Are Big Pharma murderers?

An book review in the NYTimes today focuses on Melody Petersen, a former reporter of the Times, who has written a book against  Big Pharma's marketing tactics called Our Daily Meds: How the Pharmaceutical Companies Transformed Themselves Into Slick Marketing Machines and Hooked the Nation on Prescription Drugs. In the book, she asks:

“Could drugs be killing people but escaping all blame, leaving them to harm even more Americans until someone, finally, catches on?” Ms. Petersen asks.

Few of us have. Most of America hasn't. Petersen outlines in great detail – the point of repetition according to Janet Maslin's review – Big Pharma's propensity for skewing clinical trial results so that their drugs perform better than placebo, the increased and ubiquitous DTC marketing, and the "payola-dispensing drug company representatives."

(“Hotel too cold inside,” one said, in an evaluation of a June 1998
drug company program, adding, “Resort places preferred.” From a
different doctor, miffed at the lack of a chauffeur at another event:
“Hired car would have been much preferable.”

Petersen also covers Big Pharma's tactic of fixing side effects of medications by creating medications to fix the side effects leading to medication on medication.

And when the side effects of sleeping pills or antidepressants mean
more elderly people fall down, the solution is not likely to be the
scaling back of such prescriptions. “Instead,” she writes, “the
companies have used the statistics on falls to create a new blockbuster
pharmaceutical market for drugs they claim will reduce the chances of
breaking a bone.”

According to the Maslin's review, the book calls for non-government watchdog agencies and closer oversight on published studies, which Petersen says are ghostwritten by pharma spokespeople. Overall, Petersen's book sounds like a must-read for anyone who is skeptical of Big Pharma's activities. However, I doubt her book will get much press or coverage considering that you can't read any major publication without turning the page and seeing a drug ad then the required 2-page side effect warning that everyone skips over. If anyone reads the book, I'd like to know your thoughts about it.

Sorry if this post sounds hastily written. I'm off to an interview to freelance for a company.

Blood test for efficacy of antidepressants in the future?

Scientists have found that a biomarker for depression could show whether a person's antidepressant is working. The discovery could lead to something everyone in the psych world has been waiting for: a blood test of some kind.

The researchers looked at the interaction of neurotransmitters and a protein called Gs alpha. In brain cells, the protein acts like a kind of butler, passing messages from neurotransmitters on the outside and amplifying their messages, [study co-author Mark] Rasenick explained.

When the protein is working properly, it's like a butler whose "hands are just flying, cooking and cleaning at the same time," he said. But when the brain is depressed, "it just sits there in the corner."

That's an interesting observation. This might finally explain the difference between "depressed" brain activity and normal brain activity on an MRI. (By the way, has anyone had an MRI performed for depression?)

Researchers compared the proteins in the brains of people who committed suicide as a result of depression to those who did not. "They found the protein would have worked less effectively in the brain cells of the suicide victims."

Dr. Gregory Simon conceded that doctors cannot determine which antidepressant will work for which person.

"There's a long history of research using patterns of symptoms or biological measures — chemicals measured in blood or spinal fluid — to predict response to a particular antidepressant. None of those hoped-for predictors have significant value.

[Genetic tests] would not eliminate trial-and-error, but it would reduce the waiting time with each trial. But it's a long way from a study like this one to a test that's useful to patients and doctors."

Good news for the skeptics about this research study: It was funded by the U.S. Public Health Service and the American Foundation for Suicide Prevention. But a test simply to see if an antidepressant is working has the smell of pharma somewhere on it.

(Hat tip: Ephphatha)

Loose Screws Mental Health News

An article in the NYTimes addresses the issue of diagnosing mental health in developing countries. A startling fact:

Depression and anxiety have long been seen as Western afflictions, diseases of the affluent. But new studies find that they are just as common in poor countries, with rates up to 20 percent in a given year.

In India, as in much of the developing world, depression and anxiety are rarely diagnosed or treated. With a population of more than one billion, India has fewer than 4,000 psychiatrists, one-tenth the United States total. Because most psychiatrists are clustered in a few urban areas, the problem is much worse elsewhere.

Looks like depression is really more than just a whiny rich American kid who chooses to be upset because he’s got nothing better to do. That’s “emo” for those who aren’t hip-to-the-jive. 😉

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On The Elite Agenda, Dr. Fred Baughman mentions Swedish writer Janne Larson who asserts that “over 80 percent of persons killing themselves were treated with psychiatric drugs.” Thank God for FOIA that provides the docs to back this up:

According to data received via a Freedom of Information Act request, more than 80 percent of the 367 suicides had been receiving psychiatric medications. More than half of these were receiving antidepressants, while more than 60 percent were receiving either antidepressants or antipsychotics. There is no mention of this either in the NBHW paper or in major Swedish media reports about the health care suicides.

I guess Sweden isn’t the only country in the world that wants to sweep unfavorable mental health coverage under the rug. By the way, Sweden also is considered to be the seventh happiest country in the world.

While the FDA has recognized that antidepressants can cause an increase in suicidal behavior (as indicated by the “black box warning”), antipsychotics seem to have fallen under the radar. In fact in 2002, Clozaril was approved to combat suicidal behavior in schizophrenic patients. Since then, research has shown that antipsychotics can increase suicidal behavior in schizophrenic patients twenty-fold.

Akathisia – a serious side effect that has occurred for nearly all psych drugs in clinical trials – has been found to be linked to suicidal behavior with not only antidepressants but also in conjunction with antipsychotics.

Finally, Baughman closes with this:

It is important to note that nearly every school shooting that has happened in the United States over the last decade has been conducted by young males who were taking antidepressant drugs. The drugs not only cause suicidal behavior, they also seem to promote extreme violence towards other individuals. In most school shooting cases, the young men committing the violence also committed suicide after killing classmates and teachers. These are classic signs of antidepressant use.

I don’t know if that’s wholly true but it’s a trend I’ve seen with Cho, Kazmierczak, and Eric Harris of Columbine. Since 1996, there have been 55 major school shootings all around the world; 43 of them occurred in the U.S. Makes you wonder how many of these gunmen were on a psychotropic drug – prescribed or not – of some kind.

(Image from Style Hair Magazine)

Today's lesson: Paxil and Lexapro are not great antidepressants

Dawdy at Furious Seasons wrote a post on an editorial in the LA Times by Summer Beretsky’s experience with Paxil. After reading her editorial, I’m reminded that my own experience with one antidepressant wasn’t all that unique. Her drug was Paxil for panic attacks; mine was Lexapro for depression following a 3-month (on-and-off) stint with Paxil. I’m struck by the similarity of our experiences; not only did the same thing happened to me but I was also a communications major in college as well.

Paxil had one pretty undesirable effect on me: I started to lose interest in just about everything. I stopped initiating social activities (who needs that sort of thing?) and was no longer motivated to perform well academically.

My emotions had flat-lined: I hadn’t cried in months, nor had I proverbially jumped for joy. I felt — nothing.

I can still remember sleeping in bed at home on a weekday when I should have been at class. It was 2 in the afternoon, around the time my copy editing class was to begin. My boyfriend at the time (now my husband) lived in Kentucky while I attended college in New York. He planned to visit me that weekend but was getting fed up with my depression and listlessness. He called from work to tell me to get up and go to class. I mumbled on the phone, half-confused, and said no. He demanded, “Why not?” I said quite plainly, “Because I don’t care.” He said, “If you don’t get up and go to class, I won’t visit you this weekend.”

I replied, “I don’t care.”

Blogs around the way

I’m catching up on reading my fellow bloggers’ posts (see Blogroll to the right), so if you’re not reading their site already, I’d encourage you to do so. Below  are some posts that caught my attention. Some might be a little dated.

Gianna at Bipolar Blast: Has a video up of Gwen Olsen, an ex-pharma rep who says that pharmaceutical companies aren’t in the  business of curing but in the business of "disease maintenance and symptom management." It’s nothing new but here are two quotes that caught my attention:

"And what I’m saying is provable is that the pharmaceutical industry doesn’t want to cure people. You need to understand specifically when we’re talking about psychiatric drugs in particular that these are drugs that encourage people to remain customers of the pharmaceutical industry. In fact, you will be told if you’re given a drug such as an anxiolytic, or an antidepressant, or an antipsychotic drug, that you may be on the drug for the rest of your life. And very frequently, people find that they are on the drug for a very long period of time, if not permanently, because they’re almost impossible to get off of. Some of them can have very serious withdrawal symptoms – most of them can have extremely serious withdrawal symptoms if they’re stopped cold turkey – but some people experience even withdrawal symptoms when they try to titrate or they try to eliminate the drug little by little, day after day."

"We have got to start making the pharmaceutical industry accountable for their actions and for the defective products they’re putting on the market. It won’t be long before every American is affected by this disaster and we need to be aware of what the differences are between diseases between disorders and between syndromes. Because if it doesn’t have to be scientifically proven, if there are no tests, if there are no blood tests, CAT scans, urine tests, MRIs – if there is nothing to document that you have disease, then you in fact, do not have a disease, you have a disorder and it has been given and has been diagnosed pretentiously and you need to get yourself educated and understand that there are options and those options are much more effective than drugs."

I’ve always wondered why doctors don’t run tests to diagnose any psychiatric disorders. From NIMH:

Research indicates that depressive illnesses are disorders of the brain. Brain-imaging technologies, such as magnetic resonance imaging (MRI), have shown that the brains of people who have depression look different than those of people without depression. The parts of the brain responsible for regulating mood, thinking, sleep, appetite and behavior appear to function abnormally. In addition, important neurotransmitters–chemicals that brain cells use to communicate–appear to be out of balance. But these images do not reveal why the depression has occurred.

If MRIs have shown that the people with depression have a part of the brain that functions abnormally then why isn’t it standard for all people diagnosed with depression to have an MRI done to confirm this? I have one of two hypotheses:  it’s too expensive to get an MRI done for each person and that insurance won’t pay for it or the abnormal functioning cannot be detected in the brain of every depressed person.  Therefore, is major depressive disorder really a made-up diagnosis?

Selective publication on antidepressant efficacy and data

After the release of the U of Hull study on Tuesday, the AFP has written an article about doctors who are urging patients on antidepressants to continue taking them.

Louis Appleby, national clinical director for Mental Health, told the Press Association: "… the message to patients and doctors remains the same — anti-depressants are an appropriate treatment for moderate or severe depression."

I agree that patients on antid's should not cease medication cold turkey. (Trust me on this one. Even with proper tapering, the side effects are not pretty.) I waver on the idea that antid's are "appropriate treatment" for moderate-to-severe depression rather than a "form of treatment." Antidepressants can help, but I'm not sure I like the term "appropriate." But I likely am arguing semantics.

Since the results of the study originate from Britain (despite the fact that it also includes data from the FDA), I can only assume that news reports on this are more widespread over there. In my Philadelphia, USA-world, it seems a little bit off the radar to me. Let me know if I'm wrong.

To Mr. Appleby's credit, he has acknowledged that the British government plans to rigorously pursue routes of alternative treatment in light of the study.

The government has plans to expand the availability of psychological therapies as an alternative to drugs, Appleby explained, with extra investment and more psychological therapists.

"The evidence shows that these therapies are effective and often preferred by patients."

WebMD also covered the recent study.  Dr. Nada Stotland of the American Psychiatric Association insists that the study is not reflective of real psychiatry.

"We know that many people who are depressed do not respond to the first antidepressant they try," she says. "It can take up to an average of three different antidepressants until we find the one that works for a particular individual. Therefore, testing any single antidepressant on a group of depressed individuals will show that many of them do not improve."

Stotland has a point. Patients usually do not respond to the first antidepressant that is prescribed to them. About 30 percent of patients do not respond to antidepressants or experience no improvement until several weeks later.  Even then, patients who are on antidepressants for long-term maintenance, experience the return of depressive symptoms. An article from The New England Journal of Medicine evaluated the selective publishing of antidepressant trials with a positive efficacy:

Among 74 FDA-registered studies, 31%, accounting for 3449 study participants, were not published. Whether and how the studies were published were associated with the study outcome. A total of 37 studies viewed by the FDA as having positive results were published; 1 study viewed as positive was not published. Studies viewed by the FDA as having negative or questionable results were, with 3 exceptions, either not published (22 studies) or published in a way that, in our opinion, conveyed a positive outcome (11 studies). According to the published literature, it appeared that 94% of the trials conducted were positive. By contrast, the FDA analysis showed that 51% were positive.

The authors' conclusion: "Selective reporting of clinical trial results may have adverse consequences for researchers, study participants, health care professionals, and patients." It's an obvious statement; so obvious, it can be easily overlooked.

While it's important to shed light on the issue of treating depression with antidepressants, it seems as though many authors are cherry-picking favorable results to publish. Considering that much of these research studies are backed by drug companies, it's no surprise. Also, I can't fault the authors only. I recently freelanced for a medical publication and learned that many of the submitted articles are heavily rewritten by the editors. Editors are hard-pressed (and probably loath) to publish a piece that criticizes antidepressants when their biggest advertisers include such big names as Wyeth, Eli Lilly, and GlaxoSmithKline. Run enough of those pieces and a publication is quickly on its way to folding.

That's why it's stunning to read the U of Hull study that has somewhat of a negative slant toward antidepressants' effectiveness. While doctors are wisely advising patients to continue any antidepressants they may be on, currently drug makers have launched into damage-control mode.

In a statement, GlaxoSmithKline (GSK) representatives express "disappointment" at how the study was being reported by the media, suggesting that news reports may have caused "unnecessary alarm and concern for patients."

Of course these news reports are "unnecessary" to GSK. Letting patients know that their antidepressants might not work better than sugar pills isn't good for business. However, GSK's reps were kind enough to balance out their statement, adding "counseling and lifestyle changes" also are important aspects of treating depression. Then, the company accuses the researchers of selectively reporting their data:

"GSK fully endorses public disclosure of clinical trial results for its medicines and is actively committed to communicating data relevant to patient care," the statement reads. "All the data related to GSK's clinical trial results of [Paxil], regardless of study outcome, are available at the company's clinical trials register at 20 www.gsk.com."

Tell that to the estimated 5,000 Americans who have filed a lawsuit against GSK regarding Paxil. Still, Kirsch, who has received consulting fees from Squibb and Pfizer, insists "the [drug companies] certainly do publish selectively."

I'm inclined to agree.

The Zoloft-rage/violence connection

[This post is quite lengthy so I suggest you grab a cup of coffee or tea and sit down and read it. The following is not for the faint of heart (or those with a lack of time).]

It’s been amazing to me that I’ve received numerous comments on Zoloft inducing rage. I’m humbled by having a Pittman supporter visit my site and post some comments from the ChristopherPittman.org forums. Read the following:

In my senior year in high school I was diagnosed as being severely depressed and put on medication. The first medication that I was on I took for 5 months and it made me really aggressive. My friends and family noticed the change and I told my doctor about it and she changed my meds. After that I was fine. I am normally a very passive person and will let just about anything fly. But the medication made me really aggravated and aggressive toward my friends and family and it seemed that I wasn’t overcoming my depression. I just got done watching the 48 hours investigation on the Discovery Times Channel and felt a connection with Chris. I felt that I had to write this to let you know that Chris is not the only one out there that had these side effects. I think there should be a study done to see how many people that take antidepressants have increased aggression. The problem is that the pharmaceutical industry has deep pockets and many lobbyists. I hope this helps in some way.

And another:

I remember the case when it happened.

At the time I thought, “Zoloft right”.

Let me tell you my physician put me on Zoloft and it took about three weeks for my to become psychotic and I’m a 50 year old woman.

I have three children and I don’t make a lot of money but please let me know if I can do anything for the Pittman boy.

The jury should have been placed on Zoloft before they made they decision. Unless you’ve experience it you simply cannot believe its’ effect.

I did a bit of quick reading/research into Zoloft triggering violence in people who otherwise would have never been violent and it seems that are a few stories out there to support the assertion. I found a few comments on depressionblog.com that mentioned a link between Zoloft and rage fits. A Salon.com article published a story antidepressants inducing rage in 1999. Apparently, Brynn Hartman, the wife of famous comedian Phil Hartman, killed herself and her husband while taking Zoloft. While close friends attribute the sudden behavior on the antidepressant, others attribute it to a combination of the medication with cocaine and alcohol in her system. (Zoloft does have a warning against alcohol use in conjunction with the drug.)

One interesting thing I learned from the article is that this kind of behavior is often labeled under the name akathisia on patient safety guides. Most – if not all – of the major antidepressants list akathisia as a side effect. Here’s the initial description of this condition from Wikipedia:

Akathisia, or acathisia, is an unpleasant subjective sensation of “inner” restlessness that manifests itself with an inability to sit still or remain motionless… Its most common cause is as a side effect of medications, mainly neuroleptic antipsychotics especially the phenothiazines (such as perphenazine and chlorpromazine), thioxanthenes (such as flupenthixol and zuclopenthixol) and butyrophenones (such as haloperidol (Haldol)), and rarely, antidepressants.

Akathisia may range in intensity from a mild sense of disquiet or anxiety (which may be easily overlooked) to a total inability to sit still, accompanied by overwhelming anxiety, malaise, and severe dysphoria (manifesting as an almost indescribable sense of terror and doom).

No real mention of extreme anger or irritability mentioned there. But if you read on…

The 2006 U.K. study by Healy, Herxheimer, and Menkes observed that akathisia is often miscoded in antidepressant clinical trials as “agitation, emotional lability, and hyperkinesis (overactivity)”. The study further points out that misdiagnosis of akathisia as simple motor restlessness occurs, but that this is more properly classed as dyskinesia. Healy, et. al., further show links between antidepressant-induced akathisia and violence, including suicide, as akathisia can “exacerbate psychopathology.” The study goes on to state that there is extensive clinical evidence correlating akathisia with SSRI use, showing that approximately ten times as many patients on SSRIs as those on placebos showed symptoms severe enough to drop out of a trial (5.0% compared to 0.5%).

Loose Screws Mental Health News

"Can an antipsychotic drug from the 1950s be paired with a 1980s antibiotic to shrink 21st-century tumors?"

That's the first line from the NYT's recent article on biotech companies mixing two unrelated generic drugs to treat medical problems. Alexis Borisy, the executive of CombinatoRx, is spearheading the movement to mix and match two different generic drugs in the hopes that the combo will cure or effectively treat a disease that may be unrelated to the drugs' initial purposes.

"Orexigen, in creating its obesity drug Contrave, took a treatment used for drug and alcohol addiction and combined it with an antidepressant sometimes used to help people quit smoking." (My guess is that the antid was Zyban.)

It's a nice concept, but I'd hate to see risk of side effects doubled. One med can be a doozy; coupled with another could turn out to be problematic.

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More from the NYT: Pharmaceutical companies pay psychiatrists (to push their products) more than doctors in any other specialty.

"For instance, the more psychiatrists have earned from drug makers, the more they have prescribed a new class of powerful medicines known as atypical antipsychotics to children, for whom the drugs are especially risky and mostly unapproved."

The bipolar child paradigm.

Vermont officials disclosed Tuesday that drug company payments to psychiatrists in the state more than doubled last year, to an average of $45,692 each from $20,835 in 2005. Antipsychotic medicines are among the largest expenses for the state’s Medicaid program.

Over all last year, drug makers spent $2.25 million on marketing payments, fees and travel expenses to Vermont doctors, hospitals and universities, a 2.3 percent increase over the prior year, the state said.

The number most likely represents a small fraction of drug makers’ total marketing expenditures to doctors since it does not include the costs of free drug samples or the salaries of sales representatives and their staff members. According to their income statements, drug makers generally spend twice as much to market drugs as they do to research them.

Doesn't the last sentence make you feel all warm and fuzzy inside? It's great to know that getting people to use drugs are more important to these companies than making sure these drugs are safe to use. Yeah, yeah, I know, it's a company and companies are only out to make profits. Whatever kind of optimist is in me wants to believe that maybe there's one doctor out there who is more motivated by helping others than by pharma-backing money. But I'm only a slight optimist.

Take two pills and call me if there's a birth defect

A recent article in the NYT reported that two studies released in The New England Journal of Medicine claim that an antidepressant could potentially increase the risk of a baby being born with a birth defect, but, uh,  it's unlikely and "confined to a few rare defects."

Benedict Carey, author of the article, points out that the studies didn't have a good sampling to really prove that assertion:

"In both studies, researchers interviewed mothers of more than 9,500 infants with birth defects, including cleft palate and heart valve problems. They found that mothers who remember being on antidepressants like Zoloft, Paxil, or Prozac while pregnant were at no higher risk for most defects than a control group of women who said they had not taken antidepressants."

So what's it's sounding like for me is that researchers got a group of expecting moms together, basically said, "Hey, have you taken an antidepressant?" and the ones who said yes were placed in one control group and the ones who said no were placed in another. How reliable.

Having been part of a clinical trial for bipolar disorder, I know it's likely these women got paid for their participation in this study. (Most people do, from what I understand.) So some could essentially have lied in the hopes they could snag $100. It doesn't sound like these women agreed to have their past medical history released to researchers that could prove they've been on antidepressant medication, they could have just been like:

"Uh, yeah. I took the antidepressant with the happy little egg sad face thingy."

Doctor: "Zoloft?"

"Yeah, yeah! That one. It maketed me alllll better."

Remember – it's mothers who "remembered" being on antidepressants while pregnant, not medical histories that proved that they've at least been prescribed the medication.

One doctor, not involved in the research, had reservations about the so-called findings:

"These are important papers, but they don't close the questions of whether there are major effects" of these drugs on developing babies, said Dr. Timothy Oberlander, a developmental pediatrician at the University of British Columbia, who was not involved in the studies.

Despite the seemingly positive outcomes that "support doctors' assurances that antidepressants are not a major cause of serious physical problems in newborns," both studies uncovered some pretty serious – but considered rare – conditions.

"One of the studies, led by Carol Louik of Boston University and financed in part by the drug makers GlaxoSmithKline and Sanofi-Aventis, found that use of Paxil was associated with an increased risk of a rare heart defect, which the company had previously reported.

The other study, led by Sura Alwan of the University of British Columbia, found that use of antidepressants increased the risk of craniosynostosis, a condition in which the bones in the skull fuse prematurely. Rare gastric and neural tube defects may also be more common in babies exposed to the medication, the studies suggested."

But don't worry, pregnant moms – the risks are low, "appear remote, and confined to a few rare defects." So, hey, even if your baby DID develop a rare defect, at least it's rare! [sarcasm]

I'd take the chance of depression if it meant my baby had a better chance of being born healthy. I'm lucky – I couldn't take Lamictal if I got pregnant. I wish antidepressants would have the same instruction.

YouTube vs. Big Pharma: Round 1

We seem to have a lot of contenders today. Kevin M.D. has a post (linking to PharmaGossip which links to Advertising Age) about the video "exposés" on pharmaceutical companies that have been popping up.

GlaxoSmithKline now has its own one minute, 43-second video on YouTube for Restless Legs Syndrome. Ms. Wetzel said she believes more drug companies and ad agencies will adopt such an approach. "The conversation about health care goes on," she said, "and we're going to have to deal with it."

My job blocks YouTube so I can't see the video, let alone link to the one I'd like to reference, but the other day, I saw (at least) a minute-long TV ad for Celebrex, but oh man, was it awful. See the craptasticness of it at celebrex.com. While I'm all for pharmaceutical companies being upfront and honest about their products, from a marketing standpoint, this commercial is an unbelievable disappointment. (Who agreed to this?) It's one of the most boring commercials I've ever seen and goes on and on for – oh say, a minute – about all the side effects of Celebrex before getting to the positive aspects about the drug. Has the FDA changed the rules on advertising NSAIDS that I'm not aware of? Here's your sampling:

"Lately, there has been some confusion about arthritis pain treatments. It is important to know that there are risks with all pain medicines, including the 3 most common NSAIDs: CELEBREX, naproxen, and ibuprofen. In fact,the FDA requires all these NSAID pain relievers, including CELEBREX, to have the same cardiovascular warning. Understanding the risks and benefits of different NSAIDs is important. All NSAIDs, including CELEBREX, help relieve arthritis pain, but only you and your doctor can decide which one is right for you. An NSAID like CELEBREX might be an option."

* I just timed it: It was 2½ minutes long.