Wednesday, March 31, 2004

An Activist Pediatrician is Opportunistic, Too.

As a Wednesday Special, I am suspending my usual rule against posting ad hominem attacks.

Articles on the Washington Post website become inaccessible after two weeks. As it happens, the author also posted a complete copy of the article I am writing about, so you can see it here after the WaPo copy goes underground. The author, Dr. Lawrence Diller, is an activist pediatrician who has made a fortune selling books that are critical of his colleagues.

Keeping Doctors in the Dark

By Lawrence Diller
Wednesday, March 24, 2004; Page A21

The Food and Drug Administration issued an official warning this week on the increased risks of suicidal tendencies when taking antidepressants such as Prozac. The makers of Prozac and of nearly every other major antidepressant used in this country (Paxil, Zoloft, Wellbutrin, Effexor, Celexa, Lexipro) will have to include a new warning on the package label. This action is the culmination of more than 10 years of efforts to bring to light potential dangers of these medications.

The new warning alerts doctors and patients that in the first days and weeks of treatment, side effects such as agitation, panic, irritability, insomnia and severe restlessness may occur, contributing to an overall increase in the risk of suicide. More than a decade ago similar concerns over Prozac were beaten down in U.S. courts by an onslaught of "expert" testimony of industry-sponsored researchers and legal arrangements that gagged victims and their families with large monetary settlements.

[...] It seems that only the trial lawyers have a vested economic interest in following up on medications. That's a costly post-marketing surveillance system, both to the society that absorbs the legal costs and to the people hurt by a medication, before enough publicity or economic pain is felt by the manufacturer to change the label or withdraw the drug. Nearly 80 percent of respondents to a poll on my Web site said they'd pay at least a 1 percent surcharge on their medications to fund independent, systematic follow-up on pharmaceuticals.

The FDA decision to issue its warning on antidepressants is a vindication, albeit a much delayed "bitter pill" to the families that lost a child to suicide as a result of taking what might have been no better than placebo treatment. How many more children must die from other questionable drugs before our government takes the necessary actions to "heal" the sick regulation of the pharmaceutical industry?

Go ahead and read the whole thing, if you want, but there is not much point; you get the picture from the first two and last two paragraphs. Of greater interest is the comparison between Doc Diller's article and one recently published on Reason online.

Suicide Watch

Why is the FDA scaring people about antidepressants?

Jacob Sullum
March 26, 2004

The pediatrician Lawrence Diller, writing in The Washington Post, says the Food and Drug Administration has issued "an official warning...on the increased risks of suicidal tendencies when taking antidepressants such as Prozac." This is probably how most Americans interpreted the FDA's recent public health advisory covering 10 antidepressants.

Yet the FDA emphasizes it "has not concluded that these drugs cause worsening depression or suicide." Despite more than a decade of publicity about the alleged suicide-triggering properties of Prozac and its cousins, the FDA says, "a causal role for antidepressants in inducing such behaviors has not been established."

It is therefore hard to understand why the FDA is requiring that manufacturers of these drugs add a conspicuous suicide warning to their labels. The warning advises health care providers to "carefully monitor patients receiving antidepressants for possible worsening of depression or suicidality, especially at the beginning of therapy or when the dose either increases or decreases." It says "health providers should be aware that worsening of symptoms could be due to the underlying disease or might be the result of drug therapy."

The FDA defends the warning by arguing that it makes sense to keep an eye on depressed patients even if there's no truth to the claim that antidepressants make people kill themselves. "We think this is good advice whether the drugs did it or not," an FDA official told The New York Times, "If someone commits suicide, it doesn't really matter whether it's the drug or the underlying disease. In either case, you need to pay attention."

Putting aside the issue of whether people who feel happier after taking antidepressants are suffering from an "underlying disease," this rationale is rather strange. By the same logic, the FDA could require a warning that a heart drug might raise the risk of myocardial infarction not because there was good evidence that it did but because people with heart disease should be closely monitored.

[...] This distinction does not really follow from a concern about suicide. Severely depressed patients are especially likely to kill themselves, meaning that not only the benefits but also the risks (if any) of taking antidepressants are higher for them. Conversely, mildly depressed people may enjoy less dramatic benefits, but any suicide risk also would be lower. It seems the controversy over antidepressants and suicide has become a cover for other, unarticulated concerns about the appropriate use of chemicals to tweak one's mood and personality.

Mr. Sullum has a good point in the concluding sentence. Unfortunately, he does not provide any evidence to back up his allegation that the "controversy over antidepressants and suicide has become a cover for other, unarticulated concerns about the appropriate use of chemicals to tweak one's mood and personality."

It probably is not possible to prove such a claim. After all, who really can know the motivations of another person? As it happens, we do have some ancillary information that suggests Mr. Sullum is correct in his allegation. I would add another allegation: that Doc Diller is not only an activist, he is an opportunistic activist who is making a ton of money by ignoring the scientific principles of medical practice, pandering to a market of other anti-psychiatry activists and unwary parents.

I personally don't care if other anti-psychiatry activists waste their money on his books. But I do object to him feeding on the fears of parents and fanning the flames of litigation.

I hasten to add that I cannot prove that he is doing these things. This is my opinion. But there are some facts to support these allegations. I hasten to add also that Mr. Sullum is hardly beyond reproach. He is the author of Saying Yes: In Defense of Drug Use. So he has a financial pony in this race, too.

I suppose if there were ever any hope of me making money off this blog, I could face the same accusations. But I assume most of my readers know the chances of that.

Back to the point. What is the evidence that Doc Diller is trying to make a buck, in a way that is unscrupulous? I did not quote the entire Sullum article, but in it, he points out that the "FDA's decisions are not supposed to be based on anecdotes, which are emotionally compelling but scientifically unreliable." This is one of the most fundamental principles of medical science. The literature is full of case reports of one or two patients who exhibited some unexpected drug response. These reports are posted just in case some kind of pattern emerges. Then, someone can justify doing a formal study to prove the point.

For example, I recall seeing, about ten years ago, a report about two patients with schizophrenia who got better after being given Pepcid for gastroesophageal reflux. Pepcid is an H2 blocker that does not cross the blood-brain barrier very well. So it was not expected to have any effect on the brain, much less having a salutary effect on schizophrenia. Did anything ever come of it? No. Just two anecdotal reports that are lost in the dustbin of letters to the editor in some obscure journal.

Another example: The premarketing studies of the antidepressant Remeron included three cases of neutropenia (low white blood cell count). This was dutifully reported in the package insert. The statistical analysis indicated that it was as likely as not to be a fluke. Was it? Yes. After the drug had been given to millions of people, no additional cases emerged.

It is important to recognize that this kind of thing happens all the time. If you do 20 independent lab tests on a patient, there is a 50% chance that one of them will be abnormal, even if there is nothing wrong with the patient. Part of the practice of medicine is learning to suspend judgment, to not draw any conclusions, based upon isolated observations. Surely Doc Diller knows this. Yet, look at what he has posted on his website:

I've been a doctor for twenty-seven years and thought I was pretty accustomed to the sad and difficult stories I heard about kids in my practice of behavioral pediatrics. Still I wasn't prepared for the tales of devastation and woe as I listened to parents and children speak earlier this week at the Food and Drug Administration meeting on the adverse effects of the anti-depressant drugs on children.

This is ridiculous. I spent six months in training, in a children's hospital, and I'm sure he has a lot more experience in pediatrics than I do. He has had to tell parents that their kid has cancer, or cystic fibrosis, or any of a number of awful things, hundreds of times. He has seen all kinds of "devastation and woe". It is his job to be able to withstand that with complete æquanimitas. He goes on:

The problem facing the FDA, though, is that many of these extreme acts could have been the product of the disorders these drugs were meant to treat. Yet only two parents of about forty personal witnesses spoke of the value of the medications. They also happen to be representatives of the National Alliance for the Mentally Ill (NAMI) which has close ties to the psychiatric establishment and drug industry.

I personally know several members of NAMI. The ones I know are among the kindest, most altruistic people on this planet. Yes, they do get grants from pharmaceutical companies. Although I cannot speak for the two parents that Doc Diller saw at the meeting, the NAMI members I know are serious advocates for patients, usually because they have family members who are afflicted with mental illness. To cast doubt upon their credibility because NAMI accepts corporate contributions is irresponsible. NAMI has a high rating among charitable organizations, and they publish openly their financial resources. See their 2003 annual report (162 KB PDF) for details. Notice that many of their large donors are insurance companies. Insurance companies have an interest in keeping costs low, so they tend to have an agenda opposite that of the pharmaceutical companies. Other large contributors to NAMI are philanthropic organizations, and there are many individuals and estates that make contributions. If he means to imply that NAMI is a shill for Big Pharma, he needs to find some actual evidence.

Now look at some excerpts from his presentation to the President's Council on Bioethics:

Just again, like all psychiatric diagnoses, there are no biological or psychological tests for ADHD, and more interesting to me is looking at the use of stimulants in America, and in the wide variation which points -- you don't know how many people have ADHD for sure, but you can be much more certain of who is using Ritalin, and we will find out in a short time why.

No tests? This is a summary of tests accepted as evidence by Purdue University when a student requests accommodations on the basis of ADHD:

The basic diagnostic instrument is the clinical interview. Commonly several other diagnostic instruments are used to provide a broader foundation of information upon which to base a diagnosis and to identify the student's functional status. The following information is provided for the purpose of reference for professionals using other assessment instruments.

The common functional areas and the frequently used diagnostic instruments for each are:

Cognitive Functioning – provides a wealth of information on how the student copes with a variety of verbal and visual/spatial tasks. Using one instrument: Wechsler Adult Intelligence Scale-III (WAIS-III) all subtests (as appropriate); or Woodcock Johnson Tests of Cognitive Ability-III.
Alternating and Divided Attention – provides information about mental flexibility (the ability to shift focus) and the ability to simultaneously attend to multiple demands. Using at least two instruments: Wisconsin Card Sort; Attentional Capacity Test (ACT); Paced Auditory Serial Addition Test (PASAT); Trail Making Tests, Parts A and B; or Kagen Matching Familiar Figure Test (KMFFT)

Target Focused –provides information about sustained and selective attention over time. Using one instrument: Tests of Variable Attention (TOVA); Connors’ Continuous Performance Test (CPT); or Gordon Diagnostic System (GDS).

Executive Functioning– provides information about problem solving methods, frustration levels, restlessness, and distractibility. Using at least two instruments: Halstead – Reitan Category Test; Porteus Maze Test; Tower of London (sequencing and planning); Stroop Neurological Screening Test (SNST); Wisconsin Card Sort; Rey-Osterrieth Complex Figure Task; or Letter Cancellation Task.
Memory Functioning– provides information about long term and short term memory. Using one instrument. Wechsler Memory Scale- III (WMS-III); California Verbal Learning Test (CVLT); or the Verbal and Nonverbal Selective Reminding Tests.
Self and Other Reports – provides information about functioning from questionnaires. Using two instruments (one from a significant other [parent or sibling completing the checklists as it pertains to the student] and the other from the student): Wender Utah Rating Scale (WURS); Barkley Self-Rating Symptom Checklist for ADHD Adults; Copeland System Checklist for Adult Attention Deficit Disorders; Connors’ Adult ADHD Rating Scales (CAARS); or Brown ADD Scales (Adult).

It is true that there is no single test that is conclusively diagnostic of ADHD. A trained, experienced psychologist has to do a battery of tests, conduct an interview, etc., but to say there are no tests is just plain wrong.

How good of a grasp of science does Doc Diller have? See this excerpt from one of my earlier posts; this is also from the December 12, 2002 presentation to the PCBE:

[...]it is a special pleasure and privilege to welcome Dr. Lawrence Diller to the council this afternoon. In an area in which there have been zealots and radicals on all sides, this is a man who has occupied the sober middle voice of moderation, and of care, and of proper concern.

Dr. Diller has occupied the sober middle, a good place for someone talking about a controlled substance. The man in the sober middle has this to say about the mechanism of action of methylphenidate:

Now, a little bit on the drugs themselves. The way that these stimulants work, is that they block dopamine receptor sites, and therefore increase the neurotransmitter at the synapse, and tagged dopamine seems to show up more at the pre-frontal cortex and the local cerruleus [sic] in the brain.

Now, compare this with the following text from Psychiatric News September 21, 2001 Volume 36 Number 18 p. 18: (The Psychiatric News article is a summary of the findings reported originally in The Journal of Neuroscience, 2001, 21:RC121:1-5.)

[...]Although methylphenidate has been prescribed for nearly 50 years, its mechanisms of action have been understood only poorly. A central nervous system stimulant, the drug is believed to block both the dopamine and norepinephrine transporters responsible for clearing the neurotransmitters out of the synapse after a signal has been transmitted from one neuron to the next, in the same way that an SSRI blocks the reuptake of serotonin.

PET scan images, taken at the level ofthe striatum (left) and the cerebellum (right) of a radiotracerspecific to dopamine D2 receptors, show reduced binding of thetracer in the striatum after administration of 60 mg of oralmethylphenidate (bottom) compared with placebo (top).[...]

Notice two things: 1) The mechanism of action of methylphenidate involves blockade of the dopamine reuptake transporters, not the dopamine receptors, and 2) The increased dopamine shows up in the striatum, not the prefrontal cortex. (The dopamine displaces the radioactive tracer from the receptors, so the treated patients show less radioactivity where there is more dopamine released.)

Dr. Diller may be sober, he may not be a zealot or a radical, but in his work helping to refine science policy for the President of the United States, he made two factual errors in one sentence.

Turning to his WaPo Opinion article, the last sentence of his opening paragraph is: "This [FDA announcement] action is the culmination of more than 10 years of efforts to bring to light potential dangers of these medications."

When I was in medical school, I was taught that it is important to monitor patients for suicide risk shortly after starting an antidepressant. That would have been in the early- to mid- 1980's. None of the medications mentioned in the FDA announcement had even been put on the market yet. The fact is, the risk he is talking about is not news. It just isn't. The fact that the FDA has issued a warning is news, but it does not represent new scientific knowledge. There are two points about this: First, the FDA is a government organization that serves a regulatory function. It is not fundamentally a scientific institution. Second, the FDA issues warnings almost every day. For example, they issued 37 medication warnings in February 2004. (If you want, you can sign up for e-mail alerts of these warnings.) We cannot know for sure what motivated Doc Diller to write about this one particular warning, but looking at his website, it is apparent that he has a particular interest in bashing psychotropic medication.

Further on in his Opinion article, he states. "It seems that only the trial lawyers have a vested economic interest in following up on medications." If this is true, why is it that the FDA issues such frequent warnings? Are we to believe that trial lawyers instigated all these warnings? No, the fact is, the FDA and the pharmaceutical industry are paying close attention to safety issues. Usually, they act on these issues when it appears to be appropriate. Yes, there have been some significant failures in the system, including some unconscionable cover-ups. But even Doc Diller has not established a case for the contention that there has been a cover-up of the possible link between antidepressants and suicide.

Dr. Diller wrote his Opinion piece and got it published in the Washington Post. I am sure this has attracted some attention to him, and his books, and his website; no doubt, he continues to profit from this. If only he would spend more time studying the science of medicine, he might be able to write something that actually is accurate and newsworthy.

At the Center of the Storm Over Bush And Science
---
Junk Science or Junk Logic?

There was an article in NYT by James Glanz, on March 30, 2004, entitled At the Center of the Storm Over Bush And Science. The article did not bring much new to the issue, but it did include some information about Dr. John H. Marburger III, President Bush's science adviser. This included some content from an interview with Dr. Marburger. I posted a comment in the NYT Forum: Join a Discussion on Science in the News.

Commentary on James Glanz's At the Center of the Storm Over Bush And Science, published: March 30, 2004:

Mr. Glanz brings a fresh perspective to the topic of the allegations of the Bush administration systematically suppressing, distorting, and misusing science. The background on Dr. Marburger is particularly interesting. For a collection of opinions on this, as well as a more detailed history, see:

http://corpus-callosum.blogspot.com/2004_01_01_corpus-callosum_archive.html#107533447761570611

and
http://corpus-callosum.blogspot.com/2004_02_01_corpus-callosum_archive.html#107663777074330170

as well as
http://corpus-callosum.blogspot.com/2004_02_01_corpus-callosum_archive.html#107699093373408572

One person replied:

norbertzangox - 11:14 AM ET March 31, 2004 (#4592 of 4594)

I read most of the text on the first of your links. What I found was standard issue liberal paranoia about anyone who works for an organization that actually produces anything. The article described the attempt of the CDC to replace good Democrats with "Individuals with known industry connections." That phraseology portrays persons who work for an industry as horned devils without exactly saying so, by using the description "known connections", which we normally reserve for descriptions of relationships that persons may have with the Mafia or drug dealers.

It is a well-worn and tiring technique for laying adverse impressions between the lines. Its usual purpose is to create negative feelings when the author lacks sufficient data to create a sound case for his poor opinion of the person he is describing.

About the claim that the article makes, ". . . EPA administrator for air and radiation, blocked studies of bipartisan clean air proposals because they would undercut support for President Bush's weaker Clear Skies initiative.", I ask, how does the claimant (Senator Edwards, whom we all know to be an impartial observer of the present administration) know that the bipartisan clean air proposal would undercut President Bush's plan if no one has doe the analysis? Why don't those who are so convinced that their plan is better do an analysis? Let them lay it out there so we all can assess it.

For believing that the rest of the issues constitute misinformation, it is necessary to believe that carbon dioxide is causing climate change and that the existing levels of pollutants in the air are harming health. There are perfectly logical and scientific reasons to dispute both contentions.

Carbon dioxide is not a pollutant. Anthropogenic emissions of carbon dioxide are not the cause of climate change. The sun is the more likely culprit, if culprit is even a proper adjective. All indications and observations from history and the present are that warmth is better than cold. Ice ages are murderous. The medieval warm period was a period of prosperity, good health and beneficial social change.

EPA health effects studies greatly overestimate the toxicity and danger of existing concentrations of air pollutants. Air pollution is not causing health problems in this country. In China perhaps, but not in the US.

I believe that the essay at http://www.greeningearthsociety.org/wca/2004/wca_ [...], presents a more insightful and interesting analysis of the ongoing debate about science and junk science. You might want to give it a look.

Mr. Norbertzangox is correct. The sun is the major factor in climate change. If there were no sun, the climate would remain stable for a really, really, long time. He is correct also, that the article portrayed those who work in lead-related industry as horned devils. Yes, this is an expression ("known connections") normally reserved for Mafia or drug dealers. However, the point of the article was not to impugn the persons who were appointed to the CDC's committee on lead toxicity. The point was to impugn the Bush administration.

As it happens, I am familiar with the Greening Earth Society's web site. The commentary on climate change includes the following:

Junk Science

In a city swept by major maelstroms, a smaller but not insignificant one swirling through our Nation's Capital concerns a purported Republican effort to employ something called “sound science” to loosen environmental regulations. What keeps this one spinning is pressure by Democrats to purportedly strengthen regulations using what they too deem to be “sound science.”

Sound science is science its proponents find to be agreeable. What they find scientifically disagreeable is labeled “junk science.” Sad to say, whenever you hear someone using the term “sound science” you'll hear a lot of the first word and not see very much of the second. [...]

Let's begin with a reality check. Science isn't the Simon Pure beast your grammar school teacher made it out to be. It's not even a particularly logical enterprise. Further complicating matters, today's sound science can become tomorrow's junk science. This is because scientists tend to work within what the great historian of science, Thomas Kuhn, called “paradigms” or overall belief systems. Kuhn first advanced this concept in a number of academic papers in the 1950s, and more comprehensively in his oft-quoted Structure of Scientific Revolutions, a book first published in 1962 and still a top seller on the topic.

A Band of Rebels

Kuhn notes that most scientists spend their lives working to shore up the reigning world-view and that those who disagree with it are by definition much fewer in number. The outsiders tend to find inconsistencies within the current paradigm. As a consequence, they tend be unpopular among their peers and are derided. But often they are more logical and (dadgummit) they frequently turn out to be right. The few eventually overwhelm the mass, but it happens against impressive resistance.

This model very neatly fits the evolution of climate change and global warming.[...]

This is a peculiar argument. Yes, Thomas Kuhn did point out that major shifts in scientific thinking start out with a small number of dissenters. But the argument appears to be that, since the the scientists who disagree with the theory -- that anthropogenic CO₂ is implicated as a cause of climate change -- are in the minority, they are likely to be correct.

This obviously is not a logically supportable conclusion. Another problem with the whole pro-CO₂ argument is this: while it is difficult to prove, conclusively, that anthropogenic CO₂ is the cause of global warming, that is not really the point. The point is this: can reducing the output anthropogenic CO₂ of reduce the impact of climate change? This really is a separate issue. Regardless of what caused what in the past, what we need to know is: what can change things for the better, in the future?

Tuesday, March 30, 2004

Suicides in the Military

Army sent mentally ill troops to Iraq

By Mark Benjamin
United Press International
Published 3/12/2004 5:53 PM
View printer-friendly version

WASHINGTON, March 12 (UPI) -- The Army appears to have "inappropriately" deployed soldiers to Iraq who already were diagnosed with mental problems, according to documents obtained by United Press International.

More than two dozen suicides by U.S. troops in Iraq, and hundreds of medical evacuations for psychiatric problems, have raised concerns about the mental health of soldiers in Operation Iraqi Freedom. An Army Medical Department after-action report obtained by UPI suggests that the Army sent some soldiers to war who were mentally unfit in the first place.

"Variability in predeployment screening guidelines for mental health issues may have resulted in some soldiers with mental health diagnoses being inappropriately deployed," the report said. That could "create the impression that some soldiers develop problems in theater, when, in some cases, they actually have pre-existing conditions."

The October 2003 report said the Army should consider quickly changing course to prevent deploying more soldiers with mental problems. In a massive troop rotation now under way, more than 100,000 troops are heading to the region.

"Perhaps stricter predeployment screening is required to keep at-risk soldier from deploying," the report said. That would help in "identifying soldiers that may become non-functional in theater due to mental health problems."

It says that idea, among others, "must be passed on in a timely manner since units will more than likely be deploying in the near future."

A number of veterans' advocates say signs of widespread mental problems among soldiers from Iraq shock them -- one in 10 soldiers evacuated from the war on terror to an Army hospital in Germany were sent solely for mental problems. The Pentagon says that number is not out of line. It also is investigating more than two dozen suicides in Iraq and Kuwait but says the rate is not alarmingly high.

Analysis: In a randomly selected group of people in the USA, out of 100,000 people, in one year, you would expect about 10.7 suicides. The Pentagon said that the number of suicides -- "more than two dozen" -- is "not alarmingly high." Looking at the most recent complete figures at NIMH Suicide Facts, and crunching a few numbers, and making some assumptions, we seen that among males ages 20-24, we would expect 20 suicides in a group of 100,000 in one year. (The assumption is that all of the deployed soldiers are male, and that all of those who killed themselves are male. Probably not exactly true, but close enough.) There are some factors we cannot quantify. Suicide risk is increased among those with ready access to firearms, those with a history of violence, those with substance abuse problems, and so forth. Although we can't quantify this, it seems reasonable to think that among male soldiers in a combat zone, an increased risk of 20% above baseline is reasonable. Therefore, 24 suicides is about what one would predict. Although I would love to say that the number of suicides is an indication that there is something wrong with the military, the numbers do not support that position.

Furthermore, efforts to predict suicide in individuals have not proven to be very accurate; and efforts to demonstrate reduction in suicide via suicide prevention programs largely have been futile. So it does not seem likely that the military has much chance of actually reducing the risk. Still, on humanitarian grounds, they should increase their screening and not deploy soldiers at risk. I doubt this would have a measurable impact on the suicide rate, but it easily could reduce the amount of chronic posttraumatic stress disorder and reduce the incidence of exacerbation of pre-existing serious mental illness.

My wife used to work with at-risk veterans. Her group consisted of about 50, mostly male, who had the most days in-hospital of all the veterans in the area. Two of her patients committed suicide over a period of several years (despite intensive case management and individualized treatment). Several of them had been sent into combat (mostly in Viet Nam) even though they clearly had been exhibiting signs of serious mental illness prior to deployment. I don't know if those two suicides could have been prevented, but I do think that those patients would not have had such severe illness if they had been screened out, and not sent to combat.

"Of All Our Enemies, the Most Real and Dangerous is Fear Itself."

There is a good essay in The American Prospect, by Jane Smiley and James Squires, publication date 4/1/2004. Go ahead and read the entire thing if you want; I am just going to point a few excerpts to make a point.

Fear Factor
Our hype-driven culture thrives on confusing reality with fantasy and on making us afraid

[...] The 2004 election could be stolen, too, as many of the weaknesses in the 2000 balloting process have gone uncorrected and some reforms, such as touch-screen and other computer-based election machines, have been shown to be unreliable and easily manipulated. But the real threat is not that Democrats or Republicans will steal a critical state again, or that another president will be appointed by the Supreme Court; it is the possibility that fear is being replaced in the political process by fear-mongering, employed in the high-tech world of instant communications by the skilled and unscrupulous mind manipulators of today's advertising culture. And the integrity of our political process is evaporating as quickly as the moral principles that once set us apart and made us a model for great nations of the world.

[...] It took nearly half a century for entertainment and advertising to overwhelm the institution of the free press, which used to function as America's public voice. And it took about the same length of time for the press's successor in that role -- television -- to change the process by which the human brain makes decisions.

Recent scientific advances that allow the mapping of brain activity suggest that children who grow up watching television receive and process information differently and more rapidly than their parents who did not. Not unlike muscle development, brain development varies with use, so the more different parts the brain employs, the more efficient it becomes. As a result, the audio-visual communication of information is more efficient when employed by those who have grown up watching television. As more and more people have used audio-visual communication over the years, and as technological sophistication has increased, the structure of capitalism has also changed. When television became the marketplace, people began to gather in front of the screen, ready for their brains to be washed. And no institution in society keeps up with moving targets as well as the American marketing industry.

[...] All presidents spend their first terms running for re-election, but the Bush administration has relied on the principles of advertising unceasingly, almost without recourse to any other mode of communication. And so far that's been its crowning achievement.

[...] Repeated terrorist alerts, new assessments of reinvigorated bin Laden minions, and resumption of the culture war leave little time for dull, irrelevant economic and social truth. So the Republican strategists' idea of the perfect presidential debate would be an image face-off: a doctored photograph of the probable-Democratic nominee, Senator John Kerry, attending an anti-war rally with Jane Fonda, in contrast to two 15-second film clips of the wartime president, one with him in a flight jacket aboard an aircraft carrier and the other of him leading "NASCAR dads" in prayer at the Daytona 500. The Democratic strategist, of course, prefers another juxtaposition of images: that of young war hero Kerry in combat gear moving through a Vietnam jungle while, to the sound of car-bomb explosions, a smirking Bush challenges terrorists to "bring it on" in Baghdad.

Of course, none of these images approaches the whole truth, which remains as elusive in our system and among our leaders as nobility and statesmanship. But in election 2004, they might be the closest the democracy can come to substantive debate in our current climate of fear. And this is why, back in another time, when images were slower and truth easier to find, an unquestionably great wartime president warned us that of all our enemies, the most real and dangerous is fear itself.

The essay makes a number of points, and in the process, bashes politicians left and right. The point I would like to emphasize is in their concluding paragraph: "of all our enemies, the most real and dangerous is fear itself."

Why is this so? Because fear, perhaps more than any other emotion, has the potential to derail a logical thought process. It is hard to think clearly when you are fearful. People who are afraid are easier to manipulate, because their capacity for logic fails them. This happens to have been the topic of my first and second posts.

Sunday, March 28, 2004

Another Exercise in Connecting the Otherwise Unconnected

A modest amount of blogbuzz was generated by the article in The New Republic, The Web Won't Topple Tyranny. I was poking around to see what people had to say about it. For reasons not entirely clear, I ended up seeing this post on Rodger Payne's blog.

Saturday, March 27, 2004

Draft
Some time ago, I referenced the basic "military math" that slows further implementation of the Bush Doctrine. Put simply, the US doesn't have a sufficiently large armed force to carry out additional Iraq-like invasions and occupations. Most of the force is already deployed somewhere important, and the rest is either training to deploy or resting from a recent deployment

Additionally, anecdotal evidence suggests that re-enlistment rates may be down as well, which will further limit the President's apparent aspirations.

Conscription, of course, could alter this equation -- though it would take awhile to draft and then train new (likely much less motivated) soldiers.

In any event, I recently read an interesting piece on AlterNet by Conner Freff Cochran suggesting that a draft is coming. Don't expect to hear the Republicans talking about this before the election.

Dr. Payne also provided information from the Selective Service Annual Performance Plan 2004. Part of this involves getting volunteer registrars in most if not all high schools, and to increase staffing at local draft boards. The Dept. of Defense went so far as to post a notice asking people to sign up to be board members for the Selective Service.

Curiously, the notice has been removed. Some foresighted people saved copies, such as this one at the Memory Hole:

Defense Department Deletes Notice About Draft Boards

>>> On 23 Sept 2003, the Defense Department Website called "Defend America" posted a notice for people to join local draft boards. "If a military draft becomes necessary," the notice explained, "approximately 2,000 Local and Appeal Boards throughout America would decide which young men, who submit a claim, receive deferments, postponements or exemptions from military service, based on Federal guidelines."

In early November, that notice started to receive media attention, with articles from the Associated Press, the Seattle Post-Intelligencer , the Oregonian, the Toronto Star, the BBC, and London Guardian (unsurprisingly, none of the major papers or networks in the US covered it).

In a familiar turn of events, the notice suddenly disappeared from the Website. (Thanks to LG for pointing this out.) We've mirrored the page and posted the text below.

Serve Your Community and the Nation
Become a Selective Service System Local Board Member

The Selective Service System wants to hear from men and women in the community who might be willing to serve as members of a local draft board.

Prospective Board Members must be citizens of the United States, at least 18 years old, and registered with the Selective Service (if male). Prospective Board Members may not be an employee of any law enforcement occupation, not be an active or retired member of the Armed Forces, and not have been convicted of any criminal offense.

Once identified as qualified candidates for appointment, prospective Board Members are recommended by the Governor and appointed by the Director of Selective Service, who acts on behalf of the President in making appointments. Each new member receives 12 hours of initial training after appointment, followed by 4 hours of annual training for as long as he or she remains in the position. They may serve as Board Members for up to 20 years, if desired.
Local Board Members are uncompensated volunteers who play an important community role closely connected with our Nation's defense. If a military draft becomes necessary, approximately 2,000 Local and Appeal Boards throughout America would decide which young men, who submit a claim, receive deferments, postponements or exemptions from military service, based on Federal guidelines.

Positions are available in many communities across the Nation. If you believe you meet the standards for Selective Service Board Membership, and wish to be considered for appointment please visit our web site at: http://www.sss.gov/fslocal.htm

Regarding the posting and subsequent removal of the notice, a spokesperson for the Selective Service System was quoted as saying:

"This not even remotely resembles efforts to kick it up a notch," said Dan Amon, a public affairs specialist for the Selective Service System.

He said the Selective Service routinely sought applicants to fill 11,000 slots on local draft boards nationwide to be ready if the draft ever were reinstated. The terms on these voluntary boards are for 20 years, and many are now expiring, he said.

"We're just going through a cycle," he said. He said when the information was posted on the Defense Department Web site, it raised some alarms. "We're not even quite sure how it got there," he said.

"We're not even quite sure how it got there." Right.

More information on the Selective Service program can be seen in the Vancouver paper here. This refers to two pieces of legislation, S 89 and HR 163, AKA the 'Universal National Service Act of 2003'. Thomas.loc.gov lists the currents status of the legislation as follows:

H.R.163
Title: To provide for the common defense by requiring that all young persons in the United States, including women, perform a period of military service or a period of civilian service in furtherance of the national defense and homeland security, and for other purposes.
Sponsor: Rep Rangel, Charles B. [NY-15] (introduced 1/7/2003) Cosponsors: 13
Related Bills: S.89
Latest Major Action: 2/3/2003 House committee/subcommittee actions. Status: Executive Comment Requested from DOD.

According to an article on AlterNet.Org, the Selective Service's current plan calls for a final report to be submitted to the President on March 31, 2005. If that happens, an actual draft lottery could be up and running by June 15,2005. That happens to be a little over a month after my son's 18th birthday. (In case you were wondering why I took the trouble to write this, which is a little off my usual subject matter.)

Blog commentary on this is universally negative, as far as I could tell. Conservative blogs such as the Evangelical Outpost and conservative sites such as CATO express concern that reinstating the draft could lower the quality of the military services. Hear the CATO commentary here (Realaudio link). Francis has a website named BushDraft.com that includes a collection of links about the draft. Another can be found at the Information Clearinghouse. Lisa Bralts-Kelly at Handbasket? meet Hell expresses a negative opinion here. Likewise, Tom at Livejournal/user/yesthattom is opposed to the draft. Kevin Brennan at Tilting at Windmills opines that the notion of reinstating the draft is an urban legend. This is based upon Rivka's post at Respectful of Otters. She raises some good points that would seem to suggest that the draft is not coming back anytime soon. She adds,

[...] it seems to me that we have enough to worry about with what Bush is actually doing. We can't afford to spare any outrage for things he's not doing."

This leaves us not knowing what the government is really up to. Perhaps they do not know themselves what they are up to. All this brings me back to where I started, which was the article called The Web Won't Topple Tyranny. It may not topple tyranny, but it will sure help us keep track of what is going on.

More on Suicide
---
Facts, Opinions, Experience, and a little bit of Nonsense

In the NYT, there is an article by Gina Kolata, one of the best science writers in the business. The title is: Why Test Animals to Cure Human Depression? Ms. Kolata has picked up on the issue of antidepressants possibly causing suicide, and posed some interesting questions to some of the people who do research in the area of drug development.

OF MICE AND MEN

Why Test Animals to Cure Human Depression?

By GINA KOLATA

YOU might think if questions were raised about whether antidepressant drugs can make patients suicidal during the first few weeks of treatment, that scientists would turn to animal testing for further investigation.

After all, suicides are rare enough that there are no firm human data on whether the drugs can cause them. But you can do experiments with animals - examining their brains, giving them high doses of drugs - that you could never do with people.

That might seem like a reasonable course of action, especially after the Food and Drug Administration announced last week that it was so concerned about a possible, though very slight, suicide risk that it wants antidepressant drugs to carry warnings on their labels. But it turns out that animal experiments are not an option.

The reason, said Dr. Alan Schatzberg, chairman of the department of psychiatry and behavioral science at Stanford University's School of Medicine, is that "we don't have an animal model of depression."

[...]Those symptoms, he noted, involve the prefrontal cortex, a brain area not highly developed in animals. So, he asked, "How do you model it in an animal?"

[...] Some psychologists say they can make animals exhibit signs of depression by putting them in situations where they feel helpless to control their fate. "All this stuff about animals don't feel sad or hopeless, that's some huge leap," said Dr. Martin Seligman, director of the Positive Psychology Center at the University of Pennsylvania. He said that the only sign of depression that could not be elicited in animals was suicide.

What if, by chance, researchers stumbled on an animal test that predicted whether an antidepressant drug might prompt suicide as a rare side effect in people?

"We would immediately go back and test all of our drugs," Dr. Ruffolo said. If the animal tests indicated that the drugs were linked to suicide, he added, the company would use the test to search for other drugs that were not. [...]

Ms. Kolata points out that one of the difficulties in doing research on suicide is that it happens infrequently in the context of a research study. Suicide is the 11th leading cause of death in the USA, but that amounts to only 1.3% of all deaths per year. In 2001 there were 30,622 deaths by suicide (or that were ruled to be due to suicide) out of almost 300 million people. This means that, each year, about 0.01% of people will die via suicide.

After a suicide, the most important question is: why did the person do it? Obviously, it is very difficult to get the answer to that question, since you can't ask the only person who really knew. Suicide notes, when they are found, may not always give the real reason.

The only definitive way to study an aspect of human behavior is by doing a randomized, double-blind, controlled, prospective experiment. Nobody is going to do a study in which people are knowingly exposed to a risk of suicide, so there never will be a definitive study of the causes of suicide. For similar reasons, I think there never will be an animal model for suicide risk. If someone developed a putative animal model, it would only be useful if validated. In order to validate it, you would have to demonstrate that the behavior of the animals is correlated with the behavior of humans.

To complicate matters further, drugs can be associated with an increased suicide risk even if they are not psychiatric medications. Accutane and interferon have been associated with suicide, and they have no known direct psychotropic effects. As a result, it is difficult to postulate a model pathophysiology for suicide risk. Without an idea about how, on a molecular level, a drug could promote suicide, there is little basis for establishing an animal model.

The F.D.A., Antidepressants and Suicide Risk (3 Letters)

o the Editor:

Re "Regulators Want Antidepressants to List Warning" (front page, March 23):

There is much to be lost and little to be gained by the new Food and Drug Administration warning. It is true that there have been suicides by adults who happen to be taking antidepressants. But information about these suicides is based only on anecdotal reports, not scientific studies, and we know few details.

Do they involve people suffering from bipolar disorder who become manic when given antidepressants indiscriminately by general practitioners? Are these people using street drugs concomitantly and not telling their internists?

Unfortunately, the F.D.A. warning will scare many people away from taking a medication that would otherwise lead them to have happier and more rewarding lives. Rather than preventing suicides, this warning will create the risk of more suicides.

PETER KUDLER, M.D.
New York, March 23, 2004

To the Editor:

The Food and Drug Administration, with good intentions, has overreacted and opened the floodgates of fear and malpractice litigation ("Overprescribing Prompted Warning on Antidepressants," news article, March 24).

It would be ironic if this action caused patients to abruptly discontinue their medication out of fear and misunderstanding, which could trigger severe rebound depression, withdrawal and suicide.

Imagine the trial lawyers licking their chops ready to blame every suicide not on the disease but on the therapy. The F.D.A. has acted irresponsibly and foolishly.

MITCHEL L. GALISHOFF, M.D.
Valley, Ala., March 24, 2004

To the Editor:

The current brouhaha over antidepressants (front page, March 23) is another example of the medical profession's refusal to understand depression as a serious medical illness. Many internists dispense antidepressants to depressed patients and blithely instruct them to return in six months, as if they were treating a common allergy.

This practice is encouraged by managed care companies to rein in costs. Yet for the last 40 years, psychiatrists have known that depressed patients are at great risk for suicide in the earliest stages of recovery.

JUDITH EBENSTEIN, M.D.
Irvington, N.Y., March 24, 2004

See this post for a thoughtful, personal account of the appearance of suicidal thoughts after starting an antidepressant.

Category: Things found while looking for other things
Subcategory: WTF???

Do you suppose the FDA should put a warning label on feminists?

GOP Desperation Tactics

Found via Talking Points Memo, here is a link to an article about fundraising from blogs:

GOP criticizes Democratic House candidate's Internet fund-raising

Posted on Thu, Mar. 25, 2004
CHET BROKAW

Associated Press

PIERRE, S.D. - Republicans have accused Democratic U.S. House candidate Stephanie Herseth of maintaining a secret Web page to receive campaign donations raised from ads on liberal groups' Internet sites.

But a Herseth campaign official scoffed at the charge, saying the Web page is not secret and can be found easily with a standard search of the Internet.

Herseth faces Republican Larry Diedrich in a June 1 special election to fill the vacancy left when Bill Janklow resigned as South Dakota's lone member of the U.S. House.

Jason Glodt, executive director of the South Dakota Republican Party, said the Herseth campaign arranged the special Internet donation site to prevent most South Dakotans from knowing about Herseth's relationship with such liberal groups.

The Herseth Web page takes campaign donations from people directed there from Internet sites called "blogs," which are online bulletin boards that feature journals, opinionated articles and messages.

[...]

"I think the real point is you judge a person by the friends they keep, and look where she's focusing her fund-raising efforts," Glodt said. "Anybody can look at these blogs and the content, and realize the values they are promoting are completely contradictory to the South Dakota values she purports to represent."

Five comments: First, where do they get off saying that blogs feature "opinionated articles"?

Second, who cares if the blogs that carry the ads have content that is "contradictory to the South Dakota values she represents"? That is like criticizing a candidate who runs ads in a newspaper, when some of the articles in the newspaper are objectionable. Are we to infer that the opinions expressed in the blogs represent the opinions of the candidate?

Third, what good would a fundraising page be if it were secret? That would be like NPR stopping all broadcasting during their fund drive.

Fourth, if using the internet to solicit donations is so wrong, why does Larry Diedrich solicit donations on his main campaign site?

Fifth, is it true that most South Dakotans do not know about Herseth's backers? on the Daily Rebuplic web site, a newspaper in Mitchell, South Dakota, readers can leave comments. After an article on the campaign, a reader had this to say:

Reader Comments

Posted: Wednesday, March 17, 2004
Article comment by: Marcy Mattern

I really enjoyed the article about the upcoming congressional race. I would however like to see more information about Larry Dietrich. I wonder why you haven't reported that Ms. Herseth is being supported by Emily's List, NARAL and Planned Parenthood?

Perhaps Dietrich's campaign would be served better if he could come up with some substantive issues. Complaining about internet fundraising is a non-issue.

Another Problem with the Family Marriage Amendment
---
Sex Isn't Black and White

Long ago, I was watching an episode of Leave It To Beaver. The show ran between 1957 and 1963, so I would have been five years old, at the most. The show was in black and white, as the illustration shows.

In one of the episodes, Ward Cleaver -- the father figure -- was lecturing to Beaver. The Beaver had done something morally ambiguous, and was trying to weasel his way out of being blamed for it. In response, Mr. Cleaver said something like: "Beaver, something is either right, or it is wrong, and that was wrong."

At the time, I recall thinking that some things really are not all that clear-cut. Later, I was peripherally involved in collecting data for a project that was supposed to define the boundaries of the various categories of anxiety disorders. I learned that trying to nail down a definition of a human trait is exceedingly difficult. The devil is in the details, and the more complex something is, the more details there are. And the more devils there are, too.

Stop and think of aspects of human biology, and try to think of one that illustrates a clear-cut, either-or dichotomy. Life vs. Death? Well, no, actually hospitals have to have lengthy guidelines to follow to decide if a patient is alive or dead. What about Male vs. Female?

Clearly, the notion of an absolute distinction between females and males is a core belief in every culture. Children are aware of this distinction even before they have any knowledge of procreation. We are so accustomed to being able to tell the difference between males and females that it does not even occur to us that there might be some situations in which gender assignment is less than obvious.

The Family Marriage Amendment would define a marriage as a union between one man and one woman. That would mean that men cannot marry men, and women cannot mary women. A very clear distinction.
Mr. Cleaver was aptly named. He could cut right to the heart of the matter. He could separate the meat from the bone, so to speak. And he always could tell right from wrong. Like I said, it was a black and white show.

But even Mr. Cleaver might not have such an easy time distinguishing female from male. Take the case of 21-hydroxylase deficiency. This is an hormonal disorder that causes a developing female fetus to produce too much male hormone. As a result, the baby looks like a male, even though it has two X chromosomes.

There are many other causes (eMedicine) of gender confusion. In some cases, it takes a team of doctors a fair amount of study to decide if a newborn is male or female. Sometimes not everyone on the team can agree.

Sometimes it seems as though nature always has another surprise waiting for us. Just when we think we have an absolutely clear way to distinguish females from males, nature tosses in another variation that we had not anticipated. Here is a description (from eMedicine) of the genetic basis for true hermaphroditism:

The most common karyotype is 46,XX, although mosaicism is common. A translocation of the gene coding for HY antigen from a Y chromosome to either an X chromosome or an autosome presumably explains the testicular material in a patient with a 46,XX karyotype. More problematic is how a true hermaphrodite with a 46,XY karyotype can have ovarian tissue, since two X chromosomes are believed to be necessary to normal ovarian development. Possibly, unidentified XX cell lines are present in these patients.

So it is possible that some individuals will have XY in some of their cells, and XX in others. Or they will have what appear to be two X chromosomes, but one of the X chromosomes has Y chromosome genes in it. So you can't distinguish males from females by looking at the chromosomes, with absolute reliability. For every rule, there will be an exception.

In fact, it is quite likely that there are many couples in the USA, in which one member of the couple looks entirely male, but is genetically female. Sometimes this is discovered during an infertility workup. Usually there are other symptoms that lead to the diagnosis earlier in life, but not always. Are we going to require that all couples in the USA undergo a complete genetic and endocrinological workup before they get a marriage license? Are we going to require the same of all couples already married, just to be sure that there aren't already some same-sex marriages? After all, either it is right, or it is wrong. And if it is wrong, it should be stopped. Right now.

Note: persons with some kind of ambiguous genitalia or hermaphroditism are called intersexuals. Society often is not nice to them. See Bodies Like Ours and Intersex Society of North America for more information. And try to be nice to people, all people, even if their very existence threatens your belief structure.

Saturday, March 27, 2004

Public Reply to Comment on Antidepressants and Suicide

Corpus Callosum comments by Haloscan

Thanks for the link. Just started the whole blogging thing and haven't decided whether I really need trackback.

I enjoyed your article. I have a close friend who is a pharm sales rep and we've have a lot of discussions about the use of anti-depressants (his field). Obviously I'm not an FDA fan for many reasons, and didn't go into a lot of the "evidence" I had researched on the net and gathered from my friend. However, somewhere in my archives is a longer rant about the issues regarding drugging children. While there are obviously instances where it may be appropriate, I think we should be more hesitant to prescribe these meds (and others) to children.

Anyway, thanks for the link. I've bookmarked your site - look forward to checking back on some of your stuff.
Norman | Email | Homepage | 03.27.04 - 9:13 pm | #

The topic of pediatric psychopharmacology is an important one, and as you point out, there are serious ethical issues involved. This is reviewed, from a perspective that is only slightly biased, in the book, Beyond Therapy, published by the President's Council on Bioethics.

One reason that pediatric psychopharmacology is important, from a public health standpoint, is that there is evidence in adults that treating depression today can make relapses less likely tomorrow. No one knows if treating persons with depression at a young age would make a difference in their longterm outcome. However, if that turns out to be true, we will be in a situation where we will have to pay very close attention to see if we can have a positive, long-term impact.

Major Depression is estimated to cost the country about $45 billion dollars a year. Most of this is due to lost productivity. (The reference is in one of my earlier articles). If comprehensive treatment of children could reduce this, it would make a high difference in the economy and it the quality of life for millions of people.

Of course, this does not make the ethical issues go away; it merely highlights the importance of considering all sides of the issue.

Regarding the second issue: TrackBack. I suppose you do not need it, and the fact is most people who have it do not seem to use it. It is a bit of a hassle to do the TrackBacks manually each time. I like it., though, because it makes it easier to do research on topics in the Blogosphere. Someday it all will be automated and it will be used much more.

When I write a serious essay and post it on my blog, I always do an informal blogosphere survey just to make sure that I have something to add to what is already out there. Comments, trackbacks, and blog search engines greatly facilitate this.

By the way, when I was researching for the Antidepressants and Suicide article, I used Waypath for the first time. It seemed to be better than some of the others (Bloglines, Blogdex) at finding pertinent articles on the 'net. It also makes a nice graph, if you want, showing the amount of "buzz" that certain topics create.

You just go to their Weblog Post Analysis form, then enter the permalink URL of a post that deals with the topic you are interested in. It returns a list of related articles.

One final comment. I appreciate the fact that you made your comment a reasonable one. Half the comments I get from people I don't know are needlessly inflammatory. I tried to add your blog to my aggregator, Bloglines, but it did not find an RSS or Atom feed. SInce you use Blogger, why not go to the settings page and turn on the Atom site feed? If you are really into it, you can then go to Atom2RSS and set up an RSS feed. Atom2RSS formats the RSS feed perfectly, unlike some of the others.

If you are trying to figure out how to do this kind of thing, sometimes you can go to a blog that has successfully implemented the feature you want, use the View menu on your browser to "View Source" and study the HTML code to see how the feature was implemented.

You can screw up your blog pretty badly doing this, so be sure to make a backup of your template.

Good luck.

Antidepressant Medication and Suicide
---
A Meta-Review of the Blogosphere

There is concern that there could be a link between antidepressant drugs and suicidal thoughts and behavior. This is something that has generated a lot of commentary in the blogosphere:

I would like to take some time to pull together the recent medical information, news reports, and blogger commentary; then provide my own views on the subject. I conclude with some recommendations. If you already are familiar with this topic, just skip down to the recommendations.

Starting with the medical information, the Canadian Medical Association Journal has three articles of interest:

These articles are in the Commentary section. As such, they are not original, peer-reviewed research articles. I included them because the perspective of persons in Canada is likely to be different from that seen in the USA. They have a single-payer health system rum by the government. The effect of politics, finance, and lobbying will be different in Canada. See the bibliography in the CMAJ articles for links to the original research that has prompted all this buzz.

The FDA has issued reportss:

Not all of the recent scientific articles about antidepressants and suicide have concluded that there is a risk; some have indicated a reduction of risk::

There are many news articles and editorials; representative examples include:

From the blogosphere:

There are others, of course, but I could spend all day tracking them all down. I stopped when I got the impression that I was unlikely to find many more new ideas.

None of what I have to say will make any sense unless you have wither been following this topic closely, or you have read at least one good summary paper. If neither is true for you, I suggest you scan the article #2 in the first group: Antidepressants and adverse effects in young patients: uncovering the evidence.

Summary: drawing from the links above, and my persona experience, I would like to present a summary of all of this. It appears that the opinion in the blogosphere is split. Some persons feel that the suicide risk is an example of a cover-up, that it is a reason to not prescribe antidepressant, or that it is a reason to turn to alternative medicine instead of refined pharmaceutical. Many people express concern about the influence of financial concerns when it comes to marketing and regulating medications. Some express the belief that the FDA is being overly zealous in requiring warnings about suicide risk. Some people point out the difficulties of making sense of all the available information on the link between antidepressants and suicide. Most notable are the articles from The Toxicology Weblog (#1 above) and Blogcritics (#3). One commentator speculated that the FDA issued the warnings in order to help shield pharmaceutical companies from litigation (#14).

In an attempt to get a clear picture of how best to think about this topic, I thinks it is good to get a sense of the fact that what we are talking about is the probability that something bad could happen as a result of trying to make something good happen. It is important to recognize that, for persons with major depressive disorder, there is no risk-free option. That is, there is going to be a risk of suicide no matter what you do. All you can do is alter the probabilities.

For persons with MDD, there is a risk that they could commit suicide on and off medication, and that if on medication, that the suicide could be caused by the medication or by something else. Note that this is an oversimplification. In most cases, suicide is a complex event. There are multiple factors that lead to suicide in an individual, and in practice it is going to be very difficult to identify a singular cause. Despite that complication, it still is useful to enumerate the possible risk scenarios:

Person with MDD, off medication:

Risk of suicide due to disease
Risk of suicide unrelated to disease

Persons with MDD on medication:

Risk of suicide due to disease
Risk of suicide due to medication
Risk of suicide unrelated to disease or medication

Note that, in the unmedicated group, there will be a subpopulation of people who do kill themselves, who would not have done so if they had been on medication.   Keep in mind that the goal here is to minimize total risk, because it is the total risk that affects the patient's prognosis. Thus, if you do something to increase one risk, but also lower the risk in a different area, the total risk may go down. Thus, even if antidepressant use can increase suicide risk in some situations, it might lower the risk in other situations, with a new effect being that overall risk is lowered. Note also that that the risk of suicide due to antidepressant medication, in the unmedicated group, is zero (by definition). Therefore, if there are any suicides related to medication in the medicated group, the risk of suicide due to medication will not be zero.

Some commentators have wondered how it could be that we do not actually know the relative risk for these subpopulations. But think for a moment about what you would have to do to get really solid information. First of all, you would have to do a very large, randomized, placebo controlled study. To average out the effects of age, health care delivery system, geography, and other confounding variables, you would have to have a multi-site study, preferably including centers in several different countries. You would have to keep close track of thousands of people all over the world for at least several months; years would be better. You also would have to have some objective way to tell which suicides in the medicated group were due to the medication. It is not obvious that there is any way to do that.

Such a study would be enormously expensive. Pharmaceutical companies could sponsor it, but no one would accept the result uncritically in that case. It would have to be sponsored by the World Health Organization, NIMH, on some other neutral agency with deep pockets. Would this be the best use of the resources needed to conduct the study? Remember, if this study is done, that would mean resources would not be going toward understanding HIV, SARS, cancer, etc. Suicide is a fairly common cause of death, but it is not in the top ten causes. Therefore, it is not likely that the definitive study will be done anytime soon.

Therefore, we are left having to make important -- life changing -- treatment decisions, while we know full well that we do not have the information we need to accurately judge the relative risks of the treatment vs. no treatment.

One thing I noticed, especially in reading the blogs, magazine articles, and editorials, is that a lot of people have really strong feelings about the topic. In some cases, it appears that people equate the issue of suicide risk due to antidepressants with the global question of whether antidepressants are good or bad. This is somewhat like using the alleged breast cancer - abortion link as a proxy battleground for the pro-choice/pro-life debate. I submit that this fuzzy overgeneralization is not helpful.   It only confuses the issue.

There is another source of potential fuzzy thinking that should be clarified. Let us say that we do somehow find a way to quantify the pertinent relative risks. What would we do with the information. Remember, the relative risks are valid for large populations. They may or may not be applicable to any given individual.

Also, remember that the statistics could be used as a guide to develop public policy that is good for the population as a whole, but not necessarily to any given individual. A good example of this is pertussis vaccine. If everyone gets the vaccine, the population is better off. But some individuals will have serious reactions. Because there can be a difference between what is good for the group and what is good for the individual, we could end up seeing people promoting the wider use of antidepressants on public health grounds, while a separate group argues against it on for individual reasons. This is a kind of an argument that is difficult to resolve.

One thing that is apparent from the articles cited above is the there may bee an important difference in the relative risk for adults compared to children and adolescents. Most commentators agree that we need to be careful especially when it comes to treatment of children.   Unfortunately, there is a severe shortage of trained child psychiatrists. In the USA, there is a dearth of hospital beds for young persons with mental illness. Even when hospitalization is an option, it is difficult to keep the patient in the hospital for more than a few days.   Also, most children are limited in their capacity to understand what is happening to them, and to report problems when they should. For these reasons, we need to be especially careful about exposing children to medication that could have serious risks.

Some people have been critical of the FDA for its stance that in cannot render a definitive statement about the risk of antidepressant-related suicide risk. However, seeing that there is a tremendous amount of data, some of it contradictory, I think the FDA is correct to refrain from making a final pronouncement. Another criticism of the FDA has been that they do not have a lot of specific recommendations. WHile they do post several recommendations, they are all general tips that represent basic good medical practice. It is not clear that they are recommending anything other than a vague 'be careful' warning.

My recommendations: I would like to see a big multi-center study set up to try to resolve the question of possible antidepressant-induced suicide risk. If the study is done, regardless of whether it shows an increased or decreased risk, or no effect, it is likely to conclude with a recommendation for more careful attention to premarketing drug trials; publication of articles with negative results, just as prominently as those with positive results; and closer follow-up of persons treated with antidepressant medication. All of this will cost money, of course. There are some simple, practical things to do in the meantime:

If a patient calls to make an appointment for evaluation of depression, they can try to schedule two or three appointments all at once, at weekly intervals. The first would be for an evaluation, the subsequent ones would be for follow-up. In actual practice, it often is hard to schedule a follow-up appointment for just one week after the initial assessment. If you schedule both up front, you are sure to be able to get in within a week of starting medication.
Any patient who gets an Rx for an antidepressant should be instructed in how to make contact in emergencies. They also should prepare themselves mentally for the fact that, if there is a crisis, they may need to go to an emergency room or talk to an on-call doctor whom they do not know. No one likes to do this, but if one is prepared to face it if it comes up, it tends to go better.
Physicians should explain to patients that there are no risk-free options, and that the medication can have adverse effects. It is helpful to mention that adverse effects generally are reversible: they go away when the drug is stopped; and that most adverse effects can be treated easily. Akathisia, for example, responds to treatment with beta-blockers, benzodiazepines, or Periactin. Patients may fear that if they report adverse effects, they will be taken off the medication. This is not necessarily the case. They may fear that any adverse effect they have will be permanent. This misconception could lead to hopelessness and contribute to suicide risk.
If the person prescribing antidepressant medication does not plan to see the patient weekly, appointments should be offered with the clinic nurse, if in a primary care setting; or with a psychologist or other counselor, if in a mental health clinic. Even a scheduled phone call could help. Doctors should set aside time in their schedules for phone calls, and/or use a secure e-mail system. Some patients will send an update by fax to the doctor's office, with a note such as 'I just wanted you to know about this (possible adverse effect), please call me if this should be addressed.'
Insurance companies should not erect bureaucratic and financial barriers to appropriate evaluation and follow-up. They should not authorize just one visit when the patient or the doctor's office calls for preauthorization of services. They should automatically authorize two or three sessions, so that it will be more likely that proper follow-up will occur.
Accrediting agencies should monitor closeness of follow-up as an index of quality of care.
If patients have a known risk of suicide, their family and their treatment providers should ask them what would get in the way of their reaching out, should they become suicidal. Anticipating the barriers ahead of time often makes the barriers go away.
For mild depression, consider using psychotherapy and/or lifestyle modifications before trying medication.
If you do decide to take use antidepressants, use them properly. Use a med box to help guard against skipped doses. Do not take more than recommended. In most cases, do not stop suddenly. Be very careful about alcohol, nicotine, caffeine, illegal drugs, over-the counter medication, and herbal or alternative-medical products in combination with antidepressant medication.