Another Pharma Trick for Overstating the Effectiveness of their Drugs: The Will Rogers Phenomenon

Will Rogers

Big Pharma has a number of ways, many of which have been described in this blog, of making their drugs look a lot better than they actually are. And some psychotherapy researchers use the techniques to push their favored school of thought. I recently came across another one of which I wasn’t aware. 

It is easiest to see with drugs used for cancer chemotherapy, but can be applied in other cases.

It is called the Will Rogers phenomenon (and is also called Stage Migration). It is an apparent epidemiological paradox. The Rogers reference comes from a remark made by the famed humorist Will Rogers about migration during the American economic depression of the 1930's: "When the Okies left Oklahoma and moved to California, they raised the average intelligence level in both states."

With cancer drugs, it comes from changes over time in the way the severity of the disease is assigned to patients - how the various stages of a disease are determined in each case. (Stage I is when the cancer is smallest, has not spread, and is usually the most easily treated. Stage IV is the most advanced with metastases). The issue comes about because the technology for staging a cancer in a given patient has improved significantly. This can produce spurious improvements in stage-specific prognosis, even though the outcome of individual patients has not changed.

New imaging tools have allowed detection of cancer metastases before they became evident clinically. As a result, more patients are classified into the more severe metastatic disease stage from the less severe single tumor stage. Such a 'stage migration' resulted in an improved survival of patients in both the less and the more severe disease stages. (Multiple sclerosis is another disease where this sort of thing has taken place).

Some studies compare a new treatment to the treatment of so-called historical controls who had received other treatments. This is usually done because carrying out placebo-controlled studies in potentially dying patients is unethical. The Will Rogers phenomenon is recognized as one of the most important biases limiting the use of historical controls groups in experimental treatment trials. 

Essentially, the use of different diagnostic criteria may generate spurious improvements in the medium-term prognosis which then may be wrongly interpreted as treatment effects.

In psychiatry and psychology, placebo controlled studies can be done ethically, but a variation of the Will Rogers phenomenon can still take place because of how rigorously DSM diagnostic processes are applied to patients. When I first started training, the criteria for major depression and mania were rigorously applied in treatment studies; now they are often applied sloppily – on purpose. 

Chronic unhappiness, which may respond very well to cognitive behavioral psychotherapy, is often now misdiagnosed as the more serious major depressive disorder. If you have a bunch of those folks in your psychotherapy outcome study, CBT can be “shown” to be effective in major depression by including people in your study who really don’t have major depression.

The more serious depressions respond better to antidepressant medications. Since most antidepressants are now generic, drug companies who want doctors to use other, more profitable drugs like Latuda can do the same thing to “show” that antidepressants are actually less effective than they actually are. Placebo response rates in antidepressant studies have gone up about 10% every decade, and this is what I believe to be the reason.

For Big Pharma, Charity Begins at Home - and at Taxpayer Expense

Martin Shkreli

According to an article in the British Medical Journal, from 2011 to 2014 drug companies have increased the prices of four of the top 10 drugs sold in the United States by more than 100%, and the prices of the remaining six by more than 50%. 

Most people are familiar with the story of Martin Shkreli, former chief executive of Turing Pharmaceuticals. In August 2015, he purchased a generic drug called Daraprim that treats toxoplasmosis—a life-threatening parasitic infection that many AIDS patients contract—and immediately raised its price by more than 5,000 percent. He has not been alone. The price of many generic as well as brand-named drugs has skyrocketed. In psychiatry, an old antidepressant named Parnate, available since the early 1960's, can cost over $250 per month. It probably ought to be one of those five dollar generics.

What a lot of people may not know is that these price increases are part of what seems to be a scam to bleed tax dollars from Medicare. According to a recent article in Bloomberg News, within days of increasing the cost of Darapin, Turing contacted Patient Services Inc., or PSI - a charity that helps people pay for the insurance copayments on costly drugs. Turing wanted PSI to create a fund for patients who had the AIDS complication that could be treated with Daraprim.

PSI, as it turns out, is one of seven patient-assistance charitable organizations commonly known as a copay charities. There are also many smaller ones. They offer assistance to some of the 40 million Americans covered through the government-funded Medicare Part D drug program.

Having just made Daraprim much more costly, Turing was now seemingly offering to make it more affordable. But that is hardly the whole story. It is also a story about how U.S. taxpayers support a billion-dollar system in which charitable giving is, in effect, a very profitable form of investment for drug companies—one that may also be tax-deductible!

Drug companies know that, all other things being equal, the more expensive they make a drug, the fewer people will purchase it. However, if insurance pays for the drug, then this is is no longer much of an issue. The kicker is that when the Part D Medicare drug law was passed, it included a provision that Medicare, with its leverage on negotiating drug prices created by the size of its insured population, cannot bargain with drug companies for lower prices. If the insurance company uses a "charity" which covers patient co-pays and the so-called donut hole, patients will fill their prescriptions and taxpayers end up paying the huge price increases.

As the Bloomberg article points out, "A million-dollar contribution from a pharmaceutical company to a copay charity can keep hundreds of patients from abandoning a newly pricey drug, enabling the donor to collect many millions from Medicare. The contributions also provide public-relations cover for drug companies when they face criticism for price hikes."

The article added, "Fueled almost entirely by drugmakers’ contributions, the seven biggest copay charities, which cover scores of diseases, had combined contributions of $1.1 billion in 2014. That is more than twice the figure in 2010, mirroring the surge in drug prices. For that $1 billion in aid, drug companies get many billions back.

According to a recent article in USA Today, charity-run funds are now facing new scrutiny by prosecutors in two states and by The Department of Health and Human Services' office of the inspector general. But the focus is only on whether or not co-pay charities favor donor companies' drugs over those sold by other companies. No one is challenging the whole scheme.

Those who are concerned that the government spends too much money and that the national debt is too large should ask themselves why politicians prohibited Medicare from negotiating volume discounts with Pharma companies, thusly creating these lucrative opportunities for them at taxpayer expense.

Latuda and Bipolar Depression

Have you seen them? The brand new, direct to consumer (DTC), ads touting the drug Latuda for bipolar depression? The drug company just received the indication for this purpose from the FDA a very short time ago, but the drug company, Sunovion Pharmaceuticals Inc., was ready to roll.

Latuda is a dopamine blocking drug, which makes it an antipsychotic medication and not an antidepressant.  We have known since the 1950’s that all antipsychotic medications have some effectiveness in bipolar disorder, although primarily for the prevention of the manic phase of the illness. We have known that they also may augment an antidepressant for those who only get a partial response to the antidepressant in both unipolar and bipolar depression. A colleague of mine routinely used the antipsychotic Navane to augment the old tricyclic antidepressants in the 1970's.

Only two other antipsychotic medications have official FDA indications for bipolar depression, probably because the other drug companies did not spend the money to get it.  If doctors know one member of a class works, they’ll know that the others probably will too, so why bother?  One of these two drugs that has the bipolar indication is actually a combination drug containing an antipsychotic medication (Olanzepine [Zyprexa]) AND the antidepressant Prozac. The other is Quetiapine [Seroquel].

The main problem with using an antipsychotic instead of an antidepressant in this condition – aside from the unequivocal fact that antidepressants are way more effective – is that antipsychotics have much more potential toxicity. Latuda is probably one of the safer ones in this regard, having a low incidence of the two biggest concerns, metabolic syndrome (weight gain, higher cholesterol, diabetes - horrible and very common problems with Zyprexa and Seroquel) and the long-term neurological side effect, tardive dyskinesia.  Interestingly, the FDA won’t let Sunovion make that claim despite the fact that it’s true!  Go figure.

Almost simultaneously with the start of Latuda's DTC ad campaign, two research studies of the drug’s use in bipolar depression were published in the February 2014 issue of the flagship psychiatry journal, the American Journal of Psychiatry (AJP). The studies showed that the drug was effective by itself for the disorder, and also effective as an adjunct treatment when combined with either of the two major anti-manic drugs, lithium and valproate.  Weirdly, the  “effect size” of the improvement in patients, a measure of how much better patients got, was less (0.34) with combination therapy than it was in the case of the drug by itself (0.51). Both of these effect sizes are moderate at best, btw.

That difference is particularly odd in the case of valproate, since there is zero evidence that it is effective for the depressed stage of bipolar disorder (lithium sometimes is, but not usually). Does valproate somehow make Latuda less effective than it would be otherwise?

There is a big issue here:  the question of whether antidepressants alone are the better choice for treatment of bipolar depression.

The last author of the first AJP Latuda  study is Gary Sachs, someone I have discussed previously in this blog [ 10/31/11].  He is the author of a major study that claimed to show that antidepressants were completely ineffective – worse than placebo – in the treatment of the depressed phase of bipolar disorder.  

He conveniently neglected to point out in the earlier paper that the sample of patients he used in this study had already proved to be resistant to antidepressant medication in the first place, and continued to dissemble about this omission when I had the opportunity to confront him about it. Some subjects of his had even failed a trial of a combined antidepressant and antipsychotic. The conclusion of the study as presented in the study was bogus as hell.

A defender of Dr. Sachs made this point: Dr Sachs and colleagues in the abstract did not say that they had proven that antidepressants were ineffective in bipolar depression. They reported their finding and immediately called for additional long-term well designed studies - what I have called plausible deniability.

The more recent Latuda article which Sachs co-authored did in fact state the following: “There is limited evidence of the use of standard antidepressants for the treatment of bipolar depression.”  I guess that isn’t exactly the same as saying they don’t work, is it?  Might as well be, though! It's not what you say, it's what people hear.

Furthermore, I learned from the article that Dr. Sachs is a paid consultant for Sunovion pharmaceuticals!  

The article’s reference for the statement about antidepressants not being effective was one study that was a meta-analysis of existing studies of antidepressants in bipolar depression (a study which combines the statistics from several other studies). In an editorial in the same AJP issue publishing the Latuda studies, one R.H. Belmaker restates the opinion that “the evidence that antidepressants can be useful seems less and less convincing.”  

His reference for this statement? It is an editorial he himself wrote in the same journal as the original bogus Sachs article appeared [New England Journal of Medicine 356 (17), 4/26/07 (NEJM)]!  I went and got a copy of it.  These folks seem to all run in the same circles, as well as in the same circular reasoning.

In that editorial, he mentions the same meta-analysis that was mentioned in the AJP Sachs article.  But he also mentions that there are two other meta-analytic studies, both totally ignored in the AJP Latuda articles, that showed that antidepressants could be “highly beneficial” in bipolar depression.

There is fairly subtle obfuscation of the evidence going on here, since the other two meta-analyses never seem to be mentioned in articles touting antipsychotics for bipolar depression any more.  I wonder why that is?

In Belmaker’s original NEJM editorial, he opines that maybe the condition is heterogeneous and that subjects in studies outside of the United States may be different than they are here. The two positive metastudies were by authors from outside the USA.

Aside from the fact that there is absolutely no clinical evidence for that whatsoever, Belmaker neglects to mention that at least one of the two meta-analyses showing that antidepressants were effective did not limit itself to studies done overseas, but included studies done in the States! (I could not get a hold of the second, but this is probably also true of that one as well).

Of course, the issue of antidepressants causing bipolar patients to switch into mania is also brought up again and again ad nauseum all over the place, even though everyone agrees – even the original Sachs article in NEJM - that the anti-manic drugs like lithium and divalproate prevent this.  Since true bipolar patients should be on one of those drugs to begin with, this is a superfluous issue.

I also have my doubts that all of the subjects in the Latuda studies were even diagnosed correctly, since one of the diagnostic tools used was the Bipolarity Index, which includes the items, “Episodes with characteristic symptoms of hypomania, but symptoms, duration or intensity are subthreshold for hypomania or cyclothymia” and “baseline hyperthymic personality when not manic or depressed. " 

For a discussion of the significance of that nonsense, see my posts about treatment resistant depression and bipolar disease mongering.

These folks are doing nothing but trying to sell expensive and potentially toxic drugs to both doctors and the public when more effective and safer alternatives already exist.

The American Psychiatric Association: the Good, the Bad, and the Ugly

On his blog Real Psychiatry, psychiatrist George Dawson, put up a post that was highly critical of the American Psychiatric Association (APA) and its current president, Jeffrey Lieberman. He accused the organization of catering to managed care mismanagement of psychiatric benefits with its focus on collaborative care models. The organization has also been criticized for being in bed with Pharma, although it has taken steps to reduce its dependence of Pharma money. Surprisingly, at long last they even eliminated the very popular Industry-Sponsored Symposia at the Annual Meeting, in which drug companies used free food to attract large audiences to highly biased “educational” presentations by their own hired “experts.”

George Dawson, M.D

I agree with a lot of the criticism. I am particularly annoyed by the way the APA gives lip service to so-called scope of practice issues - which really boil down to whether insurance companies will ever pay psychiatrists (who are physicians first) to do more than write prescriptions - while continuing to basically ignore the issue of psychotherapy disappearing from the practice of psychiatrists all across the United States. The fact that psychiatrists are not taking complete histories any more, which leads to frequent bogus diagnoses and the unnecessary and potentially toxic medicating of children and adults alike, also gets little attention.

This situation leads to the question of whether ethical psychiatrists should boycott the APA. I say no, because I think we need to have more good psychiatrists active in the organization. On Dawson’s blog, I got into the following discussion about this issue in the comment session with psychiatrist James O’Brien:

ME: I wonder if there is any way like-minded people can get together with us to better sound the alarm about this travesty of psychiatric "care." Blogs are easy to ignore.

James O’Brien: This was an excellent article. In response to Dr. Allen's question, the answer is for turkeys to stop paying dues to the American Thanksgiving Association.

ME: If that would make the APA change it's policies or even go away, I'd agree. But since they are probably here to stay, we need people on the inside to at least try to keep its negative tendencies in check.

James O’Brien: Dr. Allen, I wish that were a possibility, but the APA is dominated by academics on salary who love theory over reality and don't understand or are indifferent (or even hostile) to the economics of private practice. Paying dues to APA and AMA is selling them the rope to hang us with. 85% of doctors realize this about AMA but for some reason, many private practice psychiatrists have trouble dumping APA even though they should be horrified by Lieberman's comments. And BTW, if you enjoy APA CME activities, you can still attend at a higher cost. Frankly, I think they are pretty basic and you can do better if you shop around. Lieberman is doing more damage to psychiatry than Scientology can dream of doing.

ME: Maybe so, but what's the alternative? A small chance of having an impact is still better than no chance at all.

James O’Brien: You have more chance of getting them to pay attention by hurting them in the pocketbook than changing their minds through dialogue. All APA Presidents in recent years are cut from the same cloth. I don't see why APA has to be a monopoly. Psychologists who were sick of their APA formed the Association for Psychological Science which is a superior organization.

ME: Well, we did have Harold Eist a few years ago. Granted, no one like him since. I just don't think there's enough of us to hurt the APA in the pocketbook, frankly. I wish we had an effective alternative to the APA, but right now there isn't one. As to the psychologists, CBT'ers who grossly exaggerate their evidence base, ignore human relationships, and deny funding to other types of psychotherapy outcome studies still dominate clinical psychology, so I don't know how much good that other organization is really doing. I'm certainly open to anyone with new ideas about how to better get the word out.  

At least at the APA annual meeting, opposing voices do have a forum. Mark Zimmerman presented on the evils of symptom checklists and about patients with borderline personality disorder being misdiagnosed as Bipolar. My colleague from Australia, Peter Parry, presents the other side on pediatric bipolar disorder. I presented on the neglect of social psychology by the field. And folks like us get up and challenge nonsense with questions after stupid presentations. We need more people like us at the meetings, not fewer.

The APA is certainly a mixed lot these days. There’s something for everyone to criticize, especially with Lieberman. On one of my issues, time spent with patients, Lieberman was recently quoted in Psychiatric News, the APA’s newspaper for members: “The psychiatrist of the future will likely have less regular face-to-face time with patients (like our colleagues in other medical specialties)…We will have to do more with less.”

Oh, so short changing and mismanagement of patients is something we just have to accept, perhaps because there’s not enough of us to go around? That is outrageous. As I have said before, accepting such a managed care perspective is just like a cardiac surgeon agreeing to only do single bypass surgery on all patients even when triple bypass surgery is called for. 

If there’s a doctor shortage, let’s do something about that. There has not been an increase in post-doctoral residency training slots since the mid nineties. Society doesn’t want to pay for more? Too bad for them. Not our fault. The answer to the doctor shortage is not to short-change the patients we do see.

Then there is the matter of the skyrocketing number of bogus diagnoses of ADHD and treatment with stimulants in both children and adults, a frequent topic on this blog.  As reported by a recent article in the New York Times:

‘Could you have A.D.H.D.?’ beckons one quiz, sponsored by Shire, on the website everydayhealth.com. Six questions ask how often someone has trouble in matters like “getting things in order,” “remembering appointments” or “getting started” on projects. A user who splits answers evenly between “rarely” and “sometimes” receives the result “A.D.H.D. Possible.” Five answers of “sometimes” and one “often” tell the user, “A.D.H.D. May Be Likely.” In a nationwide telephone poll conducted by The Times in early December, 1,106 adults took the quiz. Almost half scored in the range that would have told them A.D.H.D. may be possible or likely.

These are the questions:

1.     How often do you have trouble wrapping up details on a project, once the challenging parts have been done?

2.     How often do you have difficulties getting things in order when you have to do a task that requires organization?

3.     How often do you have trouble remembering appointments or obligations?

4.     When you have a task that requires a lot of thought, how often do you avoid or delay getting started?

5.     How often do you fidget or squirm with your hands or feet when you have to sit down for a long time.

6.     How often do you feel overly active and compelled to do things, like you were driven by a motor?

As I discussed in my last post, The APA’s own Psychiatric News e-mail alert reported, “The authors speculate that “better detection of underlying ADHD, due to increased health education and awareness efforts,” may be the reason for the increase of ADHD diagnoses among American children.” The more likely explanation - that acting out kids and adult are being saddled with diagnoses made without any evaluation of psychosocial problems - was not mentioned at all.

Still, there are forces in the organization that seem to be paying more attention to things, so good doctors resigning from the organization is counterproductive. The APA has started paying attention to another horrific managed care problem – the response of the industry to the so-called “parity law” passed by the US Congress, which stipulates that insurers must cover mental disorders the same as they cover physical disorders (however bad that coverage is, unfortunately). 

Even Lieberman was alarmed. He was quoted thusly in the 8/16/13 issue of Psychiatric News: “Despite passage of the 2008 legislation, many insurance companies have manipulated its intent and purpose through vague medical necessity standards, lengthy approval processes, bureaucratic delays in service requests, and complicated appeals progress.”  

They have also ratched down fees paid by psychiatrists, leading to many of them resigning from some of their provider panels, so the patient is “covered” but cannot find a doctor!

In terms of so-called medical necessity (whether the insurance company will deem a given service as reimbursable), the insurance companies often would not tell doctors – or its customers for that matter – what standards the company was using to make a decision about that. They called it a “trade secret!”

The APA lobbied the federal government hard to stop these unfair practices with some success, resulting in the recently released final rule regarding implementation of the parity law. Insurance companies at least now have to disclose their standards for determining “medical necessity.” Of course, insurance companies will continue to be ingenious at finding ways to deny care.

So maybe there’s hope for the APA yet. Psychiatrists no longer have the luxury of being politically inactive and letting the APA continue to wander in the proverbial wilderness. Any concerned psychiatrists need to join the organization and let their voices be heard.

Pharma Still Up to its Old Tricks

It looks as though big Pharma is still up to one of its most disturbing practices: not publishing or making public studies that show that its products might be ineffective. As described by my colleague Peter Parry later in this post, we had thought this problem was successfully addressed back in 2010.  

Apparently not.

And do not think this problem is unique to psychiatric medications. 

Of course, as I have pointed out several times in this blog, recruitment and assessment of subjects for many research studies these days has become so warped by financial incentives that many of the studies, published or not, are not worth the paper they are printed on to begin with. 

And some studies are purposely designed to mislead readers into believing that certain generic drugs, particularly antidepressants, are not effective when in fact, when used properly for the right patients, they are among the most effective drugs in all of medicine. But that's a 'hole 'nuther issue.

To get back to the issue at hand:

From Medscape, 10/29/13: 

An analysis of nearly 600 registered clinical trials published online October 29 in BMJ has shown that 29% remained unpublished 5 years after completion, that no results were available in ClinicalTrials.gov for three fourths of those unpublished trials, and that industry-funded trials were nearly twice as likely to go unreported as studies that had not received industry funding.

Previous studies have shown that published trials contain less than half of the patient-outcomes data contained in company-controlled documents.

Dr. Jones and colleagues from the University of North Carolina, Chapel Hill, conducted a cross-sectional analysis of trials that had at least 500 participants and had been prospectively registered with Clinical Trials.gov and completed before January 2009. 

Their analysis included 585 registered trials, 171 of which (29%) remained unpublished. These unpublished studies included nearly 300,000 participants.

"By focusing our investigation on studies with at least 500 participants, we greatly limited the possibility that non-publication of trials in this cohort was due to rejection of manuscripts by journals or a lack of time or interest on the part of investigators or sponsors," the authors write.

The non-publication rate was 32% for industry-funded trials and 18% for those without industry funding (P = .003), and 78% of the unpublished trials also had no reported data in ClinicalTrials.gov.

From Peter Parry (on the webpage TheConversation.Edu.Au):

Dr. Peter Parry

A large proportion of drug trials, particularly those sponsored by pharmaceutical companies, never get published, skewing our picture of drugs' effectiveness and safety.

Research published in 2010 showed results unfavorable to sponsored drugs are less likely to be published, or selectively published to put a favorable spin on poor results.  And internal pharmaceutical industry documents released from court cases show concealment of data is a widespread practice.

A colleague and I assessed such documents about psychiatric medications from five pharmaceutical companies. The papers suggested widespread overstatement of benefits and understatement of adverse effects. Other researchers have found similar problems with different drugs.

In response, some medical journals voluntarily agreed to publish only studies registered on a website of the US National Institutes of Health, ClinicalTrials.gov. At least studies with unfavorable results would not be buried by drug companies. But the BMJ article confirms that many registered studies still don’t get published.

The AllTrials initiative aims to make the (de-identified) results and methodology of drug trials available to independent researchers so journals can publish in-depth articles based on all of the full data.

In 11 months, the campaign’s petition has gathered over 59,000 individual signatories and over 400 medical and health-care organizations. These include many British medical colleges and learned academic medical science institutions, such as the Cochrane Collaboration and the British National Institute for Health and Clinical Excellence (NICE).

Although the campaign is progressing slower outside the United Kingdom, it is managing to get some traction internationally.

The World Association of Medical Editors (WAME), the South African Medical Research Council and the Canadian Agency for Drugs and Technology in Health have signed.

Maybe there is still hope this problem can be rectified.

Docs and Drug Reps

If you’ve been to a doctor’s office any time recently, you’ve probably seen them.  Nicely dressed in suits or pant suits.  Dragging their little bags that look like the carry-ons with wheels you see at airports.  Mostly nice looking and young, male or female. Patiently waiting for the office staff to call them to come in the back.

You don’t generally see what’s going on in the back with them, but these are the drug reps.  The detailers.  The pharmaceutical company salesmen.  They used to bring assorted gifts to the office like pens and other paraphernalia with drug logos on them, but now they mostly come bearing drug samples and lunch.  Due to a recent change in the law, doctors have to “report” any such favors into a database, but hardly anyone looks at it.

The drug reps are there to tell the docs about their latest products. They have to stick to the information approved by the Federal Drug Administration. The doctors certainly need to hear about the newest medications. So what’s the harm?

Well, potentially, plenty.  Most “new” drugs do pretty much the same thing as old established drugs.  Sometimes they have different side effects, some of which are better for the patient and some of which are in fact worse.  Being under patent, they are of course way more expensive than generic drugs which are often just as good or just as tolerable.

As readers of this blog know, the drug companies have been studying the psychology of doctors for decades, and have developed a lot of tricks and misleading tactics to increase sales of their brand named drugs. These techniques are quite powerful, and many doctors do not understand how they are being manipulated, sometimes to the significant detriment of their patients.

As a critic of these marketing techniques, I belong to a group called “Healthy Skepticism.”  Many members of this group argue that doctors should have NO contact at all with drug companies in any form whatsoever. They point to the fact that most doctors think they are not being unduly influenced, and yet believe that most of their colleagues are! The high sales of brand named drugs when generics are available prove, they go on, that no doctor is immune to pharmaceutical marketing tactics. So therefore drug reps are the enemy.

You think I would agree, but I do not. Just because a lot of doctors think they are not being influenced but actually are does not mean that some doctors believe they are not being unduly influenced, and in fact are not. Not everybody kids themselves. It is true that everyone is influenced by others to some degree. So by that reasoning doctors should avoid talking to members of Healthy Skepticism, because then they will be unfairly influenced against the drug companies.

How are we really going to understand misleading marketing techniques if we never personally witness them? How do we keep our eye on Pharma if we are averting our eyes?

Also, there’s that troublesome little fact that we live in a capitalist country, and if capitalists are properly regulated, that’s a good thing.  While I believe deceptive advertising should of course be stopped far more effectively than it has been, I nonetheless do believe in the company’s right to portray their products to physicians in the best light.

Also, when a new drug first comes out, the drug rep may actually be a good if not the only source of information - provided the doctor listens with a critical  ear.  

As Carolyn Rabinowitz, former president of the American Psychiatric Association, was quoted as saying in the September 20, 2013 issue of Psychiatric News, “Drug Companies perform a useful function, and they must make money or they won’t invest in our field." 

I do not blame the drug companies for misleading doctors as much as I blame the doctors for not knowing when they are being misled.

Adriane Fugh-Berman, M.D.

Sanita Sah and Adriane Fugh-Berman of Georgetown University, the leaders of industry watchdog Pharmed Out, recently pointed out in the same article that if doctors know and understand their marketing techniques, then they are in a fairly good position to see what they are doing and to not be taken in. 

Maybe I’m kidding myself, but I let the reps buy me lunch, and yet I still almost never prescribe brand-named psychiatric drugs unless a patient does not respond to, or is completely unable to tolerate, generic drugs in the same class. And so called “diagnostic inflation,” so that everyone seems to need a drug – well readers of this blog know how I feel about that.

For most of the time that I was the director of a psychiatric residency training program, the drug reps provided lunch for the residents at certain classes and for "journal club." The reps were allowed to give the residents a short sales pitch for one of their new drugs, and then they would leave leave the room. After the reps left, I  would critique what they said and point out any exaggerations or misleading information. That way, hopefully, these future psychiatrists would learn to be wary consumers of this type of information.

Now, the drug reps have been banned from providing lunch for the residents, so the residents no longer get this valuable training. When they graduate, they will be less able to resist a sales pitch, not more able. Bad idea.

The biggest psychological trick that drug reps use is taking advantage of our natural tendency towards reciprocity. You do something for me, and I feel obligated to do something for you. It’s not the pen or the pizza, it’s the relationship with the person who brings you those things.

Drug reps are hired more for their likeability and social skills than anything else. As the article states, “And flattery, whether it’s a pleasant conversation over the archetypal pizza or an invitation to speak at a prestigious meeting, gets them everywhere.”

Doctors need to learn this, but most have not. There oughta be a course in medical school about his. Forewarned is forearmed.

Antidepressant Medication and Bipolar Disorder: The Lies and Confusion Continue

The continuing stoow-ry of psychiatric research that has gone to the dogs

In my last book, How Dysfunctional Families Spur Mental Disorders, I discussed my theory that the drug companies of Big Pharma seem to go out of their way to demonize entire classes of drugs once they are mostly available as generics, so that practitioners will use their new brand named drugs instead - regardless of whether or not they are as effective or more dangerous. This happened with benzodiazepines, which now seem to be referred to absurdly as the most addictive and dangerous substances on the planet and full of "side effects" - which don’t actually occur in the real world in the vast, vast majority of patients who take them.

(BTW. demonizing generics does not just occur in psychiatry. One patient told me that a relative was given an anticoagulant that was more dangerous than generic Coumadin because, according to the doctor, “That’s what the drug companies want us to do”).

I wrote that I suspected that the same strategy is now being applied to antidepressants. Most of them have gone generic. (The ones that haven’t yet are Viibryd, Cymbalta, and Prestique.  Although no more effective that the generics, it amazes me how many doctors seem to use them as first line drugs). All of sudden we are being deluged by both news and journal articles questioning whether the drugs are effective. I have written in previous posts on this blog that placebo response rates for antidepressants have gone up significantly every decade, indicating that the patient population being used in the studies is changing. 

Specifically, so-called contract research organizations are being given financial incentives for finding patients that they can diagnose with major depression, and potential patients are given financial incentives for exaggerating their symptoms so they can get paid for being research subjects. So the studies are using patients that don’t really have the diagnosis they are supposedly being treated for. No wonder they have a high placebo response rate. This higher rate makes the advantage of the drug over placebo in these studies seem highly questionable.

A similar process is happening in doctors’ offices all over the country. Diagnostic interviews are getting sloppier and more slipshod all the time. A new study published by Psychotherapy and Psychosomatics, according to the June 2013 issue of the newspaper Clinical Psychiatric News, seems to be highly consistent with this idea. The authors ascertained whether patients who were identified by their doctors as depressed actually met DSM criteria for major depressive disorder. Results with 5639 participants showed that only 38.4% of these patients actually met the criteria!

This phenomenon has led to a couple of ironic developments. First, the rabidly anti-psychiatry zealots point to the bad studies as “proof” that psychiatric meds are a hoax, while of course completely ignoring all the earlier studies that show that antidepressants are highly effective. The more severe the depression, the more likely a patient is to respond to them.

Second, people both inside and outside of the psychiatric profession unfairly rail against the diagnostic manual, the DSM, for not having valid criteria, when the real problem is in many cases that many doctors are not applying the criteria to the patients in making "diagnoses!"

Then there is the matter of the use of antidepressants in the depressed phase of bipolar disorder.  Of course, as I have said many times, the duration and pervasiveness criteria for bipolar episodes, either manic or depressed, are more and more often ignored, which calls into question whether the diagnoses in studies are even correct.

Anyway, in my book I brought up a study by Sachs and others in the New England Journal of Medicine, the most prestigious journal in all of medicine, that purported to show that antidepressants work worse than placebo in this population. I showed how the authors of the study used a sample of patients that were especially treatment resistant, having already failed a trial of at least one previous antidepressant, but did not acknowledge this fact in the paper at all. I was even able to question the author through a third party, since my e-mails directly to Sachs were ignored, and he steadfastly refused to answer the question, “What percentage of your sample had failed a previous antidepressant?”

Now comes another bogus study that purports to show the same thing as the Sachs study. According to an article in Medscape on May 20, 2013, “Investigators at Brown University in Providence, Rhode Island, found there was no difference in hospital readmission rates among patients who received antidepressants and those who did not." Since the authors are strongly implying that the patients had to be readmitted because their antidepressant was not working, this is taken to mean that antidepressants don’t work in bipolar depression.

That antidepressants do not work in bipolar depression is a flat out lie. Psychiatrists like myself have been using antidepressants successfully in bipolar patients for thirty five years. Of course, true bipolar  patients need to be on a mood-stabilizer first, preferably lithium, so they don't switch from depression into mania.

So what’s wrong with this study? Well, just about everything. First of all, we do not know if these patients were correctly diagnosed for the reasons discussed above. Another huge problem: all over the country, hospitalized patients with borderline personality disorder are being misdiagnosed with bipolar disorder because of the “everything is bipolar" craze, coupled with the fact that insurance companies will often not pay for hospital stays if the patients are given the correct, "lesser" diagnosis! 

The subjects in this survey were undoubtedly a very mixed lot. The study did not address whether the patients even took their medication after they were discharged. Non-compliance rates for all medications are very high according to every available study that has looked at this issue. Also, we do not know what percentage of these patients may have fallen into the “treatment resistant” category described above. Most depressed patients are treated as outpatients, not inpatients, so the ones that are hospitalized have often failed a trial of outpatient medication.

Adding to this is the fact that antidepressants do not work for at least a couple of weeks, while managed care insurance companies will not pay for that length of stay. Therefore, patients on antidepressants are often discharged before the doctor knows whether a particular antidepressant even worked. Often patients do not respond to one antidepressant but do respond to a different one. 

Hence, discharge and re-hospitalization rates tell us pretty much nothing about the effectiveness of antidepressants in the depressed phase of bipolar disorder.

The International Society for Bipolar Disorders (ISBD) Task Force recently released its long-anticipated recommendations on antidepressant use in bipolar disorders. "The take-home message is that antidepressants have a questionable benefit-risk and should only be used in certain cases in bipolar disorder," said Dr. Eduard Vieta, who presented the recommendations on behalf of the ISBD Task Force, in an interview.

Eduard Vieta

"First, they shouldn't be used in mania or in mixed episodes, they should only be used in bipolar depression in patients with a history of a good response in the past to antidepressants and no history of rapid cycling or switches into mania right away," he said.

“Further, antidepressants should not be used in patients with bipolar disease with mixed features during a depressive episode or some manic symptoms during depression.” 

The recommendations said that antidepressants should not be used as monotherapy for bipolar depression, or in rapid cycling. 

I have a few reactions to this.  

1. Duh! We've known about the risks of using antidepressants alone in Bipolar I patients since the sixties. We've also known that they are perfectly safe and highly effective if a bipolar patient in a depressive episode is on an effective mood stabilizer, preferably Lithium.  

The way that the recommendation is made, however, is highly misleading. Antidepressants indeed should not be used as "monotherapy," but not because they are ineffective for depression. It may sound to some doctors that this is what is being said. The real reason is because patients need to be on a second drug to prevent switching into mania.

2. What are they defining as "rapid cycling?" A majority of patients who get this diagnosis nowadays are not bipolar at all, but have anxiety disorders, mixed anxiety and dysthymia, and/or personality disorders - otherwise known as 'crappy childhood syndrome." A lot of drugs can cause these folks more harm than good if improperly used!  Why single out antidepressants?

3.  How are we supposed to know if a patient will respond to an antidepressant in cases of patients who have never taken one, if we are not supposed to use them unless the patient already has a history of responding to them? That would be quite a trick! Additionally, a history of a switch into mania is not a contraindication for antidepressants unless this history took place when the patient had been adequately medicated with a mood stabilizer. If they switched when not taking one, that fact would be completely irrelevant. Even the Sachs study showed patients on a mood stabilizer don’t switch into mania with antidepressants.

4. As for so-called mixed episodes, they are in reality manic episodes, with the difference being that the patient feels really uncomfortable instead of the more typical euphoria. Since they are in a manic state and not a depressed one, of course antidepressants should not be used!