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David Axelson

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David Axelson, M.D., is the director of the Child and Adolescent Bipolar Services Clinic at the University of Pittsburgh Medical Center and an associate professor of psychiatry at the University of Pittsburgh School of Medicine. Here he discusses the process for diagnosing bipolar in children; the difficulty of finding appropriate treatments for them, both medically and in the existing health care system; and his clinic's decision to avoid funding from pharmaceutical companies. This is the edited transcript of an interview conducted on Aug. 2, 2007.

Seven years ago, I was sitting down with several doctors, and someone at NIMH [National Institute of Mental Health] described child psychiatry as being in the Dark Ages. Do you think we've advanced in the last seven years since then? ...

I think we have advanced in that we can offer treatments for many kids that can really help them, so describing it as the Dark Ages wouldn't be accurate. We have different medication treatments that have been shown to be effective for many disorders. Also, some psychosocial or therapy-type treatments have been effective for treating kids with anxiety, depression and whatnot.

We have still a long ways to go, and we don't fully understand how the brain works and causes some of the disorders that we see. But we still are able to help kids and families and make a difference in their lives. I'm very optimistic about where we are and where we're going.

Tell me a little bit about how the field has evolved since you were initially trained.

Well, we certainly have had a lot more research into different kinds of treatments. We have many more medications available than compared to when I was in my training. And I think I have a better appreciation for the wide range of disorders that can occur in kids.

We have a better appreciation for depression and bipolar disorder. It's not only illnesses of adults, but illnesses of children as well. I think that we have done a better job about applying diagnostic criteria and DSM [Diagnostic and Statistical Manual of Mental Disorders] for diagnostic criteria.

But it is a slow process. So that hasn't changed immensely over the past seven years. And [there's] still a long way to go. ...

So ... it's progressed, but maybe not as fast as you'd like.

Well, I'd always like it to be faster. I'd love to be able to help diagnose kids more accurately and more quickly, be able to choose treatments the first time around that work instead of having to sometimes try one thing and see if that works, and if that doesn't work, then try the next thing. ... But that's a problem with a lot of medicines still, and I don't think that's necessarily unique to child psychiatry. There are things that I would like [to be] better, but I think we are doing a good job and able to help many of the families that we work with.

One of the main issues, I think still, is there are very few child psychiatrists, and if these services aren't available generally to people who want them -- and we're still working with education of the public and stigma and resistance to seeing that children can have brain disorders as well as adults, and that that doesn't mean that it's faulty parenting or that these kids really are to blame or bad kids. I mean, these are kids that we work with. Parts of their brain aren't functioning well. That's an illness, and that's something that we can help treat.

I was here in Pittsburgh during the bipolar conference, and [NIMH director] Tom Insel was in some ways kind of scolding the crowd, saying that too much of the research focus is on how well the meds work instead of understanding what's truly going on. Do you agree with that?

I agree with it in part. We have to have a balanced approach. The brain is extremely complicated, and it's going to take us a long time to figure out these problems. And these disorders are multifaceted, multifactorial. There's lots of things impacting on them.

It's going to be a bit of a slog for us to figure out what circuits aren't working, what is causing this spectrum of disorders in kids and adults with psychiatric problems, so I don't think we can wait to find out precisely what's going on before we start looking at treatments and seeing what treatments work better than another, because we have to also treat the patients who are here and now and families that are suffering, and we have to do a better job at it. That requires research as well. ...

I appreciate Dr. Insel's desire for us to have a better understanding of what is going on in the brain in folks who are suffering from mental illness. That certainly is something that's very important to me, and I think that is a way we're going to be able to advance treatments further and make a big leap. But I also know that it's going to be complicated and long, hard work, and I don't think we can simply focus ... on just studying how the disorders are occurring, the pathophysiology, which brain circuits aren't working well and things like that.

When you talk about brain circuitry, most kids understand what's going on as "I have a chemical imbalance in my brain." Is it more chemical imbalance? Is it more a problem of circuitry? ...

... [I]n some ways, it's a little of both. The brain uses chemicals to communicate. You can think of it almost as a complex system of interconnected wires and little nodes of processing.

Those circuits use electricity to propagate information. Then the neurons, or the wires, also communicate to the other wires using a chemical message, and that message gets released, or those chemicals get released, and that can influence whether the next wire or circuit fires.

So there is a chemical aspect to it. But it's really probably better to think of it in the crude way that we know about it now: that certain areas of either processing or signaling through the network of wires or neuronal circuits we have in our brain aren't working well.

... [T]hese kids, although when they're ill can have a lot of problems, they still have many parts of their brain which are functioning great, and some even better than other folks'. So it's not that the whole brain is the problem for most of these kids. It's really that some parts, some networks, aren't working very well. Others are.

We still understand so little about the brain now. We know that certain areas tend to communicate with other areas. They send wires or circuits or white matter tract, ... but precisely how those interact when they reach there -- it's a complicated network, and so much is interconnected. And a lot of the processing in our brain is distributed, so it's not like there's a discrete area that does all that function. Or at least it's influenced by other parts of the brain.

We were just at this place called Brain Matters, where they're looking at blood flow, and they were showing these scans to families and saying, "This should be more red than green," or, "This is more green than red, and therefore it shows you have bipolar." Is this something that is as clear as they were portraying it?

No, it's not so clear. It would be wonderful, and hopefully someday we will be able to use some sort of objective test or brain scan or whatnot. But we don't know what's causing this disorder, and it's unfair to families to purport or pretend that you know.

We're barely getting started at figuring out what might be wrong in these kids' brains, and just because one part has a little bit more blood flow than the average kid [has] in one area, that doesn't -- nothing is diagnostically specific at this point.

It's absolutely not accurate. There are certain areas -- the amygdala is one area of the brain that, on average, seems to be different in size in bipolar kids. But that's not even that specific. There are bipolar kids of a certain age that are going to have normal or typical size. These are things that are, on average, different, nothing that's diagnostically specific.

How do the medications work for bipolar? Do you guys have a sense of why it's helping?

We don't have a good idea about how these medications work. We have some leads. Certainly there are some groups looking at the molecular cascades and signaling cascades that occur when medications are administered.

Husseini Manji, [chief of the Laboratory of Molecular Pathophysiology at NIMH and the director of the NIMH Mood and Anxiety Disorders Program], and his group have done some real pioneering work looking at what happens when lithium is administered. But we can't look inside the actual human brain as it's working. We can't look at the molecular contents right now. We just don't have that kind of imaging resolution.

We can look at it in cell culture. We can look at it in functional imaging. In general, we can look at overall areas of the brain and how much some of the chemical constituents [are] there. But we don't have the specific ways of looking right now in depth. So we have some leads, some ideas, and there [is] some great research going on. But we're not there yet, unfortunately.

... I'm hoping you'll clarify some of the misconceptions out there. You hear some weird stuff. One thing that was confusing is a few [child] psychiatrists in the Denver area ... were saying, "I can tell if a child has bipolar if they don't respond well to the medication, and that's how I make my diagnosis."

Well, one thing that's complicated is bipolar disorder is probably not a single unitary concept or a unitary disorder. It's probably ... a collection of symptoms that are related.

Our medications, we know ... they block certain receptors in the brain. We don't know how that interacts with other parts of the brain and why blocking that receptor, why that causes a symptom to improve. But they are not always specific to a certain illness.

For instance, ... certain antidepressants work very well in treating anxiety disorders in kids who are not depressed but just anxious. The medications we use to treat bipolar disorder can also help with severe explosive aggression. It can help with autistic spectrum symptoms. It can help with treating hallucinations and psychosis. So that doesn't necessarily mean that the person is bipolar just because they respond to an antipsychotic or mood-stabilizing medicine.

But in the end, really, our goal in psychiatry is to match up patients with symptoms and syndromes with treatments. And if we find an effective treatment for somebody that's helpful and doesn't cause any significant side effects, whether that's definitely bipolar or something else, it's still matching the treatment well with the symptomatology, if it's improving.

How do you assess if someone has bipolar? Tell me the process you go through.

Well, it takes a fair amount of time to assess. We have [a] pretty comprehensive diagnostic interview, where we cover a number of different areas, including the family setting, the social environment that the child has to function in, past history, developmental history. ...

The way that we work to try to find out whether somebody has bipolar illness is a fairly complicated process. It's time-intensive ... at an initial assessment, and sometimes it takes us seeing somebody, a child, over many different visits to clarify the diagnosis. We look at many different factors, psychiatric symptoms, and really home in on trying to focus on symptoms that we know are specific for the illness. With bipolar disorder, the manic and depressive symptoms can overlap with other child psychiatric illnesses, including ADHD, including depression.

So we have to differentiate that. One way we do that is by looking at symptoms that aren't part of attention deficit hyperactivity syndrome or disorder or depression, things like extremely elated, expansive mood, way beyond just a normal child in a happy circumstance. Oftentimes we're able to get a description that it's very unusual for that particular child even.

It's a change compared to their normal happiness, their normal belief in themselves, sort of an expansive, grandiose, inflated view of what they can do [and] their importance in the world. Not sleeping very much and not needing the sleep, a term we call decreased need for sleep -- [a] child getting much less sleep than usual or compared to other kids their age and yet functioning with extreme energy.

We look for a collection of the symptoms happening at a similar time point and try to tease out distinct episodes of mood difficulties that come with the other symptoms, like increased energy, hyperactivity, impulsiveness, explosive anger, not needing to sleep very much, talking very fast, thinking very fast.

When kids are manic, there's an acceleration on a number of different levels: their physical activity, their mental activity, which we can oftentimes tell by just how fast they're talking and how fast they move through different ideas.

Families will often report that, during those times, their child is very hard to understand, because they ask them a simple question, and the child starts there but then moves on through seven different topics within a minute or so and seems to have many different thoughts all in their head. But those things happening together at a similar time point, I think, is really key. It's not one isolated symptom, like "My child has hyperactivity," or, "My child talks faster than other kids." Does that mean that he has bipolar disorder or she has bipolar disorder?

It's really the cluster of the extreme mood change, the activity-level change, the speed-of-thinking change, and the sort of boldness that oftentimes happens with kids who are manic. They interpersonally suddenly get very -- I don't know what the term [is] -- they can get very interpersonally intrusive or very interpersonally confident, so kids that are usually shy and retiring are suddenly the life of the party, coming up to strangers that they don't know, showing off. And it can get to extreme circumstances, where they're actually doing very inappropriately social things, and even -- and what can be very difficult -- inappropriate sexual behavior, which is something that occurs frequently in manic adults but also can occur in kids with bipolar disorder.

And less depression in kids.

Actually I think that there is a lot of depression in kids, although it looks like from the research that we have in several other groups that it tends to be sort of mixed or more alternating with the manic symptoms. So they go back and forth quite a bit more than adults.

That makes it a challenge to diagnose, because these phases of manic symptoms or depressive symptoms tend then to be briefer or mixed up together, so it's hard to tease out or identify clear, specific symptoms of mania. It complicates the diagnosis.

Many people talk about the bipolar fad. Do you think there is a fad?

Well, bipolar disorder has become a very common, popular diagnosis for kids, and I think that there is a risk of it being overdiagnosed. However, I still think that in certain cases we're missing the diagnosis or underdiagnosing it.

It certainly is more common than what we originally had thought 10 years ago. We have help from learning from adults who have bipolar disorder, recalling what it was like when they were kids or teenagers. Very frequently, they recall having distinct symptoms of mania or depression when they were younger.

We don't have any problem saying that bipolar disorder exists in adults, and if these adults are talking about having these similar symptoms when they were younger, then we should be seeing this or being able to identify those episodes in kids.

But there is a risk of this being something that is a label that's given inappropriately. So we have to be very careful and cautious about diagnosing a child with this illness.

This place specializes in really homing in on the diagnosis. Bipolar clinics didn't exist 10 years ago. Maybe you can tell me a bit of the history of why this came about and why it's different.

Our clinic is the genesis of [the] effort of a number of different people: generosity from our chairman, Dr. [David J.] Kupfer, and Ellen Frank, who are both very interested in research in bipolar adults; and Dr. [Boris] Birmaher, who has had a very long-standing interest in children with mood disorders and has, from his work, noticed many kids who presented as depression that actually looked like they had bipolar illness.

I was actually a postdoctoral fellow, just starting my research career after residency, and had an interest in this area as well. So with some seed-money funding from the Stanley Foundation -- that was [with] facilitation by Drs. Kupfer and Frank -- we were able to hire an administrative assistant and a part-time nurse.

Then Dr. Birmaher and I donated our time to start to see kids who were referred for this illness. Oftentimes it was not uncommon that there would be parents with bipolar disorder who started noticing what they were going through starting to happen in one or more of their children, and would identify it and be referred to see us. But over time, ... [by] going out and doing lectures and through word-of-mouth and treatment, we've been able to build up a group of folks interested in treating these kids and been able to build up a clinic over time of over a couple hundred kids in the clinic.

... [S]tarting a clinic and being able to understand a little bit about the illness and showing that we can identify these kids has helped us be able to obtain research grants to better study and understand the illness. And that has played a major part in our role of being able to both build a program and to provide good treatment for the kids.

What is this clinic's relationship to the pharmaceutical industry?

We really have no relationship to the pharmaceutical industry except that [pharmaceutical companies] do provide occasional samples of medication for kids. That is the extent of the relationship. Neither I or Dr. Birmaher do any speaking for the pharmaceutical companies, get payments from them.

We actually don't do any pharmaceutical-supported research. All our research is supported by the National Institute of Mental Health and foundation work. But I will say that the samples of medication can be very helpful for some kids in this complicated insurance environment.

With mental health really not receiving the same kind of support in the health care system that other disorders do, sometimes having access to those medications can be a lifesaver for some kids. So I don't want to minimize that that can be helpful.

The decision not to have pharmaceutical money here, not take it, how did that come about? ...

Well, for a couple reasons we decided not to take pharmaceutical money. One is that we had success getting grants from federal sources and foundations, so we've been fortunate enough to be able to build a program without needing those resources.

A second is that I think it's very important for research to be independent of, as much as possible, economic, business motivations, and most studies with pharmaceutical companies, the pharmaceutical company does have sort of the final say in a lot of the decision making. That's not something that I want as part of my research career. I want to be able to have full access to the data, to control the data and to write the paper, to make the interpretation.

So we haven't really been actively engaged in seeking out pharmaceutical grants. That doesn't mean that all research from pharmaceutical companies [is] bad. They've done some wonderful things. And we're very lucky to have the wide range of medications that they have been able to provide through their efforts. So it's much appreciated. For us, it didn't match up with our research goals.

What happens when pharmaceutical companies sponsor clinical trials? How is it that it affects the data?

Well, it depends, because there's different ways that the pharmaceutical industry and academics interact. I'm not an expert in the area because I haven't done much work with them. One way is there could be an investigator-initiated trial, where the investigator[s] themselves say, "I've got this great idea; it involves using this particular medication." [They will] propose it to the company, and [the company] will say, "Yes, we'll give you some money to do it and support it," or no. Those are pretty independent, from what I understand.

There can be more large-scale registration-type trials for the FDA ... [which] require many sites, because they have to be quite big. Companies will oftentimes then solicit or get consultation from leaders in the field to ... help them design the study and then implement it. ... Papers published from these large-scale trials, there's a variety of different levels. Some of them are quite independent, where the investigators had pretty much complete control over the content of the paper. There are others, from my knowledge, there's been more control over it from the companies. So it really varies.

But the companies also report this data, if it's a registration trial, to the Food and Drug Administration, and there's [a] certain standard that that has to follow. They're very rigorous and well done as far as making sure that they catalog adverse events, make sure that the data is very clean and well obtained. So we don't want to say that those are bad studies.

Talk to me a bit about the clinical trials and kids. What is the difficulty of conducting them. ...

Well, it's challenging doing research studies in kids for a number of different reasons. One is that you always want a child to get the best possible treatment, and when you're doing a research study, if it's going to give you answers about what the best treatment really is, you have to ahead of time say some kids are going to get one thing and other kids are going to get a different thing. And it may turn out that one of those things really was better than the other, and you've assigned children to the treatment that maybe wasn't as good.

However, essentially, without research, we do that in clinical practice every day, because we don't know really for sure what treatment is better. So the research, in some ways, is really designed to help improve practice in that way. It can be difficult when a placebo or sugar pill is involved in a trial, because people oftentimes think that that means if you're not getting them the active component that you're not getting something as good.

For some folks, that really might be the case. And that's where, if that's going to be part of a trial, it really has to be very close monitoring to make sure that the child doesn't deteriorate or there are serious problems associated with that. However, without placebo, we oftentimes can't figure out whether a medication really truly works.

It would be a terrible thing for medications that maybe cause side effects that actually aren't really any better than just taking a sugar pill and expose thousands of children in the clinic then without really knowing whether it works, because some psychiatric problems do very well with just lots of attention, assessment and caring individuals working with them. There can be some improvement, so that makes it a challenging issue.

There is an academic debate over what bipolar is in childhood and how to identify it. Where are you in that spectrum, if [Dr. Barbara] Geller is at one end and [chief of pediatric psychopharmacy at Massachusetts General Hospital Dr. Joseph] Biederman is at the other?

Well, I think I fall more in the middle -- although Dr. Geller and Biederman actually agree on some aspects of things, so it's not that they're necessarily polar opposites. But for me, it's important really to be conservative about the diagnosis. It's important to look for symptoms that are very specific to the syndrome in addition to just sort of explosive anger and hyperactivity and impulsivity. It's also helpful to try to discern discrete episodes of mood changes and behavioral changes. These children are oftentimes chronically ill or chronically have problems. But within that sort of chronic presentation of mood and behavior difficulties, one can identify periods of time where there's a distinct cluster of manic or depressive symptoms.

They may not be that long, and that's one area that we're very interested in research, is that perhaps as this illness starts, there may be relatively brief but multiple periods of manic symptoms. Then as it progresses, it may get more clear over time. But finding those distinct periods, I think, can be helpful and diagnostically specific.

It may even be symptoms that don't cause many problems. For instance, some families will tell us: "It's kind of fun when they're in an elated mood. It's certainly better than them being explosively irritable and angry." For some families it is majorly impairing, the silly moods or the elated moods, but it may not be impairing. But it may give us a diagnostic specificity that says, you know what? This isn't just mood problems in a kid or an explosive, angry kid; there is more to this that may be more specific to bipolar disorder.

When you look at the academic debate, do you think that there is one? And why does it exist?

There clearly is an academic debate, and a debate among clinicians, too. There's a wide spectrum even within child psychiatry, pediatrics, pediatric neurology. People fall on a spectrum even in the clinical field about whether this illness is prevalent or not and what sort of criteria we should use. I clearly think there is.

We still are in a phase where we're trying to better define and identify the illness, and we do have to rely on history reported by parents or caregivers and observation or a child's perspective on what they've experienced and observations that we have face to face or in a clinical setting. Since we don't have much time to see these kids, things are brief. Most work now is really done as an outpatient.

It can be hard. There are kids that don't show up for that half-hour in a manic or depressed state. Or there are very commonly kids and adults who, when they are in a structured clinical setting, will be relatively calm and not show symptoms, are able to pull it together for that period of time. But yet when you hear about what is going on at home or at school or with friends, they have very clear symptoms.

Then maybe seven or eight visits later, it does show up in the office, and you're like, "Well, that's what Mom and Dad were talking about." But if we wait that long and don't take the history and put significant stock in the history that the caregivers give, we're going to be missing a lot of diagnoses, and we'll also be spending a lot of time with kids untreated or treated the wrong way.

Obviously environment is also very important, and parenting skills can have a positive or negative impact on how a child behaves. How do you deal with that? ... People have a hard time admitting that they may not have the best techniques to calm their child down. What advice do you give parents when you sense [that]?

One thing I tell parents is that children with this illness don't respond to regular rewards and consequences, especially when their mood illness is really active. They don't respond the same way [as] other kids. And your child didn't come with a special book that says this is the way to do it. We're still learning just what clinically is the best way for folks to handle behavior in the home when the kids are having problems with mania or depression.

So remove some of the blame, because these kids, when they are ill, are extremely difficult sometimes to manage. The parents and caregivers are doing their very best, and it's extremely wearing and stressful. So one, to remove blame; and then to take a problem-solving approach and help folks understand that what might work for other kids or what might work for your child when their bipolar illness is under good control may not be the way to handle things when they're in a mood episode. So we educate about maybe two different ways or two different styles, depending upon where the child is in their illness.

The other thing that's important is that the therapeutic and psychotherapeutic treatments and behavioral treatments that we use to help have to be in a kid that is relatively stable. When they're acutely manic, we need to use the medications to help them get under better control and help their brain process more accurately.

Then suddenly the parenting skills that the parents have, it actually starts to work. An acutely manic child, there's nothing behaviorally that's going to cure the mania. It may make it safer, it may be able to manage the child better, but it's not going to cure the illness. So unfortunately, medications have to be a part of the treatment. But sometimes after the medications are started and starting to work, then the family's parenting skills and the way they manage the child can actually really improve and really help the child.

These medications are pretty complicated. They don't work all that well; they stop working; they have tremendous side effects. You must deal with this all the time. Tell me a bit about that complexity.

Yeah, the medications are complicated to use, and they're not as effective as we would like them to be, though they do help many of these children. The problem is we can't ahead of time, when we see a child, say, "This child's going to respond to this particular medicine," because there's different classes of medications that are actually effective for bipolar disorder in adults and seem to be effective in children.

Even within those classes, sometimes there's different ones that a child might respond to or is an alternate one they wouldn't. ... That's frustrating, and sometimes we try the first one, and it doesn't work. Then we have to try a different one or sometimes add on a medicine if the first one works partially but not enough.

... The side effects can be, in rare cases, pretty problematic. We really try to minimize that by doing a careful history, monitor closely, have families call us if there's problems, do some laboratory monitoring, test monitoring as well, some blood work, and work together with the child and family.

Our goal is for the child to get better. So if they're having significant side effects or problems and they're not going away, the child isn't better then, even if their mood is better. So we have to help the family and child make the decision about where we're talking about the benefit versus the problems.

Some of these medicines, though, there may be temporarily some sense that it may be a little sedating or not, make the child feel sort of slowed down or things like that. But over time, after a couple of weeks, sometimes that abates. So helping everybody be patient and wait and let those temporary side effects kind of run their course can be helpful, because we don't want to give up on a medication too fast as well.

It's hard, because this illness does wax and wane or go up and down. Sometimes you might do something with a medication and things get better and you think that you've done a wonderful thing, and that may have just been [that] the illness was going to get better on its own for that week or whatever. By the same token, it may be that you raise a dose and mood or behavior problems get worse, but that may have just been the course of the illness. You don't want to give up, necessarily, at that point on that particular medicine or combination.

How do you detect bipolar in a child?

Well, that is complicated, because in some young children, the symptoms can be fairly obvious. In other young children, it's really impossible to tell the presentation from other psychiatric illnesses, and it's going to take time and following the child before we're really clear. We have seen clear manic symptoms in kids as young as 3 that we followed then over time and over several years, and it really is clear that they have the illness.

Other kids, though, it presents maybe early on as more just severe anger, mood-behavior problems, impulsivity, aggression and hyperactivity, [and] we can't really discern it or separate it out from what could [be] many other possible disorders.

Is there a danger of giving these kids [who] are sort of unclear and you're not sure what they have a medication that's specific to bipolar?

It is a difficult situation, because we have problems both ways, in some ways, because the illnesses that are probably most commonly, in the differential diagnosis, attention deficit hyperactivity disorder or perhaps depression, if we use medication treatments to treat those disorders, and the child ... truly is bipolar, there is the opportunity to make the illness worse with that medication treatment.

That's why we can't just say, "Go ahead and do the standard medication treatments," and just go forth from there. If there's a clear possibility of bipolar disorder, one needs to be very careful about what other medication treatments that you would use. Often in very young children, we really want to be quite sure, or as sure as we can be, of the diagnosis ...

[So you would also want to try] a bunch of other stuff like cognitive behavior therapy and family therapy and --

Unfortunately, I think for a bipolar illness, medication has to be a first line of defense. ... All the psychosocial treatments that have been looked at in adults and some of the studies that we're starting to do with children have used those treatments as adjuncts or in addition to medication treatment. Unfortunately, when the illness is clearly bipolar, medication generally has to be part of the treatment, especially if there's acute symptomatology, if the person is symptomatic at the time.

The only exception to that would be if there's a clear depression and there's no manic symptoms at that time. It may be reasonable, especially if the diagnosis isn't clear, to use some form of therapy, psychotherapy, and try to treat the depression that way, and follow along until the diagnosis gets more clear.

Jessica [one of the children featured in the FRONTLINE report] -- was this sort of an unusual case that landed in your office? ...

Well, the interesting thing about Jessica is she did really present in the office with symptoms, which, like I mentioned, that can be unusual or not typical, especially early on. That was actually helpful in some ways. It made the diagnosis easier. Otherwise, her case was not that different from some other young children that we've treated.

The exception to that would be that she had a two-to-three-week period of depression when she was, I think, 4 1/2 years old. That kind of very distinct, melancholic depression looked very similar to what you would see in an adult who was severely depressed. She was not caring for herself, not getting out of bed. She was just sort of staring at the wall, not eating, not interested in anything, marked retardation or very little movement. That's not so common to get that kind of distinct picture every day for several weeks. And that, again, did make the diagnosis more clear in her compared to some of the other younger children that present to us.

There's a video with her that you took in your office and you're asking the questions. Tell me how this video came about ... and what you saw that day.

When Jessica and her family presented to the office, we had seen her, I think, for about a month, and we had been using a low dose of an antipsychotic medication just to manage troublesome behavioral explosions, because I wasn't sure that that was the diagnosis at the time. I was very suspicious that bipolar disorder was the diagnosis, but I wasn't sure.

That day that she presented to the office, she was clearly euphoric and agitated and expansive and very active and impulsive. I know that Jessica's mom and dad had gone through a lot, and also -- they're wonderful people -- that they wanted to teach [others] even at that early stage. ... I asked them: "This isn't common to see this in an office setting, and many people don't think that children can have bipolar disorder. Would it be OK if we took a videotape and I asked Jessica and you guys some questions so we can show other folks and teach them about the illness?" They were very generous folks and allowed us to do that.

Jessica actually did a terrific job answering questions and talking about her experience, even at age 5 being able to talk about her feelings, that she was all-powerful, and she talked about angry feelings and wanting to kill other people and things like that. That wasn't her usual -- it was because she was in a manic state at the time.

It was very helpful for me and I think for others to actually see, yes, this does exist. I've shown that videotape to many different folks over the years. Her family has been wonderful about saying, "We really want other people to understand the illness." It always impresses, and people will say, "Yeah, I can see why that 5-year-old child would be diagnosed with bipolar disorder." That's a big step, that people were able to see that.

When I show this video on television, some people may say: "Yeah, my kid also talks about -- maybe she doesn't talk about being Superman. She just seems giddy, and all kids get giddy."

Well, one has to think about the circumstances, because all children do get giddy. All children in certain settings are impulsive and talk fast. Take them to an amusement park, and many children are going to be extremely giddy and silly. However, Jessica's circumstance -- this was in an inappropriate setting, number one, you know, a doctor's office, and this was happening recurrently, back and forth, throughout the weeks leading up to this, in inappropriate settings. The intensity also. Although sometimes it's hard to capture it on a videotape, the intensity of it is beyond just normal child silly happiness.

And Jessica, when she was in this state, really was well beyond that sort of normal happiness. Also, mixed in with it, a great deal of aggression and morbid thoughts and grandiose thinking that she could do anything that normally she didn't have. So that was a big change for her, which can be helpful.

But yes, we do have to think about circumstance, environment. In certain environments, all children are going to be silly and giddy, are going to be impulsive, going to be active. We also have to think about age, too. A 4-year-old is definitely going to have more mood lability and silliness and high activity levels in unstructured settings than a 12-year-old will. So making sure that you're thinking about what's developmentally appropriate for the age of the child and the situation is really key in helping to make the diagnosis.

Once you see Jessica and she's in your office and she's manic, what was the next step?

Well, the next step was talking things over with her folks about different medication treatment options. There had been a family history of bipolar disorder and a good response to lithium in that family member, so that's actually where we started with Jessica, ... and added a small amount of an antipsychotic medication to help with agitation, problem[s] sleeping, and the fact that she was having some hallucinations as well.

Initially, actually, she responded pretty well in looking back at her chart. But then [she] would have breakthrough symptoms of irritability or aggression or giddy periods, and we'd have to raise the medication dose. After about a year of doing that, she developed very, very intense -- peeing very often. Lithium can make the kidneys not concentrate your urine very well, so she was drinking lots of fluids and peeing a lot.

It was causing a great deal of trouble for her, because she would wet herself sometimes. So we elected to take her off of the lithium because of that. That side effect went away after stopping the medication. But we then had to go through a serious of different combinations of medications before we hit upon a good combination that she actually responded very well to.

We've been very happy with the fact that she's had long periods of really stable mood. One thing that Jessica still had was some residual problems that were fairly significant as far as attentional difficulties, distractibility and some impulsivity that really appeared to be attention deficit hyperactivity disorder in addition to the bipolar disorder. That's a common combination.

We did then cautiously add a stimulant medication to help address those symptoms, and it really made a world of difference in her performance at school. She immediately started reading much better. She was behind in school and really caught up within a few months. It was very impressive. It really allowed her to be able to do the work that she wanted to do, that the illness was preventing her [from doing]. It didn't make her do the schoolwork or do the reading or learn; it just gave her the ability to do it, her natural ability. So that's been a good combination.

When did the tics come about?

Actually, Jessica had tics even before she started any medication. Her initial presentation back when she was 3 years old was primarily symptoms of obsessive compulsive disorder. She had very regimented rituals that, at bedtime, could be an hour or so, where if her parents didn't do it exactly the right way, she'd have a fit and scream and make them try to do redo it. That was actually her presenting psychiatric symptoms with then-occasional tics as well.

The tics have waxed and waned over the years. But it's a genuine comorbidity that, in my recollection, was there even beforehand, that the medications didn't cause. That was one thing we have to be careful about, is problems happen that are not necessarily caused by medications, that are part of whatever psychiatric illness the person has. Not always, but sometimes.

How would [you] explain all the comorbidities that happen in her?

Well, I wish I could. We know that it's very common for folks with early-onset bipolar disorder to have other psychiatric syndromes as well, both from our work looking at kids and then also looking at adults who recall having the illness when they're kids. Those adults have more comorbid illnesses as adults than other folks with adult-onset bipolar disorder.

Why that is, I don't think we have a good idea. These brain circuits that might affect mood also modulate other circuits as well -- that might be related to some of these comorbidities -- or if there's developmental problems in certain areas that may be generalized to other areas. But we don't have a good idea about the pathophysiology of how these things happen.

Sometimes we have to be careful, because in Jessica's case, it was different. But sometimes bipolar disorder presents as lots of hyperactivity and impulsivity and distractibility. If you treat the mood disorder, that stuff goes away, and the person doesn't actually have attention deficit hyperactivity disorder. It was all the bipolar illness.

... How has she developed as a child over time? You've seen her many years.

It's been really wonderful to be able to. One luxury we have is being able to follow children over time and really get to know them, their families, and have a good sense about what they are like when they're doing well, because that helps us understand when problems start that this is not the normal presentation for the child; it's actually their illness coming back.

We've been able to see her do wonderfully in school, compared to when she was starting school, in early grade school, really struggling. We've been able to see her make friendships and relationships with other kids, whereas early on she really had extreme difficulties with peers. She and her sister have their spats and normal sisterly difficulties generally, but compared to when things were first starting, there was a lot of aggression toward her sister. It's been wonderful seeing their relationship develop to be a more normal sibling relationship, that when her illness was active and impairing really did color their relationship quite a bit.

Has she responded well to medications?

Yes, overall she's responded well. It took us a little time, but she has had extended periods -- we're talking about years at a time -- with very few mood symptoms. We had one point where we did sort of taper off one of the medicines that she was on, and she did well for a month or two, and then started getting some pretty significant irritability and aggression and mood lability.

We added a different medicine, and that went away. So it's clear that she still needs the medication. The other nice thing is, on the combination that she's on right now, she really has minimal to no side effects. She's tolerated the medication very well, and that's really our goal, to let the child develop their normal self, their normal personality; be able to reach their full potential. And I think Jessica's been able to start to do that over time.

When we talked to them about her future, Elizabeth sort of breaks down and cries and says: "I don't think she'll ever be able to be a mom. I'm not sure what will happen to her down the road." And Jessica seems really worried about her future. Is that something they should be worried about?

Well, I wish I could predict. On the positive side, for her to have extended periods of normal mood and behavior I think bodes well for a future of doing well. But this illness is unpredictable, and it can be very difficult after even doing well for extended periods. So there's no way to predict. We've seen some kids go into young adulthood doing very well, and we've seen some who have really had difficulties.

We're just early on in the research to figure out are there any predictors or anything that we can do to make sure it's a good outcome versus a not-so-good outcome. So it's understandable that they're concerned, and it's reasonable to be concerned. But one also doesn't want to be paralyzed by it, because a lot of things are going well for her and may continue to.

If you give medications early, are you preventing it from getting worse later on?

That's our hope. There has been a theory among even researchers of [adult] bipolar that the more mood episodes you have, the more difficult the illness gets. So if you're able to prevent future episodes, then the overall course is going to be better. We're hoping that we're interrupting the progression of the illness, but we don't have proof of that.

One thing we do know that we're doing is we're allowing kids to perform in the developmental phase that they are in. [If] they were very severely symptomatic, they can't do the things that an 8-year-old should be doing as far as learning in school, developing some tentative, slight independence from parents and being comfortable with peers and things like that.

When this illness is active, kids can't do that. So in some respects, although we can't say for sure it's preventing progression of the illness in the future, it is allowing, when we have success, kids to reach the developmental phases and milestones that they need to meet.

[Where is the U.S. today on this issue of mental illness? How does the health care system affect psychiatric care, both for patients and physicians?]

... [O]ne reason we're very fortunate [is] that, in our clinic, we do have some resources and time to do a careful diagnosis. And that takes money. Right now the way the health care system is structured, psychiatry, and child psychiatry in particular, isn't reimbursed for the effort that it takes. Therefore, my colleagues in other clinical settings don't have as much time or resources to be able to do this. That's not their fault.

Sometimes people are like, "Why did they miss this diagnosis?" Well, people are really doing the best they can with pretty minimal resources. And if we want to be able to help these kids and prevent, really, the cost to society, we do have to invest more in our mental health care system and treat it like we do other illnesses.

Like I said, we're fortunate to have the luxury of a little bit of time to be able to interview. But in a standard clinical setting, [for] psychiatrists, an hour is a luxury, and they don't have a team of individuals working together, generally.

[Do you see certain trends] in the mental health [of] the nation's children? ...

As far as overall trends, I think that there is a greater appreciation that severe mood disorders like bipolar disorder can be present in kids. There's a greater acceptance among many children themselves who have the illness and their peers that this isn't something that's blameworthy. Some kids are very comfortable talking to their friends about their illness -- "I have ADHD," or, "I have bipolar disorder." And other children will be like, "Yeah, I take medicine for this, too," or, "I see a therapist." That gives me some hope that they don't see it as the same level of stigma that perhaps has existed in the past.

On the downside, there hasn't been a whole lot of change in the structure of the reimbursement system. In fact, it's actually gotten more difficult rather than less difficult. There's more management from insurance companies, more hoops for us to jump through compared to even seven years ago, more approvals that we have to get. Expert physicians and therapists who work with the kids for many years are still having to write out, "Can I do this?" to an insurance company manager.

That is a terrible waste of time and waste of resources. That's time that could be used to talk to kids and families and figure out what's going on. It's been pretty counterproductive. [Do] you think a surgeon would say, "Are you allowed to prescribe this antibiotic to the child after their surgery?" and then an insurance company person saying, "No, you can't. We don't think that's appropriate"?

Why is this happening?

Well, I think it's for a couple reasons. There's a lack of appreciation that actually investing some resources into mental health care is actually going to save society pretty significantly in the long run, that there's benefits as far as kids being able to progress better, stay out of trouble, learn better, families able to function better because they're not tied up in trying to help their children every minute and supervise them.

... I think there's also a lack of appreciation of the importance of mental health care compared to other aspects of medicine. And it does cost some money. Some of these medicines are expensive, some of these treatments. Seeing somebody for several sessions does cost some resources. But our treatments actually, although they're not perfect, do make a difference for many folks, certainly as good as any other treatments in pediatric medicine.

We should be more equitable about it. Actually, the morbidity of mental illness is the biggest problem for kids. Suicide is the third leading cause of death. Accidents [are] also very high. Those are directly related to mental health treatment, way more than all kinds of other diseases that we spend billions of dollars on. So if we really want to make a difference in kids' lives, we should be putting more of our money there. And it hasn't been happening.

[Why are we seeing more bipolar or mental illness in kids today than in the past?]

... My father is a child psychiatrist and has practiced in this area for many years, and he mentions that: "Well, maybe I missed some of these bipolar kids way back 30 years ago. But," he says, "I don't remember seeing kids like this nearly as frequently."

We don't really know whether the true prevalence of mental illness is increasing in children or whether we're just better at identifying it and catching it earlier. But it's an open question, and some of it may be that people are just more comfortable bringing it to the attention of therapists and physicians. It may be that pediatricians and other health care professionals are better at sorting out and identifying it and referring. But certainly we are getting a little better at getting people access to care compared to before, and people are more comfortable entering treatment.

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posted january 8, 2008

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