Unpublished figures show that nearly 4,000 children under the age of 10 were prescribed antidepressants last year, including 553 children under five and 48 babies, even though no antidepressant is approved in Australia for the treatment of depression in children and adolescents,The Australian reports.
"At first pass, it is beyond comprehension that more than 500 Australian children - aged one to five years - have received an antidepressant drug," Gordon Parker, executive director of the Black Dog Institute, a non-profit devoted to education about depression and bipolar disorder, tells the paper. "When the particular drugs are considered, the risk of significant side effects - let alone their efficacy - is of key concern. It strikes me that there would be wisdom in having the doctors justify such prescriptions to determine whether there are any justifiable reasons for such surprising data."
The figures are based on Pharmaceutical Benefits Schedule data that covers only people who received a subsidized prescription, according to the paper, which notes that most antidepressants are sold privately. A spokesman for the pediatric division of the Royal Australian College of Physicians was unable to explain the prescribing patterns: "The college would like to know who is prescribing these drugs to such young children and why."
Parliamentary Secretary for Health and Ageing Jan McLucas tells the paper that the government would be "very concerned if antidepressant medications were being inappropriately prescribed and dispensed, particularly to children." And the government's Therapeutic Goods Administration issued a statement saying it was powerless to regulate the use of off-label med, but maintained there might be medical practice and medico-legal implications associated with prescribing a drug beyond approved indications.
The Adverse Drug Reactions Advisory Committee warns doctors against prescribing any of the SSRI antidepressant drugs to children under 18 - aside from two that are approved for obsessive compulsive disorder in children aged over six years - and points out that drugmakers themselves advise against their use for any condition.
There are numerous examples in the Health Department figures that show doctors are ignoring the warnings, according to the paper.
Wyeth's Effexor carries this statement: "Do not give Effexor XR to children or adolescents under 18 years of age. The safety and effectiveness of Effexor XR in this age group have not been established." Yet, 3,347 children and teenagers were prescribed the drug last financial year. Eight were babies, 19 were aged two and three and another 15 were five years old. A Wyeth spokeswoman tells the paper the drug was not indicated for use in children and adolescents below 18 years of age, and it had never recommended its use in this population.
Two SSRI antidepressants have Therapeutic Goods Administration approval to treat children as young as six years for Obsessive Compulsive Disorder; and other, older antidepressants can be prescribed by doctors to treat bedwetting. But even allowing for these conditions, Royal Australian College of Psychiatrists spokesman Peter Jenkins tells the Australian the figures were mysterious and worrying.
The Health Department figures were obtained by the Citizens Commission on Human Rights, a Church of Scientology-backed lobby group opposed to anti-depressant therapy.
The most comprehensive research into SSRI anti-depressants and their use in children and adolescents in 2004 led to drugmakers being forced to include a warning in product labeling, stating the drugs could increase the risk of suicidal thoughts and behaviour in children. This followed the results of an extensive analysis of clinical trial data by the FDA in the US.
According to the Health Department figures, the most commonly prescribed antidepressant for children and adolescents aged under 18 years is Prozac, with 7833 given the drug in the past year, including 863 children aged under 10.
Source: The Australian
27 Comments
"A Wyeth spokeswoman tells the paper the drug was not indicated for use in children and adolescents below 18 years of age, and it had never recommended its use in this population."
Sure, so they're blaming the doctors. But I bet you anything that their sales people come up with roundabout ways to "suggest" its use in this population. I don't think it's the doctors alone coming up with this brilliance.
Off Label prescribing is merely a get out clause for big Pharma, same way as the Patient information leaflet that accompanies these type of drugs, for instance the term 'talk with your doctor' is used over 30 times on the current Seroxat [Paxil] patient information leaflet.
So tell me, what do doctors know about withdrawal problems with SSRi's?
This off label practise is a disgrace, it's basically loading an empty chamber with bullets.
Thanks for highlighting Ed.
Fid
To all Pharmalot Readers,
Take a hard look at the baby photo Ed has placed here. What type of Medical Prescriber would prescribe Effexor to a baby?... A Psychotic one comes to my mind.
One influenced by money Lisa
Fid
"Therapeutic Goods Administration issued a statement saying it was powerless to regulate the use of off-label med, but maintained there might be medical practice and medico-legal implications associated with prescribing a drug beyond approved indications."
I agree with the above statement. I was taught that even though off-label prescribing is legal if you do it you need to have extremely good reasons and documentation otherwise you could be liable.
For example if there are numerous good scientific articles, it's written in textbooks, and is considered as the standard of care. No more documentation than usual for an approved indication may be necessary.
When research is relatively widely known but still ongoing on the usage. Documentation in the medical record should probably include the articles supporting the use and much more monitoring and documenation of the effects both regarding individual efficacy and safety. Plus reporting of any findings, especially safety issues. (This is typically not done).
When there's little information (e.g. based on an observation or a theoretical reason) you sure better have an extremely good reason (e.g. last resort) and extremely good documentation and possibly even get consults and buy in from an ethics committee.
I've prescribed off-label in all of the above situations and followed these rules of thumb.
I believe drug companies have been promoting the idea to physicians that they can prescribe anything they want off-label without giving them any idea of the legal jeopardy they're putting themselves in.
Opinions expressed are my own and do not necessarily reflect the opinion of the FDA.
FDA Reviewer,
There is no scientific evidence to support the prescribing of antidepressants or antipsychotics in infants, simply put, its a "chemical lobotomy". One has to question the sanity of the prescriber, heck, Dr. Bierdeman has been described as a child psychiatrist with a "short fuse"
FDa reviewer....one point you missed. The patient or parent of the patient needs to be fully informed about the off label use. That is sorely lacking today.
You don't have to go to Australia to find hundreds of very young children who are being prescribed antipsychotics off-label.
Below are a few current and recent Risperdal studies done with young children in the U.S. All are off-label studies, and J&J never applied for approval for any applicable indications.
Risperidone Versus Olanzapine for Mania in Preschool Children 4 to 6 Years of Age With Bipolar Disorder Mass General Hospital: http://clinicaltrials.gov/ct2/show/NCT00181935?term=risperdal&rank=37
Ages Eligible for Study:4 Years to 6 Years Estimated Enrollment:40 Study Completion Date:July 2004
Study to Determine the Effectiveness of Risperidone in Bipolar Disorder in Children and Adolescents Johnson & Johnson Pharmaceutical Research & Development, L.L.C.: http://clinicaltrials.gov/ct2/show/NCT00076115?term=risperdal&rank=63
Ages Eligible for Study: 10 Years to 17 Years Estimated Enrollment: 162 Study Completion Date: December 2005
Pharmacogenetics of Risperidone in Children With Pervasive Developmental Disorder (PDD) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): http://clinicaltrials.gov/ct2/show/NCT00166595?term=risperdal&rank=65
Ages Eligible for Study: 4 Years to 21 Years Estimated Enrollment: 100 Study Completion Date: March 2005
CYP2D6 Pharmacogenetics in Risperidone-Treated Children Children's Hospital Medical Center, Cincinnati: http://clinicaltrials.gov/ct2/show/NCT00783783?term=risperdal&rank=85
Ages Eligible for Study: 3 Years to 18 Years Estimated Study Completion Date: December 2009
Placebo Controlled Trial of Valproate and Risperidone in Young Children With Bipolar Disorders Children's Hospital Medical Center, Cincinnati: http://clinicaltrials.gov/ct2/show/NCT00221403?cond=%22Affective+Disorders%2C+Psychotic%22&rank=25
Ages Eligible for Study: 3 Years to 7 Years Estimated Enrollment: 60 Estimated Study Completion Date: July 2009
Liquid Risperidone in the Treatment of Acute Agitation in Psychiatrically Hospitalized Children Stony Brook University: http://clinicaltrials.gov/ct2/show/NCT00790075?term=risperdal&rank=91
Ages Eligible for Study: 4 Years to 12 Years Enrollment: 24 Study Completion Date: December 2004
Side Effect Study of Antipsychotic Medicines to Treat Childhood Bipolar Disorder (PAMS) University of Maryland: http://clinicaltrials.gov/ct2/show/NCT00746252?term=risperdal&rank=219
Ages Eligible for Study: 8 Years to 12 Years Estimated Enrollment: 40 Estimated Study Completion Date: July 2012
A Study of the Efficacy and Safety of Risperidone in the Prevention of Relapse in Children and Adolescents With Conduct and Other Disruptive Behavior Disorders Johnson & Johnson Pharmaceutical Research & Development, L.L.C: http://clinicaltrials.gov/ct2/show/NCT00236470?cond=%22Attention+Deficit+and+Disruptive+Behavior+Disorders%22&rank=21
Ages Eligible for Study: 5 Years to 17 Years Estimated Enrollment: 225 Estimated Study Completion Date: July 2004
Effectiveness of Combined Medication Treatment for Aggression in Children With Attention Deficit With Hyperactivity Disorder National Institute of Mental Health (NIMH): http://clinicaltrials.gov/ct2/show/NCT00794625?term=risperdal&rank=159
Ages Eligible for Study: 6 Years to 12 Years Estimated Enrollment: 270 Estimated Study Completion Date: April 2013
How do you determine depression in a baby? They cry a lot in the first place, and sleep a lot - it's hard to tell those apart from other things (I didn't think the cause of "colic" had been determined, for example). Not eating might fit if there were no organic cause, but that could be a long list too (allergies?). The parents might have been unhappy that baby wouldn't stop crying, but the doctors would have had to have some idea that antidepressnts might help, and I don't know where they would have gotten that idea.
This seems too stupid and self-destructive to be acts by doctors simply on the behalf of pharmaceutical companies.
Robert,
So who do you blame, The uninformed Parent or the Narsistic Behaviour by the Physician?
If "careful analysis by the FDA of clinical data" and a black box warning does not stop prescribing, what is the point of hoping that this will finally happen with the atypical antipsychotics for individuals up to age 24? Unless the Obama Administration decides to do a total makeover of the FDA and of the rules of lobbying, nothing will change. People will die, and that's that. Lawsuits don't seem to stop the behavior, either. Mass tort lawsuits ban the plaintiff from sueing the doctor. Gotta keep the doc prescribing, as that's the bread and butter for pharma.
The easy answer for most of you is to blame pharma, but clearly something more is going on. Significant growth in the use of antidepressants (eg, Prozac and Zoloft) has occurred after many of the products have lost their exclusivity. Thus, there is little to gain by the original manufacturer. (This same issue does not apply, however, to the antipsychotics.) This may be something of a chicken or an egg story. It may not be that this increase in prescribing is entirely or even primarily the fault of pharma. Perhaps, a breed of physician willing to aggressively diagnose and treat (or, for many of you, overdiagnose and overtreat) is equally or more responsible for the increase in prescribing.
I'm also trying to understand how to diagnose depression in a baby.
Atlex,
I was quite pleased to see that you used the word "most".. When antidepressants and antipsychotics are prescribed to Infants and Toddlers, I question the sanity of the Prescriber. I guess I consider myself in the overdiagnose and overtreat category. I have also seen or heard, quite often, children being misdiagnosed. I also place a lot of blame on Health Insurance Companies, thats a beef for another day.
LVS,
Both (although more the doctor than the parents - the parents may not know better, but the doctor probably should). The doctor may do it under pestering from the parents, or he may just not have a clue. Of course, one might ask why Australia pays for the drugs in babies and young children if they are potentially harmful and lack a notable benefit. The prescribing doesn't make as much sense as, say, hiding the boatloads of money one pulls from drug companies while running supposedly unbiased psychiatric drug trials - it doesn't seem to be in drug companies' or doctors' financial interest to be that stupid, and so I would see it as more crazy or stupid than evil.
Atlex,
You have to have an idea that depression is the cause of whatever problems the baby has - since you can't tell that and there are lots of other potential causes (some of which are druggable), giving antidepressants to a subgroup (babies) for which it has no known effect and large potential liabilities (black box warnings) doesn't exactly sound like aggressive treatment, but stupidity. If the risk from depression to the baby were higher, you might also take a flier on antidepressants, but in this case it seems more like buying a lottery ticket as a method of achieving financial security.
This probably isn't pharmaceutical companies' fault anyway - advocating treatment of babies or young children with antidepressants seems financially suicidal for them. Lots of (potential) lawsuits and not much profit doesn't make any sense from any perspective.
Robert Bird and atlex - I agree with both of you to a point, but how do you reconcile what you're saying with a case like Beiderman and J&J? Or the studies that Ima Misfit mentions? Do you think that a study of a drug for an off-label use can encourage doctors to prescribe off-label? Or the recommedation of a KOL like Beiderman? They obviously got the idea from somewhere, right?
I realize that Beiderman is a long way from Australia, but it seems unlikely that doctors would spontaneously start prescribing antidepressants off-label to babies without some sort of influence. I think the next step would be to go back year by year and see if one could pinpoint where it picked up speed and try to find out why.
Harpy,
I'm a little confused by your comment. In order for an indication to go from off-label to on-label the drug must be studied in the patient population. I am not going to make a value judgment one way or the other regarding the existence of mental disorders in the very young or, subsequently, in the treatment of these same patients. I'll leave that to folks are are more expert than I am in the subject. However, if a respected academic wants to test his/her treatment hypothesis, he/she must conduct a controlled study. Can this study subsequently encourage other clinicians to try that same treatment--you bet. That is a consequence of conducting and publishing on new treatment paradigms.
Atlex
Atlex,
Beiderman has been involved in randomized double blind placebo controlled clinical trials when they are designed and paid for by companies and these typically include patients in the 13 -17 year old range. These are studies that the companies are going to use them for approval purposes. However if you look at the studies themselves, e.g. for Zyprexa they're mainly 15 - 17 year old patients with the most severe cases of mania (average mania score of 32 with SD of ~2).
Whereas what has been pushed is usage in kids down to as young as 4 and from the descriptions probably have mania scores in the single digits.
If you look at his publications his published support for this usage are nonrandomized historical case series. In essence he's saying I put these kids on drugs and I thought they did better. It's not even clear that a proper diagnosis has been made or there's any oversight. It is these publications that he leverages into promoting use of the drugs in younger populations. I doubt that the companies themselves or the FDA would accept these as adequate and well controlled.
It's easy to look some of these up. Just go to ClinTrials.gov
Harpy - I don't know enough to say. Giving babies antidepressants (to treat something it doesn't seem anyone knows they even have) is doesn't seem to be in drug companies' interest, let alone the babies'. In other cases, I would assume if someone suggests that a drug might have an off-label use, someone else will probably try it (and that might be part of the intent of the suggestion) - in this case, though, the suggestion seems too distinct from the consequence (giving babies antidepressants) and seems to have too little benefit to the babies for it to make much sense.
Maybe I'm optimistic, but I'm assuming that pharmaceutical companies aren't stupid enough enough to market antidepressants for use in babies - their self-interest probably isn't served in doing so. Of course, I wouldn't have figured that doctors would prescribe it, so maybe my estimate of the lower limit of stupidity is too high.
Salmon,
Again, you misread my statement. was broadly commenting on Harpy's concern that clinical studies of off-label indication encourage physicians to prescribe off-label. I mentioned that the only way to get a new labelled indication is to do one or more studies on indications that are off-label. I made no mention or judgment of Biederman.
Atlex
To All
You are all debating on label, and off label prescribing of psychytropic drugs in children..I just have one question,... are any of you willing to accept the responsibility... for the death of the child?
Atlex,
I don't believe I misread your statement at all.
You were talking about how studies by a KOL can influence prescribing. I was agreeing with you. However I thought your post may have inadvertantly implied that it was only appropriate studies by Biederman that influenced prescribing.
What I did was simply point out that Biederman's studies may not all be appropriately done and as a KOL his publications (and presentations) should not be done in such a way so as to give any credence to irrational and unsupported practices. As a KOL he should know that just having a name and title and/or a tenative conclusion can influence prescribing.
Salmon
Lisa,
Off-label prescribing can be either done appropriately or inappropriately. Even when done appropriately there may be deaths and that makes inappropriate off-label usage and its promotion even more abhorent to me than usual. Even labeled usage can result in the inappropriate deaths of children if the labeling is inadequate.
It is not uncommon in medicine that even the most careful and attentive person does what the science says is the best at the time only to find out later that it was inappropriate. For a child to die under those circumstances is tragic.
What I have problems with and which is clear, is that the industry is promoting inappropriate usage (both on-label and off-label) and in my mind under those circumstances for a child to die is criminal and whoever from the industry, academia, or FDA who are involved should be held accountable.
Things are not all black and white. There are shades of gray. That said there are things that are black and white that the pharmaceutical industry tries to make us see as shades of gray.
The only way for us to know what is truly appropriate is to get all the data.
"Of course, one might ask why Australia pays for the drugs in babies and young children if they are potentially harmful and lack a notable benefit."
One can ask the State of New Jersey the same question. Their medicaid prescribing data is just as appalling as the Australian data.
"That said there are things that are black and white that the pharmaceutical industry tries to make us see as shades of gray."
Now that's a statement I can agree with. It's that situation that the problems happen, and people are harmed.
They are using these babies as guinea pigs.. It is that simple.. The pharmaceutical companies are aware of this... Does that make them responsible?..
Sorry, atlex, I wasn't very clear. What I was trying to get at is how does a treatment so bizarre - giving babies antidepressants - become so widespread, and seemingly so quickly, without someone encouraging it? Does the fact that a prominent KOL (like Beiderman) doing a study on a use for a drug lend it credibility as a treatment - even if the results are not definitive? I know I've read of situations where one or two studies were done, the company did not pursue a new indication with FDA, and the drug becomes commonly used for that purpose (but please don't ask me to cite). I'm not trying to lay blame - only to understand how one reaches a conclusion that it is appropriate to give a baby/child a powerful mindaltering drug.
I guess I'm asking more about the socio/psychological aspects of off-label prescribing. How does something that on the face of it is so appalling (at least to me) become a fairly accepted practice? Justice? You around?
No matter what way you dress it up, or no matter what way you attempt to deflect it, the reality is prescribing Anti-depressants to babies is abuse..
The doctors, psychiatrists and pharmaceutical companies who are involved in this all share equal blame here..
It is absolutely and totally unjustified to prescribe SSRI's to babies and children..
As an adult who was prescribed this drug at 21 years of age, I can attest that these drugs are highly dangerous at any age..
Anyone involved in the marketing an promotion of these drugs should be deeply ashamed of themselves..