in June. I simply couldn't--and cannot--afford the premiums, and I make too much to qualify for government programs. Nice bind, eh?

Look at how staggering the costs have gotten:

"This year, premiums averaged $12,106 for a family of four, with workers paying, on average, $3,281 of that. Premiums to cover a single person cost $4,479, with employees paying $694.

"Families typically pay 28 percent of their premiums, while single people pay 16 percent, the survey said, and those proportions have been stable. But the amount workers have been paying has nearly doubled since 2001. This year, monthly contributions averaged $273 for families and $58 for single workers."

So this is what managed care and medical innovation have gotten us over the last 14 years? Apparently. I cannot even begin to guess at a solution as I doubt the Canadian, French or British systems would translate well here--and perhaps we don't want them to. All the same, there's got to be a better way.

The Zyprexa Chronicles: Egilman Writes

Most of you know who David Egilman is by now, so I'll dispense with the preliminaries and get right to this post he did on The Pump Handle, which is a public health blog. He's referring to silence on the part of docs who are in the know about all manner of threats to public health but remain silent:

"This blanket of silence is becoming so heavy that doctors are forgetting where their loyalties lie. The medical director of one asbestos company was asked why he hadn’t warned his patients, those who developed asbestosis and cancer from their work, of the hazards of asbestos. He explained that he had indeed warned his patients; that the company was his “patient.” I refuse to go the way of that doctor and remain silent on issues important to the public health, for the cost is always the loss of innocent lives.

"When I graduated from medical school, I took an oath to protect the public health. That oath supersedes all other agreements, including those that prevent me from protecting public health by releasing information. My obligation to the health and safety of others is the same as that of a physician who informs the police about a patient who has “in confidence” threatened injury on another. My obligation is the same as that of a pediatrician who “violates” confidentiality to report possible child abuse to the police.

"If Lilly has “secret” documents that indicate that its drugs are safe or that their marketing practices were appropriate, they have the right to release them and it is in their interest to do so. Their silence is deafening."

I expect to interview Egilman in the near future.

SSRIs Good For Dementia?

That's according to this Canadian study which found that the anti-depressants worked as well as antipsychotics in calming agitation in elderly dementia patients. It was Celexa versus Risperdal in this small trial.

I find it a bit puzzling that an SSRI could beat what is essentially a tranquilizer, but I'm sure someone can explain that to me.

Reality TV Goes Pharma, NAMI Helps AstraZeneca

Via CL Psych comes edrugsearch.com's list of 10--count 'em--pharma reps who've landed gigs on reality TV shows. I knew there was a reason I hated these shows.

And, via The Trouble With Spikol, comes news that NAMI National--the nation's voice on mental illness--is helping AstraZeneca spread the word on the company's "A Day in the Life" essay contest concerning what it's like to have bipolar disorder or schizophrenia. There's a $1,000 prize.

Why is NAMI National once again helping out a company with tons of advertising money in its attempts to gain some copy for soft advertising? Is that the proper role for an advocacy group?

ADHD Or Bad Vision?

There's a rather surprising story in today's New York Times, just as interesting in its way as the adhdroadmap.com television ad. A California child was withdrawn and wouldn't make eye contact and avoiding reading and writing and did poorly in school. Doctors diagnosed her with autism spectrum disorder, neurofibromatosis, attention-deficit hyperactivity disorder, and anxiety disorder. She was given meds for ADHD and depression.

And then a smart doctor performing a simple test figured out that the kid had convergence insufficiency--seeing double because the eyes don't work together as a unit. That was fixed in this case and now the child is reading at grade level.

I haven't the faintest idea how vision problems correlate with ADHD and other psych diagnoses in kids--this California case could be a strange outlier--but it sure makes you wonder how kids are being examined by doctors these days before being placed on powerful, and sometimes dangerous, drugs. It also makes you wonder how smart--or not--some pediatricians are these days.

Adverse Events And Deaths Way Up For RXs

Yesterday, the Archives of Internal Medicine published a study asserting that there's been a huge increase in adverse event reports over prescription drugs to the FDA from 1998 to 2005. Press coverage here. The annual number of serious adverse event reports went to 89,842 in 2005 from 34,966 in 1998. The number of fatal adverse drug events increased nearly 300 percent to 15,107 in 2005 from 5,519 in 1998.

This is a completely untenable situation and argues for an overhaul of the FDA's safety monitoring system--meaning the FDA should actually do some safety monitoring and act upon what they find instead of consulting with Big Pharma over what they should do a la Zyprexa. This situation also argues against the medicalization of human life. If you are going to connect every ache and pain in exist to a condition needing treatment and pharma companies just happen to have a product for it (RLS anyone?), then you had better produce some results. Positive ones.

Study authors say there is plenty of blame to go around--there usually is--but I really think doctors and, to a lesser degree, patients are doing a poor job of managing chronic health conditions. Some of the drugs leading the list for causing problems were insulin, OxyCodone and Fentanyl. The latter two are opiate pain killers.

The number of adverse events grew four times faster than did the number of prescriptions in the same time period. As much as I'd like to blame DTC advertising for this situation, I cannot. Chronic medical conditions don't generally need ads to generate sales. Except for psych meds for some reason.

I haven't seen the full paper yet--anyone care to send it to me?--so I cannot say if any psych meds showed up among the key offenders. All the same, how the FDA handled safety information concerning Zyprexa (and I am just using this one as an example) is instructive.

By the late-90s, the clinical literature was littered with reports about weight gain and hyperglycemia. Even Lilly was being tipped off by doctors in Southern California. The FDA did nothing. In 2002, both the Japanese and European health authorities required that Zyprexa carry warnings about diabetes, hyperglycemia and the like. The FDA did nothing. Oh, but it did meet repeatedly with Lilly officials who pressed their case that all atypical antipsychotics caused glycemic problems, even though there was decent evidence to the contrary. In 2004, the FDA finally issued a black box warning for this class of drugs. How many people died or were injured as a result between 2002 and 2004 is anyone's guess. (Lengthier reporting of the Zyprexa/FDA situation can be found here.)

It similarly took the FDA a decade to issue the first black box warning on anti-depressants, which the agency did in late 2004.

Why would anyone trust the FDA anymore? The FDA won't even tell the public what studies were used to approve certain drugs, arguing that it's private information. Um, precisely who do these "public servants" work for? You and I, or Big Pharma? It's time for Congress to step up to the plate and force some changes.

Take The International Bipolar Disorder Survey 2007

Or leave it for that matter. Some of you know that the British actor Stephen Fry recently did a series of documentaries with the BBC on bipolar disorder. Fry is what I call a late diagnosis bipolar. He was diagnosed at 38-years-old. The classic pattern is for the disorder to be diagnosed somewhere between the mid-teens and mid-20s, but there has been a lot of late diagnosing going on in recent years--perhaps as much as has been done with the very young--and Fry is part of that trend. One of the group's advisors is John McManamy, another late-dx bipolar, and author of Living Well With Depression And Bipolar Disorder.

Anyhow, Fry is now associated with Equilibrium, a new British non-profit aiming to the foremost group working to improve treatments for bipolar disorder. Among others, the group is funded by Organon UK, Eli Lilly, and Pfizer. What's more, the group's evidence-based treatment section continues to talk about Zyprexa as if it's an effective maintenance treatment for bipolar. Apparently, news travels slowly to the UK. Interestingly, the group claims that 12 million--or 4 percent!--of the US is bipolar. Funny thing: NIMH has it at half of that. Guess Equilibrium must be using pharma's estimates.

So, the group is doing a survey on bipolar disorder and if anyone is interested in participating, you can follow this link. And I offer the above as caveats to the whole thing. Personally, I am not sure why anyone needs yet another survey on bipolar disorder aside from giving them an opportunity for a big press release when the survey is over. But, as usual, I link, you decide.

Babies On Anti-Depressants In New Zealand

This is just startling: In recent years, hundreds of prescriptions have been written for anti-depressants in young children in New Zealand. Almost 5,000 anti-depressant prescriptions were written for children under 10 in 2004/05, but the figure dropped to 2,425 in 2006. Some of those getting the meds were less than one-year-old. Good Lord.

Insert my usual babble about depression not existing in babies and there being no research whatsoever to support such treatment, etc. Why on earth would you even give a baby cough medicine much less an anti-depressant? Then again, in the US we have the Rebecca Riley case to point to as an example of just how out of whack our medical culture has become. I bet there are many other Rebeccas out there.

What kind of social experiment are some doctors conducting in this world? What the hell is wrong with these kids' parents? I mean I can understand the justification for medicating children in extremely rare circumstances, but not on the scale on which some docs are playing the game these days. (Thanks to a reader in New Zealand for passing this along.)

Elyn Saks: Schizophrenic, Law Professor, Amazing

A few weeks ago I noted that a USC law prof, Elyn Saks, had written an account of her life as a schizophrenic. It's a book called The Center Cannot Hold. I didn't realize at the time that she'd kept her condition under wraps for years. Or much else, frankly. An article in today's Los Angeles Times goes into her history, which must've taken more courage and resolve than most of us can imagine.

Interestingly, friends sent her flowers when she developed breast cancer, but not when she was in a hospital. And she was handled very forcibly in American mental institutions versus her experience in hospitals in the UK.

Interestingly, she's written an academic book called Refusing Care: Forced Treatment and the Rights of the Mentally Ill. I'm not sure where she lines up on the many complicated issues there, but from what I can glean she is against the use of restraints.

BTW, did you know that New York tries to bar lawyers with schizophrenia and bipolar disorder from practicing the law?

Brains Of Conservatives And Liberals Work Differently

Apparently, the liberal brain is more open to ambiguity while conservatives are not. Or so says a new study in Nature Neuroscience. So I think the appropriate solution here is to medicate the liberals. Or maybe the conservatives. I don't know. I'm kind of feeling ambiguous about the whole thing.

The Zyprexa Chronicles: Egilman Disputes Lilly's Answers That Matter

On Sept. 7, David Egilman, a Brown University professor and expert witness in one of the Zyprexa class action lawsuits, and Eli Lilly settled outstanding claims related to Egilman's leaking of court-sealed documents in the case last year. The settlement includes a $100,000 payment from Egilman to Lilly which Lilly is donating to charity.

Following the settlement, Lilly issued a press release. In it, the company characterized what Egilman agreed to in the settlement as:

"[V]iolating a protective order in the Zyprexa litigation and illegally passing confidential Lilly documents to an Alaska attorney in a failed attempt to evade the protective order."

And:

"'Dr. Egilman has now confirmed in writing what Lilly has been saying since the Times published these documents: he was selective in which documents he released and they unfairly portrayed Lilly's activities in its interactions with doctors, patients and the Food and Drug Administration,' said Michael J. Harrington, deputy general counsel, Eli Lilly and Company. 'We hope that putting this issue behind us will help to ensure vulnerable patients will not be deterred from treatment based on misleading and inaccurate information. Our intent all along has been simply to have a fair legal process,' he added."

Over the weekend, Egilman left a comment on Pharmalot, which has covered the affair extensively, taking exception to Lilly's claims:

"I admitted responsibility for violating the protective order that kept Lilly’s documents secret. I did not admit to any illegal conduct. I agreed to pay the company $100,000. I admitted that Lilly has told a different story about the side effects of Zyprexa, but I do not believe, and did not admit, that Lilly’s “story” is based in fact. And notably, although Lilly claims that the stories that ran in the Times did not accurately reflect their marketing practices or their knowledge of Zyprexa’s side effects, Lilly has refused to release documents that they claim paint a different picture. Even today, Lilly fights in court to keep those documents secret from the public."

I suppose the truth lies in how you parse the term illegal as it relates to court seals. Torts Prof has some thoughts on all of this. The WSJ Healht Blog also has some interesting insights into the parsing party. Other news organizations covered the settlement as did some blogs.

Egilman's point that if Lilly has exculpatory evidence, then it sure has a funny way of sharing it is, in essence, what I have been saying since February. If the rest of the documents obliterate the evidence Egilman leaked and which the New York Times, myself and others reported on, then the company should make those documents public. I'd be happy to review them.

In an un-bylined article on Sept. 8, the Times quotes one of its attorneys:

"'We continue to believe the articles we published about Zyprexa were newsworthy and accurate and provided important information to the public,' said George Freeman, a lawyer for The New York Times Company."

And adds that the documents "are still widely available on the Internet." Actually, as far as I know, this blog, and a German website are the only sources for the documents. But thanks for thinking my reach is wide. I'm pretty sure it exceeds my grasp. BTW, the Zyprexa documents have now been archived at two major medical schools and have been accessed by numerous academics (perhaps some of them will write an academic paper or two someday). Several hundred others have downloaded the documents as well.

I hope we will one day hear from Egilman on what prompted him to leak the documents in the first place. Still no word on a settlement between Lilly and Jim Gottstein. Stay tuned.

The Age Of Anxiety: Writing Students Under Microscope

Thanks to the Virginia Tech massacre, some universities are looking into how to respond to creative writing students who write what are deemed to be disturbing stories, poems and plays. Inside Higher Ed has some more details on this.

One Virginia Tech prof notes:

“'It may well be that the traditional way of dealing with disturbing writing — relying on the sensitivity and intelligence of the creative writing instructor to respond to a troubled student — is best,' says Ed Falco, director of creative writing at Virginia Tech."

I agree. But given the gravity of what Cho did and how it may have been telegraphed in his creative work at school, you can bet some universities will begin requiring students to undergo mental health evaluations for riffing off of "Good Country People" or "Tell The Women We Are Going" or "The Lottery." Count on it. Of course, this ignores the possibility that a Cho could just as easily have been an accounting student or mathematician.

Either way, I am concerned about the drift in our culture toward climbing up students' butts over what they write and feel. Students are supposed to be experimenting, at least the artistically-inclined should be. Sometimes, in order to grow creatively, students have to write some weird work just to find out where the edge of the creative box is for them. I hope we don't muzzle that tradition.

To me, this represents the same sort of drift we are currently seeing some quarters in the psychiatric community. Nowadays, having one or two symptoms of bipolar disorder, as opposed to having five, can get you labeled as having subthreshold bipolar disorder. And that disorder, at present, doesn't even exist. And of course there is a raging debate about whether the definition of depression has been so softened that we are now diagnosing sadness as clinical depression. Or whether depression is bipolar disorder. And so on.

Well, at least no one is proposing that the definition of schizophrenia be loosened. But stranger things have happened. (Thanks Jonathan.)

The Zyprexa Chronicles: Egilman And Lilly Settle On Zyprexa Documents

Pharmalot is reporting that David Egilman, the Brown University doctor and expert witness who was instrumental in getting the infamous Zyprexa documents into the public realm late last year, has settled with Eli Lilly on claims the company had against him as a result of a court order back in February. According to Pharmalot, Lilly's PR machine is already weirdly spinning the settlement and Egilamn's lawyer is firing back. Read the details at Pharmalot. Some background from me is here.

Egilman is paying Lilly $100,000, which the company is donating to a group that runs clubhouses for people with chronic mental illnesses. That's nice of Lilly. Perhaps, the company could also kick down for some free glucose meters in the bargain. (Note to Lilly and its outside attorneys: I am only kidding about the glucose meters.)

No word yet on any pending action involving Jim Gottstein, the Alaska lawyer who was also involved in getting the documents into the public realm and against whom Lilly reportedly has legal claims.

Great work by Pharmalot's Ed Silverman, who beat the New York Times and the rest of the media on this story.

The Times Fails To Disclose Conflict Of Interest In Interview On SSRIs And Suicide

Yesterday I noted that Sanjay Gupta, a psychiatrist at the University of Buffalo, fibbed when he claimed there was no proof of a link between suicides and suicidality and anti-depressants, specifically Prozac. Not only was his claim incorrect, but as it now turns out Gupta has received honoraria and other funding from Eli Lilly in the past. This was not noted in his interview which recently ran in the New York Times.

Here's a disclosure from a paper Gupta authored in 2001:

"Dr. Gupta is a consultant for Eli Lilly; has received research/grant support from Eli Lilly, Janssen, and Abbott; has received honoraria from Eli Lilly, Janssen, Forest, and Pfizer; and is on the speaker or advisory boards of Eli Lilly, Janssen, and Forest."

Today, I sent the paper a letter to the editor and pointed out this inexcusable discrepancy. It will be interesting to see if the paper of record decides to print my letter and correct the web version of its interview with Gupta. I know the paper has written quite aggressively about conflicts of interest that some psych researchers have, so I find it odd that this one evaded the paper's foolproof radar.

I'll let you know when I know.

Many thanks to CL Psych for the tip.

2004 Suicide Data: Sound And Fury And Perspective

Most of you already know that the CDC released data yesterday showing a rise in the teen suicide rate in the US in 2004. Of particular concern was an increase in suicides among girls aged 10 to 14 years old. The media went nuts over this information and allowed several alleged experts in the psych world to link the rise to the 2004 black box warning which the FDA required pharma companies add to anti-depressants specifically for children and teens up to 15-years-old due to many documented cases of suicides and suicidality among kids who'd been on anti-depressants.

The move by the FDA was very controversial at the time and represented something of a compromise as there were some people who wanted to warnings applied to adults as well. There are of course plenty of documented cases of suicides and suicidality among adults on anti-depressants. (I would be one of those cases.) There are also many documented cases of people who've benefitted from anti-depressants (I would also be one of those cases. I have natural biases in both directions on this issue), just as there are many documented cases of researchers and advocacy groups who've taken money from companies making anti-depressants and then gone on to say glowing things about said drugs.

My point is that there is a boatload of conflicting evidence about whether anti-depressants have ever induced suicide in patients or whether they are a super-duper anti-suicide technology. Many researchers continue to talk as if SSRIs and the like are the Rosetta Stone to the soul. They are delusional. Just as delusional are those who claim that the black box warning is to blame for the increase in suicides in 2004. Drug Wonks had a howler of a post on this yesterday.

Guess what? The 2004 black box warning was issued on October 15, 2004. At worst, the warning could only affect about 10 weeks of suicides. Which sort of shoots down the anti-black boxers out there. And makes me wonder if there aren't a few media organizations out there who ought to be running a correction or clarification.

But I want to talk some more about 2004's suicide data because I have a special relationship with suicide that year, and because I think the media and the CDC are missing the big story on suicide. Unfortunately, I cannot speak to the suicide situation in other countries, principally because I am not as conversant in the evidence. But I think the same questions of anti-depressant-induced suicidality pertain elsewhere.

Oh, yes, something else about the release of the 2004 data and the press coverage of the ceaseless divide over anti-depressants and suicide. From Slate:

"Traci Johnson's body was discovered on Feb. 7, 2004, hanging by a scarf from a shower rod in an Indianapolis laboratory run by the drug company Eli Lilly. The 19-year-old college student had been serving as a test subject in a clinical trial of the experimental antidepressant duloxetine. Investigators from the Food and Drug Administration rushed to Indianapolis to determine whether the experimental drug was related to her death. The probe was inconclusive.

"This left researchers in a quandary: Was the drug safe or not? Could duloxetine trigger suicide, as some experts suggested? Or was Johnson's death an "isolated tragedy," as Eli Lilly claimed?"

She was taking Cymbalta in a trial of the drug for stress urinary incontinence, not depression. There was not one mention of Johnson in any of yesterday's press coverage, and as far as I know her name was not mentioned by anyone at the CDC despite the fact that she was a suicide in 2004 in exactly the age cohort driving the CDC's press release who killed herself by the precise method over which the CDC is properly concerned about an increase amongst youngsters--hanging.

Traci is the very tragic poster child for the situation. How did the media miss that? Her story is known.

Look, the only controversy isn't about whether or not anyone has had a suicide induced by anti-depressants. The controversy is about what do you ask and what do you tell.

But back to 2004.

CYNTHIA DOYON

In August 2003, a much-beloved DJ at KUOW-FM, Seattle's NPR station, killed herself on the University of Washington campus. About a week later, I began doing what reporting I could on what happened because it struck me that it was a good way to write about the unending problem of suicide in America. I was stonewalled by her colleagues and friends for almost two months before people began talking. What developed was a very sad picture, of course--the aloof, depressed loner with a hand gun.

Along the way, I began looking at national and local suicide statistics going back into the 1950s. What struck me was how little the rate of suicide had changed in the years since the advent of the Prozac revolution. From what I could figure at the time, the rate had decreased by about 10 percent, depending on what years you used as endpoints, and given that we were pouring $20 billion a year or so into anti-depressants in the US, it struck me that we had a technology that wasn't working as advertised. I interviewed many experts in the field including Kay Redfield Jamison about suicide and the anti-depressant/suicide disconnect. After a time, I determined they were clueless and had little more than stock answers to offer for why suicide continued to rage in our culture.

I went to my editors and asked them to let me write about Doyon and wrap my own story about depression, bipolar disorder and meds around her story. They agreed. I wound up writing a very angry article that ran in January 2004. In it, I attacked the media--especially the New York Times--for practically ignoring the problem of suicide in American culture except where teens were involved. Statistically, teens (classed as 15 to 24 year olds in national data for some reason) are not the big driver of suicide rates in America. About 4,500 of 32,000 suicides each year are by teens--making them about 17 percent of the problem--and you could see that even if you could eliminate 20 percent of teen suicides, or about 1,000 suicides, it would barely touch the overall national rate (this holds true for the 2004 data as well). I couldn't understand why the media and mental health advocates spent so much time on teens--as they were at the time--to the exclusion of every one else. Except of course they are kids and anything affecting kids is always something editors and news directors and policy makers want to jump on. I suppose their impulses are noble enough.

I had no idea what kind of response the article would get and what fallout there would be for me personally since it was one of those naked first-person pieces you write once in a career. In the end, my paper ended up getting over 1,000 emails about the article and I stopped counting at 400 phone calls. The next week, I went on KUOW to talk about Doyon and suicide. (For those of you amused by such things, an archived version of the interview is here.)

In the article, I took a few swings at meds, calling them "neutron bombs." Several readers wrote to tell me that I would kill people by saying such things, even though I had gone nowhere near the anti-depressant-induced suicide issue. No one had any idea if Doyon had ever been diagnosed with depression or if she took meds. I also heard from a few readers who were actively suicidal and in each case was able to talk them out of the bad place they were headed to. But there was one man I couldn't reach.

THE END OF PHILIP DAWDY

One afternoon in May 2004, my work phone rang. On the other end was a cop identifying himself as a detective with the New Jersey State Police. "Are you Philip Dawdy?" he asked.

"Yes."

"Philip Dawdy the writer?"

"Yes. What's this about?" Being in Seattle, I didn't get too many calls from Jersey cops.

The detective proceeded to tell me that a young man named Philip Dawdy who lived in Toms River, NJ had gone missing and could be a possible suicide. He wanted to know if I'd heard from him or if I knew him. At the time, I only knew of three Philip Dawdys in the entire country.

"No. Why would I?"

"Well, we searched his residence and found your article on his computer. If he calls, will you let us know?" He gave me his number.

I was in quite a bit of shock. Toms River is about 30 miles from where I went to high school and the odder coincidence of someone with my same name--my last name is rare enough, but first and last?-- reading my work and possibly going off and doing something regrettable was a bit much to handle. Even though the article is pretty strongly life-affirming in its angry, rambling manner. I spent the next two days near my phone at work and checked my email from home constantly. I hoped Phil, as he was called, would contact me on some impulse and that hopefully I could talk him back to Earth.

But he never did contact me. Soon, I heard from the family's priest that Phil's body had been found in a field in Eastern Pennsylvania. I don't know much about Phil or what was driving him--whether he was depressed and taking meds or not taking meds or whether he was responding to some kind of life crisis. I still don't know. I just hope he's at peace. And that the wounds have healed as much as they can for his family and friends.

WHITE MEN DON'T COUNT

As I noted above, teen suicides--tragic as hell and heartbreaking, of course--get the big attention in our culture while not being much of a driver of the suicide rate which in 2004 stood at 10.9 per 100,000 people. Suicide is the 11th leading cause of death in the US. The federal department of Health And Human Services has a goal of halving the suicide rate by 2010. The goal was set in 1999 when the suicide rate was about 10.5 per 100,000. So we are clearly getting nowhere in a hurry.

When I was reporting the Doyon article in 2003, I interviewed numerous public health officials, mental health experts and suicide prevention groups. When I asked them how I should be writing about suicide, they almost all stressed that I should be writing about teens and "disadvantaged groups," as one put it, where disproportionality loomed. What groups were these? "Native Americans," one interviewee told me. I almost fell out of my chair. I knew that the rate of suicide among Native Americans was very high--on the order of twice the national average, if I recall--but again we were talking about a group that comprised about 200 suicides a year. I didn't think those lives weren't important. But again it was a problem of if you wanted to cut suicides in half, wouldn't you be going where the action was? If you were in the media, wouldn't you be covering the astounding body count among men--and, to be very pointed about this, white men?

At the time, men made up about 75 percent to 80 percent of all suicides. White males comprised about 67 percent of all suicides. In 2004, according to the CDC's data, the numbers are:

Total suicides: 32,439 Rate 10.9 per 100,000
Men: 25,566 Rate: 17.7 per 100,000 or 79 percent of all suicides in 2004.
Women: 6,873 Rate: 4.6 per 100,000 or 21 percent of all suicides in 2004.
White Men: 21,214 Rate: 21.6 per 100,000 or 65 percent of all suicides in 2004.

White males make up about 30 percent of the US population. Talk about your disproportionality. So why is it that the CDC and the media are choosing to focus on teen suicide, once again, as the big problem? Beats the hell out of me. I simply know that if the problem of teen suicide is big news, then white male suicide is even bigger. But too big for news coverage and emphasis by public health officials? Please.

Why is it that men like Phil Dawdy, who killed himself in 2004, get very little attention? Is it because public health officials are so desperately politically correct that they won't dare point to white men as the problem here because white men are allegedly the oppressors in our society? Or are they just stupid while working on the public's dime? Do reporters who read the CDC's press releases even bother to go read the full report and see what's going on?

BLACK BOX HATERS: BE CAREFUL WHAT YOU WISH FOR

I hope no one understands what I've written above as some kind of twisted teen hatred. It's not. Speaking of teens, the CDC reported:

"In absolute numbers, from 2003 to 2004, suicides increased from 56 to 94 among females aged 10--14 years, from 265 to 355 among females aged 15--19 years, and from 1,222 to 1,345 among males aged 15--19 years."

It was suicides among these groups that drove yesterday's news. Let's assume for a moment that the 2003 numbers were "normal." Taking the 2003 and 2004 numbers for the groups together, you'd see an increase of 251 deaths. There is no indication from the CDC whether or not those 251 teens were diagnosed with a mental illness, and there is no information as to whether or not they were taking meds. Yet the assumption among critics of the FDA's black box warnings are that somehow these 251 people were denied access to meds because of the warnings.

Let's assume for a minute that all 251 had been diagnosed with depression and were receiving anti-depressants--in other words the black box would have no impact even if it were in effect for all of 2004. Let's further assume that these anti-depressants performed on these obviously very depressed people along the lines of what we know about anti-depressant performance in the real world. About 30 percent of them saw very good results (84 lives saved), about 20 percent saw mixed results (50 people among whom half would commit suicide and half would live for a net of 25 lives saved) and a full 50 percent who'd see very little effect (no lives saved). A total of 109 lives would be saved from these groups.

I know that's a very back of the envelope calculation, but basically yesterday's hubub in the media was about 109 lives, if you want to be very persnickety with where the CDC spent its public relations dollars. Out of 32,000-plus suicides, that's just not very impressive. And makes me wonder if the black box argument is even worth having.

In addition, who's to say that these same youngsters were not all recent bipolar disorder diagnoses who were maybe taking a mood stabilizer plus an antipsychotic plus an anti-depressant? No one is to say, of course, because we just don't have data on that level right now. But let's assume that these were all people who were on Zyprexa, Risperdal or Seroquel (and I bet some were). Would the black box haters then come out against the black box warning for diabetes and hyperglycemia, etc. on atypical antipsychotics because it was scaring bipolar teens--among whom we know there has been a massive explosion in diagnoses of bipolar disorder in recent years, perhaps even replacing some diagnoses of depression--away from medication? What proof do the black box haters have that everyone who commits suicide should be diagnosed with depression and be taking an anti-depressant, when a good number of these youngsters could just as easily be bipolar?

Maybe we'll find out. The CDC did say in one article I read that it intended to look very closely at these age groups. I hope they do. Right down to the level of what diagnoses these poor people did or did not have and to what meds they were or were not taking. Hopefully, they'll make the results public as well.

Then, we'll see if they can summon the nerve to talk about white men.

When Doctors Lie About SSRIs

The New York Times today has an interview with Sanjay Gupta, a psychiatrist at the University of Buffalo not the CNN TV doctor. In his interview, Gupta asserts:

"Q. What is the current thinking on a connection between selective serotonin reuptake inhibitors, or S.S.R.I.’s, and suicide in adults?

A. In my opinion, there is no connection. It was thought many years ago that Prozac, the first S.S.R.I., could cause suicidal thinking in adults, but that was never proven."

Gupta is either a liar or he is lazy in his research. For example, earlier this year a Lilly-sponsored study of Prozac found:

"Hot off the presses is a research study asserting that 14 percent of patients in the study who did not have suicidal ideation at the beginning of the study wound up with suicidal ideation after being given 20 mgs. of Prozac. "Relatively common" in the authors' estimation. The study lasted 12 weeks and involved 414 patients, 59 of whom reported suicidal ideation during the study."

The medical literature is littered with studies like that one, and David Healy wrote an entire book, Let The Eat Prozac, which delved into the phenomenon. And SSRIstories.com is filled with accounts of suicidal behavior by patients on Prozac and the like. So what lack of proof is Gupta referring to? Or is he just waiting for an honorarium and consulting fee to speak the truth?

His answers about anti-depressants and weight gain and how people with depression are likely bipolar were funny as hell too. (Via Beyond Blue.)

How do these asshats get so much credibility with the media? Has the NYT ever published a Q&A with a patient who got screwed up by these meds?

Correcting Subthreshold Bipolar Disorder

There was an interesting correction in the Archives of General Psychiatry this week. In it, researchers corrected an assertion in a paper from May which stated that so-called subthreshold bipolar disorder (ie, mild agitation now equals full-blown bipolar disorder) was real and strongly implied that patients needed to be medicated for it. Now, the researchers claim that they overstated their case and that only people with BP1 and BP2 need meds.

As CL Psych noted yesterday, it's a bit hard to believe that such an assertion could have made it past the original authors, the article's peer reviewers, and the journal's editors. But whatever. Perhaps, their reading and reasoning skills were subthreshold at the time.

CL Psych, myself, and others ripped apart this alleged new form of bipolar disorder back in May. In short, it struck us collectively as a way to so expand notions of bipolar disorder so that pretty soon about 5 percent of the American public would be declared bipolar and pressed to take meds, when perhaps only 2 percent of the American public can be claimed to have either bipolar 1 or 2.

It's nice to see that the docs have stepped away from this a teensy bit, but they sure aren't backing away from the bipolar ultra light diagnosis which strikes me as being an excessive application of medicine to human psychology and behavior. But then there are a lot of concerns these days about whether depression has acquired new, softened diagnostic criteria to the point where we are medicating sadness. Certainly, you can make the case that the whole bipolar child business is a subthreshold disorder--and god knows that's expanded diagnoses of bipolar disorder in kids and teens by 4,000 percent.

This is a very weird moment in mental health in America when these kinds of claims are roaming about the land. And if you aren't bothered by that, then perhaps you aren't paying attention.

CL Psych notes another problem:

"Here's the problem. News stories have already circulated indicating that subthreshold bipolar is real and requires treatment. Not a single news story will cover the latest turn in events, in which the study authors retract their conclusion that subthreshold bipolar requires drug treatment. The damage has already been done. This reminds me of a post I wrote in June where I wondered how we could amplify news such as this? A major conclusion of a study is withdrawn but who will ever know? Let's face it, not many people read the Archives of General Psychiatry (even including psychiatrists), and those that read it don't usually skim through the bottom of a page at the end of a reference section (where the current retraction was located) looking for corrections. Might journals want to post corrections in a more accessible manner? Might the so-called health media want to report on these corrections?"

We shall see.

Bruce Lee Award: Robert Fiddaman

Bob Fiddaman, who authors the Seroxat Sufferers blog, has gone scorched-earth over some ads for Paxil/Seroxat/Aropax that appeared on the website of the Delphi Centre in Australia. That would run counter to the law in Oz which, wisely, does not permit DTC ads of pharmaceuticals. He wrote to the Therapeutic Goods Administration, their FDA, and the TGA claimed the ads were down. Last time, Fiddy checked the ads were still up. He wrote to the TGA:

"Are you lying to me or do you just have incompetent staff?

It's just gone 3am here in the UK and a quick glimpse of the webpage shows that GSK are still blatantly advertising Aropax here -http://www.delphicentre.com.au/conference/sponsors.htm

I've taken 3 snapshots of the webpage too - see attached. What are you going to do about this?

Sincerely

Mr Robert Fiddaman"

Oh, I just love it when Brits get angry. I had a bad go of it on Paxil, as have many others, but Fiddy has certainly taken former-patient anger to where it properly belongs--right into Glaxo's snoot.

The ad for the drug was still up when I visited this page at 12:18 a.m. PDT today.

Fiddy has also been linking to a New Zealand documentary on Paxil/Seroxat/Aropax.

For being a one-man wrecking crew, Fiddy gets my first Bruce Lee Award--a small man from Seattle and Hong Kong who kicked everyone's ass and had epic amounts of courage.

Preventing Bipolar Disorder In Kids, Hold The Meds

David Miklowitz, a psychologist at the University of Colorado, has begun a study to determine if family-focused therapy, of which his is the father, can work to prevent bipolar disorder from developing in kids. While the evidence is mixed that bipolar disorder even exists in preadolescents and, if it does exist, whether alleged risk factors in kids would ever blossom into a full-grown case of bipolar, it's refreshing to see someone taking a non-meds approach. (At least from what I can determine, no meds are involved.) It'll be interesting to see what his research determines. The study focuses on youths aged 9 to 17, according to the above press release. It ought to be a hell of a lot less problematic for the bodies of the patients than was Yale University's PRIME study.

Or maybe not. Another Miklowtiz-led two-year study of family-focused therapy uses meds such as Seroquel in its treatment arms.

If I've accessed the correct study in the clinicaltrials.gov database, then I am troubled by the inclusion criteria for the study. For a kid to be admitted, then his or her parents must have a diagnosis of bipolar disorder 1 or 2 and their children must meet "at least one current mood symptom meeting DSM-IV Criterion A and at least one depression or mania symptom meeting DSM-IV Criterion B." Meaning a kid with bipolar parents simply needs to be agitated or to have low-grade episodic depression and so forth to be tossed into the great bipolar net.

That's simply too low of a bar for my tastes and how might you measure clinical improvement in the patients? Less agitation? Maybe, Mom took the Pop Tarts away and cut back on the kids' computer time. OK, perhaps I am being too much of a skeptic here, but I am less than convinced of the prevention paradigm in youth that seems to be an emerging focus of researchers. It seems to me to be part and parcel of this whole subthreshold bipolar disorder nonsenseand America's rush to dub as "crazy" and "impaired for life" people who barely tip the scales of abnormality.

Miklowitz is one of the PIs on the STEP-BD study and in April published an article showing that psychosocial treatments used as an adjunct to meds were somewhat successful in treating bipolar depression. I previously wrote about the study here.

BTW, I am also aware of recent groundbreaking studies in Australia and the US on psychotherapy in treating bipolar disorder. I'll get to those when I have some more time.

The Many Mysteries Of Schizophrenia And Culture

Over the last few days, I have bumped into several interesting items concerning schizophrenia and culture. An article this week in the Washington Post which examined, post-Cho, problems faced by many immigrants in the DC-area with mental illness, especially schizophrenia. One of the big takeaways is that cultural barriers prevent immigrants from getting properly medicated American style. Nice simplistic thesis, especially in light of an article in the same paper two years ago by Shankar Vedantam, examining why schizophrenics in India do so much better than schizophrenics in the US and other developed countries, but which the present reporter fails to mention or account for in her piece. Nice 'dissing of your colleague! Wouldn't it be kind of interesting to ask about that little socio-cultural dynamic?

Whatever the case in the US, the fact remains that schizophrenics do much, much better in lesser-developed countries than in glossy high-tech ones. Which brings me to a fascinating book review in the current American Journal of Psychiatry. Thus:

"Outcome from schizophrenia is routinely better in developing world settings, and this difference becomes apparent during the initial 2 years of illness. But even for developing world patients with a poor early course, outcome is superior to that of developed world patients with an equivalent early course. Employment rates are substantially greater for developing world subjects, and some authors have attributed this to the freedom from the economic disincentives to employment that can accompany the provision of disability benefits in the industrial world. The editors, who include a well regarded medical anthropologist, are cautious about attributing the improved developing world outcomes to specific cultural factors. Shantytowns may not be ideal "communities of recovery," they point out, and extended families can be tyrannical as well as supportive. They conclude, however, that family involvement may be a key positive factor. They point to "the extraordinary engagement of Indian families in the course of treatment," coupled with low criticism and reduced demands. They also point to a startling difference in one component of social inclusion. Nearly three-quarters of Indian subjects with schizophrenia were married at follow-up, compared with about one-third of people with the illness in the developed world centers."

Well, lift the scales from my eyes. Looks like this op-ed Robert Whitaker penned in USA Today five years ago was dead on. And, it sure makes the Hearing Voices Network people look like geniuses. I don't really have any good answers for why folks do better in other countries than in the US, aside from families and support systems, but we are clearly doing something wrong in this country when most schizophrenics continue to see a lifetime of repeated psychosis, unemployment, rejection by families and friends, and the hard fist of the streets. And, here, I am thinking of the ones who take their meds and play by the rules--and get fucked up by their meds--and don't smoke crack and the like. Why?

I'm not sure that evolutionary theory holds too many clues for us. But there is this fascinating piece from Nature going into a study asserting that schizophrenia genes--whichever ones those are exactly!--must have an evolutionary purpose, because they made it through eons of natural selection processes just as robustly as did other human attributes. The study authors cannot account for why. But perhaps it's just possible that a given set of schizophrenia genes in a Homo sapien in one environment and culture lead to one set of results and the same genes in a similar Homo sapien in an environment and culture such as America's lead to completely different, and much worse, outcomes. In which case, one could argue that this has a whole lot to do with environment and evolution--or God, if you prefer--must be mighty pissed off at Western cultures.

Whoever sorts this business out to the good of these poor folks will get a free ticket courtesy of me to pick up their Nobel Prize. Until then, we are going to be stuck in a mystery unless someone in a position of influence starts pushing the game a bit differently. Something tells me that person will not be Fuller Torrey. He stopped asking questions decades ago.

09-04-2007 Media Madness

The whole world is apparently watching the news around the massive increases in diagnoses of bipolar disorder in kids, teens, and adults. My earlier post on this is here. Hundreds of references from the mainstream media and news sites such as CNN. I'm glad to see many in the media are layering all of this with appropriate skepticism and that some docs are pointing out that so many kids they see diagnosed with bipolar disorder have been misdiagnosed. One doc puts it at four of five patients. This from the Los Angeles Times/Newsday:

"Dr. Gabrielle A. Carlson, a psychiatrist at Stony Brook University, said only 1 of every 5 children referred to her with a diagnosis of bipolar disorder actually has it. The rest have autism, depression, anxiety or another psychological disorder. All these conditions involve different treatments, either with drugs or behavioral therapy, or both.

"Carlson, who has studied the increase in bipolar diagnoses, said some parents seemed to prefer a diagnosis of the disorder because the illness, thought to be largely genetic, absolves them of blame. "They don't have to deal with their chaos, their psychiatric disorder, their marital troubles or abuse." She said in some cases providers diagnose psychological problems in children as bipolar disorder to obtain insurance reimbursement for hospitalizations, a practice called upcoding."

Now that's skepticism.

Even Slate got into the act a bit, although as usual Bill Saletan is too glib by half. Several blogs have taken this up as well, including Schools Matter and NPR, which is discussing the matter on "Talk of the Nation."

John Grohol at PsychCentral has a good discussion of the diagnosis explosion story. Now that I have read the full paper, I share his concerns that many of these youths appear to be getting diagnosed and medicated by PCPs. If I recall, that's the same pattern we saw with the ADHD explosion of the 1990s and PCPs are diagnosing and treating on the order of 80 percent of all cases of depression. And their patients are doing so well! I have several other concerns upon reading the paper, which I will get to later. The point here is that PCPs just don't have the time or expertise to be doing mental health work in a consistent reliable fashion. That's not a slap at PCPs. It's an acknowledgment of clinical reality.

Danny Carlat has an amazing item on a psych professor who had a paper appear under his name but is now denouncing it as a piece of commercial crap. Read it.

CL Psych's blog has blown up with comments over the Rita Pal affair in the UK. I have never seen nastier comments in the mental health world and I am glad that the Pal haters decided to steer clear of my blog. Probably because I moderate comments. CL has had to turn on his comment moderatin' software and has encouraged people to get a new hobby. Personally, I find the Pal affair discouraging on so many levels, but I am looking forward to its resolution in the British High Court where I guess the name of my little old blog will get mentioned. In addition, CL has another fabulous skewering of Charles "Ghost Authorship" Nemeroff.

Grohol also has an interesting analysis of an article in Reason magazine that defends the status quo of our deeply conflicted pharma-academia industrial complex. Reason is one of my favorite publications, and I am generally an adovcate for free market solutions, but the article's author Ron Bailey might want to consider not being a lap dog for pharma. The conflict-of-interest-o-rama that is the world of mental health treatment, for example, has been an utter disaster for real world patients and, in my opinion, a huge black eye for academia. Mauricio Tohen anyone?

Souful Sepulcher goes ripshit on my earlier item about a Harvard researcher declaring 50 percent of America DSMable.

Meanwhile, my friend Liz Spikol is taking it easy in Paris. Good for her. Smoke a Gitanes for me, please.

And many thanks to the Wall Street Journal's health blog for linking to my post of yesterday on Lilly's experimental schizophrenia drug.

Bipolar Disorder Diagnosis Is Up, Up And Away

A new article in the Archives of General Psychiatry asserts that diagnoses of bipolar disorder in children and teens up to 19 years-old increased 4,000 percent between 1993 and 2003. The study also notes that diagnoses roughly doubled in adults, mostly in women. I haven't seen the paper itself yet, but most of the press accounts have cast this news as being all about children. I'm not convinced that teens and adults aren't just as important.

Keep in mind that the increase in diagnosis is likely to be higher now, four years after this study stops looking at data.

According to one press account, one of the study authors is even critical of the diagnosis of bipolar disorder in youths. I am, too, since there is very mixed evidence on whether it even exists in kids younger than about 12. This issue was recently taken up by Australia's ABC radio. Here's a transcript.

But whatever one makes of the diagnosis itself, I think the psych researchers who have been pushing this paradigm for unruly children should be ashamed of themselves. That's because the treatment paradigm of mood stabilizers and antipsychotics has barely been studied in children and teens, and has not been studied at all long-term. The injuries that can be caused by these drugs are well known. And to judge by what I glean from places like the bipolar groups on MySpace, it appears that these treatments are not proving to be effective in long-term use. And clinicians and researchers are well aware of this. My own view is that most of these drugs are not acceptable for long-term use except in extreme cases.

You'd think that should argue for some caution in the psych world and maybe some introspection about what it is that is apparently making America's youth (and adults) so much screwier than in 1993. But there's little except for silence on that front, and nothing but bloviating from the defenders of the faith at Harvard. No one is asking why they aren't making anyone well much less making them whole.

Have we become so lazy as a culture that this is the best we can do?

Harvard Researcher Says 50 Percent Of America Is Mentally Ill

No, I am not making that up. In a paper in lthe June 2005 Archives of General Psychiatry, Ronald Kessler, a Harvard psych researcher, asserts that 46 percent of Americans meet the criteria for some kind of DSM-IV diagnosis at some point in their lives.

By this standard, I'd say at least half of the psychiatry department at Harvard is insane. I'm only half-joking.

Here's how Kessler breaks down the numbers:

"Anxiety disorders, 28.8%; mood disorders, 20.8%; impulse-control disorders, 24.8%; substance use disorders, 14.6%; any disorder, 46.4%. Median age of onset is much earlier for anxiety (11 years) and impulse-control (11 years) disorders than for substance use (20 years) and mood (30 years) disorders. Half of all lifetime cases start by age 14 years and three fourths by age 24 years."

Guess what Kessler proposes doing about this? "Interventions aimed at prevention or early treatment need to focus on youth," he writes. Right, let's medicate the kids even though we have slim research data on how these treatments affect adults much less youths. As for prevention, I'd like to know what studies Kessler cites indicating that psych meds prevent mental illnesses in the long-term real world we all live in.

Still, the fact that a leading researcher can make such claims either means that we need to throw out most of our assumptions about abnormal psychology because if half of our country checks out with a DSM diagnosis, then that would hardly make them abnormal. It would put them right under the bell curve of normality. Either that, or the DSM has simply become far too loose in its definitions and that is dangerous for the field of psychiatry and patients of every stripe.

What do you think?

UPDATE: I originally stated that Kessler's study was from August 2007. It is actually from June 2005 and I have corrected the entry. My bad. Thanks, John.

Lilly's Experimental Schizophrenia Drug May Show Promise

Or maybe not.

I don't usually post on holidays, but there have been many articles--and many readers forwarding me articles--on a forthcoming paper in Nature Medicine about initial results of Eli Lilly's experimental schizophrenia drug, currently known as LY2140023. In recent first phase clinical trials in Russia, the drug performed as well as Zyprexa in treating schizophrenia but caused no injuries as Zyprexa often does. I have not seen the paper yet, so I cannot give you head to head results. But I want to caution that the phase 1 trials were only 28 days long and involved fewer than 200 patients. That's not enough of a dataset to say much of anything about side effects, especially since most patients who suffer injuries such as diabetes, hyperglycemia, massive weight gain, movement disorders, and boosted cholesterol levels on antipsychotics do so well after the time scope of short-term trials.

But, then, phase 1 trials exist to determine very basic efficacy and safety data for an experimental drug. Sadly, pharma companies rarely run long-term trials of a drug even after it hits the market much less before (because the FDA doesn't make them even though psych meds are clearly intended for long-term use), so we may not know much about side effects of LY2140023 until it's been used clinically for six months to one year on a particular set of patients. That's why I am a bit puzzled that some media accounts basically paint the news here as "as good as Zyprexa but now with no side effects." I am also puzzled as to why researchers like Jeff Lieberman are saying such nice things about the drug based on such limited data. Please.

What is interesting is that LY2140023 is not a dopamine drug but goes after glutamate receptors in the brain. Treating schizophrenia by way of dopamine receptors has been with us for 50-plus years now, and has not played out well whether the drugs are first or second-generation antipsychotics. Everyone in the clinical world knows we need a new and better way to address schizophrenia, but let's see how going after glutamate receptors plays out in the real world as opposed to some promising animal studies.

All the same, I am as anxious as anyone else for schizophrenia treatments that don't destroy patients in the process. But, then, isn't that what researchers and pharma companies said Zyprexa was an example of?

In other words, don't believe the hype. Not yet anyway. Besides, on at least one measure, Lilly's press release identifies that the new compound was about 20 percent less efficacious than was Zyprexa.

If further clinical trials are promising, then the drug could hit the marketplace in 2010 or 2011. Just in time for Zyprexa's patent expiration in 2011.

Two things also jumped out at me from the press coverage. One, the New York Times puts the total market for antipsychotics at $18 billion a year worldwide and at $12 billion in the US. Thats much higher than other estimates I have seen, but, if accurate, would make antipsychotics almost as big a market as the one for anti-depressants. That gives you an idea of just how much psychiatry has changed since 2000 and an idea of just how important bipolar disorder is to Big Pharma, when you compare that market with where the world was at in 2000, say. And given how Big Pharma and allied forces are working to make darn sure that notions of what constitutes bipolar disorder become so expansive that even a minor gust of weirdness in one's life creates an imperative for lifetime treatment with medication coupled with injuries antipsychotics have caused, then I am simply agog at how large the antipsychotic market has grown since 2000.

The other interesting bit is that LY 2140023's developer, Darryle D. Schoepp, a toxicologist and pharmacologist who's been with Lilly since the late-1980s, recently left the company to go to work at Merck. If you had invented a promising new drug and helped to develop a new treatment paradigm wouldn't you want to stick around to see how things played out? Unless you already knew something.