SUSAN DENTZER: Now that we've been through this controversy almost a year in duration over these antidepressants in children and adolescents, what do you think the real issue is here?
DR. LARRY DILLER: I think the real issue is a culture clash. It's the difference between a society that looks at children's problems in terms of their brain and biochemistry, and responds in like with the use of medication, and a culture that's just a little bit more skeptical about that approach, and here I'm referring primarily to Western Europe -- actually, the rest of the world, to be honest. But here are the British who looked at the very same data that the FDA had and came up with very different conclusions -- a culture clash.
SUSAN DENTZER: Who is right?
DR. LARRY DILLER: Well, you know me, I prescribe these medicines all the time, but I have a real respect for them and a real concern that we move too quickly and overuse these medicines all the time. So I find it ironic that the impetus had to come from overseas because within our country there is such a lock step toward this notion of using medication with children that it really takes people looking from outside in to say what's going on here.
The need for more evidence
SUSAN DENTZER: What do you think is happening with respect to use of these drugs in children? Are we using them willy-nilly, are we overusing them, are they being over-prescribed for children?
DR. LARRY DILLER: Well, I would say that for sure we are prescribing them with virtually no evidence that they work. Now, whether or not that's a wise policy or not, that remains to be determined. We have a 60 to 70 percent improvement just on placebo, and it doesn't appear that these medications improve that cure rate much more. We have a doubling of the rates of suicidality when these pills are compared to placebo, and that's what led to the British decision, the lack of evidence that it works and a higher rate of complications.
Does that mean we're using this medicine too much? I leave to the viewer.
SUSAN DENTZER: Many people at the (FDA) advisory committee meeting, and since then, have said that there is a real danger here that people will be unduly dissuaded from using these medications. Parents will be scared off using them for their children, children will go untreated who should be on these medications, and that there's a real risk here that actually more injury will result to children as a consequence of them not being on this medication. How do you feel about that?
DR. LARRY DILLER: But I find the remarks a bit sanctimonious. Here we've been listening to American psychiatry for the last 10 or 15 years, parading brain scans in front of us, parading all this science, and suddenly there is no science. I mean, I'm not saying these children don't get any better, but again, the placebo rate itself takes care to explain in a sense much of the improvement that goes on. And this notion of parents unnecessarily becoming afraid and children not using this. I think in terms of our Hippocratic Oath, which is first do no harm, and the other thing I think of is informed consent. This is just good knowledge for parents to have.
SUSAN DENTZER: Well, what do you say to parents now, given this controversy, given the weight that we have in store now with the analysis of the (antidepressant) data by Columbia University, what are the experts at Columbia -- what are you telling parents to do with a child who is obviously suffering?
DR. LARRY DILLER: ...I've always been more careful in prescribing this class of antidepressant to children, let's say compared to using a stimulant drug like Ritalin for ADHD (Attention Deficit Hyperactivity Disorder). We just have a much better track record with the stimulants than we do with this class of antidepressant. That said there's still probably a place for this medicine, though I'm still trying to get results that prove it.
I think the take-home message to the families is a critical one here that's different from the previous one. If a child is started on this medicine and is doing worse, whether or not they're acting erratically, or not having new thoughts about killing themselves or killing their classmates, in the past the doctor would have said, "Just stay on that medicine a little bit longer." Or maybe the doctor would have said, "Let's increase the dose." Or not uncommonly, the doctor would have said, "Let's add another medicine to deal with what's going on here."
I think the message now should be let's stop the medicine for two or three weeks. If necessary, we'll put the child in the hospital on no medicine just to see what happens. And I think this is the tragedy of overlooking what happened 10 years ago, that we've lost children and adult lives unnecessarily to this medicine because of belief one that it was working, and two that it didn't cause these kinds of side effects.
SUSAN DENTZER: [Data has been presented at a conference] suggesting that during the time these antidepressants have been in use, there has also been a 25 percent decline in the rate of suicide among adolescents roughly age 15 to 19. Could it possibly be the case that we, in fact, are seeing a result of a lower rate of suicides because of these drugs?
DR. LARRY DILLER: Possibly, but I happened to be sitting next to Julie Zito and Dan Safer, the premier pediatric epidemiologists in child psychopharmacology, and when they heard that, they responded with this is an ecological study that he's referring to, it's not a specific drug study. There are too many variables involved, including an improving American economy, that might explain these kinds of findings. There's still no beef in this medicine.
SUSAN DENTZER: You were at that (FDA) advisory committee meeting. What got to you about some of those episodes that were described by parents where children did kill themselves?
DR. LARRY DILLER: It didn't just get to me, it got to every single individual in that room. I saw hardened reporters and doctors in the field, like myself, just putting their heads in their hand in story after story of a child suddenly changing their behavior, parents believing in the medicine, and then discovering their 14 year old hanging in the closet by their pants belt.
Now, again, these are human tragedies. Was the disease, depression, responsible for that? That's the question. But it also happened to people taking these medicines for migraine headaches, or for anxiety, where there was no depression at all.
So I think there is something there. Again, to the families who are taking this medicine, you don't necessarily have to stop if you're on the medicine and doing well. I don't know if it's the medicine that's working or placebo, but you've passed the critical phase.
There's a small group of people and children who will respond poorly to this, and they have to get that other message -- stop the medicine.
SUSAN DENTZER: Many people said this has been an old story with all antidepressants, that there is this phenomenon of a rollback where people feel worse before they feel better, or where people feel more energized to carry out actions that they've thought about while they were very depressed. They feel more energized as soon as they're on the drugs, and therefore they have to be watched very closely in this case.
So the suggestion is that we're not seeing anything new, we're seeing an old story play out with a new class of drugs in a new population, which is children.
DR. LARRY DILLER: Then why weren't we told this 10 and 15 years ago when Prozac came out? Why was Prozac touted as the safest medicine that primary care doctors could hand out like candy? Why in 1993 when Prozac was attacked in the courts, did an onslaught of industry-paid experts told the jury that they had nothing to worry about with Prozac? If this is common to all the drugs, why weren't we told? Not just the patients, the doctors weren't told either. And we aren't even getting into the back files story in terms of the studies at the FDA. I'm a little bit angry, you can tell.
SUSAN DENTZER: Psychiatrists are saying what's at issue here is not so much a problem with the drugs as a problem with treatment and a problem with prescribing use of the drugs but then monitoring use of the drugs by physicians, and at least in terms of the psychiatric profession, they seem to be saying that what's really at the core here is that children are not being adequately treated by pediatricians and other family care providers, and they're not being adequately monitored by those physicians. Is that the problem?
DR. LARRY DILLER: This is a familiar complaint, and has a lot of legitimacy in my opinion. However, no professional organization's guidelines has ever been able to affect physician prescribing practices. It's based on economics and publicity.
In that sense, I think the publicity associated with this FDA advisory is a very welcome thing because it will give those primary care doctors some hesitancy before they prescribe.
Now, what is going to happen to those children? Where are they going to go? There's not enough child psychiatrists and behavioral developmental pediatricians to do that adequate studying and follow-up. However, just handing the kid a pill seems to be inherently having some danger to it. But what stops doctors is the threat of suit and adverse publicity, and it's long overdue in this area.
A more holistic approach to treatment
SUSAN DENTZER: So you do agree that there is a problem, then, with over-prescription by physicians who are not specialists in this field.
DR. LARRY DILLER: Absolutely. However, I'm not entirely sanguine with the psychiatrists taking over because it seems to me many of them are doing 15 and 20 minute visits and follow-ups and just adding another medicine every time they come. What's missing here is a more holistic approach to the children, and I'm not against the medicines. I prescribe them every day. But here the child psychiatrist is sitting in his office spending 15 or 20 minutes in medication follow-up where he could be working with those parents, or could be visiting the school and really organizing something much more coherent for this child in terms of treatment, but money is driving this in terms of where the doctor gets paid more, and that's a very sad story for our country.
SUSAN DENTZER:Let's talk about this whole episode that arose around the fact that it was the British who exposed the fact that these drugs were not showing up as effective in children.
DR. LARRY DILLER: Well, again, it was British skepticism that led to an exploration of the FDA records and data on this class of antidepressant. And in the process what came to light was eight unpublished studies performed by the drug companies so they could get their patent extended under something called the pediatric rule, but under no obligation did they have to publicize or publish those findings. And what we learned was the previously published studies showed three out of seven studies showing some kind of useful or positive effect coming from this class of antidepressant.
What we didn't know, and what the British brought to light, were their eight additional studies that didn't show any value, but showed higher rates of complications using this medicine. Suddenly now we have only three of 15 studies showing any positive effects, and about 10 or 12 of those studies showing negative effects.
So how, as a doctor on the front lines, am I supposed to make clinical relevant decisions here when I'm only getting half the information, and the information in a sense has been censored or spun by the drug companies with the legal complicity, I see, of the FDA. So that was really a very disturbing discovery kind of confirming some things I had believed, but very, very disturbing.
SUSAN DENTZER: What do you think should be the case going forward with publishing that kind of information?
DR. LARRY DILLER: Well, the drug companies' response is this is proprietary information. We don't have to publicize this because it would be disadvantageous to our profits and our stockholders. And I say if you're going to make money with the pediatric rule, then this data has to be available to everyone. If it's going to the FDA, it may not be published, but there should be a repository where any doctor can go online and find out all the studies that the FDA has. That's called transparency.
And I think another very important thing is the lack of a systematic follow-up of these medicines.
SUSAN DENTZER: What do you mean, systematic follow-up?
DR. LARRY DILLER: Well, right now we have a situation that once a drug is approved by the FDA, and it's costly to get that done, I think the drug companies are entitled to their profits. But once a medicine is approved, it can be used forever for any purpose. That's called off-label prescribing, and we never find out really what the drugs do. There's no economic incentive to find out if the drugs are working or not, particularly if they're not working.
And so what we have here is a system based -- for profit, that the only people who can possibly make a profit here are the trial lawyers. So the trial lawyers have to wait until individuals get hurt, and then to the society we have this enormous legal cost working, for the trial lawyers take a lot of money, and a lot of people have to get hurt. It's a ridiculous system, but our country is based on making money.
There's nobody making money in follow-up. However, on my Web site I offered a proposal. Would consumers be willing to pay, let's say, 1 percent of the drug's cost as a surcharge for an independent, systematic post-marketing surveillance system. That's what we call it officially. Eighty percent of the people who responded to this poll said they would be willing to pay 1 percent. And Susan, I can tell you, with an $11 billion industry of antidepressants, 1 percent funds a lot of studies.