Medscape Psychiatryby Robert L. Findling, MDJuly 31, 2014"Hello. I’m Dr. Robert Findling, Director of the Division of Child and Adolescent Psychiatry at Johns Hopkins University and a vice president at the Kennedy Krieger Institute in Baltimore. The US Food and Drug Administration [FDA] issued a warning in 2004 that treatment with antidepressants could lead to an increased risk for suicidality in young people. Today I will talk about a new study that examined the impact of this FDA warning. This article was published in BMJ, and the first author is Christine Lu."
"Suicide in teens is not only tragic but is a leading cause of death in youngsters. A major risk factor for suicide is depression, so safe and effective treatments for depression are needed. Among high school students, 8% say that they have attempted suicide, and 30% of those youngsters have made a suicide attempt that required medical attention. Suicidality in teenagers is all too common. Moreover, it is associated with a reasonably high rate of morbidity and a real risk for mortality. For that reason, it’s important to consider events that could alter the rates of suicidality. The impact of the FDA warnings has already been examined. This paper asks more and different questions…"
"What did the study find? First, there was a 31% reduction in the rate of antidepressant prescriptions. Second, there was an increase of 21% in the rate of psychotropic drug poisonings in adolescents. Finally, the study did not find an increased rate of completed suicides. An accompanying editorial commented that the net effect was that the FDA warning led to more harm. The data from this study suggest that adverse events not only can occur from medicines but also as a result of warnings. This leads to the unanswered question: How do we communicate treatment-related outcomes and treatment-related concerns effectively and openly to ensure improved patient outcomes without unwanted consequences? I’m Dr. Robert Findling. Thank you for watching."
They’re all similar, the studies purporting to either refute the warning or to say that it has caused harm. They seem to all rely on some large population study with a proprietary database showing that suicidality hasn’t fallen or has actually risen in the aftermath of the warning. They all document that the prescription of antidepressants to adolescents has fallen since it was issued [or at least not continued to rise]. The authors are an odd lot: adult psychiatrists, statisticians, bio-mathematicians, a conservative think-tank, etc. They imply that the Black Box warning resulted in withholding needed treatment from depressed kids. Like the Medscape presentation above, they leave out the fact that any literature that suggests that these drugs are effective in adolescents show minimal effects [if any] and are notorious examples of the experimercials of the era [eg Paxil Study 329]. They have resulted in multiple settlements against pharmaceutical companies for damages and false advertising.
So is there some evil genius in the background pulling the strings trying to dampen the impact of the warning? or maybe have it removed? Some of it has been PHARMA driven, at least early on, but it’s still coming even after all the antidepressant patents have expired. Dr. Findling may or may not be PHARMA friendly, but there’s no point any more. PHARMA may have started this mess, but they’re long gone now. So my hypothetical evil manipulator isn’t likely in that camp anymore. How about some other source – maybe among the ranks of Managed Care? They certainly stand to gain if people give antidepressants to kids rather than something else that costs the insurers more money [particularly now that the generic antidepressants are widely available and cost very little]. They’re a good candidate and the studies often use their databases. Actually, that’s who the author of the study discussed by Dr. Findling above [Dr. Lu] works for studying cost containment.
But there’s another factor, one suggested by a lot of activists and critics of psychiatry – that psychiatrists just like to give out pills. Yet another possibility – maybe they really think that antidepressants help depressed kids. I personally think there’s a simpler explanation that doesn’t postulate an arch-fiend in the background or even demonize or dumbify child psychiatrists. They don’t know anything else to do. Seeing the kid frequently and getting to the bottom of the problem isn’t in vogue, nor is it reimbursed. There’s no hospital for the really sick, at risk kids. In the modern world that focuses on diagnostic groups [as in the unitary domain – Adolescents with MDD], evidence-based medicine has no place for the kind of single-case model that asks "What’s wrong in the world of this unique adolescent who is floundering at a time in life when floundering is more rule than exception?" Most of the kids survive, but the consequences can and do play out in problems that persist for a lifetime in the enduring identity formed in the teen years. Dramatic? That’s intentional.
I’m sympathetic to this skeptical point of view but we also have to be aware of the insidious nocebo effect which is as real of a phenomenon as the placebo effect.
There is no easy answer to this. You have to report adverse effects but you also have to be aware of the power of suggestion.
James,
It would be helpful to readers to define “nocebo” for those who don’t know the term. Any references?
Here’s a decent lay article on the subject:
http://harvardmagazine.com/2005/05/the-nocebo-effect.html
To clarify: I’m not saying that suicide risk isn’t real…I’m saying that it being out there in the informed consent creates it’s own subliminal risk.
The unpleasant activating effects of antidepressants for some people, the extreme being akathisia, are well-documented.
If you doubt that akathisia can lead to suicide, please see the accounts from the people who have suffered it http://akathisiainfo.wordpress.com/2013/08/13/my-akathisia-experience/#respond (also see comments) and imagine its effect on a child.
To respond to Dr. Mickey’s point, pharma may be out of the game now, but the intensive propaganda funded by it and its allies for 20 years has done its work. I’ve seen this in action among a general audience as well as the authors he mentions in his article: There is a genuine belief that antidepressants save lives and the risks are insignificant compared to the good they do.
The risks are so insignificant, in fact, that many exist only as figments of the patient’s imagination.
This is a well-intentioned belief — who would want to be against saving lives — grounded in crap science, as Dr. Mickey has taken such pains to show. So you have both good intentions and nonsensical beliefs.
Please, please do not underestimate how deeply two decades of bad but well-publicized science, KOL speaking engagements, clueless articles in the mainstream press, Astroturfed patient organizations, medical textbooks, peer pressure among doctors, and so forth to sell antidepressants has changed thinking among physicians and the general public.
These wrong assumptions even lead to the advocacy of widely prescribing powerful hormonal disruptors — for that is what antidepressants are — to children, pubescents, and teens to stamp out the scourge of suicide, which justifies burning down the village to save it.
Correction: 30 years of propaganda.
The NY Times today looks back at the Prozac cultural phenomenon: http://nyti.ms/Z6JZwi
This pathological defense of antidepressants for teens is a symptom of psychiatry, I think, and it’s a byproduct of a de-personalizing and objectification of children, especially of teens, that is ubiquitous in the U.S.
A lot of people fear and hate teenagers and cannot tolerate the moodiness and broodiness that a lot of teens go through. Granted, violence is much higher among teens and young men, than the general population, but that in itself should be investigated as a possible cause of “depression” and anxiety. I think the whole field of psychiatry, in spite of what good it has done, is crippled by its narrow vision and sore lack of training in the humanities and communication.
The solution to this problem of drugging teens habitually is lost in the wholly tangled mess that is for profit medicine today in the U.S.. In the long run, it would likely cost much less for most people to be treated as individuals with problems that are too complex to reduce to “depression” whether drugs are used or not. With truly informed consent, I say ‘each his own’, but it would likely cost much less if people who were truly crippled with psychosis could spend enough time in a safe place to get all the help they needed before being handed a prescription and turned out into the community. But the insurance companies and all other for profit medical businesses operate quarterly.
And, as Ben Goldacre points out, not only is medicine not properly studying new drugs, there has been precious few proper studies on the drugs and other interventions that have been used for the last twenty years. Medicine is a mess, and I think it’s often not safe for people who don’t know how to question authority and advocate for themselves.
Every time I see one of the defenses of antidepressants for teens I think about that study in the U.K. showing that for the Caribbean islanders who were more likely to suffer mental illness, the whiter their neighborhoods, the more likely they were to succumb. Structural violence takes a toll, and declaring those who are overwhelmed by it to be lacking in “resilience” is the act of a privileged bully.
Do bullied teens need antidepressants more than they need for the abuse to end, for example? The overwhelming problems people can have are legion. It seems nearly a sin to me to hand out antidepressants as a first measure to someone who has so little power in our society and who cannot legally consent themselves to some interventions while those who intervene are not learning substantially more significant things about the “depressed” than how they “feel”.
“To clarify: I’m not saying that suicide risk isn’t real…”
I don’t know why I bothered…
But if it’s cathartic to flame people who basically agree with you, knock yourself out. BTW, what is your profession?
BTW the NYT piece on Prozac was actually pretty balanced.
Peter Kramer isn’t a bad guy and he isn’t Nemeroff or Scott Reuben/Russell Portenoy who both made a complete mockery out of pain management.
He just fell into the trap of believing something he wanted to believe. That describes most of the blog entries on the Psychiatric Times or Clinical Psychiatry News. I’m all over further flights into wishful thinking over evidence and I give them that feedback.
Please, let’s balance constructive criticism with some acknowledgment that these medicines have helped some people. Talk about burning villages.
I’m not into “hangings” which some have suggested, I’m into solving problems. Over the top rhetoric doesn’t help.
There’s a rational middle between being a KOLCHO and being antipsychiatry.
Life in the middle is the hardest path, I think. As an Internist, I used medications that were way more dangerous than ADs ever were, but it was a good thing because the diseases were so much worse. Certain kinds of Lupus can destroy kidneys quickly and forever without radical immunosuppression. Rampant RA can leave a lifetime of disability. The steroids we used in my day could cause a lot of bad things too, but no-one objected because doctors and patients alike were well informed about both sides of the coin, and in a high state of alert for signs things were going badly. Now they use antimetabolites, anticancer drugs, with much less in the way of everyday side effects, but they too can pack a real whollop at times.
The thing that makes the business with psychiatric medications so difficult is that only some cases are catastrophes, but even more, we have lived in a world were accurate information was not available for doctor and patient – something other than a correct and widely known risk/benefit ratio, or a correct set of data on efficacy and adversity. In the cases I’ve seen or know about where there has been akathisia or an SSRI suicide, the people involved have been trying to do the right thing, including the patient, but missed what was happening until it was too late. In fact, the low incidence actually amplifies some of the problems. The fact that these cases don’t show up in these population studies doesn’t surprise me at all.
Instead of this presentation, it would be fine with me if Dr. Findling would spend his time trying to figure out or encouraging his colleagues to look into the how and why rather than ignoring the what – why this happens so regularly, even if it’s uncommon.
Not to be a butthead, but I think the problems are far more fundamental than the integrity and lack of integrity in medicine, psychiatry, and drug testing or prescribing.
It seems obvious to me that there is too little investigation into how and why the brain/mind functions without pretending that the mind is actually understood and can be reduced to the brain is a mechanical object that can be tweaked (in order to function better on behalf of institutions that are themselves dysfunctional and exploitative). That’s such a confoundingly stupid supposition being carried out as if it were a matter of settled science that’s marketed as a universal human truth, that it’s hard to take apart without seeming iconoclastic and throwing all the babies out with the bathwater. It’s 19th Century dualism with 20th Century chemistry and 21st Century global corporate power.
I’m not saying that it does not do good and that drugs themselves can’t be valuable to necessary, but that the whole philosophy of it, and scientific legitimacy of it is kaput and it’s being ruled by predatory wealth and power.
I don’t think things are that much clearer in many areas of internal medicine. Look how long it took to get to the truth about low fat diets. And there are many cost benefit controversies about statins which may or many not be neurotoxic depending on what study you believe.
Remember folks, the Trifu–ta of ruining psychiatry by academia was Hopkins, Harvard, and Stanford. They redefined pimping and whoring to a T.
What about Emory and my alma mater Pitt, where a new “dimension” of COI was hatched. Not to worry, it’s been cleared by APA ethics.
I have an aunt that was a nutritionist who worked in hospitals. I learned to ignore dietary advice in my teens and as an adult I went to a conference with her, i.e. corporate food marketing orgy.
In many ways, the dietician field has paved the way for corporate medicine. When me and the cousins were little kid at her house, we’d scare up the ubiquitous bag full of Hershey bars and frozen concentrate orange juice and take it to our hideout under a bush to gorge. Sugar = energy. It was that sophisticated and isn’t much more so now.
Dr. OBrien: Regarding your alma mater Pitt post: That’s hilarious!!! Very clever. Loved it.
James,
Thanks for the Nocebo article. It’s a good one. In reviewing Clinical Trial reports, both the Placebo Effect and the Nocebo Effect are really striking. You might think you understand it, but then the intensity is always a surprise. Letting my psychoanalytic roots show some, I wonder if both don’t have something to do with regression when placed in an environment of care and attention – analogous to the transference cures and the negative therapeutic reactions described in the psychotherapy and psychoanalytic literature. Some trials have a “continuation phase” and there are “relapses” in both the drug and placebo group responders [medication continued but frequency of visits drastically changed]. It makes the results difficult to evaluate…
My apologies, Dr. O’Brien. “Nocebo” is one of my hot buttons. I’ve heard it used many times to dismiss real adverse effects, particularly withdrawal syndrome.
The nocebo effect might result in queasiness or other transitory symptoms. I doubt a warning about suicide as a drug risk would plant a new idea in anyone’s head or cause anyone to go through with it.
I believe that the concept of suicide as an end to unbearable suffering is as human as the concept of hope. Everyone knows about it.
It my be hot button but it is very real and has been studied extensively by Barsky and others. if you give people a sugar pill and tell them it may cause drowsiness they will be more likely to feel drowsy. Because it does not apply in your particular case doesn’t mean it isn’t a known phenomenon.
It is also know that there are epidemics of copycat suicides based on suggestion. That’s why anti-suicide groups were so upset by “You’re free, Genie” when Robin Williams died. It’s not a perfect analogy, I know, but suggestible people are vulnerable to all types of ideas. I’ve seen people on MAOIs have “tyramine reactions” to Velveeta. But there was no real medical crisis once they were examined.
Because it does not apply to your particular situation (and I would like some elaboration please because now I am interested) does not mean it is not a widely known phenomenon.
That’s very interesting, Mickey. Regression is very real and powerful psychological process. I’ve moved so much and pick up accents so quickly that when I was first in college, I could tell how regressed I was at times by my accent when I was working out problems in therapy.
While caring for a girl with R.A.D. I could instinctively tell when she was truly regressed and helpless (I have a recording of her keening like an infant when she was seven years old) and when she was faking it.
Regression was also an issue when caring for a liver transplant candidate. Over the course of around two and a half years, he regressed more and more with each mini coma he went into and came out of. From being in his mid twenties in his mind to being sixteen in that span of time while he was in his mid thirties. I managed to deal with him when he was in a regressed and keep it from his daughter until the very end (before his transplant). The last time though, he thought he was sixteen and was ‘waiting for his mom to pick him up.’ His daughter caught on that he didn’t recognize her and that he thought he was a teenager and started screaming for him to look in the mirror.
Mein Gott. Seeing the way he was shattered (temporarily) by looking in the mirror and seeing his real age was tough. Once his memory returned in full, he didn’t remember that harrowing experience at all (as usual). That’s an extreme example, but I think all of us slip in and out of different ages to some degree without being conscious of it, especially when feeling in a child like position or when one that speaks to our childhood.
A little more detail into some examples and some experiments:
http://www.skepdic.com/nocebo.html
I was reading an article recently that said placebo responses in antidepressant trials had increased 7% per decade over the three decades. This is probably because more subjects had self limited conditions. You wouldn’t necessarily see more nocebo effect. Placebo effect can be either power of suggestion or the condition got better because it was self limited. With these antidepressant trials, it’s pretty obvious what is happening.
How many kids on antidepressants are actually being treated by a child psychiatrist or referred to any kind of therapist? A lot of family medicine folks are doing the prescribing, and they don’t have time/aren’t trained to do “counseling”. Massachusetts has a higher concentration of psychiatrists than other parts of the country, and, even here, there’s a shortage of child psychiatrists. Here, it’s probably pediatricians. We did get a state-funded program where pediatricians can call psychiatrists for a phone consultation. (MCPAP)
Dr. O’Brien — I understand the nocebo effect very well, having been involved in this debate before.
The human mind is a wonderful thing. Given the very wide range of human experience, generalizations will not apply to everyone.
Observations of the nocebo effect are usually limited to isolated or very short-term events. The patient says Velveeta is a problem, this soon passes. (By the way, Velveeta that’s been in the fridge for a while can develop tyramine and other offensive amines as it…uh…ages.)
On the other hand, patients who develop symptoms they’ve never even imagined, that last a long time, are not suffering from the nocebo effect. For example: Post-SSRI brain zaps that last for 6 months. Or post-SSRI akathisia lasting for years.
Or, the mysterious “parethesia” listed as a common withdrawal symptom. Most patients have no idea what this is. Yet when they develop strange unprecedented sensations in their limbs or elsewhere, they quickly find out.
No one could possibly anticipate what these symptoms feel like, even if they’ve closely read the package insert on withdrawal syndrome, which hardly anyone does.
Unfortunately, my generalizations do not arise from my own personal experience, but 1,400 case histories here http://tinyurl.com/3o4k3j5
Most of these people have gone from doctor to doctor and psychiatrist to psychiatrist to find out what is wrong with them. Being told in one way or another that the symptomology is “all in your head” is very common, even for those who are textbook cases of withdrawal syndrome. (The other very common reaction is that this strange constellation of symptoms must be a psychiatric disorder NOS.)
It is very hard for me to believe that a child, adolescent, or teenager would incline towards suicide as a nocebo effect. First of all, minors are not the recipients of whatever passes for informed consent when a psychiatric drug is prescribed. The number of those who might be influenced by the package insert must be vanishingly small, as few adults even read it.
And lastly, as I said before, accomplishing suicide takes a lot more than merely hearing a mention of it.
And that goes for copy cats post-Robin Williams or any other well-publicized suicide. Suicide takes a lot of intentionality, focus, and effort. It’s never been a secret that one might direct one’s will to that end.
Altostrata, the public understanding of drug withdrawal/discontinuation may actually be the same understanding a lot of doctors have of it, is oversimplified. It takes a full year after quitting nicotine for the brain to return to natural functioning, and a lot of the hard jonesing that happens along the way that is often treated as psychological is quite physiological. Nicotine and alcohol are pretty well studied and their effects are much more limited than the effects of SSRs and “antipsychotics” can be for a lot of people. I would like to see more studies that attempt to understand all the effects these drugs can have and how the brain achieves homeostasis when those drugs are discontinued. I’d also like to see a whole lot more studies done on how adding one drug to another one in a regime effects the brain and how each of these two drugs behave with one another.
But I want these studies to be carried out by pharmacologists and neurologists and perhaps interdisciplinary teams that include psychiatrists and cell biologists. I feel confident that drugs that pass the blood/brain barrier have effects that have nothing to do with what we believe or think.
The placebo and nocebo effects are real and consequential, but they have their limits and I don’t think that the nocebo effect would make people commit suicide in numbers that would be statistically significant either.
But I could always be wrong. That’s my motto.
I’m not sure if you’re an attorney or a patient who had a bad experience from your post.
There were 2000 suicides in Europe following Goethe’s success with the romantic novel Werther:
http://en.wikipedia.org/wiki/Copycat_suicide
There are also symbolic invitations to suicide, i.e. the Golden Gate Bridge, at least there was now that they have tried to suicide proof it.
Here’s an interesting story about a rash of volcano enabled suicides in Japan with general observations about the phenomenon (and its attraction to the young).
http://drvitelli.typepad.com/providentia/2013/02/the-volcano-suicide-craze.html
Surely, suicide rates are highly influenced by culture, and Japan is an outlier in that regard. Which reminds me of Yoshiki Sasai —
http://impactethics.ca/2014/09/23/accountability-for-research-misconduct/
Could institutional protocols have prevented the downward spiral that led to his suicide?
Hmmm….I wonder if better statistics on suicide were kept in Goethe’s era than are recorded now.
So…symbolic invitations to suicide — which would incite action only if someone had already given it a lot of thought. 10 million visit the Golden Gate Bridge annually, in 2013 there were 46 suicides, a rate of .00046%.
In 2009, the rate of suicide in the US was .012%. The Golden Gate Bridge is not a very effective invitation to suicide, though for a few it might be the ideal dramatic location. (I’ve seen it almost every day for the last 40 years. To me, it means high fines for exceeding the speed limit.)
Dr. O’Brien, could not I (or wiley) be an interested and informed non-physician rather than a weasely attorney or a patient with a grudge?
As it happens, I am one of the world’s experts in antidepressant withdrawal syndrome (and sadly, adverse effects, as so many of my case histories include them as well). I take no particular pride in that, as there are so few of us, and I deeply believe this should be the province of psychiatry, which has so far belittled the problem.
With all due respect, what are your academic qualifications to be one of the world’s experts in antidepressant withdrawal? Have you testified in court on this issue? Have you been retained?
There is no doubt that the Golden Gate bridge is (or was) a suicide magnet. It has the second most suicides in the world. People drive across the Bay Bridge to jump from it, although the former would have done the deed just as well.
http://en.wikipedia.org/wiki/Suicide_bridge
You could be interested for reasons that are not personal or related to your job but my experience is that is not how people are wired. People are passionate for reasons related to bad experience or money. It’s interesting that you haven’t laid your cards on the table.
With all due respect, I am a non-physician who has studied antidepressant withdrawal syndrome for 10 years, which is as long as I have suffered it. I’ve read most of the scientific literature in withdrawal syndromes and adverse effects.
My cards have always fully been on the table.
For 9 years, I have been a peer counselor for people who are interested in tapering or need support for prolonged post-discontinuation syndrome. I’ve collected case histories for 3 years.
If you know of anyone with academic credentials, an M.D., any kind of advanced degree, or a physician who would do this work, please do share those persons’ contact information, as there are many people who wish to avail themselves of their knowledge, and I would like to hand the responsibility over to those who might get paid for it.
In the meantime, I function as an educated lay person without the anointment of academia. You may judge what I have to say on its content rather than a pedigree.
PS A magnet, by definition, draws a specific population of elements. It does not inspire movement in non-magnetic substances.
People seek the GG Bridge out to jump from it, they’re not irresistibly drawn to it against their wills. I’m sure they drive a lot further than from Oakland if the GG Bridge suits their vision.
The Wiki article says the GG Bridge is the second in the world for suicides among bridges. That is not a terribly significant fact (if it is true). There are only so many inexpensive ways you can kill yourself, and jumping from a great height is one of them. Might as well be from a beautiful bridge.
(I used to live in Ithaca, NY, there was a famous suicide bridge there, too, over a deep gorge. I have already heard many hours of discussion about suicide and bridges.)
I don’t believe the sight of a bridge or of a boxed warning compels people to commit suicide against their will. The nocebo effect does exist, but these are poor examples of it.