*********************************************
ADHD RESEARCH UPDATE - Vol. 33, July 2000
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In this issue...

* How well do parents and teachers agree on the diagnosis
   of ADHD?

* Recommended guidelines for medication treatment

* Patterns of brain activity linked to positive medication
   response

- Subscriber Question -

"My child is 8 and was put on Ritalin by his pediatrician
at the very end of the school year because of problems he
had with attention during the year.  The teacher didn't
notice much difference during the last week of school and
we haven't either during the summer.  Now that school
will be starting again in a few weeks, the doctor wants
to try bupropion since the Ritalin did not seem to work.
Does this seem like a reasonable thing to try?"
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                            ISSUE OVERVIEW

Dear Subscriber:

I hope that you have been enjoying the summer.

This issue of ADHD RESEARCH UPDATE reviews three interesting
studies and also addresses an important question from a parent about
medication.  The first study reviewed - How well do parents and teachers
agree on the diagnosis of ADHD? - looks at the important issue of
correspondence between parents and teachers in their reports of a
child's ADHD symptoms.  As the results of this study make clear, the
correlation between what parents and teachers report is often quite low,
and diagnostic decisions based on one source alone are likely to be
inaccurate as a result.  The implications of these data for the ongoing
monitoring of a child who has been properly diagnosed is also
considered.

The second paper reviewed - Recommended guidelines for medication
treatment - is not a research study.  Instead, it presents the
recommendations from a team of ADHD experts about a framework
for prescribing medication to treat ADHD that is based on the best
research data available.  These guidelines are quite important to
review if you are considering medication for your child, and can also
be helpful if your child's treatment with medication has already been
initiated.  I think it is reasonable to speculate that the guidelines
presented are very different from what often happens in clinical
practice, and hopefully they will come to have an influence on what
physicians in this country actually do.

The final study reviewed - Patterns of brain activity linked to positive
medication response - is a preliminary but very nice piece of research.
The authors of this study took a careful look at what changes in brain
activity occur in children with ADHD who show a positive response to
medication compared to children who fail to respond.  The data indicate
that in medication responders, there is a decrease in slow wave
brain activity after taking medication and an increase in higher
frequency brain waves.  In children who fail to show improvement
after medication, the reverse is true.  These data support the idea
that ADHD may often result from underactivity in the prefrontal
cortex.  For those who are interested in neurofeedback treatment,
the data are also important because this is exactly what neurofeedback
treatment teaches children with ADHD to do - i.e. inhibit slow wave
activity and enhance higher frequency activity.

Finally, I address an important question from a subscriber about
medication for their child.  The subscriber's question illustrates
some important potential difficulties with how children are often
given meds in ways that are inconsistent with the newly published
guidelines reviewed in this article.

I hope that you enjoy the issue below.

Sincerely,

David Rabiner, Ph.D.
Licensed Psychologist
Duke University

* HOW WELL DO PARENTS AND TEACHERS AGREE
  ON THE DIAGNOSIS OF ADHD?

One of the more frustrating experiences for parents that I have
encountered is the extent to which their perceptions of their child's
behavior can differ from that of their child's teacher.  This seems
to generally take the form of teachers reporting problems at school
that parents do not observe at home, but the reverse situation
occurs as well.  A sometimes unfortunate consequence of these
different parent and teacher perceptions is that communication
and trust between parents and teachers can suffer.  Parents can
come to believe that the teacher must be mishandling their child
(which, of course, can sometimes be the case).  Teachers can
interpret parents' report of no problems at home as reflecting
either deliberate denial of their child's difficulty or an obliviousness
that results from an absence of involvement.  When such impasses
occur, it is unfortunately the child who frequently suffers because
there is no agreement between parents and teachers/school
about how to proceed.

Just how well do parents and teachers generally agree on information
related to the diagnosis of ADHD?  This was the question addressed
in a study published recently in the Journal of the American Academy
of Child and Adolescent Psychiatry (Mitsis, E.M. et al; (2000). Parent-
teacher concordance for DSM-IV ADHD in a clinic referred sample.
Journal of the American Academy of Child and Adolescent Psychiatry,
39, 308-313).  The answer to this question has important implications
for the evaluation and management of ADHD, and I believe the data
from this study are quite instructive.

Participants were 74 children (60 boys and 14 girls) from 7 to 11 years
old who were referred to a clinic because of problems related to disruptive
behavior.  The parents and teachers of these children were interviewed
separately via phone using a highly structured psychiatric interview
(the interview used was the Diagnostic Interview Schedule for Children -
DISC) so that the presence/absence of each specific symptom of ADHD
could be obtained from both sources.  These interviews enabled the
researchers to determine whether the child qualified for a diagnosis
of ADHD, and the specific subtype the child qualified for (i.e. Combined
Type, Inattentive Type, or Hyperactive/Impulsive Type) according to
each source, and when parent and teacher information was considered
jointly.  (Note: It is important to remember that the figures reported
below refer to the percentage of children in a sample referred to a
clinic for behavior problems who met diagnostic criteria for ADHD.
These figures are much higher, of course, than would be found in
a general population.)

RESULTS

How well did parents and teachers agree?  As it turns out, not very
well.  Among the 74 children, 85% met criteria for any subtype of
ADHD according to parent information (this means that 85% met
diagnostic criteria for either the combined, inattentive, or hyperactive/
impulsive subtypes according to parents).  Using the information
gathered from teachers, 76% met diagnostic criteria for one of the
ADHD subtypes.  Parents and teachers agreed on the presence vs.
absence of any type of ADHD diagnosis (e.g. if diagnosis based on
parent data was the combined type and diagnosis based on teacher
data was the inattentive type it was considered an agreement) 74%
of the time.  This means they disagreed on the presence or absence
of ADHD more than a quarter of the time.  (This is not really very
impressive when you consider that chance agreement alone would
be 50%).

Agreement for the particular subtype of ADHD was especially poor.
Among 55 children who met criteria for ADHD, Combined Type,
according to parents or teacher, parents and teachers agreed on only
17 cases.  Agreement between parents and teachers for the ADHD,
Hyperactive/Impulsive subtype was only 2 of 24 cases and for the
Inattentive subtype it was only 2 of 20 cases.

The authors also examined how diagnoses based on combined parent
and teacher data compared to diagnoses based on each source alone.
These comparisons are quite interesting and are shown in the chart
below. (Note: ADHD-C=combined type; ADHD-H/I = hyperactive/
impulsive type; ADHD-I = inattentive type).

=====================================================
                 Percentages of Diagnoses Based on Parent, Teacher, and
                                  Combined Parent-Teacher Information

                             Parent            Teacher            Combined

no ADHD                15                    24                        7
ADHD-C                 61                    37                      87
ADHD-H/I              15                    19                        4
ADHD- I                 10                    20                        3
======================================================
(Note: The numbers in the table above reflect the percentage of children
who were diagnosed with each subtype of ADHD, or who were not
diagnosed with any subtype of ADHD, based on parents alone, teachers
alone, or the combination of parent and teacher information.  For example,
the first entry indicates that 15% of children were not diagnosed with any
type of ADHD based on the parent report alone.  The fact that the percentage
of children diagnosed with the inattentive or hyperactive/impulsive subtypes
in the combined column are so low reflects the fact that when both parent
and teacher data is combined, almost every child diagnosed with ADHD
received the combined type diagnosis.)

Several things are noteworthy here.  First, it should be stressed that when
information from parents and teachers is integrated in the diagnostic
process, children are more likely to be diagnosed with ADHD of some
type (i.e. only 7% had no diagnosis in the combined condition vs. 15%
and 24% for parents and teachers respectively.  This is probably because
each reports certain symptoms that the other does not observe, and when
these reports are then combined, a greater number of symptoms is
reported than for either source considered separately.) It is also evident that
when combined information is used, the combined subtype is by far
the most common, and that relatively few children are diagnosed with
either of the other two subtypes.

How do parents and teachers compare directly?  First, it is interesting
that using teacher data alone was less likely to result in a child being
diagnosed than using parent data alone (i.e. 24% of children received
no diagnosis based on teacher data compared to only 15% using parent
data.).  Second, even though teachers are less likely to report ADHD
symptoms overall than parents, they are more likely to see children as
being highly inattentive (i.e. 20% of children diagnosed with inattentive
subtype according to teachers compared to only 10% according to
parents).  This is most likely because teachers observe children in a
context where problems with attention are much more likely to be
evident.

How do parent reports of their child symptoms at school compare
to teacher reports?

The data reported above is based on parent report of symptoms they
observe in their child at home.  Parents were also asked, however,
about symptoms they believed their child to display in school and these
were compared to what teachers reported about the child.  The
percent agreement for each symptoms was assessed and ranged from
50-76% for hyperactive/impulsive symptoms and from 43-78% for
inattentive symptoms.  This is not especially good when one would
expect agreement to be 50% by chance alone.  In fact, after correcting
for chance agreement, it was found that parent and teacher agreement
on individual symptoms was rarely better than chance.  When reports
were treated as a composite score using the different hyperactive/impulsive
and inattentive symptoms, rather than considering each symptom
individually, a modest but significant correlation was obtained.  Thus,
there was at least some significant consistency between parent and
teacher reports of how the child behaves at school when a more global
rating of hyperactive and inattentive behaviors was considered.

SUMMARY AND IMPLICATIONS

The results of this study highlight the importance of obtaining information
from both parents and teachers in the evaluation process.  As is clear
from the data above, parents and teachers do not necessarily agree on
the presence or absence of sufficient number of symptoms to warrant
any type of ADHD diagnosis in a large number of cases (i.e. 24% in
this sample).  This is the case even when parents have sought an
evaluation because of behavior problems their child was displaying.
In cases where parents are less concerned about their child's
functioning - as often occurs when a child is having problems at
school but not at home - one might expect that agreement between
parents and teachers would be even lower.

Even in this sample, however, the level of disagreement on specific subtypes
was surprising.  Having parents report on their child's behavior at school
in addition to their child's behavior at home is no solution to this problem,
as agreement with what teachers report observing for individual
symptoms is often no better than chance.  Even for more global measures
of ADHD symptoms, agreement remains relatively modest.

The clear message from these data is that relying on a single source
for diagnostic purposes - in reality, this would generally be the parent -
runs the substantial risk of misdiagnosis.  These data suggest that
when only one source is used, children who perhaps should have
been diagnosed with some type of ADHD will not be.  The concern,
of course, is that this will preclude a child from receiving treatment
who really needs it.  Of course, the opposite is also possible - i.e.
relying on a single source will result in a child being diagnosed with
ADHD who should not be.  The authors of this study argue that
the use of data from both parents and teachers is essential to
arrive at the most accurate diagnosis possible - a conclusion with
which I would strongly agree.  Unfortunately, we know that for a
variety of reasons this often fails to happen and children are diagnosed
by physicians when information has been obtained directly from
teachers.

It should also be emphasized that obtaining data from both parents
and teachers is also critically important for the ongoing monitoring
of how a child who has been diagnosed is responding to treatment.
Knowing how a child's treatment - regardless of what that treatment
consists of - is affecting behaviors specifically targeted for
improvement is critical for determining whether treatment is being
successful or needs to be modified.  As this study makes clear, a
treatment provider who relies solely on parent reports for information
about a child's behavior at school is likely to receive a different -
and probably less accurate - account of what is going on than if
the data about school behavior was obtained from the child's
teacher.  It is thus quite important for parents to insist that periodic
feedback from the child's teacher be obtained and conveyed to
their child's treatment provider so that appropriate decisions
about treatment can be made.  (Remember, this is what I developed
the ADHD Monitoring System to do.  If you have not yet
received your copy, just send an email message to
monitor@www.helpforadd.com and it will be sent to you automatically.)

Reprint requests to:

Dr. Jeff Halperin
Dept. of Psychology
Queens College
65-30 Kissena Blvd.
Flushing, NY 11367

* RECOMMENDED GUIDELINES FOR MEDICATION
  TREATMENT

Even though stimulant medication treatment is generally believed to
be a safe and effective treatment for most children with ADHD, based
on the results of numerous studies, even proponents of such treatment
would agree that they way in which meds are often prescribed is
problematic.  Among the problems that have been noted are: 1) the lack
of a careful evaluation to establish that ADHD is a proper diagnosis
prior to initiating treatment; and 2) failure to collect systematic information
on a child's response to medication so that well-informed decisions
about continued use can be made.  As a result, many children are probably
placed on stimulant medication who really do not have ADHD, and others
who really have ADHD are not prescribed medication in a way that
is likely to be as helpful as it could be.  Evidence in support of the latter
were results from the recent multi-modal treatment study of ADHD, where
it was found that children treated with medication as part of the study
did better than children who were treated with medication by community
physicians.

In response to the recognition that medication treatment for ADHD is often
not done in a careful and systematic way, efforts are underway to
develop clear guidelines that such treatment should follow.  Recently, a
set of such guidelines was published by a group of ADHD experts
(Plizka, S.R. et.al., (2000). The Texas children's medication algorithm
project: Report of the Texas Consensus Conference Panel on the medication
treatment of childhood ADHD. Journal of the American Academy of
Child and Adolescent Psychiatry, 39, 908-927).  This is an important effort
because the authors attempt to provide - based on the best currently
available evidence - a specific set of recommendations for how medication
should be prescribed that is quite different from the far less-systematic
approach that is generally used.  These guidelines are summarized below.

Note: The authors of these guidelines emphasize, of course, that the use
of medication treatment is predicated on the fact that the diagnosis of
ADHD has already been carefully established.

Also, the authors do not specifically recommend that medication should
always be the first or certainly the only treatment initiated, and specifically
emphasize that psychosocial interventions (e.g. behavioral treatment) play
an important role in the treatment of ADHD.  Instead, if medication is
going to be used, they try to lay out a careful and systematic procedure for
doing this that can be feasibly implemented in most primary care
settings.

Children who meet criteria for a manic episode, any psychotic
disorder, or a pervasive developmental disorder would be excluded from
the recommendations below.

It should also be noted that separate algorithms were developed for those
children who have an anxiety or depressive disorder in addition to ADHD.
The guidelines presented below apply to children diagnosed with ADHD
but without either of these other types of disorders.  For children with
ADHD and either depression or an anxiety disorder, the trial begins with
stimulant medication as described below, and then recommends the use
of separate meds to treat the depression and/or anxiety symptoms depending
on whether or not these show improvement when the ADHD symptoms
are reduced.  Space considerations do not enable me to include
this entire algorithm.

I expect that other groups - particularly the American Academy of
Pediatrics - may be issuing similar guidelines in the months ahead.

RECOMMENDED PROCEDURE

The guidelines below are intended to apply to children with ADHD alone, as
well as to those who have ADHD along with other types of conditions including
oppositional defiant disorder or conduct disorder.  The authors also note that
although the recommendations below should be appropriate in the majority of cases,
any stage can be skipped depending on the particular child's presentation.

Stage 1: Medication treatment for ADHD should begin with one of the
stimulants.  Typically this would be Ritalin/methylphenidate (methylphenidate
is the generic form of Ritalin) or amphetamine (e.g. Dexedrine or Adderall).
The authors note that there are no current clinical predictors indicating
which child will respond to which stimulant.  Thus, the choice of which type
of stimulant to begin with is up to the physician and parent.  (Note:  Recently,
however, several studies have been published to suggest that Adderall may
be a more effective medication for the majority of children with ADHD and
also requires fewer doses per day for most children.  It may therefore
be reasonable to begin a child's medication treatment with Adderall.)

The important point to note here is that medication treatment for ADHD
should almost always begin with one of the standard stimulants, rather than
with other types of meds or with a combination of meds.  There may
certainly be situations that warrant an exception to this recommendation,
but one would want to be clear about why a deviation from this generally
recommended place to start was being made.

The guidelines also specify the way in which medication should be prescribed
and how the impact on the child's functioning should be monitored.  A key
point here is that a full range of doses should be used with the initial medication
prescribed because body weight can not be used to predict what will be
the best dose for an individuals child.

What this means specifically is that a child would be started on a low dose of
whichever medication is tried initially, and each week the dose would be
increased until a maximum recommended daily dose is reached.  For example,
for methylphenidate (MPH), the child would be started on a dose of 5 mg
twice per day.  Each week, the dose is raised by 5 mg so that in the 4th week,
(4 weeks is the recommended length for this initial titration trial) the child would
be receiving 20 mg twice per day, with the possibility of a 3rd dose during the
day added at the physician's discretion.

At the end of each week, parent and teacher ratings of the child's behavior
(the recommended scale is the Abbreviated Conners Rating Scale, a 10
item measure of ADHD symptoms) and a side effects scale developed by
the authors.  As long as side effects are reported to be mild or non-existent,
the increase to the next dose occurs - even if it appears that the child has
done well on the current dose.  The quantitative data from the Conners
Scales is combined with clinical impressions to obtain an overall sense
of the child's degree of improvement on a 1 ("very much improved")
to 7 ("very much worse) scale.  (This scale is called the Clinical Global
Impressions Scale  - i.e. CGI).

After the 4-week trial is concluded, the child and parent meet with the
physician to determine whether any of the doses used during the trial
yielded significant benefits in the child's functioning (i.e. a CGI rating of
either 1 or 2), and, if so, what  the most effective dose was.  Assuming no
intolerable side effects were observed, this would be the dose the child is
maintained on.

The really important point here is that regardless of which medication
a parent and physician choose to start the child on, there is an initial
4-week trial in which a range of different doses are used and systematic
ratings of the child's functioning is obtained from parents and teachers
after a week on each dose.

The reason this is so important is that physicians often stop a child's
trial at the lowest dose that seems to produce benefits.  Thus, if a child
is reported to do better on the initial dose prescribed, this is the dose
the child is often maintained on.  The problem with this is that, in many
cases, even though the child received some benefit on the initial dose,
he or she would do substantially better were a higher dose to be tested.
As a result, many children are maintained on doses of stimulant
medication that really fail to provide the child with as much benefit
as would be possible.

By trying a child on a full range of doses, and comparing standardized
behavior ratings on these different doses, the likelihood of finding the
best dose for the child increases dramatically.  Although not specifically
stated in the guidelines, if a child's response to two different doses seems
to be equivalent, one would generally maintain the child on the lower
dose.  If a child clearly did better on a higher dose, however, and no
adverse side effects were reported, then it would make sense to continue
the child on the dose that provided the greatest benefit.  For some children
this will be lower doses and for others it will be higher doses.  Because
this can not be determined in advance, a procedure like that recommended
here is essential.

(Note: It should be noted that these guidelines do not advocate the use
of a placebo-controlled trial in which parents, teachers, and children are
unaware of when the child is on medication and when the child is on
a placebo.  The authors of these guidelines did not issue this recommendation
because they did not feel it would be practical for physicians to routinely
implement such a trial.

One especially  important benefit of using a placebo-controlled
trial, however, is that sometimes what can seem to be side effects to
the medication are actually reactions that occur during the placebo week
as well.  In the absence of a placebo trial, there is not really a good way
to detect this.  Unfortunately, when this occurs, a child's medication can
be stopped because of apparent side effects that are really just a placebo
response.  In addition, sometimes what looks like a very positive
response to medication is really just a placebo response as well.)

Stage 2: If the child fails to respond to the first stimulant tried, or has side
effects that make its long-term use inappropriate, the same procedure is
repeated using a stimulant not used in Stage 1. The range of doses
appropriate for that particular medication would be used across a similar
4-week trial period.

The important point here is that one does not give up on stimulants
if a favorable response is not obtained to the initial stimulant tried.
In many cases, a child who does not respond well to the first type
of stimulant used - or who experiences adverse side effects - will
respond quite well with no side effects to a different stimulant.  So,
before moving to an entirely different class of medications, or giving
up on meds altogether, a second stimulant would first be tried.

Stage 3: Some children will not respond favorably to either stimulant
tested in the first 2 stages.  In this case, the recommendation is to move on
to pemoline (i.e. the brand name is Cylert) and use a similar titration
trial procedure using the range of doses appropriate for this medication.

Because of the concerns about the potential for adverse effects on
liver functioning, the authors stress that pemoline requires that liver
functioning must be monitored twice monthly.  In addition, parents need
to be made fully aware of the potential risks.  And, the use of pemoline
would only be suggested if the stimulants tried initially were not
effective in managing the child's ADHD.

The authors noted that as a result of these concerns, many parents
and physicians will prefer to skip this stage and go directly to stage
4. (Note: As new stimulant medications receive FDA approval and
come on the market, the guidelines may change to trials of additional
stimulants before moving on to a new class of medication.)

Stage 4: In stage 4, it is recommended that the clinician and parent
select either bupropion (i.e. a newer type of antidepressant; the non-
generic name is Wellbutrin) or one of the tricyclic antidepressants
(e.g. TCAs, imipramine or nortriptyline).  There is no data currently
available to suggest which of these antidepressants is more effective
for ADHD than the other.  If a TCA is prescribed, heart rate
monitoring (i.e. ECG) at baseline and during treatment is indicated.
The authors note that bupropion should not be used in children with
a seizure disorder.

As with the stimulant medications, a range of doses appropriate
for these particular medications would be used.  For the tricyclics,
parent and teacher rating scales are collected after each week, and
the first week where significant improvement is reported would be
the dose the child is maintained on.  Thus, on the tricyclics, one
does not necessarily go through the full range of doses.  For bupropion,
because it can take as long as 4 weeks to obtain benefits, the
behavioral rating data is not obtained until the end of the trial.

Stage 5: If the first antidepressant tried does not produce a
beneficial result, or is accompanied by adverse side effects, a second
type of antidepressant would be tried as the next step.

Stage 6: If a positive response has still not been obtained, the final
recommendation is a trial of clonidine.  The authors note that the
safety and efficacy data for the use of clonidine for the treatment of
ADHD is not as well established as one would like.  If clonidine
is tried, they note that office visits are required each week to
monitor blood pressure and pulse, and that these indices should be
obtained with the child both lying down and standing.  A child
would generally take clonidine for 2 to 8 weeks at the maximum
dose tolerated to assess its response, with a total daily dose
ranging from .05 mg/day to 4 mg/day. After the child has been
on the maximum dose tolerated for 3 to 4 weeks the behavioral
rating data would be collected and the CGI rating made.  If the
CGI score is 1 or 2 (i.e. the child is rated as very much improved
or much improved) and there are not troublesome side effects,
he or she would be maintained on that dose.

SUMMARY and RECOMMENDATIONS

It is important to emphasize once again that these guidelines are
not intended to convey the impression that every child with ADHD
should necessarily be treated with medication.  The authors
note that non-medication options can certainly be considered prior
to beginning the medication algorithm, and that even if medication
treatment is initiated, psychosocial interventions will often be
a very important part of a child's treatment.

The authors are also careful to note that the management procedure
they outline always need to be used in the context of the individual
clinical situation and the clinician's judgment about what is most
appropriate for an individual patient.  Thus, these guidelines are
not published with the intent that they be rigidly followed in every
situation.

Instead, the value of these guidelines is that they provide physicians
with a systematic approach to medication treatment that should result
in a greater likelihood that such treatment can provide the child
with the maximum gains from medication that are possible.  They
also educate parents about an approach to medication treatment
that has been developed by experts in the field based on the best
data currently available.  Should your child's medication treatment
for ADHD be substantially different from what is discussed in these
guidelines (for example, your child is being treated simultaneously
with multiple medications) it would seem reasonable to inquire about
the reasons for this with your provider.

If your child is taking a conventional stimulant medication, but was not
initially tested with a full range of different doses, you should consider
the possibility that the dose your child is being maintained on would not
be the optimal one.  You may also wish to discuss this with your child's
physician. (Note: If you are using the ADHD Monitoring System to
track how your child is doing at school on a regular basis you should
be in a good position to evaluate how well your child's symptoms are
being managed.  If they are clearly being managed quite well, there
would generally not be any reason to consider an adjustment to
treatment.  If they are not, however, then such adjustments would
be important to consider with your child's physician.)

New data that may influence the guidelines described above may
certainly be published in the future, of course, and new and hopefully
more effective medications for treating ADHD are being developed.
As these changes occur, the guidelines for medication treatment will
change as well.  (You can find the web site where such changes would
be posted by going here, although when I recently checked, the ADHD
treatment algorithm was not yet posted.)

One important aspect of medication treatment not covered in these
guidelines is the need to monitor a child's treatment on an ongoing
basis even after a maintenance type and dose of medication has been
decided on using an approach such as that described.  Remember,
even when a child's symptoms are being managed well, this can
change over time for a variety of different reasons.  Thus, the fact
that a particular medication is working well at one point in time does
not guarantee that things will still be going well later on.  Monitoring
a child's functioning over time in a consistent and systematic way
can thus be critical to promoting a child's healthy long-term development.

Reprint requests to:

Dr. Steven Plizka
UTHSCSA
Dept. of Psychiatry
Mail Code 7792
7703 Floyd Curl Drive
San Antonio, TX 78229-3900
 

* PATTERNS OF BRAIN ACTIVITY LINKED TO POSITIVE
  MEDICATION RESPONSE

A recent issue of the journal Biological Psychiatry contains a brief but
very interesting report that relates patterns of brain activity in children
with ADHD to a positive response to medication.  This study is
interesting for at least 2 reasons.  First, the finding that only children
with ADHD who show a particular change in brain activity in response
to medication show behavioral improvement supports a current
theory that ADHD is associated with underactivity in the prefrontal
cortex.  Second, the findings to be discussed below also provide
support for the theory and practice that underlies the use of
neurofeedback treatment for ADHD.

Before describing the study, some brief background information will
be useful to review.  First, current theories of ADHD, such as the
recent theory proposed by Dr. Russell Barkley, suggest that the
symptoms of ADHD reflect a pattern of underactivity in the prefrontal
cortex.  It is this region of the brain that is believed to be primarily
responsible for what Barkley and others refer to as "behavioral
inhibition" - i.e. the ability to inhibit or refrain from one's immediate
response tendencies so that situations can be thought through and
various options considered.  In Barkley's theory, this core deficit
in behavioral inhibition leads to a variety of other difficulties and
eventually to the observable symptoms of ADHD.

There have been several recent studies in which EEG measures
in individuals with and without ADHD have been compared and
found to differ.  (An EEG is a procedure for measuring the pattern
of activity in different brain regions.)  Studies using this procedure
have found that children with ADHD exhibit an excess of slow
wave activity (these types of brain waves are referred to as
theta or alpha depending on their exact frequency) and a reduced
amount of beta (these are higher frequency brain waves that are
associated with attention and concentration).  The basic idea is
that children with ADHD demonstrate a pattern of underactivity
in the prefrontal cortical areas, and that this is the basis within the
central nervous system for many of the symptoms they display.
Some support for this hypothesis was provided in a study reviewed
in the April issue of ADHD RESEARCH UPDATE, in which
measures of prefrontal cortical activity was found to do a very
accurate job of differentiating individuals with ADHD from those
without the diagnosis.

Studies such as these that report an association between particular
patterns of brain activity and ADHD symptoms are an initial step
in determining whether such EEG patterns play a causal role in
a child's - or adult's - symptoms of ADHD.  Merely demonstrating
that these things are related, however, is not sufficient to establish
causality.  Instead, to get closer to making any causal conclusion
about patterns of brain activity and ADHD symptoms, one would
want to try and change these underlying EEG patterns, and then
observe where there is any corresponding change in ADHD
symptoms.

This is essentially what the authors of this interesting preliminary
investigation attempted to do (Loo, S.K. et.al.; (1999). EEG
correlates of methylphenidate response among children with
ADHD: Preliminary findings. Biological Psychiatry, 45, 1657-
1660).  Participants in this study were 10 children (8 boys and
2 girls) between the ages of 8 and 13 who had a confirmed
diagnosis of ADHD.  Children in the study were brought to
the lab on 2 separate days that were about 1 week apart.
On each day, EEG recordings were taken two separate times.
The first time was a baseline reading to obtain a measure of
the child's typical EEG activity.  The second time was about
1.5 hours after taking either a 10 mg. tablet of methylphenidate
or a placebo.

There was one other important step in this study.  Right
after the second EEG recording, children were given the Conners
Continuous Performance Test (CPT), a computerized measure
of sustained attention and impulsivity.  In this test, the child sits
in front of a computer terminal and is instructed to press the
space bar each time any letter except X is presented on the
screen.  A variety of measures are computed from this test
including reaction time, errors of omission (i.e. failing to press
the space bar when letters besides X are displayed; such
omissions are associated with failing to pay attention), and
errors of commission (i.e. pressing the space bar when an
X is displayed; such errors of responding when one has been
instructed not to is associated with impulsivity).

Prior research has documented that children with ADHD perform
differently from children without ADHD on the Conners
CPT, and this measure is often used to assist in the diagnostic
process.  In addition, a child's CPT performance has been
shown to improve significantly in response to stimulant medication
treatment.   Thus, by comparing the CPT results that each
child obtained after taking the placebo pill with the results
obtained after taking the actual medication, children could be
classified as "responders" or "non-responders" to the medication
(i.e. those classified as responders had significantly better
CPT results after medication than after placebo while the
CPT results for non-responders did not show any significant
change.)  Then, by comparing the EEG changes after
medication for the responders and non-responders, the authors
could examine what specific changes in brain activity were
associated with a positive response to medication.

(Note: In this study, the authors were using CPT results alone
to decide whether or not a child was a medication responder.
In actual clinical practice, of course, it would be important to
confirm that medication was also associated with positive changes
in the child's behavior and academic performance.  Improvement
in a lab based measure without corresponding improvement in
the child's functioning in the "real world" of home and school is
not going to do the child any good. For the purposes of this
study, however, the methods employed by the researchers are
adequate.)

RESULTS

When response vs. no response to medication was determined
as described above, 7 of the 10 children were found to have
a positive medication response.  The crucial question, then, is
how EEG changes following medication in the responders
compared to EEG changes in the non-responders.  The prediction
would be that medication responders would show a decrease
in slow wave activity (i.e. alpha and theta) because these wave
patterns are associated with daydreaming and lack of concentration
and an increase in beta activity which is associated with better
attention.  For the non-responders, no such changes should have
been evident.

In general, this is exactly what was found. Responders showed
small but consistent decreases in alpha and theta activity and
increases in beta activity.  Non-responders, in contrast, showed
the exact opposite pattern.  As the authors note "...medication
appears to increase cortical arousal and increase high frequency
activity (i.e. beta) associated with concentration and attention
among children who are positive medication responders."

The authors also examined the correlation between changes in
CPT performance between the medication and placebo
condition and changes in beta activity during these conditions.
This correlation was strongly positive which means that
children who showed the most improvement on the CPT
were those who showed the greatest increase in beta activity.
This suggests - but does not prove - that increased beta
activity is what caused the better CPT performance.

SUMMARY and IMPLICATIONS

Because of the small sample size, the results of this study
certainly needed to be considered preliminary, and replication
with a larger sample would be an important extension of
this work.  With this caution in mind, however, this is potentially
a very important study.

This study demonstrated that children who responded
positively to stimulant medication as assessed by their
CPT performance were those whose EEG results indicated
increased beta and reduced alpha and theta activity following
medication.  Thus, the children who improved showed
increased cortical activity after medication.  This supports
current views that ADHD reflects lower levels of cortical
activity (some have referred to this as a "sluggish brain"),
and that increasing this activity is associated with improvement
in ADHD symptoms.

The results of this study also have potentially important
implications for the use of neurofeedback as a treatment
for ADHD.  This is a treatment approach whose efficacy
is still not considered firmly established by most ADHD
experts, but which has yielded promising results in a
number of studies.  In neurofeedback treatment, children
with ADHD are specifically taught how to decrease
slow wave activity (i.e. alpha and theta) and to increase
higher frequency beta activity.  Several studies have
demonstrated that a majority of children with ADHD can
be taught to produce these changes.  In addition, unlike
such changes which result from medication and last only
a matter of hours, neurofeedback-induced changes are
reported to persist over time.  The results of the current
study appear supportive of neurofeedback treatment
because they show that EEG changes associated with a
positive medication response are the same types of
changes that are targeted by neurofeedback.

This is certainly not "proof" that neurofeedback treatment
works,  but it does suggest that the premise underlying such
treatment - i.e. train children to decrease slow wave brain activity
and increase higher frequency activity - is a plausible account
of what successful treatment may involve.

Reprint requests to:

Dr. Sandra Loo
Univ. of Colorado Health Sciences
4200 E. Ninth Ave.
Box C-268-68
Denver, Co 80262
 

- Subscriber Question -

"My child is 8 and was put on Ritalin by his pediatrician
at the very end of the school year because of problems he
had with attention during the year.  The teacher didn't
notice much difference during the last week of school and
we haven't either during the summer.  Now that school
will be starting again in a few weeks, the doctor wants
to try bupropion since the Ritalin did not seem to work.
Does this seem like a reasonable thing to try?"

There are several issues here that would be important to consider
and discuss with your child's physician.

First, although you do not mention this, I will assume that your
child received a comprehensive evaluation for ADHD and it
was determined that the attention problems during the last
school year were determined to reflect ADHD and not some
other issue.  If this were not done, of course, you would want
to have such an evaluation before initiating any further
treatments.  For a general discussion of what is involved in
such an evaluation click here.

Based on what you describe, there are several things that I
would wonder about.  First, if your child was put on meds
during the final week of school, this is unfortunately not a good
time to evaluate their impact.  Typically, the last week of a
school year is quite different from the rest of the year.  In
many classrooms, the amount of work required is reduced
and children are having end-of-year  parties and getting ready
for the summer.  Because of the reduced academic demands,
the demands for sustained attention are also reduced.  Thus,
this is not a good time to obtain good data on how medication
may effect a child's inattentive symptoms.  (Also, as noted
above in the article on medication guidelines, you would typically
want a 4-week trial in which your child was observed on a
range of different doses.  Clearly, this can not be done when
the meds do not start until the last week of school.)

You also noted that you and your husband did not notice
much change in your son during the summer.  I would be
cautious about interpreting this to mean that the Ritalin was
not effective.  The reason for this is that you stated in your
question that your child's problems were primarily with attention
and did not mention hyperactivity/impulsivity.  If this is the
case, and your child has the inattentive type of ADHD, his
symptoms would typically be much more evident at school
than at home.  This is because the demands for sustained
attention at school are generally greater than they are at home.
As a result, you may simply not have the opportunity to
observe your child in a context where his attention problems
are most evident, and thus you would also not be able to
observe any positive impact the Ritalin may have had on his
attention problems.

Because of these concerns, I would be cautious about
moving to try an antidepressant medication like bupropion
at this time.  As reviewed in the guidelines above, it is generally
recommended that at least 2 different stimulant medications
be tried before moving to antidepressants.  Based on your
description, it does not sound as though even the initial
stimulant has been given an adequate trial.  So, it may make
more sense to make sense to do a careful trial with several
of the stimulant medications before moving on to an
entirely different class of medications.

On other point to keep in mind is that the very beginning
of the school year can also be a difficult time to obtain
good information about how a child has responded to
medication for treating ADHD.  The reason for this is that
many children with ADHD begin the year reasonably well,
and do not start to really struggle until a month or more has
gone be.  This may be because the novelty of a new classroom
environment helps them to maintain better behavior and
focus early on.  In addition, it often takes teachers at least
several weeks to get to know a child well enough that the
feedback they provide about a child's response to medication
would be most valid.

Because of these factors, it may make sense to start the
school year without your child on medication and see how
things go.  After 2-4 weeks have gone by, it would be good
to have his teacher fill out a standardized behavior rating form
such as the Child Behavior Checklist - Teacher Version or the
Conners Ratings Scale to determine whether he/she is observing
important problems with ADHD symptoms.  If this turns out to
be the case, then a careful medication trial and/or other types
of interventions could then be implemented.

Once again, please remember that this should not be construed
as medical advice.  Your child's physician is in the best position
to advise you and the discussion above is presented as options
for you and your child's physician to consider.  Remember, the
authors of the guidelines note that these are general
recommendations only, and that the situation of a particluar child
may justify altering them.
________________________________________________

Thats' all for this month...

I hope that you enjoyed this issue of ADHD RESEARCH
UPDATE and found it to be informative.

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See you next month.

David Rabiner, Ph.D.
Licensed Psychologist
Duke University