According to Reuters, the Netherlands Health Authority, acting as a reference body for the European Union, shot down AstraZeneca's application to have Seroquel approved as a treatment for depression.
"The Dutch decision to refuse approval for the medicine in MDD, because of a negative benefit-to-risk balance, comes after Seroquel XR won partial support from U.S. advisers as a treatment for the same condition last month."
AstraZeneca has submitted its application to the European Medicines Agency. The drug was reportedly approved for depression in Canada last month (news to me).
Another $385 came in yesterday from nine people, bringing the total raised so far to $1,510 from 37 people. That leaves $2,490 from 63 people to go to reach the overall goals of $4,000 from 100 people somewhere around June 5, next Friday.
Thanks to all of you who've contributed so far.
I have two substantial concerns right now: 1) I fear the fundraiser won't meet its goals or even come close and 2) I've been roundly attacked in a few comments (which I didn't post) and a couple of emails in the last 24 hours for even asking for contributions to support the work I do here. Of course they were all anonymous! Apparently some folks have a weird beef with me (whatever, have a nice day) or somehow don't get that sites like this one are rapidly becoming the new media in the US. To expect them to operate for free is sheer madness (I can assure readers that I do it for a significant discount). As it stands these days, there are plenty of political blogs that solicit their readers for contributions (or they have loads of ads or funding from a political group, neither an option for FS), so what I am doing with this fundraiser isn't so unusual and is pretty tame by the standards of your local community radio station or political blogs. One political site, truthout.org, used to send readers "Contribute or we go out of business" emails once a month. I try to limit my begging to once a quarter.
Anyway, it's Fear #1 that I'm most concerned about at this point since this site is my only means of support currently (sadly, the freelance writing market has gone to hell over the last nine months or so). Newer readers probably don't know this, but for the first two years of this site's existence I subsidized things 100 percent out of my own pocket and only turned to readers for support in 2007 when several readers requested that I do so.
If you'd like to help ensure that my cats and I don't end up on the street in the next week or so, please consider making a donation today.
As usual, the PayPal button is on the right. If you prefer snail mail, send me an email and I'll send you a mailing address.
Thanks for your support.
A new study is out in the journal Social Science & Medicine examining how Eli Lilly marketed Zyprexa, its controversial atypical antipsychotic, in primary care settings (meaning to non-psychiatrists). The paper's author, a psychology prof at Metropolitan State University in Minnesota named Glen Spielmans, relied heavily upon the Zyprexa documents hosted on this site for his trail of evidence. As far as I know, his paper is the first published academic study of how Lilly marketed the drug far outside of its approved indications (schizophrenia and mania) in the first half of this decade.
Longtime readers will remember that I first wrote about Lilly's marketing of Zyprexa for bipolar disorder type 2, for which it did not have marketing approval, and for agitation and mild depression, for which the company also had no approvals, in February 2007. I'm glad that Spielmans took up this matter and the entire history of Lilly's PCP marketing campaign, as he adds a lot of depth and texture to the story. I also understand that attorneys for Elsevier, the journal's publisher, lawyered the hell out of his paper, a highly unusual move in academic publishing, in order to keep from running afoul of Lilly's legal team.
It's an excellent paper and I encourage you to all give it a read. In addition, I appreciate the acknowledgment Spielmans gives me at the end of the paper.
My favorite part of the paper comes here:
"The relatively mild symptoms marketed by Lilly as components of ‘complicated mood’ (anxiety, irritability, disturbed sleep, and mood swings) are ill-defined and, to some extent, are likely to be experienced by a large number of people. Labeling this constellation of ill-defined and likely common symptoms as indicative of a mental condition is suggestive of ‘disease mongering’ a term referencing the effort of pharmaceutical companies to broaden the market by convincing patients (and physicians) that a large number of people are suffering from a (usually relatively mild) illness which would benefit from pharmaceutical intervention. In trade journals, pharmaceutical industry insiders have plainly stated that expanding the market for their products via 'condition branding' (an industry term analogous to ‘disease mongering’) is a highly useful tool in the marketing arsenal. Indeed, the current corpus of internal documents hints that, in addition to marketing olanzapine, sales representatives were also marketing the expanded boundaries of bipolar disorder. No longer was bipolar disorder a relatively uncommon condition relegated to treatment by psychiatrists, it was to be marketed as a common illness with a broad spectrum of severity that warranted treatment in primary care. Despite an expanded treatment market, there is a paucity of controlled clinical trial data regarding the benefits and risks of treating adults with mild symptoms of bipolar disorder/complicated mood with ‘mood stabilizers’ or atypical antipsychotics such as olanzapine."
Condition branding is such a delightful term. Too bad it creates so many artificial realities at such high costs for so many people.
Lilly should be counting its lucky stars after reading this paper because it's clear that the company off-label marketed for bipolar disorder type 2 and for agitation and mild depression, but was only rung up by the feds and about 30 states for off-label marketing for dementia. As I've said before, its $1.42 billion settlement earlier this year with the feds and states allowed Lilly to get off cheaply, albeit with a criminal misdemeanor plea.
To date, Lilly has settled about $2.7 billion in claims concerning its handling of Zyprexa--and there's likely more to go.
By the way, Zyprexa is the subject of 22,191 adverse events reports in the FDA's adverse events database as of the end of 2008, including 3,442 reports where the outcome was death.
I generally consider myself unshockable when it comes to new disorders and illnesses that some psychiatrists want to include in the DSM, but a new proposal to include bitterness in the forthcoming edition of DSM-V real shakes me up. It would officially be called "post-traumatic embitterment disorder," essentially lingering bitterness as the result of a traumatic event. And yes it's modeled after PTSD.
I'm sorry but the American Psychiatric Association is proving itself to be far worse than a tool shed if it seriously considers this a disorder--the APA would count as an entire tool factory.
At his Psychology Today blog, Christopher Lane notes:
"[I]t feels positively insulting to have our justified anger at such incompetence [he refers to the George W. Bush presidency] discussed as a sign of mental illness, doubtless because drug companies—anxious to prod their faltering revenues—are promising relief from the disorder with pharmaceutical remedies."(Imagine, if you will, the inevitable ads: 'Think it's just bitterness from job loss, foreclosure on your home, or that nonexistent pension for which you've been saving all your working years? It may be "post-traumatic embitterment disorder," a mental illness that some doctors think is due to a chemical imbalance . . .')"
No kidding. The APA should do itself a big, big favor and put a sock in the mouths of whomever is pushing for bitterness to be counted as a mental illness. The organization has already lost a ton of credibility in recent years--not that it had lots to begin with--with social anxiety disorder, bipolar disorder type 2 and the like, and it can hardly stand to lose anymore. Or will the organization not stop until it declares normalcy a mental illness?
Beyond Meds had this to say:
"I’m sure they’d happily label all of us who have been harmed by psychiatry with this disorder as we work out our dismay after realizing we’ve been had."
Yes, like stockbrokers they want to get us coming and going.
Another $90 from four people came in yesterday, bringing the total raised so far to $1,125 from 28 people. That leaves $2,875 from 78 people to go to reach the overall goals of $4,000 from 100 people on or about June 5. Thanks to all of you who've contributed so far.
Look, I'll level with you all: this fundraiser is going far too slowly for comfort and I don't know what to attribute it to. I know the economy still stinks--trust me, I know that intimately--but the last fundraiser went fairly smoothly during what was arguably a more dicey economic moment, so I'm a bit lost in all of this. Even two regular readers and contributors wrote me yesterday, concerned about how poorly the fundraiser is going to date. What causes me to scratch my head even more is that traffic on this site has been booming lately and there are just as many regular readers as there were three months ago (about 5,000).
My big hope is that today will be the day people start contributing in droves--and there have been fundraiser days in the past where 20 people made contributions--because the first of June is looming large and I can assure one and all that finances are super tight at the FS HQ. Scary tight.
So I can only ask that as many of you as possible contribute what you can today. I could really use the boost, psychologically and otherwise.
As usual, the PayPal button is on the right. Or if you prefer snail mail, then send me an email and I'll shoot you my mailing address.
Thanks in advance for your support.
There's a new study out in Neuron explaining a mouse model of depression, neurogenesis and anti-depressant treatment. Here's how it's explained in a press release:
"'[A]nxiety/depression-like changes in behavior have been linked with a decrease in cell proliferation in the hippocampus, a change that is reversed by antidepressants,' [said one of the researchers]"Dr. David, Dr. Rene Hen from Columbia University, and their colleagues created a mouse model of depressive and anxiety disorders to investigate mechanisms of antidepressant action. Previous research confirmed that long-term exposure to glucocorticoids induces anxiety and a depressive-like state in rodents and elevated glucocorticoid levels have been linked with depression and anxiety in humans. 'We developed an anxiety/depression-like model based on elevation of glucocorticoid levels that offered an easy and reliable alternative to existing models,' explains Dr. David."
To me, the model is kind of weak because 1) it rests on the assumption that you can create a comparative model of human depression in mice (animal models aren't particularly tightly overlapped with human systems except with some processes such as vision in monkeys) and, 2) it uses mouse anti-socialiaty and listlessness in mice as a proxy for human depression and that's laughable and, 3) the entire model rests on strictly biological causes of depression and last time I checked the biological basis of depression had not been proven (although maybe it has been in mice!) and, 4) I've not seen the whole anti-depressants create neurogenesis and that's good for depression established in human studies, and 5) the whole depression-is-in-the-hippocampus theory remains unproven in humans.
Other than that, I'm sure this new mouse model of depression is perfectly wonderful.
In all seriousness, it's an interesting enough model as these things go and if it ever proves out, then that'll be even more interesting and perhaps really helpful. But that'll be at least five years and maybe longer.
Stay tuned.
Another $130 came in yesterday from five people and that brings the total raised so far to $1,035 from 24 people, leaving $2,965 from 76 people to go to reach the overall goals of $4,000 from 100 people on or about June 5.
Thanks to all of you who've contributed so far.
While I've yet to get a few contributions that I know are coming in the mail, I've got to say that things are going slower than I'd like to see at this point. Most of you know the amount of work and expertise I put into this site and that there simply aren't any workable advertising options due to my criticism of Big Pharma. Unlike some mental health sites which take pharma ads and then engage in light criticism of their products, I'm not down for that kind of compromise...and that's why I've got to turn to the public to support the work I do here. On the order of 20,000 people read this site each month and some 5,000-plus are regular readers.
So I'm calling on those of you who have not contributed to date to step up and do so. It doesn't matter if your contribution is small or large, but I don't want to see this fundraiser fall short of its goal and then have to figure out how to scale back my work here proportionately. But if I have to, then I will.
If you'd like to keep me charging into the future and pestering Big Pharma, then the PayPal button is on the right. Or if you prefer snail mail, then drop me an email and I'll shoot you my mailing address.
Thanks to all of you for your support.
I'm sure most of you are at least vaguely aware of the case of Richard Borison and Bruce Diamond, a psychiatrist and a researcher at the Medical College of Georgia who were found guilty of ripping off the college to the tune of $10 million in the 1990s, running some bogus research trials and, in Borison's case, was eventually sentenced to prison. Borison did 10 years before being released on probation in 2008. Diamond was ordered to pay $150,000 in fines, $50,000 in receivership expenses, and $1.1 million dollars in restitution and forfeitures. The pair also used VA facilities in conjunction with their MCG research.
One of the beauties coming out of the newly-released Seroquel documents is evidence that the pair were also deeply involved in running clinical trials of the drug for AstraZeneca (then simply Zeneca) in the 1990s. Back in 1996 when their misdeeds first came to light, Zeneca had to scramble because the pair were involved in at least eight Seroquel clinical trials and the company had to reaudit clinical trials data from their site. Seroquel was first approved for use in treating schizophrenia in 1997, so it's likely the pair had at least some involvement in gathering patient data for the drug's initial FDA submission. Given Seroquel's very checkered history since, it all makes sense.
What's interesting about the press release Zeneca put out in 1996 is that it notes that the drug was "in development for the treatment of schizophrenia and other psychotic disorders." Clearly, the company at the time had a different vision for the drug than what it's been turned into today by AstraZeneca--the atypical for one and all disorders. ADHD, dementia, depression, anxiety, public speaking phobia, bipolar disorder, and bipolar depression.
Nice, eh?
A little over a year ago, I wrote of Gianna Kali, author of the Beyond Meds website, and the horrible struggle she's gone through due to both being wildly over-medicated with just about every psych med under the sun and then by going through huge withdrawal problems. At the time, I made the point that psychiatry really needs to properly research how to properly get people off anti-depressants, benzos, antipsychotics and the like partly because it's a matter of fairness, partly a matter of human rights and partly because of the very practical matter that with 40 million or so Americans on a psych med of some kind there are going to be a decent percentage of people who'll need to get off a medication during the course of a year either because the medication doesn't work or because it's unsafe for that person or just because it's time for that particular person to be off that med. Here we are a year later and I see no progress on this front.
Science literally knows more about how to get people off heroin, meth and alcohol than it does Paxil and Effexor. And that's because withdrawal from the former have been adequately researched and because it's seen as a social good to get people off said substances while psych med withdrawal remains a taboo subject in the mental health industry--likely because doctors and other caregivers see psych meds as a social good and the underlying diagnoses people take them for as hard, accurate and fixed when there is good evidence of high rates of bad diagnosing afoot in the land.
I bring this up again for three reasons: One, Kali is going through withdrawal hell again, this time at the hands of an alleged detox center (read this recent post of hers for details); two, I'm sick and tired of hearing the ugly withdrawal stories such as I posted on yesterday much less bumping into people in real life who admit to me that they are hooked on Prozac or another anti-depressant and have been for decades despite numerous attempts to get off them; and, three, this site has a fair number of readers for the National Institutes of Health, the FDA, various other government health research agencies, numerous pharma companies and numerous research universities and I'm just wondering if some of you all can put your heads together, drum up some funding and get some research going on this matter. It's long past time for a STAR*D of psych med withdrawal to happen.
Or perhaps you'd like to explain to me why that doesn't make any medical or human sense.
I suspect many of you remember--because how could you forget?--that last year I noted reports that Risperdal, a widely-used atypical antipsychotic, was causing teen boys to grow breasts due to the drug's propensity to boost prolactin levels and cause gynecomcastia. Now CBS News has caught onto this and last night had a piece on one of the boys. Sadly, the boy in question thought he was a girl, according to his mom, and still thinks he's a girl at 19-years-old, despite a double mastectomy. He was given the drug for ADHD.
The piece also notes that a boy who was 4-years-old developed breasts from using the drug.
Of course, the drugmaker Janssen told CBS that it had done nothing wrong and had adequately warned of gynecomastia in the drug's labeling. I'm sure they'll have much success making that argument in court.
Here's the video. It's a bit on the graphic side so I'm not sure if it's safe for work or not.
Anyway, it's nice to see one of the major networks pay attention to problems with these drugs, which I've only been pounding on for four years or so.
UPDATE: 5/31/09: I took down the embedded video because it was auto-starting and some readers found that annoying. Instead, here's a link to the video on CBS' website.
Since Saturday's update another $110 has come in from four people, bring the total raised so far to $905 from 19 contributors. That leaves $3,095 from 81 contributors to go to reach the overall goals of $4,000 from 100 people on or about June 5 (next Friday).
Thanks to all of you for your contributions to date.
This is really the week where the fundraiser needs to start gaining steam and with 5,000-plus fairly regular readers of this site that shouldn't be too difficult a goal, especially if many people contribute what they can. I certainly hope that I've justified your support lately, especially with all the Seroquel documents I've begun rolling out and today's posting on just how problematic an anti-depressant Pristiq is turning out to be--let's just say it's a true Son of Effexor.
As usual, the PayPal button is on the right. If you prefer snail mail, send me an email and I'll shoot you my mailing address.
Thank you all in advance for your support.
Some of you remember that last year the FDA approved Wyeth's new anti-depressant Pristiq for use in depression. The drug is a metabolite of Wyeth's soon-to-go-off-patent Effexor, so it's essentially old wine in a new bottle. At the time, Tufts University psychiatrist Danny Carlat was quite critical of the drug on his blog, especially over the drug's slim effectiveness.
Last June, a Wyeth executive even publicly admitted that the company expected the drug to have withdrawal problems, much as Effexor does. Ever since, I've been getting sporadic reports of problems with the drug from people who've taken it, including two late last week which I reproduced below.
To put this in perspective, Pristiq was approved early in 2008 and has already generated 1,272 adverse events reports to the FDA through the end of 2008. That's a lot in such a short period of time, especially considering that this drug isn't exactly widely used. The company didn't even detail Pristiq's 2008 sales in its press release on its 2008 results, so it's obvious that sales were small (Effexor, however, sold $3.9 billion in 2008). The company also didn't detail Pristiq sales for the first quarter of 2009.
It's discouraging that 17 of those reports involve completed suicides through the end of 2008. There are also 48 reports of suicidal ideation through the end of 2008. Other reported side effects through the end of 2008 include nausea, dizziness, confusion, tremor, drug-induced mania and so on.
It sounds like Wyeth has another winner on its hands.
Meanwhile, here are two recent patient comments on the drug:
"I took Pristiq for 8 days and while I started to feel better from my minor depression, my blood pressure went through the roof so I had to stop taking it. I am on day 3 off of it and I can barely function and that's after taking it only for 8 days. I was told I didn't have to taper off because I was only taking 50 mg and for such a short amount of time. I am dizzy, nauseous, can't stop crying, having suicidal thoughts and basically uncontrollable emotionally. I never imagined I would suffer so much coming off of it after only taking it for 8 days. This medicine should not be sold. It hurts more than it helps. I pray this goes away soon before I lose everything that matters to me."
I hope it goes away too. It's worth noting that high blood pressure has turned out to be one of the main problems associated with Effexor.
Here's another patient:
"Pristiq seemed to work for my depression but I went off of it (and went through the horrible w/d sxs!) because I am trying to 'de-chemical' my life. I went through neurofeedback and thought I could go off of Pristiq safely. Wrong."So now I am thinking of going back on it. The body aches, depression and lack of motivation for ANY activity may be worse than the thought of being on a chemical.
"But then again, I hate that we don't know what these chemicals actually do to our brains!!
"I am between a rock and a hard, hard place."
I hope this person is able to resolve whatever withdrawal symptoms they are experiencing without going back on the drug, as that's how people turned into anti-depressant junkies for life. Or become physically-dependent, if you prefer.
Next month, the FDA's psychopharmacology advisory committee takes up AstraZeneca's application to have its atypical antipsychotic Seroquel approved for the treatment of schizophrenia in kids aged 13 to 17 and for use in so-called pediatric bipolar disorder in kids aged 10 to 17. Seroquel is not currently approved for use in pediatric populations for any indication. The committee will make a recommendation to the FDA on whether to approve or not approve the drug for these disorders, but the agency is not bound by its recommendation.
AZ's submission to the FDA has not been made public yet, so it's not clear what kind of safety and efficacy data the committee will see, but from the recently-released Seroquel documents (all lawsuit-related) it is clear that the drug caused multiple cases of glucose dysregulation and potentially diabetes in some kids under the age of 18 who were given Seroquel off-label. There have also been reported cases of deaths in this population associated with use of Seroquel.
These details come from the following document dated Dec. 14, 2004 which is entitled "Review of all pediatric reports for Seroquel through 30 September 2004." It is an internal company document, labeled confidential and likely created in response to FDA queries. The document is sizable (13.8 MBs) and I respectfully request that you only download it if you have a serious research or journalistic need for it, as I do have bandwidth limits on this site.
On page 135 of the report, 27 cases of glucose dysregulation are identified with the majority of the reports involving patients aged 12 to 18. Several of these cases resolved into diabetes mellitus. How connected that is with Seroquel use is unclear, but what is clear is that the report identifies several cases of successful dechallenges--take away the Seroquel and away goes the glucose problem--and that's a clear indication of some kind of link between drug use and condition, at least in some of the patients.
Several of these children were being given Seroquel for pediatric bipolar disorder, conduct disorder, Asperger's and, in one case, ADHD. That's exactly the type of patient population that the advisory committee will be reviewing safety and efficacy data about in June and one hopes they pay attention to any glucose dysregulation data presented to them by the FDA and AZ. But there's only one problem: that data is almost certain to come from short-term clinical trials and glucose dysregulation doesn't usually happen immediately. So one hopes that members of the committee somehow gain access to the report I've made available above.
For itself, the AZ report notes that the company did not consider any of the data in the report to contain indications of safety problems in pediatric populations.
Another $225 came in over the last 24 hours from five people, bringing the totals to date to $795 from 15 people (one from the Seattle metro area!). That leaves $3,205 from 85 people to go to reach the overall goals of $4,000 from 100 people on or about June 5.
Thanks to all of you for your contributions to date.
If you'd like to join them, the PayPal button is on the right. Or if you prefer snail mail, drop me an email and I'll shoot you my mailing address.
Have a nice Memorial Day weekend.
Another $190 came in yesterday from four contributors, bring the total raised so far to $570 from 10 people. That leaves $3,430 to go from 90 people to hit the overall goals of $4,000 from 100 contributors around about the end of June 5.
Thanks to all of you for your contributions to date.
So far, there's not been a single contribution from the Seattle-Tacoma area--I have a goal of 10 contributions of $10 or more from my local area--so it'd be great if some Seattleites stepped up.
As usual, the Paypal button is on the right. If you prefer snail mail, send me an email and I'll send you my mailing address.
A new study of schizophrenia and violence out this week in JAMA can't be anything but bad news for Fuller Torrey and his Treatment Advocacy Center, prime proponents of forced medication of people diagnosed with schizophrenia and bipolar disorder. That's because the Swedish study shows a slightly elevated risk of violence from people with schizophrenia compared with the general population, but that risk is mostly confined to people with schizophrenia who are also substance abusers. In other words, it's primarily substance abuse combined with schizophrenia causing most of the problem.
The study was unable to measure whether people with schizophrenia--violent or not--were medicated. In one press account, a researcher noted:
"'[T]he idea that people with schizophrenia are generally more violent than those without is not true,' says Dr Niklas Lľngström, one of the researchers behind the study. 'People with schizophrenia but no co-occurring substance abuse are insignificantly more violent than people in general.'""Dr Lľngström hopes that the results could help alleviate fears about mental illness.
"'The stigmatisation of the mentally ill increases their alienation and makes people less likely to seek the help they need from mental health services,' he says. 'Our results demonstrate once again the importance of preventing, discovering and treating substance misuse in efforts to reduce violent crime.'"
My own experiences as a reporter are that the people with schizophrenia I've known of who were in trouble with the law usually had problems with alcohol or crack cocaine (for whatever reason I didn't run into cases of marijuana or meth use--and when I am speaking of alcohol use I mean drinking way too much, not like someone having a drink or two). I can completely understand why someone with schizophrenia would want to get high--one man told me once that it was his only way to escape the deadness of antipsychotics--but it sure doesn't do them much good.
There's been a fascinating two-part series in the Rio Grande Sun concerning what appears to be the over-prescribing and off-label prescribing of Seroquel to jail inmates (part one here, part two here). Were there tons of inmates with schizophrenia? Nope. Just a psychiatrist who was convinced that he was treating undiagnosed PTSD in inmates and helping them sleep. The paper notes several former inmates claim, however, that the doc never diagnosed them with PTSD and Seroquel is not FDA-approved for PTSD. The whole thing is very, very weird.
The paper reports that by November 2007 fully one-third of county jail inmates were taking antipsychotics of some kind. That's simply wild and out of control.
The psychiatrist no longer works at the jail and, no surprise, the Seroquel using dropped dramatically.
One Hundred and eighty dollars from five contributors came in yesterday, bringing the total raised so far to $380 from six people. The overall goal is 4,000 from 100 contributors by the end of June 5, so there's $3,620 from 94 people to go.
Thanks to all of you for your contributions to date.
As usual, the PayPal button is on the right. If you prefer snail mail, send me an email and I'll shoot you my mailing address.
For those of you who are new to this, I did my usual what-have-I-done-that's-any-good-lately post yesterday, which ought to give you some idea of the scope of the work I do on this site.
I'm going to make this short and not so sweet: AstraZeneca knew just how big the weight gains were for patients taking Seroquel for ages and somehow justified to itself casting the fat-producing, blood sugar-boosting drug as weight neutral. You'll see just how crazy such drug marketing spin was in a second. I can assure you if I'd had even the slightest inkling that Seroquel was packing the pounds onto a significant proportion of patients taking the drug, then I would've never taken the drug in the first place in 2004. I would've told my psychiatrist "Hell, no," since part of the reason I was getting off Depakote at the time was due to weight gain (not so bad at the time but enough bad to get off it). I asked my doctor when he suggested Seroquel if it made people gain weight. He told me the research he'd seen suggested it didn't.
Oh, boy. I wish he knew then what he and I both know now.
In memo dated April 29, 2005 (and obviously dependent on data from prior years) from the recently released new batch of Seroquel documents and titled "Weight change over 52 and 104 weeks schizophrenia mono therapy," someone at AZ reports (see page 4) that 38.7 percent and 47.5 percent of patients taking the drug for 52 and 104 weeks, respectively, gained at least 7 percent of their body weight, a well understood diabetes risk factor. What's even more stunning is that 30.3 percent and 39.2 percent of patients taking the drug for 52 and 104 weeks, respectively, gained at least 10 percent of their body weight. That's just crazy.
Weight neutral, my ass. Literally.
Adding salt to the wounds, on page 8 of the memo the company claims the drug causes a "modest" amount of weight gain in patients taking the drug long term.
AZ knew for a long time that it was playing with fire in how it characterized its drug's safety profile. I cannot wait to see them defend this kind of BS in court--and we should have that opportunity sometime this summer.
After yesterday's post on the possibility of DSM-V recategorizing bipolar disorder as a psychotic disorder--it's currently a mood disorder--I got the following from a board certified psychiatrist who practices on the East Coast (yes, it's someone I know and I'm leaving his identity out of this) and he agreed to let me post his take on just what that possible DSM-V shift represents and how out of touch it made the field look. So here it is.
"The upper echelon of psychiatry has become so corrupt, complacent, and out of touch with the daily dealings in clinical care, that anyone who makes political decisions in this field that shows no consideration to the impact of diagnosis and care of psychiatric disorders as previously defined as appropriate and responsible, should be removed from whatever office or level of impact on care matters for the sake of patients and responsibly invested clinicians."And, where warranted, criminal investigations should be considered and implemented to show there are ramifications for irresponsible, unethical, unwarranted behaviors and interventions in clinical care that cause harm and malfesance. In other words, it is time for people who give a damn about the profession of psychiatry to stand up to the alleged leaders of this field and tell them to go to hell--just retire or find an alternative line of work. Leave the profession to those who take health care seriously and respect the Hippocratic Oath and practice based on principles and documented treatment interventions, not about money or standing in the profession."
I agree with this psychiatrist that the upper ranks of academic psychiatry truly seem to either be compromised by their dealings with pharma companies or are simply so disconnected from everyday street reality that they lost touch. That's not good. Psychiatry is certainly one of the most screwed up branches of medicine and has been so historically, but that's the nature of the beast.
APA president Nada Stotland recently wrote an editorial decrying the stigmatization of psychiatrists. Stotland is certainly among the peerage in psychiatry, but never defined what the mysterious stigma is that psych docs must bear and can never quite wrap her mind around the fact that psychiatry has brought much of its dubious reputation upon itself (and the APA has helped). For those reasons, Stotland's editorial is a hoot--and a must-read.
Many of you remember that in February I broke the story that Wayne Macfadden, a psychiatrist and StraZeneca's US medical officer on Seroquel and the head of CNS research at AZ, had a string of sexual affairs with women intimately involved in outside academic research of the drug as well as with writing up medical studies of the drug that were the basis for its approval for bipolar depression in 2006. My earlier reporting was based upon a filing in the case. Now, the full set of Macfadden's sexy emails with a researcher at the Institute of Psychiatry in London, England and with a ghostwriter at Paraxel MMS in the US have been released.
I'm making them public because they show how deeply conflicted the relationships between Macfadden and these women were and because the editors of the American Journal of Psychiatry and the Journal of Clinical Psychopharmacology refused to take seriously my earlier queries about whether they had any concerns about any of the data in papers published in their journals where the Macfadden affairs were involved. The FDA also blew off my query on the matter.
While the emails are mostly pedestrian (although I enjoyed reading about Macfadden's three beers and bratty kids at a Phillies game) and sometimes sexual in nature, there are some significant issues that arise from them beyond the conflicts of interest.
In an email, which is undated, Macfadden states:
"There was a crisis here about our data (again!). Turns out the effect size on the MADRS in bipolar depression was calculated wrong, and needs to be changed in the manuscript that's in press at the Am J Psych...this is especially bad, as it's the 3rd time that statistic changed since study end, and the old effect size has been on numerous posters and abstracts...too long to get into, but it's mostly worked out now......will be meeting with [NAME REDACTED, presumably an academic researcher who worked on the Seroquel for bipolar depression paper] at the APA on Saturday, trying to convince him we are not the fuck-ups we appear to be...this, along with telling him his forensic study that we agreed to fund--well, we've changed our minds and will no longer be funding it.....won't blame him if he's furious with us.....I hope alcohol will soften the blow!"
Three times they changed the effect size! Nice. I really admire and trust how research is done in the US and the AJP's integrity and attention to detail in sorting this all out!
Seriously, my hunch is the email is to the woman at Paraxel MMS and that it is from early 2005, as a Macfadden co-authored paper on Seroquel in bipolar depression (BOLDER I) appeared in the AJP in July 2005. The AJP should undertake a careful review of this paper as should the FDA with the underlying data, because BOLDER I was one of the two studies the FDA used to approve the drug for bipolar depression in 2006. The editors of the JCP might also want to take a look-see at the BOLDER II study of Seroquel for bipolar depression which it published in December 2006 just to make sure everything is on the up-and-up.
Some wonderful nonsense pops in this May 6, 2002 email between Macfadden and the British researcher:
"was assigned to be part of a 'Bipolar SWAT' team, to learn of the competitions' strategies...very cloak and dagger stuff--I wonder if I'll have a 'License to Kill.'"
Since Macfadden was heavily involved in getting Seroquel out into the world, I'd say he must've had a license to kill...or perhaps a license to ill.
The other emails mostly cover routine business matters and of course Macfadden's relations with the women.
The numbers refer to the documents' court records numbers. Happy reading.
Amidst the just-released batch of Seroquel documents is one dated Dec. 18, 2000, headlined "'Seroquel' Strategy Summary." In it, AstraZeneca executives laid out what they considered key success factors for the drug, which was only approved for schizophrenia at the time and sales of which were far outpaced by J&J's Risperdal and Eli Lilly's Zyprexa.
The document clearly states that one of the key success factors to increasing sales was to "broaden Seroquel use on and off label" and to "utilise whole selling team, educational programmes to share off label data." The spellings are as in the document.
Ed Blizzard, a plaintiffs' attorney in the various Seroquel lawsuits now underway, said in an interview that this document was approved at the very top of the company and is evidence that the company planned to market the drug off-label.
Tony Jewell, an AZ spokesman, told Bloomberg:
"'These documents do not advocate the inappropriate promotion of Seroquel,' Tony Jewell, AstraZeneca’s spokesman, said in an e-mailed statement. He noted the company’s researchers have 'invested significant resources' seeking to find new ways to have the drug help mentally ill patients."
If they didn't advocate promotion of the drug, then why would they call for the use of the "whole selling team" and "educational programmes?"
Elsewhere in the same document, AZ claims that Seroquel is "weight neutral in the long term."
"This profile is highly suited to Bipolar patients," the document states.
At the time, Seroquel was not approved for use in bipolar disorder.
That headline is no joke. News is out of this week convention of the American Psychiatric Association in San Francisco that one of the writers of the forthcoming DSM-V says that the group working on bipolar disorder revisions, which he leads, said his group has considered moving bipolar disorder from its longtime classification as a mood disorder to the category of a psychotic disorder. William Carpenter, a psychiatrist at the University of Maryland, made this statement. Carpenter, according to the school's website, is a specialist in schizophrenia.
MedPageToday.com reported:
"But he acknowledged that such a move would face strong opposition and was unlikely. 'It would happen over a number of dead bodies,' [Carpenter] quipped.On the other hand, he said, 'we hope to get rid of schizoaffective disorder.'"
I hope Carpenter and his colleagues were joking about moving bipolar disorder into psychosis-land, since the evidence I know of (published and anecdotal) tells me that most psychosis attached to bipolar disorder type 1 is fairly uncommon and short-livbed where it does occur. But if they are serious, then what would this do to bipolar disorder type 2--which is of course not even close to a psychotic disorder--and the proposed subthreshold bipolar disorder? What would this do to pediatric bipolar disorder and alleged child bipolar disorder? All that irritation in kiddie mania would now be considered psychosis?
Would the researchers be able to tease out psychoses from drug-induced psychosis? Would they be able to tease out bipolar psychosis from psychotic depression?
Lots of questions there. But it sounds like a new classification that would fail clinically. If they pursue it, I'm sure many of us would have strong feelings on the matter.
I'm not sure what the need is to eliminate schizoaffective disorder.
In other news from DSM-V land, there's much debate going on around eliminating or somehow strengthening so-called gender identity disorder.
Another batch of Seroquel documents is being released this morning by plaintiffs attorneys for people suing AstraZeneca over allegations involving its atypical antipsychotic. I'll get them myself this morning and get online what makes sense as soon as I can.
Meanwhile, the Wall Street Journal and AP got a sneak peek yesterday and picked off different pieces of the documents. The WSJ reports that:
"The documents cited plans to 'broaden Seroquel use on and off-label,' including among adolescents and patients with Parkinson's and Alzheimer's disease, at medical meetings, in sales calls and with patient-advocacy groups."Tony Jewell, a spokesman for AstraZeneca, denied that the company sought to encourage off-label uses of the drug. 'These documents do not advocate the inappropriate promotion of Seroquel,' he said. Instead, they 'show the company was seeking to explore additional indications for Seroquel and included that in clinical-development plans designed to support efforts to investigate potential additional indications,' he added.
"In an AstraZeneca public-relations plan dated 2001, one company objective was defined as to 'encourage and support' Seroquel's 'use outside schizophrenia into a broad range of other patient populations including bipolar disorder and the elderly.' The document also said there needed to be 'aggressive market penetration' among adolescents, the elderly, patients with bipolar disorder and other groups for Seroquel to grow faster than rivals."
Why does this begin to sound even more like the Zyrprexa documents all over again?
I think what the paper is quoting speaks for itself. If AZ plans to spin this kind of evidence in court as "We were just hypothesizing," then good luck to them with a jury. There is good evidence that the company encouraged off-label uses of Seroquel, including the FDA busting the company last year for off-label marketing of the drug for depression. Based upon the evidence which the agency made public, it's fair to say that there was plenty of encouraging going on. And I know of other off-label marketing of Seroquel which the company should hope I cannot continue to get on the record.
Meanwhile, the AP reports that AZ wrestled intenrally with how to cast weight gain and blood sugar increases associated with use of the drug:
"In a chain of e-mails in one document, a scientists' safety evaluation committee in June 2000 recommended removing 'limited' before the words 'weight gain' in the list of Seroquel side effects, because many patients gained significant weight."Marketing staff suggested trying other explanations, such as whether patients took other drugs that could be blamed. One marketing executive, Medical Affairs Manager Richard Owen, then wrote that such a change 'is potentially damaging to Seroquel.'
"The change in the drug's label was finally made in 2002. That was after Barry Arnold, the vice president for clinical drug safety, complained repeatedly to the physician in charge of Seroquel drug safety about 'Commercial (executives) having such an influence.'
"Yet soon after the label change, AstraZeneca trademarked the term 'weight-neutral' as an advertising slogan for Seroquel, Blizzard noted. He said data showed about one-quarter of patients taking Seroquel increased their weight by more than 7 percent.
"Later in 2002, Simon Hagger, global brand manager for Seroquel, e-mailed nearly 20 marketing staffers to say 'we are under clear instruction from the highest level within AstraZeneca at this time not to discuss details surrounding trial 41,' outside the company. That patient study, concluded that year, found elevated levels of blood sugar."
More later today.
As I do every three months, I am today beginning a fundraiser to support me and the work I do on this site. I know it's not Summer yet, but it's close enough to call it the Summer Fundraiser.
The goal for this fundraiser is $4,000 by the end of June 5 or thereabouts from 100 contributors. I also have a sub-goal of at least 10 contributions of $10 or more from people in the Seattle-Tacoma metro area, since I live in said metro area, but during the last fundraiser there were but two contributions from the area. Considering that this site has many readers from the area, it'd be great to see some more support from my adopted homeland.
One contributor already contributed $200 over the weekend, so there's only $3,800 and 99 contributors to go. With 5,000-plus regular readers of this site that shouldn't be a hard goal to hit.
Anyway, as usual the PayPal button is on the right. If you prefer using snail mail, send me an email and I'll shoot you my mailing address. For those of you who already know my mailing address, it remains the same as before (nope, I haven't moved yet for a bunch of complicated reasons, but I still plan to semi-soon).
I appreciate everyone's support.
And, now, let me remind one and all of some of the highlights from this site over the last three months.
There was a ton of news on the Seroquel front, including original reporting by me on an AstraZeneca medical officer for Seroquel who had sexual relationships with a researcher doing studies of the drug and a medical ghostwriter writing up said studies (you might call it all the ultimate conflcit of interest); proof that AZ suppressed several Seroquel studies that were unfavorable to the drug; proof that one researcher claimed that patients lost weight on Seroquel; proof that AZ issued a diabetes/hyperglycemia warning on the drug in Japan in 2002 while insisting all was well with the drug in the US.
Then I made an early round of Seroquel court documents available to the public (has any newspaper done so?) and then made the suppressed Study 15 available to researchers (yes, some took me up on the offer).
On the anti-depressant front, I reported on a major long-term women's health study which showed that anti-depressants were linked to sudden cardiac death in some women and then I rapped NBC News' knuckles for failing to report on the anti-depressant connection. I reported on a study of anti-depressants in teens where suicidality was clearly present and where researchers hid it and I noted how USA Today had basically lied to its readers in declaring no linkage between anti-depressants and the Columbine tragedy.
I also reported on recent studies linking anti-depressants to birth defects and diabetes. Both studies were ignored by the mainstream media.
I also reported on the FDA's approval of Lexapro for use in teenage depression, noting how slim the evidence was for the approval and that, in fact, the drug showed very little efficacy in clinical trials.
Then I added to a Time magazine article on why anti-depressants failed to live up to their hype and picked apart a well-written, but perhaps not so insightful article on chronic depression in the New York Times Sunday Magazine.
I did original reporting on the fact that 10 percent of people being treated for depression are now taking antipsychotics and that antipsychotics are now the top revenue producers for pharma companies, outpacing even statins. Both of these bellweather stats have escaped the mainstream media's notice. I also wrote about a significant study showing that atypical antipsychotics are causing much akathisia in patients. In addition, I tracked (and am tracking) the FDA's odd approval of the new antipsychotic Fanapt.
I also did original reporting on the STAR*D study of depression treatments and how researchers clearly downplayed suicidality that was present in the study.
Then there was that whole conflict of interest brouhaha involving a Lexapro study at JAMA where I broke the news on it ahead of the Wall Street Journal. I reported on just how much money NAMI National is getting from Big Pharma.
I reported on a study showing Depakote failed to beat placebo as a treatment for pediatric bipolar disorder.
I wrote about a fascinating study showing that housing homeless drunks saved the public purse many millions of dollars and I was interviewed by Psychology Today.
There was much more--it's been a busy three months--and I will be getting up very early this morning West Coast time to do some reporting on what could be some significant news, which I hope to write about later today.
Hopefully, all of that justifies the value of this site to you all.
Thanks in advance for your contributions.
You know, it must've been a cakewalk for pharma companies to rip off Medicaid because it seems like several of them have done it. The latest entrant in the Hall of Lame is Wyeth. From the DOJ's press release:
"The United States and 16 states have joined in two whistleblower suits filed in the District of Massachusetts against the drug manufacturer, Wyeth, alleging that the company knowingly failed to give the government the same discounts it provided to private purchasers of its drugs, as required by laws governing the Medicaid program. As a result, Wyeth allegedly avoided paying hundreds of millions in rebates due to state Medicaid programs for its drugs, Protonix Oral and Protonix IV. These drugs belong to a class of drugs known as proton pump inhibitors (PPI), which are used to suppress stomach acid."
Let's hope they get their money back without having to go to trial.
One of those occasional columns by psychiatrist Richard Friedman of Cornell University showed up in the New York Times today. I'm not sure what the occasion was, but Friedman questions why some docs (residents in particular) aren't prescribing Lithium to people with bipolar disorder as a first-line treatment versus the trend to give bipolars the latest in "mood stabilizers" and antipsychotics. His argument runs to the age-old claim that Lithium has decades of efficacy data (true, although how efficacious is open to interpretation), is established as a safe drug (debatable, depending on what he means by safe, but yes it's likely safer than Zyprexa) and has loads of evidence for its anti-suicide properties (true, for whatever reason), but doesn't get promoted to docs because it's not patentable and so docs never hear about it or consider it.
While I don't think Lithium is as benign a drug as Friedman makes it out to be (sorry, but I took the drug and sure did not appreciate the Lithium tremors), his argument is OK as an example of how pharma promotion of on-patent drugs distorts clinical practice.
Friedman's argument (older, cheaper drugs can be better than newer, spendy drugs) falls apart for me when the subject of anti-depressants crops up:
"Not long ago I saw a patient who told me she had treatment-resistant depression. She had failed to respond to multiple trials of five new antidepressants, including two from the same class of drugs."I called her psychiatrist, a smart young doctor whom I know, to ask if she had ever been given one of the older antidepressants, like a tricylic or a MAOI (for monoamine oxidase inhibitor). He had little experience with these highly effective older drugs, so he hadn’t thought to use them.
"I suggested that she try an MAOI. After six weeks, she improved remarkably.
"Now it’s true that the newer antidepressants are generally safer and more tolerable than older ones, which is an important advantage, but they are no more effective than older antidepressants."
The way this is written it almost sounds as if ye olde MAOIs and tricyclics are so much more effective than the newer SSRIs and SNRIs when, as far as I know, all classes of anti-depressants are roughly similar in effect size--and that's about 30 percent, depending on the study. It's interesting that he doesn't mention that effect size. And as far as safety goes, Friedman makes it sound as if the newer anti-depressants are super safe when that's not the case (see FDA black box warning, Nurses Study of Women's Health, etc.).
But that's just me.
Well, here's a stunner: in a study just out in the Journal of the American Academy of Child & Adolescent Psychiatry, researchers report that Depakote ER (technically, divalproex ER in the study) had no treatment effect in a four-week, placebo-controlled clinical trial of the drug in treating pediatric bipolar disorder in kids and teens aged 10 to 17. In other words, Depakote did not beat placebo.
"The results of the study do not provide support for the use of divalproex ER in the treatment of youths with bipolar I disorder, mixed or manic state. Further controlled trials are required to confirm or refute the findings from this study."
Researchers included Karen Wagner of the University of Texas and Timothy Wilens of Harvard University. Both have been subjects of investigations by Sen. Charles Grassley (R-Iowa) over underreported monies they've received from pharma companies and possible violations of federal research rules.
There's been a lot of criticism of ex-Abilify spokespatient/"Electroboy" author Andy Behrman in the wake of last week's front page Wall Street Journal article about his split with Bristol-Myers Squibb. The company had paid him a reported $400,000 to speak on behalf of the drug while, at the same time, Behrman was experiencing some wicked side effects from the drug in 2004 and 2005. While I understand some of the criticism, I'm afraid that a post at Bnet.com yesterday by Jim Edwards, who's usually pretty reasonable in his judgments, is so full of excessive judgments that I'm going to call him on them.
It appears that Edwards freaked out over a mass email Behrman sent out last week, one I received as well:
"Behrman sent a rambling email from his Blackberry to his 'friends' and '3,000+ mental health support groups' asking them 'to forward this e-mail to everyone you know.' The email is a long plug for Behrman’s new book."
I didn't find Behrman's email rambling at all, certainly nowhere near some of the emails I get (and have gotten as a reporter over the years). What's more, Behrman is very much enmeshed in the weird world of Hollywood, where it's pretty typical for people to send out mass emails to their 3,000 closest friends or they don't exist. Los Angeles is all self-promotional like that. I've been on Behrman's mail list for three or four years and he does send out a few self-promotional emails a year (such as when he has an upcoming appearance on CNN), so the one he sent out last week wasn't all that unusual.
But here's where Edwards really steps in it:
"But it [the email] is also a description of just how thin Behrman’s case against BMS seems to be. As BNET noted a few days ago, Behrman only began his crusade against BMS after the company refused to make him a millionaire. Now he is claiming that BMS is at the center of a shadowy conspiracy to prevent him from speaking. His email says:'I published an online article about the drug’s terrible side effects. I said it was the worst drug that I had ever been prescribed and that it had nearly killed me. Within twenty minutes of the article being posted on a website owned by the New York Times, the article came down. Turns out, BMS was a sponsor of the website.
'I believe that BMS will go to almost any lengths to stop me and the publication of the book.'"
Behrman first wrote about his bad experiences on Abilify in May 2006 for About.com, owned by the New York Times. The article came down very quickly and not long after I republished it on this site, pretty much as a protest against censorship (whether that censorship was the work of About.com or BMS is another story), so it's kind of interesting to me that Edwards isn't calling a Times-owned company on its journalistic integrity, which seems to be suspect in this case.
What's weirder to me, however, is that was literally the only sign of a "crusade" against Abilify prior to the recent WSJ article. As far as I know (Behrman and I stay in sporadic contact by email) Behrman has been busy the last few years trying to get "Electroboy" turned into a movie. He's sure not been out there jumping up and down about Abilify and his relationship with BMS. Hardly what you'd call a crusade.
Behrman's claim that BMS would go to almost any lengths to stop him may come off as excessive, but what I can tell you all is that there have been other things going on that I know about but cannot get not into right now (since I gave my word that I wouldn't). Let's just say that there's some high stakes intimidation going on out there.
If only Edwards had stopped there:
"[Quoting Behrman's email]'The sad reality is that the drug companies won’t tell you the truth about the side effects of their drugs …"This just isn’t true. The side effects of Abilify are right there on the drug’s web site. The very first warning is:
'Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.'"
Edwards' using Abilify's current website warning language as proof that the drug companies haven't been lying about the problems with atypicals--I'm speaking of the entire class here--for well over a decade is silly. Has Edwards missed all those Zyprexa documents and Lilly's legal settlements? Has he missed the more recent Seroquel documents? Did he forget his own blog post from last December where he noted that AstraZeneca knew of diabetes problem with Seroquel as far back as 2000? Does he not realize that BMS and other companies were off-label marketing for dementia for years before they tripped over their own feet and got busted? Please.
Look, the pharma companies have lied through their teeth about these drugs, injuring innocent people, lying to doctors and ripping off taxpayers in the process. And Edwards is cheesed off at Behrman? Nice.
What's more, when I directly asked BMS about what it knew about Abilify causing akathisia, Sonia Choi, the drug's spokeswomen, told me she didn't know a thing about it, even though there is akathisia all over the drug's clinical trials for depression. In fact, more recently, a BMS-funded study tried to obscure akathisia caused by Abilify.
I know some readers are pissed-off at Behrman over all the money he got from BMS, but I'd say the far bigger problem is BMS and other pharma companies (and the researchers who help them) and the lies they tell each day.
Here's why I end up sympathizing with Behrman. He's wound up on the right side of these issues, especially where the atypicals are concerned and he's helping get a hell of a lot of attention focused on them and their problems (you go get your personal story of injuries suffered through psych meds on A-1 of the WSJ and then get back to me). Sure, it would've been nicer if he'd gotten there in 2005, but he didn't. In fact, in December 2005, I remember seeing Behrman commenting on CNN about the fatal shooting of a man with bipolar disorder by federal air marshals--the man, who'd recently gone off-meds, claimed he had a bomb--and Behrman looked like someone who was really being slapped around by medication (yes, it was Abilify)...just utterly played out, exhausted and scrambled, his face all puffed up. I know what that place is like and I can sympathize. It buys Behrman a lot of slack with me. Maybe too much slack for some readers.
But then consider my case: it's taken me two decades to get to where I am now in my understanding and criticism of the mental health industry. Does anyone want to kick me around because I wasn't saying the same things in print in 2004? Or 1999?
We all get to our own truths in life at our own speed--Behrman, me and you.
And I'll tell you something else: if the Nemeroffs, Kellers and Biedermans of the world renounced their pharma monies, conflicted research and so on and mended their ways, I'd forgive them. Chances of that happening are pretty much zilch, but if they did, I would.
Eli Lilly, ever determined to have its long-acting Zyprexa injectable approved by the FDA, today released selected data from two long-term trials of the drug's use in treating schizophrenia. One trial was almost four years long, another was eight months.
In the four-year trial, the discontinuation rate was 46 percent and oodles of patients saw their body weight explode:
"Mean weight change was +1.88 kg, with 32.1 percent of patients experiencing greater than or equal to seven percent weight gain. Percentages of patients who increased from normal to high on fasting glucose, random total cholesterol, or random triglycerides were 5.5 percent, 5.2 percent and 14.3 percent, respectively. Mean Clinical Global Impressions-Severity scores remained stable throughout (2.9 at baseline to 2.8 at endpoint)."
Although not wildly different from results with oral Zyprexa, these results are concerning. I'm not sure how Lilly can continue to press the FDA on approving this drug when there are obviously such weight gain and potential diabetes issues attached to its use. But maybe that's why I am not in a corporate job.
Edwin S. Shneidman, a pioneer in the field of suicide prevention and one of the founders of the Los Angeles Suicide Prevention Center, died on Friday, aged 91. The LASPC is supposedly the nation's oldest suicide prevention hotline, which began service in 1958.
Shneidman was the author of many books, a professor of thanatology (death science) at UCLA and seems to have understood the deep complexities around suicide.
From the Los Angeles Times:
"Shneidman viewed suicide as a psychological crisis and -- as did Albert Camus -- as the 'one truly serious philosophical problem.'"'Suicide is a complex malaise,' Shneidman said. 'Sociologists have shown that suicide rates vary with factors like war and unemployment; psychoanalysts argue that it is rage toward a loved one that is directed inward; psychiatrists see it as a biochemical imbalance. No one approach holds the answer: It's all that and more.'"
His obituary is well worth reading.
Not a lot to say about this: the FDA today approved Risperdal CONSTA, the long-acting injectable antipsychotic, for use as a maintenance treatment in bipolar disorder and as an add-on treatment to Lithium and Depakote. Let's hope very few people wind up having to take/being forced to take this drug.
The Wall Street Journal is out with a good piece today revealing that antipsychotic use among kids is still going up but that the rate of increase slowed somewhat last year. The paper attributes this to increased attention to the side effects of these drugs, particularly in light of various lawsuits over illegal marketing of atypicals and the cautionary tale of the Rebecca Riley saga. But these drugs are still being used far too widely (and wildly) in my opinion.
Use of atypcials among kids aged 18 and younger increased by 5.3 percent in 2008, compared with an 8.7 percent increase the prior year.
Some startling stats from the article: 25 percent of Risperdal's sales came from kids and most of that would've been off-label (the drug is now generic); and, sales of atypicals among kids accounted for 15 percent--or over $2 billion--of sales of drugs in this class.
Yesterday, I was contacted by a source with vast experience in mental health systems and research, bringing to my attention patent applications filed in May 2008 in the name of the Department of Health and Human Services (meaning NIH in this case) and the University of Texas and several underlying inventors, one of them being John Rush, formerly a psychiatrist at the University of Texas who's now at the Duke University Medical School in Singapore. More on Rush and the University of Texas in a moment.
The patents applications were for a genetic screening test--an assay as they are known--that would determine if a patient would (or could) develop suicidal ideation as a result of taking an anti-depressant. Suicidal ideation (much less suicide itself) is one of the biggest problems attached to anti-depressant use, one long denied by the medical establishment and many patient advocates and some in the media. (Here's the US patent application and the worldwide one.)
These particular patent applications claimed that they had isolated certain polymorphisms (variations in specific genes) that accounted for suicidal ideation due to research conducted around the STAR*D trial of anti-depressants and psychotherapy. Rush was one of the leaders of STAR*D, which was underwritten by the National Institute of Mental Health. He also was formerly a director of the controversial Texas Medication Algorithm Project. The trial was a long-term trial of the efficacy of depression treatments and basically the takeaway message was that the best anti-depressant (Celexa in the STAR*D trial) relieved depression about 30 percent of the time with decreasing degrees of relief for each other anti-depressant tried.
But suicidality? I'm pretty up to speed on STAR*D and was very surprised by the claim I read in the patent applications (using Google Viewer, see pages 3 and 4 of this US patent application): that 120 patients in the initial Celexa arm of the trial experienced suicidal ideation while 1,742 did not. So out of 1,862 patients, 6.4 percent of them experienced suicidal ideation within three months of commencing treatment with Celexa yet hadn't experienced suicidal ideation before entering the trial. Given that STAR*D is considered a gold standard, long term trial, that finding out to shut up those in the mental health industry who claim that anti-depressants aren't linked to suicidality (yeah, there are loads of FDA black box deniers out there).
I was stunned. The press has never picked up on the matter of suicidality within the STAR*D trial, likely because it was never flagged for them by NIMH's press office or by the researchers later interviewed by the media, who tried to paint STAR*D as "proof" that depression treatment worked 67 percent of the time (a story of spin run amok for another day). I was stunned further because I had never run across any reports of anything but stray suicidality in any of the STAR*D papers (and there have been many STAR*D papers), so I wondered if the researchers had somehow covered up this finding, despite its obvious public health implications.
In this first STAR*D paper from January 2006, only six people out of a total of 2,876 who took Celexa in the first arm of the trial were mentioned as experiencing suicidal ideation. And in the two STAR*D papers that garnered much media attention in March 2006, I don't recall any mentions of suicidality.
So was there a cover up? Or perhaps an obscuring of the finding that showed up in the HHS/Texas patent applications?
As it turns out, Rush and other STAR*D researchers reported what is essentially the same finding in this June 2007 STAR*D paper in the Archives of General Psychiatry (which used a slightly different subset of STAR*D patients).
"Of 1447 participants, 124 (8.6%) subsequently reported suicidality on at least 1 visit."
Suicidality at 8.4 percent is very high. In fact, it's twice the 4 percent rate among kids and young adults that were the basis for the 2004 and 2006 black box warnings demanded by the FDA. And guess what? STAR*D was a study of adults aged 18 to 75. So it's even more striking, because the claim is abroad in the medical world that anti-depressant suicidality doesn't affect adults older than 24 years of age. So much for that claim.
So why didn't the press pick up on this? Well, the Archives paper is entitled "Association Between Treatment-Emergent Suicidal Ideation With Citalopram and Polymorphisms Near Cyclic Adenosine Monophosphate Response Element Binding Protein in the STAR*D Study." It's pretty easy to understand why it got missed by myself and others in the media. As for why the NIMH and others involved in STAR*D didn't alert the media to this startling finding, I have no idea. I don't even want to guess at their motives. But someone in that loop had to know about the level of suicidality in the STAR*D trial yet they remained silent.
Look folks, in STAR*D the researchers clearly designed the protocol to at least try to capture whatever suicidality might crop up around anti-depressant use. This wasn't an approved-by-pharma study, the kind that seek to avoid suicidality detection--and thence possible public reporting--at all costs. But keep in mind that the protocol for STAR*D was designed in the early years of this decade, well ahead of the black box warnings on anti-depressants. At the time, researchers and many clinicians were still largely in denial about an anti-depressant/suicidality link, so the fact that the STAR*D crew even went looking for any signals of that is amazing. The fact that they detected a demonstrable amount of suicidality is astonishing.
But what really blows my little mind is that none of them then went out of their way to raise their voices above a peep about what they had found. That's amazing, astonishing and disappointing.
Your tax dollars at work.
That said, I hope the gene assay described in the patent applications turns into a real winner. It could probably help save some lives, if its methodology proves out.
The listed inventors are: Francis J. McMahon, NIMH; Gonzalo E. Laje, NIMH; Silvia Paddock, Karolinska Institute, Sweden; Husseini K. Manji, NIMH; and, John Rush, then at the University of Texas.
We'll see where the assay winds up. But in the meantime, I do have some very serious questions as to why the suicidality in the STAR*D trials never got any public attention, because it obviously deserves attention.
A good number of you are aware that Andy Behrman, author of "Electroboy," was a spokespatient for Bristol-Myers Squibb's Abilify for a time and, according to yesterday's Wall Street Journal piece on him and his broken relationship with BMS, he made upwards of $400,000 speaking on behalf of the drug. Ironically, Behrman was suffering severe side effects from the drug during much of that period. Now, Behrman has recorded a video where he uses the side effects voiceover from some of the drug's TV ads and notes that he suffered many of the identified side effects. Then he adds a zinger, playing off the Abilify ads' "Ask your doctor if Abilify is right for you."
I pass this along to you for what it's worth to you.
BTW, I know several readers were deeply critical of Behrman for speaking on behalf of the drug while experiencing problems with the drug, seeing in it an inherent conflict. Fair enough. But keep this in mind: back when I took the nasty atypicals for depression and agitation (late-2000 to mid-2005), I knew I was experiencing serious problems as a result of, first, Risperdal, and, second, Seroquel, but essentially kept my mouth shut about them because, as a longtime patient, I was so used to drugs screwing me up in some fashion that I figured it was par for the course.
So what got me to wake up to problems I experienced on Risperdal? I was on a date in March 2003 and the woman I was meeting told me that my face was frozen and had no expression to it. That shook me up enough to get off the drug (on which I was experiencing other problems such as weight gain, somnolence and odd heart rhythms ). What woke me up to problems with Seroquel in 2005? My lips started moving one day in a meeting at work and my boss later took me aside and asked me what was going on with me. That got me off that drug fast (on which I was experiencing a host of other problems such as weight gain, back pain, muscle tightness, nightmares, etc.).
My broader point here is that the mental health system and mythologies around mental disorders are so strong that longtimers like Behrman and I often became trapped by them. It's like we were taught to forget about our bodies in deference to mood control. Perhaps with that in mind, you might understand why Behrman was slow to rage against problems caused him by Abilify.
Or maybe not.
There's sure been a bit of a buzz on the Net about the tale of a Rhode Island mom who gives her 9-year-old son medical marijuana, which is legal in her state, for his chronic pain and autism issues. That's an interesting choice since most parents of autistic kids with serious outburst issues typically use Risperdal, an antipsychotic, as a treatment. Here's mom's thought process:
"'s school called my husband and me in for a meeting about J's tantrums, which were affecting his ability to learn. The teachers were wearing tae kwon do arm pads to protect themselves against his biting. Their solution was to hand us a list of child psychiatrists. Since autistic children like J can’t exactly do talk therapy, this meant sedating, antipsychotic drugs like Risperdal—Thorazine for kids...."When I canvassed parents of autistic children who take Risperdal, I didn't hear a single story of an improvement that seemed worth the risks. A 2002 study specifically looking at the use of Risperdal for autism, in the New England Journal of Medicine, showed moderate improvements in “autistic irritation”—but if you read more closely, the study followed only 49 children over eight weeks, which, researchers admitted, “limits inferences about adverse effects.”
"We met with J's doctor, who’d read the studies and agreed: No Risperdal or its kin.
"The school called us in again. What were we going to do, they asked. As a sometimes health writer and blogger, I was intrigued when a homeopath suggested medical marijuana. Cannabis has long-documented effects as an analgesic and an anxiety modulator. Best of all, it is safe."
There's not much research at all on the use of medical pot in autism--or for that matter, in mood disorders--but I did note last year that one autism doctor was all for the use of marijuana in some cases.
As for how things have turned out for J., read the piece linked above.
In what's got to count as either a brilliant PR move or a cynical attempt to keep some patients from switching to generic drugs or an even more cynical attempt to guy goodwill during the current health care reform debate, pharma giant Pfizer has announced that it will give many of its drugs free of charge to recently unemployed and uninsured people. The program will cover 70 of its drugs--Lipitor and Viagra included, and probably Zoloft and Geodon as well--and will offer them to people for a year. It'll be interesting to see what bang Pfizer gets for its buck.
Interesting bit from the AP piece on this program:
"Colleagues suggested employees could donate to a fund to help support the effort, Puente said. He said some employees had tears in their eyes when discussing how they could help people who had lost jobs."
Crying pharma employees? Oh, please. And the AP quoted this without witnessing it themselves? Lame.
While I know Pfizer is trying to paint itself as pharma humanitarian of the year here, the reality is that no pharma company--hell, no corporation of any kind--does anything like this without expecting something in return and being able to predict a return. Can't wait to see what that return is.
Or maybe I am just too cynical myself to understand how wonderful and giving Big Pharma can be.
Regular readers are well aware of the tale of Andy Behrman, author of "Electroboy," who became a spokespatient in 2004 and 2005 for Bristol-Myers Squibb's atypical antipsyhcotic Abilify. But by 2006, he'd experienced such nasty side effects on the drug--jerking legs among them--that he went off it and eventually wrote a piece for my site in 2006 concerning his experiences with Abilify (a piece that had originally been published by About.com but was soon removed by the company). As I noted last year, Behrman was on the verge of authoring a tell-all book about his experiences shilling for Abilify before BMS sales reps, doctors, nurses and even patients. BMS had nothing to say about Behrman when I queried the company last year, but it has plenty to say now as Behrman and BMS are in a war of words.
Now his story has hit the Wall Street Journal. BMS paid Behrman big money to tout its product and since he's gone off the reservation on them they are fighting back with whatever they've got. The article is behind the subscription firewall and I won't reproduce it in its entirety (I respect copyright) but can offer you all some snippets.
"In 2004, Bristol-Myers held a retreat for 1,250 sales representatives, to prepare them to market a powerful psychiatric drug for a new use -- bipolar disorder."Pharmaceutical companies have taken to paying patients to help promote their products. In the case of Andy Behrman and Bristol-Myers, the relationship has backfired.
"A video of Mr. Behrman, a 42-year-old bipolar patient, filled a gigantic screen. He recounted how a Bristol-Myers drug, called Abilify, had changed his life. Unlike other medicines he had tried, Abilify had no side effects, he said. The testimonial drew a standing ovation.
"But Mr. Behrman says he had only taken the drug for four days before the video was filmed. He says he later experienced side effects -- including dazed spells and agitation in his legs -- unpleasant enough that he stopped taking the drug within a year. He says he eventually told several company employees privately about the difficulties he was having with the drug.
"Yet, he continued to talk glowingly about Abilify throughout 2004 and 2005, to sales representatives and other company employees, as well as psychiatrists hired by the company as consultants. In all, Bristol-Myers paid him $400,000."
This is literally the first time that I have heard of a spokespatient turning on a pharma company--and there are literally hundreds and hundreds of such people out there. So Behrman's story in highly unique. The fact that a spokespatient has gone south on them ought to have BMS shaking in its boots, especially since Behrman is expected to pop up on national TV very soon and has also recorded a lengthy video denouncing the drug. I expect to make the video available to readers later today or tomorrow. Behrman's actions sure can't warm the hearts of a company that is now aggressively marketing Abilify for depression and bipolar disorder. It might make BMS' competitors' days however.
Behrman is speaking publicly now because he wants the public to know about Abilify's many problems--akathisia anyone?--and about the intense marketing that goes on around it and similar drugs. Behrman also has a book proposal to shop, so going public cannot hurt those efforts either.
"The company says Mr. Behrman raised no concerns about his experience until it declined to renew his contract because he asked for too much money -- $7.5 million. Mr. Behrman denies he asked for that sum.Last year, Mr. Behrman asked Bristol-Myers to 'finance or otherwise be involved' with a new book he plans to write about his experience with the company. The company declined. Then in January, his lawyer says they approached Bristol-Myers with another proposal, in which Mr. Behrman wouldn't talk about his experiences if the company wouldn't interfere with his attempts to get speaking engagements. Bristol-Myers says Mr. Behrman was seeking compensation, and it declined that offer, too."
Behrman also strongly denied to me that he'd asked BMS for $7.5 million. BMS showed the paper an email purportedly containing that amount of money, but Behrman and his lawyer told the paper it was a fake designed to discredit him.
I find it hard to buy BMS' claim for the simple reason that $7.5 million a year to speak on behalf of a product is the kind of money that professional athletes and Hollywood celebrities get (they sometimes get much more). It's a bit hard to believe Behrman saw himself that way and would've asked for that much money.
But he did get special care and handling from BMS and outside PR folks on what to say when he spoke about the drug:
"He says Bristol-Myers's Mr. Brown touched base with him almost every day, and he worked closely with Elyse Margolis, an employee of a public-relations firm hired by Bristol-Myers. She gave him 'talking points' for his presentations, he says. Among them: To reiterate that Abilify had no side effects; to say the drug had 'saved' him; and to avoid mentioning he was being paid by Bristol-Myers. If asked about the latter, he was to answer truthfully, say he couldn't disclose the amount and 'move on.'"In an email, Ms. Margolis said when she worked with Mr. Behrman, she followed routine protocol used with speakers so they 'are prepared to accurately, and proactively, speak to the label, including potential side effects and any other issues.' She declined to comment on talking points.
"Bristol-Myers also sent Mr. Behrman to a communications consultant named Nellie O'Brien in 2005. He says she instructed him to tell audiences he was only taking Abilify and never mention other drugs. Ms. O'Brien told him to always refer to Abilify by name and to stay away from unflattering aspects of his past, he says.
"Ms. O'Brien declined comment, saying all her dealings with clients are confidential.
"Bristol-Myers says consultants are asked to 'help patients tell their story in their words.'"
Apparently, some of this was going on while Behrman was having bad experiences with the drug, but I guess $10,000 per appearance (what BMS was paying) bought a lot of sticking to talking points. Or he was befuddled enough while taking the drug--a side effect of some antipsychotics--to obscure matters on his own. It will be interesting to read how Behrman explains all of this in his future book.
"Within weeks of taking Abilify, Mr. Behrman says he felt stiffness and agitation in his legs. He says Abilify clouded his thinking. He now says the drug made him feel worse than any treatment he has tried."At the time he was speaking on behalf of the drug, he says he privately complained about side effects to several Bristol-Myers' employees. Once, after repeating during a speech that Abilify had no side effects for him, he says he turned to Mr. Brown and said: 'You know that's not true, right?' He says Mr. Brown replied, 'Yes, some people do experience side effects.' Bristol-Myers says it has no record that Mr. Brown or any of its employees ever heard Mr. Behrman complain about side effects."
Near the end of the article, the Journal's reporter notes:
"In July 2006, Mr. Behrman wrote a piece about the side effects he claims to have experienced on Abilify for a Web site."
I suspect the reporter is referring to my website, since the About.com piece had been pulled earlier in the year and then I ran it on this site--in May 2006. I don't think Behrman wrote about his Abilify experiences anywhere else. Always nice to get an oblique reference in the WSJ.
Anyway, stay tuned for what's bound to be a lot more on this little war of words between Behrman and BMS.
I just about fell over when I read this article in Time last week because here we have one of the most mainstream publications possible noting that Americans had grown enamored of the idea of taking a pill to stave off depression, but that now several researchers are openly questioning the efficacy of anti-depressants.
The mag's principal bit of evidence for this is a recent study from the American Journal of Psychiatry which asserts that the reason results from anti-depressant clinical trials never matched real world performance (keep in mind that Abilify's TV ads now claim that two-thirds of people taking an anti-depressant see little relief) is because clinical approval trials screen out patients with substance abuse issues or personality disorders. While it's understandable that researchers would want to screen out such participants so that they can measure "pure" depression, that tactic isn't likely to measure real world depression which often comes with some substance abuse (although the bar on what's substance abuse these days is quite low) and, so researchers claim, some personality disorders.
The mag's article also noted other bits of evidence for anti-depressants' lack of efficacy: last year's British study (the Kirsch study) finding that the drugs barely outperformed placebo in some of the original FDA clinical approval trials and a more recent study that "attributed 68 percent of the benefit from antidepressants to the placebo effect."
That placebo effect study largely mirrors findings from a study last year which found that almost 80 percent of patients on placebo in long-term depression studies fared as well as patients on anti-depressants, meaning that the effect size of anti-depressants was quite small--14 percent in fact. That's much less than what pharma companies, researchers, advocates and others have claimed for these drugs since the early-1990s.
The article failed to mention the Turner study from last year which established that pharma companies had been hiding negative anti-depressant approval trials for years and that, as a result, anti-depressant performance had been overstated by about 30 percent for ages.
But whatever the cause of anti-depressant underperformance and as glad as I am to see as big a publication as Time tackling the matter, one big thing is missing from the article. Since it's well-established that anti-depressants don't perform as well as claimed, then the American public has been lied to for two decades about depression treatment and often those lies (or shall we say excessive claims?) have been made in advertisements since DTC ads were made legal in the US in 1997. These lies were also spread by some reporters and news organizations who parroted the pharma line for far too long.
Where do I go for a refund?
Some of you know that the great, great, great songwriter Leonard Cohen has been on a world tour--apparently to recover monies of his lost to a bad financial manager--and, of course, Cohen is well-known for having suffered from depression for decades. Now, he's joking about all the meds he took. From a Wilmington News-Journal account of last night's show in Philly:
"'It's been a while since I stood up on stage here. It was 14 or 15 years ago. I was 60 years old, just a kid with a crazy dream,' Cohen joked in between his songs of love and hate. 'Since then, I've taken a lot of Prozac, Paxil, Effexor, Wellbutrin, Ritalin and I also turned to a rigorous study of religions and philosophies, but cheerfulness kept breaking through.'"
Interesting. Happily, Cohen appears to have escaped the antipsychotics-for-depression trend before it bit him in the ass.
One enterprising blogger and Cohen fan has catalogued the many interviews Cohen has given about depression and meds.
Sadly, I couldn't afford a ticket to Cohen's Seattle performance last month. It was that expensive.
This has to be the first positive ruling for Eli Lilly in Zyprexa litigation in ages. From Bloomberg:
"U.S. District Court Judge Jack B. Weinstein in Brooklyn, New York, said he will exclude the expert testimony of Dr. Stephen Hamburger. The doctor has offered testimony in some 20 individual Zyprexa cases, seven of which now have pending summary judgment motions before Weinstein, the judge said in a decision issued yesterday."Hamburger was 'shockingly careless about the facts in the cases he proposes to opine about,' Weinstein said. The doctor gave conflicting answers to questions about the 'claimed causal link between Zyprexa intake and medical injury,' he said.
"'Faced under oath with consistent extensive factual discrepancies in his analysis, he merely shrugged them off or flippantly shifted to new theories,' Weinstein said. 'He repeatedly and impermissibly stretched the truth to support findings of causality.'"
Something tells me that there are plenty of other expert witnesses who can be called...and that Lilly's victory is only temporary. This is of course the big remaining federal court case which could result in Lilly settling with the various unions and pensions plans suing it for billions of dollars, as Judge Weinstein has previously suggested it do. Lilly has already settled about $2.7 billion in claims regarding Zyprexa.
Many of you are already aware of the awful case of a 7-year-old boy in Florida named Gabriel Myers who last month hanged himself in the shower of his foster home. The kid was chock-full of psych meds--Symbyax, Vyvanase and had recently been on Lexapro. Now a Florida state senator is calling on the State of Florida to investigate the prescribing psychiatrist both to determine what happened and, from a medical board angle, to determine if there were any violations of sound medical practices.
Already the State's Department of Children and Families has convened a working group to look into the agency's use of psych meds.
Over the last year or so, Florida has had in place a special monitoring program to catch potential overuse of psych meds in kids. The Miami Herald reports:
"Dr. Sohail Punjwani, who was treating Gabriel, had been red-flagged by the medication program every quarter that the list was kept, one of the administrators told The Miami Herald."Punjwani did not return calls from The Miami Herald for a comment."
While I'm pleased that this case seems to be turning into a major wake-up call along the lines of the Rebecca Riley case, this kind of attention is coming at too high of a price.
Update: I screwed up. Although I couldn't tell from the materials, Parry tells me that the colleagues who will be presenting with him are actually American child psychiatrists. I regret the error and am glad to see that more American psychiatrists are helping Parry spread the skepticism around.
The American Psychiatric Association is about to have its annual convention in San Francisco. I learned yesterday that Peter Parry and a few other Australian psychiatrists will present to the APA membership on the many controversies surrounding pediatric bipolar disorder (ages 10 to 17) and alleged bipolar disorder in small children (prepubertal bipolar disorder, child bipolar disorder) and their recent findings that psychiatrists Down Under and elsewhere outside of the US find the paradigm to be largely nonsense.
From the presentation syllabus:
"Taken in conjunction with results of a similar survey of German child & adolescent psychiatrists and the British National Institute for Health and Clinical Excellence (NICE) guidelines (2006) on Bipolar Disorder, such views support assertions that PBD remains a controversial diagnosis with limited penetration outside the USA."
Much of the concern centers around cases of alleged bipolar disorder in kids under about 12 years of age, a concern I share. As Parry told an Aussie newspaper back in February:
"'If you'd told me three years ago that two-year-olds were being diagnosed with bipolar disorder my reaction would have been "that's impossible," Parry said."'Most of us in the psychiatric profession consider it extremely rare prior to puberty, let alone in a two-year-old.'"
Indeed.
As I noted when I was interviewed by Psychology Today last month, the bipolar child paradigm is a strictly American phenomenon, "as big a metaphor of our times as credit swaps, subprime loans, and government bailouts."
CL Psych had a wonderful post the other day harping on Abilify's propensity to cause akathisia in some patients taking it for depression and other disorders. What CL Psych did was uncover a recent study in the Journal of Clinical which purported to examine akathisia rates in second generation antipsychotics. Akathisia is a well-kwown clinical outcome in antipsychotics old and new and seems to be especially prevalent with Abilify. One of the drug's clinical approval trials for its FDA approval as an add-on treatment for depression showed akathisia rates at 26 percent for people taking Abilify but only 4 percent for those taking a placebo.
But in the JCP study none of that was mentioned. Hm, I wonder why.
"So Abilify causes less akathisia than older medications and it's unclear if it causes more akathisia than placebo. But, wait, wasn't akathisia related to much higher rates of akathisia than placebo in treating depression? Fortunately, the authors had a little trick to erase that inconvenient piece of evidence; they only examined trials trials involving people diagnosed with schizophrenia or bipolar disorder. So the depression studies -- POOF -- vanished, along with their damning data."Why would the authors want to censor negative data about Abilify? Well, one author is an employee of Otsuka America Pharmaceutical, Inc., and another is an employee of Bristol-Myers Squibb, companies that market Abilify. And the other authors: All but one of them have a financial relationship with Bristol-Myers Squibb. The best part:
"Editorial support provided by Maria Soushko, Ph.D., Phase Five Communications, Inc., New York, N.Y., with funding provided by Bristol-Myers Squibb.
"So a paper that excludes the most inconvenient evidence regarding akathisia on Abilify had major parts of the writing done by... a medical writer hired by Bristol-Myers Squibb."
Ah, how nice of BMS to try and obscure reality. Akathisia is, of course, serious stuff and all that internal racing and restlessness can drive people, in some extreme cases, to the brink of suicide.
In other Abilify-akathisia related news, Tufts University psychiatrist Danny Carlat describes two recent patients of his whom he prescribed Abilify to for depression. Both patients wound up with akathisia.
Nice drug you've got there BMS.
Earlier this month I noted that news had come out that Merck had--with the help of major academic medical journal publisher Elsevier--had created a fake medical journal earlier this decade, which then presented studies that were basically gigantic advertorials for Merck's products. Now there's news that the same academic publisher has admitted to creating five other fake journals earlier this decade.
The journals in question are: the Australasian Journal of General Practice, the Australasian Journal of Neurology, the Australasian Journal of Cardiology, the Australasian Journal of Clinical Pharmacy, the Australasian Journal of Cardiovascular Medicine.
Elsevier has a lot to answer for. So far, the company has blamed all of this an its Australian office.
And people think I am off-base when I point out how corrupt the research world has gotten.
There was a well-written, yet somehow problematic essay in the New York Times Sunday Magazine yesterday. It concerns the chronic, treatment resistant, suicidal depression of its author, Daphne Merkin, and her three-week hospitalization in 2008 at the New York State Psychiatric Institute in New York City. Merkin has been through the depression treatment mill since the mid-80s and has literally been on everything under the sun and done decades of psychotherapy, all of it to little avail. she walks readers through all of that and a huge bout of depression that hit in late-2007 when she was on three separate anti-depressants plus Risperdal and Lamictal.
Five meds at once for depression indicates just how severe and unremitting Merkin's depression was, as well as how aggressive docs have gotten with the meds. I can assure you there was a time--the 1990s--when docs wouldn't have used more than two meds, but now we are sure in a brave new world. There's no doubt, however, that Merkin's depression is a prime cut of Hell:
"As an adult, I wondered incessantly: What would it be like to be someone with a brighter take on things? Someone possessed of the necessary illusions without which life is unbearable? Someone who could get up in the morning without being held captive by morose thoughts doing their wild and wily gymnastics of despair as she measures out tablespoons of coffee from their snappy little aluminum bag: You shouldn’t. You should have. Why are you? Why aren’t you? There’s no hope, it’s too late, it has always been too late. Give up, go back to bed, there’s no hope. There’s so much to do. There’s not enough to do. There is no hope."Surely this is the worst part of being at the mercy of your own mind, especially when that mind lists toward the despondent at the first sign of gray: the fact that there is no way out of the reality of being you, a person who is forever noticing the grime on the bricks, the flaws in the friends — the sadness that runs under the skin of things, like blood, beginning as a trickle and ending up as a hemorrhage, staining everything. It is a sadness that no one seems to want to talk about in public, at cocktail-party sorts of places, not even in this Age of Indiscretion. Nor is the private realm particularly conducive to airing this kind of implacably despondent feeling, no matter how willing your friends are to listen. Depression, truth be told, is both boring and threatening as a subject of conversation. In the end there is no one to intervene on your behalf when you disappear again into what feels like a psychological dungeon — a place that has a familiar musky smell, a familiar lack of light and excess of enclosure — except the people you’ve paid large sums of money to talk to over the years. I have sat in shrinks’ offices going on four decades now and talked about my wish to die the way other people might talk about their wish to find a lover.
"Then there is this: In some way, the quiet terror of severe depression never entirely passes once you’ve experienced it. It hovers behind the scenes, placated temporarily by medication and renewed energy, waiting to slither back in, unnoticed by others. It sits in the space behind your eyes, making its presence felt even in those moments when other, lighter matters are at the forefront of your mind. It tugs at you, keeping you from ever being fully at ease. Worst of all, it honors no season and respects no calendar; it arrives precisely when it feels like it."
I know what she means. Merkin winds up in a psych unit, where they are sure pushing her towards ECT:
"One day early into my second week, I was called out of a therapy session to meet with a psychiatrist from the ECT unit. I still wonder whether this brief encounter was the defining one, scaring me off forever. She might as well have been a prison warden for all her interpersonal skills; we had barely said two words before she announced I was showing clear signs of being in a 'neurovegetative' condition. She pointed out that I spoke slurringly and that my mind seemed to be crawling along as well, adding grimly that I would never be able to write again if I remained in this state. Her scrutiny seemed merciless: I felt attacked, as if there were nothing left of me but my illness. Obviously ECT was in order, she briskly concluded. I nodded, afraid to say much lest I sound imbecilic, but in my head the alarms were going off. No, it wasn’t, I thought. Not yet. I’m not quite the pushover you take me to be. It was the first stirring of positive will on my own behalf, a delicate green bud that could easily be crushed, but I felt its force."The strongest and most benign advocate for ECT was a psychiatrist at the institute who saw me three decades earlier and was instrumental in convincing me to come into 4 Center. In his formal but well-meaning way he pointed out that I lived with a level of depression that was unnecessary to live with and that my best shot for real relief was ECT. He came in to make his case once again as I was sitting at dinner on a Friday evening, pretending to nibble at a rubbery piece of chicken. The other patients had gone and my sister was visiting. I turned to her as he waxed almost passionate on my account, going on about the horror of my kind of treatment-resistant depression and the glorious benefits of ECT that would surely outweigh any downside. I didn’t trust him, much as I wished to. Help me, I implored my sister without saying a word. I don’t want this. Tears trickled down my cheeks as if I were a mute, wordless but still able to feel anguish. My sister spoke for me as if she were an interpreter of silence. It looked like I didn’t want it, she said to the doctor, and my wishes had to be respected."
I love how a psychiatrist tried to lure Merkin into ECT by telling her she'd never write again without it. That's verging on an ethical violation and clearly, in Merkin's case, the evidence argues against it: It's a year later and Merkin has written. So much for that doctor's wise counsel.
The piece closes with Merkin, her depression somewhat lifted (but not by much) sailing the seas of Remeron and, drum roll, Abilify and able to get out and about to a degree she couldn't before. It's a fine piece overall, well worth a read.
Here are some quibbles.
1. There's a lot of talk of ECT in the piece, but no mention that NYC is damn near ground zero for use of shock therapy. I know a psychiatrist in NYC, who used to practice in Seattle, who tells me that ECT is used at least three times as much in NYC as it is in Rain City. I find it interesting that an editor didn't want some kind of stats on ECT use, because you could walk away from the piece thinking docs turn to ECT in all places at the same rates, when that's not the case. I congratulate Merkin on pushing ECT away, however. Good for her.
2. It's apparent that Merkin was rapidly tapered off meds (five of 'em) in about 10 days when she enters the hospital. Then a doc has the nerve to tell her she's neurovegetative, when Merkin has clearly gone through a fast taper off multiple meds, an experience that would leave any human a little dazed and scrambled and acting vegetative. It's interesting to me that Merkin seems unaware of this as an issue.
3. Merkin has been on meds for depression for over two decades and writes that she's only been off them for very short periods of time. If she's getting such crap results from medication, then why the heck wouldn't she try being off them altogether for a time and seeing what happens? It cannot be any worse for her than what she's been doing. All I know is that approach finally worked for me and I had what several psychs called treatment resistant depression (within the context of bipolar disorder, of course). Call me biased.
4. My final quibble is with the magazine itself. Whenever it runs a big essay on some mental health matter (once or twice a year), its writers typically focus on the most extreme cases where no one ever gets better (Merkin's kind of depression would only account for a thin slice of all the cases of depression out there in the land). Happily, it's not all that bad all the time in depression and bipolar land, but it sure seems like the magazine's article choosers have a tough time getting their minds around that. It's not like any journalists haven't pitched them articles in the last year or so on people who've recovered from bipolar and depression. I haven't seen anything like that in the mag. Call it institutionally-biased.
This post is directed at the commenter who recently used the handles SteveB and DavidB: Cease and desist from commenting on this site. You are banned for attacking me personally a couple of weeks ago, so stop changing your name and IP address and coming back to play games again. I'll eventually figure out who you are each time and remove your comments and ban you all over again.
Sorry to trouble the rest of you with this, but the guy refuses to use a valid email address, so this is my best way to tell him to stay off this site.
Via the Dallas Morning News comes word that Karen Wagner, a well-known University of Texas psych researcher, is being investigated both by the University of Texas and the Department of Health and Human Services (which handles most federal health research funding) over allegations that Wagner failed to reveal over $150,000 in payments to her from GlaxoSmithKine, makers of Paxil. Wagner was the subject of a letter from Se. Charles Grassley (R-Iowa) to UT officials last September. Among other things, Wagner is a co-author of the infamous Paxil Study 329, underwritten by Glaxo.
"The university system has not disciplined Wagner, who could not be reached for comment. But Vice Chancellor and General Counsel Barry Bergdorf said she has been under investigation for the last two weeks. Wagner will remain at work throughout the investigation, he said, and the UT Board of Regents has been notified."'We've taken all reasonable steps and will continue to do so,' Bergdorf said. The fact that Grassley made the report to the inspector general 'is probably of concern to Dr. Wagner.'"
Earlier Grassley had reported that Wagner pulled in $160,000 a year from Glaxo from 2000 to 2005, but had only reported $600,000 to UT officials, which could put her and the university in violation of federal research rules around conflict of interest disclosure.
Stay tuned.
There's still quite a bit of attention being paid to Wednesday's surprise FDA approval of Vanda Pharmaceuticals' atypical antipsychotic Fanapt for use in schizophrenia. Surprised was Columbia University psychiatrist Jeff Lieberman, who told Forbes.com:
"Lieberman says he is 'amazed' the FDA approved the drug. He says the approval is 'probably a testament to persistence' on Vanda's part. 'There's no harm in having it,' he says. 'It gives clinicians another option to choose from, but it doesn't really add anything in terms of any substantial advance in efficacy or safety.'"
As far as I know none of the approval studies have been published yet, so it's tough to know what the drug's safety and efficacy might be. Like almost everyone who follows these issues, I was stunned that the FDA approved a drug it had issued a not approvable letter for last year, especially in light of the fact that Vanda didn't run new clinical trials but went back to the FDA with essentially the same trials and data it had submitted earlier. So you've got to wonder if they made a scientific argument to the FDA that the agency's reviewers missed something in the data or if the company made a legal argument that the agency had to approve the drug since it had shown basic efficacy.
Forbes.com noted that it might mean the FDA is lowering the bar on approval of new antipsychotics and there are other compounds out there which could potentially gain approval.
It's hard to know since the FDA approval process is ridiculously secretive, but the whole affair has me scratching my head with both hands. As does the drug's name. Where the hell did they come up with Fanapt?
Feel free to speculate in comments.
This is one of the most discouraging stories I've read in a while. In March, a father kidnaps his sons (presumably he and their mother were split) and then kills them, then hangs himself. Now, a coroner in Illinois has found:
"The deaths of both Duncan and Jack Leichtenberg were ruled homicides by Putnam County Death Investigator Bob Cofoid. Duncan, 9, died directly as a result of quetiapine and alprazolam intoxication, while his brother Jack, 7, died of a stab wound to the back and alprazolam intoxication, the coroner said in a written statement."
No word on whose meds these were.
Who the hell are these guys who can kill their own children? (And it is usually the guys doing this kind of rottenness.)
The FDA yesterday approved Fanapt (iloperidone), an atypical antipsychotic made by Vanda Pharmaceuticals, for use in the treatment of schizophrenia in adults. I don't know a lot about this drug--it's the first antipsychotic given its initial FDA approval in years--but what I do know gives me cause for concern.
First, last year the FDA issued a not approvable letter for the drug, so there was clearly something wrong about the safety and efficacy of Fanapt at that time. What exactly we're unlikely to know, since the FDA won't release non-approvalable letters and there's little chance of the company doing so. What changed between then and now with the drug and its performance I cannot say.
Second, I strongly suspect that the drug will quickly be repurposed for use in other disorders, possibly even off-label. That's been the pattern with the atypicals over the last 15 years--get a schizophrenia approval, then a bipolar approval, then market the hell out of it off-label for everything else under the sun. There's little reason to believe that things will be different this time out, especially since the patent application for this compound clearly states that it's intended for the "treatment of affective and attention/behavioral disorders."
So maybe Fanapt can grow up to be like Zyprexa, Seroquel, Risperdal and Abilify and be used for absolutely everything from ADHD in kids to schizophrenia. We shall see. I can assure you I'll be watching this drug closely. Its patent expires in 2021.
The financial markets sure liked the news: Vanda's stock price reportedly exploded 824 percent higher in after hours trading.
Although it's been known for a few weeks that the FDA's psychopharmacology advisory committee would meet in early June to make recommendations to the FDA proper regarding approval of Seroquel, an atypical antipsychotic, for use in children and teens aged 13 to 17 with schizophrenia and those aged 10 to 17 with pediatric bipolar disorder, it wasn't clear if other drugs would be considered at the same time. Yesterday, news came out of the FDA that Zyprexa and Geodon were coming along for the ride as well. Pfizer is asking the FDA to approve Geodon for the "acute treatment of manic or mixed episodes associated with bipolar disorder, with or without psychotic features in patients 10 to 17 years old." Lilly is seeking FDA approval of Zyprexa for the "acute treatment of manic or mixed episodes associated with bipolar I disorder and the acute treatment of schizophrenia in adolescents."
Lovely.
The hearings are set for June 9 and 10 in Maryland.
That's right. As part of Mental Health Awareness Month, today is Children's Mental Health Awareness Day, as proclaimed by the fine bureaucrats at SAMHSA. On its website, SAMHSA even pimps for bipolar disorder in kids, including as one symptom "difficulty settling as babies." Seriously. Your tax dollars at work. Isn't it nice that the feds are doing this even though the alleged diagnosis of bipolar disorder in young children isn't in the DSM.
As one reader put it to me in an email, it's a shame we cannot have a "Children's Mental Health Treatment Outcomes Day." No kidding.
Most of you are aware that Sen. Charles Grassley (R-Iowa) sent a letter to the National Alliance on Mental Illness last month, asking for the organization, which lobbies Congress, to reveal how much it gets from what pharma companies. NAMI has long been known,a s I've pointed out for three years, to be receiving about 50 percent of its annual budget (around $12 million to $13 million total) from pharma companies, which is kind of interesting for a group that styles itself as "the nation's voice on mental illness." Of course, many of the group's initiatives, nationally and locally, involve getting people to understand that mental illness comes from bad brains and that bad brains require medications made by the companies supporting NAMI. It's the bio-pharma marketing model run amok. (Much past coverage of NAMI here.)
Anyway, NAMI replied to the Senator and its reply was obtained by MindFreedom, a fairly anti-meds group, and posted to its website. In it, Michael Fitzpatrick, NAMI's executive director, states that the group has received on average 56 percent of its annual budget from pharma companies from 2005 to 2009. Fitzpatrick, who defends the group's pharma dough, claims that NAMI's strategic plan is to reduce that percentage dramatically in coming years. He told me the same thing when I met with him in 2005 (back when I was still at a newspaper). Four years later, NAMI is still pulling in many millions from pharma.
In fact, NAMI is now breaking out its pharma contributions each quarter, a practice it apparently began this year. For the first quarter of 2009, NAMI took in $1,249,340 from pharma companies and foundations. You can read the list here, including $25,000 from AstraZeneca for "Exemplary Psychiatrist Awards," presumably to be presented at NAMI's annual convention. In fact, you'll be amazed at how much of that $1.2 million is aimed at NAMI's annual convention--$147,500.
Bristol-Myers Squibb, for example, gave $262,500 in the first quarter. Some $37,500 of that is for something called "NAMI Depression Initiative." BMS doesn't make an anti-depressant and NAMI, according to Fitzpatrick's letter, hasn't been bought by Big Pharma. Oh, wait, but there's that new add-on for depression indication for BMS' Abilify antipsychotic. I bet that whatever program this is at least includes a mention of using antipsychotics to treat depression.
The Law Project for Psychiatric Rights (known as Psych Rights) yesterday sent letters to several members of Congress, including Sen. Charles Grassley (R-Iowa), alleging that since the 1990s Medicaid has been paying for psych meds used in kids off-label and without inclusion in any pharmacopeia and that such actions violate federal law. There is federal law specifically instructing Medicaid to not pay for such drugs unless they are FDA-approved for a specific indication in a specific population.
If there's not some kind of exemption involved here allowing Medicaid to do this and if Psych Rights' claim is correct, then Medicaid is paying for at least $2 billion a year and possibly much more in medications it should not be paying for. That's kind of a massive problem, which I hope gets sorted out in short order.
Here's the meat of Psych Rights' letters, which you can view for yourself at the group's website:
"With respect to the second generation neuroleptics, no pediatric use of Seroquel, Zyprexa or Geodon is approved by the FDA or supported by any of the designated compendia. Risperdal is approved for very narrow uses, as is Abilify, but even when prescribed for these indications, they are almost always prescribed concurrently with another drug(s), which is not FDA approved or supported by any of the designated compendia. In 2007, through a state Freedom of Information Act Request, PsychRights was able to find out that Medicaid was paying approximately $123,000 per month for anticonvulsants prescribed to children and youth and $288,000 per month on second generation neuroleptics for a total averaging approximately $411,000 per month in improper Medicaid payments in Alaska alone. Extrapolating this to the entire country, there is over $2 Billion in Medicaid payments for psychiatric drugs to children and youth that Congress has explicitly prohibited. In truth, this is the smallest amount because typically two or more of these drugs are administered concurrently, in what is called poly-pharmacy, none of which has been approved by the FDA for pediatric use or supported by any of the designated compendia."
It will be interesting to see where this all goes.
Freda Lewis-Hall, a psychiatrist, is set to become Pfizer's new chief medical officer, putting her in charge of docs who work for the company designing clinical trials and doing marketing to other docs. Frobes.com had an interview with her yesterday. Lewis-Hall once worked at Lilly on both Prozac and on clinical trials for Cymbalta for stress urinary incontinence.
For some reason, I sensed I'd heard her name before and sure enough deep in the archives of the Net is a CBS News piece from 1999 which examines Lilly airing a 30-minute infomercial on depression (including Prozac testimonials) and Lewis-Hall defending the approach.
"'This is a phenomenal opportunity to reach people who otherwise wouldn't be reached,' says Dr. Freda Lewis-Hall of Eli Lilly & Co. 'This reaches people where they sit -- in front of the television'"...."'This has been in the making for a while, about a year or so. It is a part of our long-term commitment to outreach and education around depression. Just kind of a next step in the process.'"
Uh huh. Anyway, she told Forbes that it was time for the pharma industry to get back to basics.
"The key to improving the drug industry's reputation, tarnished by a series of high-profile controversies and a relative paucity of new medicines, is to focus on making sure patients get the drugs they need--and that they don't get medicines they don't need."'The science is evolving,' she says. 'That gives us the opportunity to discover, develop and deliver new medicines and technologies. We have loads and loads of information. We need to leverage all the available information technology to get that information to patients and physicians so the right patient gets the right medicine at the right time for the right outcome.'"
That is some of the most glittering BS marketing talk I've heard in a long time. Pfizer is not a huge player in the psych med world these days--Zoloft is generic, Geodon sales are weak and Chantix sales have cratered--but I thought I'd pass it along. Maybe Lewis-Hall can dream up an infomercial for Chantix.
The FDA today announced that it has finally approved new warning language for anti-epileptic drugs (anti-seizure drugs, so called mood stabilizers) such as Depakote and Lamictal to reflect suicidality risk. The FDA first raised concerns about the such risks with the drugs in January 2008. Today's announcement also noted that the agency had required "development of a medication guide, to be issued to patients each time the product is dispensed."
There are 11 drugs in the anti-seizure class, some of them multi-billion sellers (Lamictal, Depakote, etc.) due to their twin uses in epilepsy and bipolar disorder. Some pharma companies had apparently pushed back against the FDA and said, in effect, "Not with our drug." The agency now claims:
"The increased risk of suicidal thoughts or behavior was generally consistent among the eleven drugs, with varying mechanisms of action and across a range of indications. This observation suggests that the risk applies to all antiepileptic drugs used for any indication."
The risk is supposedly small (less than 1 percent, but spread that out over millions taking these drugs and it sure looks larger) and, according to researchers I've talked with as well as the FDA, is mostly present in people with epilepsy. The risk is also most prevalent during the first six months of taking the drug. Why there's less statistical noise around these drugs for people with bipolar disorder is anyone's guess.
This week's Newsweek had a good article on The Icarus Project and Will Hall, a leader of the group, and what's called "Mad Pride."
"I met Hall one night at the offices of the Icarus Project in Manhattan. He became a leader of the group—-a 'mad pride' collective-—in 2005 as a way to promote the idea that mental-health diagnoses like bipolar disorder are 'dangerous gifts' rather than illnesses. While we talked, members of the group—Icaristas, as they call themselves—scurried around in the purple-painted office, collating mad-pride fliers. Hall explained how the medical establishment has for too long relied heavily on medication and repression of behavior of those deemed 'not normal.' Icarus and groups like it are challenging the science that psychiatry says is on its side. Hall believes that psychiatrists are prone to making arbitrary distinctions between 'crazy' and 'healthy,' and to using medication as tranquilizers."'For most people, it used to be, "Mental illness is a disease—here is a pill you take for it",' says Hall. 'Now that's breaking down.'"
It cannot breakdown fast enough for my taste. Anyway, the article--wherein someone from the Treatment Advocacy Center defends meds and Peter Kramer says psychotic depression is a disease (good work, Kramer; pick out the rarest of depressions to defend a crumbling paradigm)--is worth a read.
BTW, the article kind of parallels a piece on Icarus and Liz Spikol in the New York Times last year, which also included a quote from TAC's annoying Fuller Torrey. Interesting how the East Coast media fails to recognize the work others are doing on these issues in other parts of the US. That's not to take away from Icarus. Just making a point about the geographical impairment of some of my colleagues in the media.
A new study is out in Health Affairs and I'll just let USA Today describe it:
"About 15% of elderly Americans had prescriptions for psychiatric drugs in 2006, double the percentage a decade earlier, according to an analysis of federal databases out today...."The biggest change came for those 65 and older: About 16% were diagnosed with a mental illness, roughly double the percentage in 1996, with 15% overall given psychiatric prescriptions. This surge in medication use was driven mostly by popularity of the newer class of antidepressant drugs — SSRIs such as Prozac — and atypical antipsychotic drugs."
It's well known that the atypicals have led to sudden cardiac death in the elderly (and others) and the drugs carry a black warning for the same.
What amuses me about the USA Today piece is that in it one of the researchers worries aloud that not enough seniors are getting access to psychiatric specialists. I'm not sure I share his concern, given the huge problems that have cropped up around use of the atypicals in seniors and little things like Eli Lilly pleading guilty to a criminal charge for off-label marketing its atypical, Zyprexa, for use in the elderly suffering from dementia.
But with a doubling in sales of their drugs to the elderly in just one decade, I'm sure Big Pharma can find a way to justify itself to itself.
This will sound like life imitating art (I'll come to that part in a second), but a Japanese study published in the British Journal of Psychiatry has found that naturally-occurring, low concentration Lithium in water supplies may offer a protective effect against suicide. (Previous studies of Lithium have found it to be literally the only psychotropic that offers this kind of protection.) Researchers examined Lithium in the drinking water in 18 different municipalities in Oita, a prefecture in Japan. Where the Lithium levels were higher, the suicide rate was lower than in parts of Oita where Lithium levels were lower.
That's an interesting finding. In his classic novel The Thanatos Syndrome, Walker Percy wrote of a community where the water was laced with "heavy sodium" and how it cured the psychological ills of the community. As I recall from skimming the book once (it's not my favorite Percy novel), the whole business was rather creepy.
In a invited commentary in the BJP, Allan Young, a Canadian psychiatrist, notes: "These intriguing data should provoke further research, which ultimately may benefit community mental health." (If someone has access to the BJP, please pass along the study and commentary.)
I'd really rather the government and researchers not get too interested in this kind of research. The possibilities for social control are endless and probably quite dangerous and undesirable. So, possibly, is the probability of kidney damage.
As if my other post today on anti-depressants (and untreated depression) being linked to premature births doesn't raise enough concerns, another new study out in the American Journal of Psychiatry reports that long-term anti-depressant use raises the risk of diabetes by 84 percent across all classes of anti-depressants, especially when used in moderate to high doses. The reason seems to be due to weight gain, but researchers were unable to pin down a full explanation. The diabetes risk is not present in short-term use of anti-depressants, researchers report.
Tricyclics increased the risk 77 percent while SSRIs increased it by 106 percent. You can read the complete study yourself to see how individual anti-depressants fared (keep in mind that for some of the drugs the effected group was so small as to make some of the findings a bit tenuous).
If you wonder that perhaps there's something about the underlying depression that's causing weight gain and diabetes risk, read how the researchers handled that question:
"Could our results be explained by the fact that depression itself and not the antidepressant drug treatment increases the risk of diabetes? It has been reported that patients with depression have a 35% increase in risk of developing diabetes as compared with nondepressed individuals. The underlying reasons for this association are unknown. One might argue that patients treated with antidepressants for >24 months are a special subgroup with an increased risk of diabetes only because of their active depressive disorder. There are several reasons why this explanation is rather unlikely. First, one would expect to see increased risks with most individual antidepressants used for >24 months if the increased diabetes were caused by the depression and not by the drug. In contrast, our results indicate that antidepressants differ with respect to their diabetogenic potential. Second, in the Diabetes Prevention Program, elevated Beck Depression Inventory scores at baseline were not associated with an increased risk of diabetes, but the use of antidepressants was. Third, in our study, all cohort members were treated with only one antidepressant during the entire follow-up period. A high proportion of long-term users probably responded to treatment, as otherwise a switch to another antidepressant would have been indicated. Fourth, in an explorative analysis using the number of days with a diagnosis of depression in the year before the index date as a proxy for depression severity, there was no indication of increased severity in long-term users. Inclusion of this proxy variable into the multivariate models did not affect our main findings."
So there you have it.
There's a fairly explosive new study out in the American Journal of Psychiatry asserting that both anti-depressant treatment of pregnant women and, separately, untreated depression itself increase the risk that a child will be born prematurely as often as 20 percent of the time (full study here). So, in other words, there's much fodder for both anti-depressant haters and treatment advocates in this new study. I won't even attempt to interpret the findings myself, as I am a bit tired of all the drama that erupts when I venture an opinion on depression and motherhood.
So here are the researchers themselves:
"A major finding of this study is a higher risk for preterm birth in infants exposed in utero to either continuous SSRI treatment for depression or continuous depression without SSRI treatment. Our study joins the converging yet controversial literature that links SSRI treatment to a threefold increase in the risk for preterm birth. Another important observation is that women exposed to depression (with no SSRI treatment) throughout pregnancy had a comparable level of increased risk for preterm birth."
I don't envy a single woman or couple planning a pregnancy these days at all.
There is very little about Big Pharma's manipulative, lies-as-marketing behavior that shocks me anymore, but this time out I am astounded: Merck has gone and created a fake academic journal, Australasian Journal of Bone and Joint Medicine, according to The Scientist. Merck products such as Fosamax were featured in "studies" in the journal, which is reportedly published by Elsevier, a well-known academic journal publishing house. Both it and Merck have got a lot of explaining to do.
From the bioethics.net blog:
"The Scientist has reported that, yes, it's true, Merck cooked up a phony, but real sounding, peer reviewed journal and published favorably looking data for its products in them. Merck paid Elsevier to publish such a tome, which neither appears in MEDLINE or has a website, according to The Scientist."What's wrong with this is so obvious it doesn't have to be argued for. What's sad is that I'm sure many a primary care physician was given literature from Merck that said, 'As published in Australasian Journal of Bone and Joint Medicine, Fosamax outperforms all other medications....' Said doctor, or even the average researcher wouldn't know that the journal is bogus. In fact, knowing that the journal is published by Elsevier gives it credibility!"
The attitude of pharma companies that they can get away with whatever the hell they want whenever they want and that they can deeply manipulate doctors and patients through various smoke-and-mirror techniques has simply got to stop. It's dangerous.
I hope someone in Congress asks Merck some tough questions.
Drug Injury Watch has more details on how this all came to light.
It's been a slow news week on the mental health front, which is good for me since my back was acting oddly the last few days, so I used the opportunity to not sit in front of my computer for hours on end. If my back holds up, I'll be back with posts later today.
And in case you hadn't heard, Botox got an FDA-mandated black box warning yesterday.