Tuesday, August 19, 2008

Investigative Journalism Par Excellence

I am a little late in reporting this story, but there is a must-read post from Jonathan Leo over at Chemical Imbalance that I must bring to your attention. Many bloggers have chimed in about the radio program The Infinite Mind broadcast about SSRIs. Most writers have focused, understandably, on the myriad unreported conflicts of interest of the guests on the show. But the conflicts of interest are not the most important part of this saga -- the terribly misleading information on the program, which aired on National Public Radio outlets, is the main problem.

Leo compares the data on SSRIs and suicide to the blatantly false statements made by the The Infinite Mind commentators. He notes, for example, that it is utter BS to state that nobody committed suicide in antidepressant trials submitted to the FDA -- in children there were no suicides, but among adults there certainly were. And kids who dropped out of the studies due to poor response or side effects, well, who knows what happened to them?

Leo also notes that the commentators were dead wrong about their alleged evidence linking decreased prescriptions of SSRIs to an increase in suicides. I also noted the same problem. He then proceeds to make point after point about the commentators overstating the efficacy of antidepressants.

As I've written before, conflicts of interest are important. But rather than just noting that people have conflicts, it is important to show the data -- are people with conflicts of interest misstating the evidence in a manner that reflects the conflict of interest? In the case of The Infinite Mind, the answer is a clear yes. Leo's post is quite lengthy, but well worth the time.

Update (08-31-08): My mistake. I had earlier called the program All in The Mind, which is vastly incorrect. The program was The Infinite Mind (as has been corrected above). This post has absolutely nothing to do with All in The Mind, which is a program which airs on Australia's Radio National. In fact, I've listened to a couple of All in the Mind broadcasts previously and found them to be well-done. Thanks to a commenter for catching my error.

5 comments:

Daniel Goldberg said...

CP,

I'll say to you the same thing I have said in conversation with Aubrey Blumsohn at his blog (and maybe here, too):

The issue with COIs is assuredly not that the existence of even severe COIs means that any particular piece of research is ipso facto invalid. Certainly, you can have high quality science even with serious COIs. Doucet and Sismondo's recent article even notes the general view that in terms of methodology, industry-funded studies actually rate quite highly.

Rather, the issue with COIs is that, over the long run of cases, the existence and extent of those COIs produces a much higher likelihood that any particular piece of research will be weak, invalid, or infirm in ways that favor the interests of the sponsoring entity.

Thus, it is true, but besides the point, to suggest in any particular case the COI is less important than the quality of the science. The point of the discourse regarding COIs is precisely that the quality of the research is overwhelmingly more likely over the duration to be weak, and weak in dangerous ways, as you point out so well on this blog.

This is not to say I disagree with either you or Leo's points: the validity of the claims adduced need to be addressed on the merits. But, like you, working in an academic medical center, I hear all too often the incredibly naive sentiment that COIs don't matter so long as the quality of the science is good. That's an unbelievably blind and simplistic way of thinking.

The COIs matter precisely because of the robust body of evidence we have showing that they are highly likely to weaken or invalidate conclusions drawn or interpretations of the available evidence.

--Daniel Goldberg
www.medhumanities.org

CL Psych said...

Hi Daniel,

One of my points is basically that incidents like these are evidence that people with conflicted interests can sometimes be way off in a direction that favors those with whom they have conflicted interests. Conflicts of interest are indeed an important part of the picture and it does us no good as a profession to have pretend that conflicts of interest do not have influence. I'm saying that conflicts of interest are one piece but that bad science is the bigger piece; I concur that there is much overlap between the two variables.

michael said...

I think the radio program you mean is "The Infinite Mind".

"All in the Mind" is the excellent program on Australian public broadcaster "Radio National". I doubt its critically minded and statistically literate host, Natasha Mitchell, would have let her guests get away with that kind of misrepresentation.

CL Psych said...

Michael,

You are correct. Mea culpa. I'll fix it now.

Thanks for pointing out my error.

Anonymous said...

Presently, for the treatment of depression and other mental disorders, some of these disorders are questionable regarding thier existence, the preferred choice of medicinal treatment are a class of medications called selective serotonin reuptake inhibitors, referred to as SSRIs, as they are the drugs of choice by most prescribers. Such meds, meds that affect the mind, are called psychotropic medications. SSRIs also include a few meds in this class with the addition of a norepinephrine uptake inhibitor added to the SSRI, and these are referred to SNRI medications. Examples of SNRIs are Effexor and Cymbalta. Presently, some compare the usage and popularity of these classes of meds as that of the usage of tranquilizers decades ago.

Some Definitions:

Serotonin is a neurotransmitter thought to be associated with mood. The hypothesis was first suggested in the mid 1960s that this neurotransmitter may play a role in moods and emotions in humans. Yet to this day, the serotonin correlation with such behavioral and mental conditions and diseases is only theoretical. In fact, the psychiatrist’s bible, which is called the DSM, states that the definite etiology of depression remains a mystery and is unknown. So a claim of a chemical imbalance in the brain as a reason for depression is not proven to be the cause of this and other mood disorders, it is only suspected based on limited science, which may or may not be valid. Observation by one's doctor is usually the determining factor for such a diagnosis.

Norepinephrine is a stress hormone, which many believe help those who have such mood disorders as depression. Perhaps this is now added to SSRIs for additional efficacy for those treated with these medications.

And depression is only one of those mood disorders, yet possibly the most devastating one. Once again, an accurate diagnosis of these mood conditions lack complete accuracy as they can only be defined conceptually, so the diagnosis is dependent on subjective criteria, such as questionnaires, as there is no diagnostic testing available to conclude objective diagnosis of such disorders. However, the diagnosis of depression in patients has increased quite a bit over the decades. While most likely a real disease, most will agree, misdiagnosis does occur due to the subjective assessment that determines the disease, as perhaps one out of every four people diagnosed with depression is inaccurate.

Several decades ago, less than 1 percent of the U.S. population were thought to have depression. Today, it is believed that about 10 percent of the population have depression at some time in their lives. Why this great increase in the growth in the assessment of this condition remains unknown and is subject to speculation. What is known is that the psychiatry specialty is the one specialty most paid to by certain pharmaceutical companies for various forms of support, as this industry clearly desires market growth of their psychotropic products, such as SSRIs, since clearly this is part of their nature and objective as a pharmaceutical company. Regardless, SSRIs and SRNIs are the preferred treatment methods if depression or other certain mood disorders that may be suspected by a doctor.

Over 30 million scripts of these types of meds are written annually, and the franchise is around 20 billion dollars a year, with some of the meds costing over 3 dollars per tablet. There are about ten different SSRI/SRNI meds available, many of which are now generic, yet essentially, they appear to be similar in regards to their efficacy and adverse events. The newest one, a SNRI called Pristiq, was approved this month and is expected to be promoted primarily for the treatment for menopause. Conversely, the first one of these SSRI meds was Prozac, which was available in 1988, and the drug was greatly praised for its ability to transform the lives of those who consumed this medication in the years that followed. Some termed Prozac, ‘the happy pill’. As years passed, this drug was preferred for children with depression. Also, a book was written praising Prozac as a euphoric entity for all to experience.

Furthermore, these meds have received additional indications for really questionable conditions, such as social phobia and premenstrual syndrome. With the latter, I find it hard to believe that a natural female experience can be considered a treatable disease. With social phobia, many would say that is a personality trait and, in my opinion, is synonomous with shyness, which probably should not be labeled a treatable disease as well. There are other indications for certain behavioral manifestations with the different SSRIs or SRNIs. So the market continues to grow with these meds- assisted by thier manufacturers. Yet, it is believed that these meds are effective in only about half of those who take them. Also, the makers of such meds create such conditions for utilization of these types of medications, in my opinion, and are active with related support groups who are funded by the makers of such drugs, such as sponsoring screenings for the indicated and not indicated conditions of their meds, including children and adolescents in particular, it is believed. Yet depression, which has clearly has been proven to be devastating to the victim, such screenings are controversial due to possible bias involved in seeking those with mental illness in this manner.

More concerning, however, is the adverse effects associated with SSRIs and SRNIs, which include suicidal thoughts and actions, as well as violence, including acts of homicide and aggression. The associations with these actions have been established with these types of meds. While most are approved for use in adults only, prescribing these meds to children and adolescents has drawn the most attention to others through the media. The reasons for this attention are the off-label use of these meds in this population, and the association with suicide. What may be most shocking is the fact that some of the makers of these meds did not release clinical study information about the risks of suicide as well as the other adverse events and true efficacy of certain types of SSRI meds, including the decreased efficacy of SSRIs, which is believed to be only less than 10 percent more effective than a placebo, until ultimately the makers of such drugs were forced to do so. Paxil, for example, caught the attention of the government regarding these issues some time ago for hiding and not presenting such important information to others, for example.

And there are very serious questions about the use of SSRIs in children and adolescents regarding the effects of these meds on them. For example, do the SSRIs correct or create brain states considered not within normal limits, which in effect may worsen thier mental state? Are adolescents depressed, or just experiencing what was once considered normal teenage angst? Do SSRIs have an effect on the brain development and their identity? Do adolescents in particular become dangerous or bizarre due to SSRIs interfering with the myelination occurring in their still developing brains? No one seems to know the correct answer to such questions, yet the danger associated with the use of SSRIs does in fact exist. It exists in some who take such meds, but not all who take these meds. Yet more need to be aware of such possibilities, some say.

Finally, if SSRIs are discontinued by those who have taken them for certain periods of time, withdrawals have been reported to be quite brutal, and may be a catalyst for suicide in itself, as not only are these meds habit- forming, but discontinuing these meds leaves the brain in a state of neurochemical instability, as the neurons are recalibrating upon discontinuation of the SSRI after being altered by the med to some degree. This occurs to some level with any psychotropic med, yet the withdrawals can reach a state of danger for the victim in some classes of meds such as the case with SSRIs.

SSRIs and SRNIs have been claimed by doctors and patients to be extremely beneficial for the patient’s well -being regarding the patient’s issues involved with thier mental illness suspected, such as depression, yet the risk factors associated with this class of medications may outweigh any perceived benefit for the patient taking such a drug, and this may want to be explored more by others. Considering the lack of efficacy that has been demonstrated objectively, along with the deadly adverse events with these meds only recently brought to the attention of others, other treatment options should probably be considered at the discretion of your prescriber.

“I use to care, but now I take a pill for that.” --- Author unknown

Dan Abshear

Author's note: What has been written has been based upon information and belief.