Child Study Center Grand Rounds 02.16.2021

March 23, 2021

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Using Meta-Analysis to Guide Assessment and Treatment of ADHD

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00:00Thank you Andreas for that lovely
00:02introduction to the introduction and
00:05for inviting me to introduce Michael.
00:07It's actually very special 'cause
00:09Michael's given me a lot of introductions,
00:11and so it's cool that I'm getting to
00:14return the favor for this grand rounds.
00:17So I think most of you are
00:20probably familiar with Michaels.
00:22You know basic baseball stats here
00:24that he got his bachelors in biology
00:27from University of Pennsylvania
00:29and then he came to Yale.
00:31So he did his medical training here
00:33at Yale and then decided to stick
00:36around to join the inaugural class
00:39of the Solemate Integrated Program.
00:41I had to include this picture,
00:43which is one of my favourites.
00:45I think Anna Stevens sent this
00:47out on a chat program and I just
00:50grabbed it right up 'cause I think
00:52this is the first four years of the
00:54Soul Net program in a very faded,
00:57appropriately faded photo.
00:58So you can probably recognize
00:59a lot of the folks on here.
01:01A lot of successful people and a lot
01:04of really kind people in this photo,
01:06and you can see a sort of self satisfied
01:10Michael Block right in the middle.
01:12So he finished the program in 2010
01:15and along the way got a Masters in
01:18Epidemiology which has served him very
01:20well and probably is part of the work
01:22he's going to present to you today.
01:26And after all this time at Yale,
01:28he thought I still have more work to do
01:31here and so he joined the faculty and
01:33has been here for the last 10 years.
01:36He's touched a lot of different programs
01:38and impacted this center in many ways,
01:41but one of them is really transforming
01:43his own little corner of the 2nd
01:45floor in the Child Study Center
01:47into the shrine to Mets baseball.
01:49You know,
01:50I hope someday that the Mets
01:52return the favor for his loyalty,
01:54but I don't know if this will be the year.
01:59And this is the part where I think you
02:01know we highlight some of the wonderful
02:04accomplishments and it's hard to do
02:06because Michael has done so very many
02:09things at the Child study center.
02:11So he's the Co director of the Tick
02:13in OC D program with Tom Fernandez.
02:16He's my Co director with the pediatric
02:19treatment Resistant Depression
02:20program that we started in late 2019.
02:22He's the Co director of the
02:24T32 program with Mike Crowley.
02:26You can see he's a Co director of
02:28many things which I think highlights
02:30how well he works with the faculty
02:33and the trainees here.
02:34He's also the associate director
02:36of the Albert J Solnit program,
02:38so really coming full circle from
02:40being a member of the first class
02:42to now shaping the future.
02:44He was also the inpatient Chiefs
02:46of the Clinical Neuroscience
02:48Research Unit up until 2018,
02:49so you can see these are very
02:52prestigious programs both within
02:53and outside the Child Study Center,
02:55and I think it's not a coincidence
02:58that Michael's fingerprints
03:00are on these programs and that
03:02they've been so very successful.
03:04Of course, what we're talking about
03:06here today is some of his research,
03:08and he's been very impactful
03:10with his clinical trial.
03:11An meta analytic work,
03:12I think he's one of the only
03:14speakers where I had to ask him what
03:17exactly are you presenting today?
03:19I mean, most people I know what
03:21they're going to talk about,
03:23but he's an expert in so many areas.
03:26Publishing really important work
03:27and depression, anxiety, OCD,
03:28trichotillomania tic disorders,
03:2980 HD and then not only in child psychiatry,
03:32but also publishing across the lifespan.
03:35I think it's hard to overstate
03:37how important his work has been,
03:39not just to child psychiatry,
03:41but to psychiatry at large.
03:43If you like to put numbers
03:45to stuff like this,
03:46he's got an h-index of 62.
03:48This is a graph looking at the
03:51h-index of Nobel Prize winners
03:52after they've won the Nobel Prize,
03:55so presumably have done some very impactful
03:57work that's been widely disseminated,
03:59and you can see each index of 62.
04:02It's pretty darn good.
04:04Very influential in the field.
04:06He's on the editorial board of
04:08all these important journals,
04:10so I think it's fair to say that he's
04:13really a modern Renaissance person
04:15here at the Child Study Center.
04:18And finally,
04:18you might worry that having you
04:20know all of these titles and
04:22doing all of this important work,
04:24you know that that might go
04:26to his head that he would be,
04:28you know,
04:29not approachable or too busy or
04:31or any of those things.
04:33And I think you know my favorite thing.
04:35Working with Michael both as a
04:37mentee and now as a partner is just
04:39how caring he is for his patients.
04:42And for trainees that they always come first.
04:44And you know,
04:45it's nice to publish papers and get.
04:48Prizes.
04:48He's got plenty of papers
04:50and plenty of prizes,
04:51but I don't think he ever loses
04:53sight of the fact that the
04:55purpose of this work is really
04:56to impact the the kids and the
04:59families that we see every day.
05:00So I'm really excited to hear what
05:02he's going to talk about today,
05:04which is using meta analysis to guide
05:07the assessment and treatment of ADHD.
05:09Go Michael.
05:14Unmute myself, thank you
05:15for the kind introduction.
05:16I'm gonna do my own introduction of
05:18myself and I may need to borrow your
05:20slides for my introduction next time,
05:22'cause I think you did a
05:23better job then I'll do it.
05:25I'm introducing myself. I guess.
05:30First thing to say is I need to get the.
05:33Sorry, let's get it working OK.
05:40OK, can people see the slides?
05:43Someone says not yet,
05:44but while you do that, Michael,
05:46I just want to add one word to
05:48the introduction of
05:49the introduction and that
05:50is that your partner in crime is part of.
05:53He's certainly worth giving a thumbs up,
05:56so Angie in the House so anyway.
05:59Back to you Michael, can you see the slides?
06:03Yep OK good OK let me.
06:06OK, so yes, the first thing we get through
06:09his disclosures and we run a bunch of
06:12clinical trials that are partially funded by.
06:16Industry, none of these really involve ADHD.
06:19I haven't really done any
06:21clinical trials in ADHD,
06:22so I don't think any of the
06:25particular disclosures are relevant.
06:28I think Jenny gave a really good
06:30kind of introduction on what I do.
06:32I think the first thing to say is
06:34what I do with the Child study
06:36Center is that I have a fairly busy
06:38outpatient practice and all the
06:40disorders that you talked about earlier
06:42in the in the Child study Center.
06:45I involved in the only training
06:48program in the T 32 and then just run
06:50a lab involved in clinical trials
06:53and meta analysis research and all
06:56these things really intersect in both
06:58the research and care of patients,
07:01and I guess the real thing I want
07:04people to get out of this lecture
07:06more so than any particulars about
07:0980 HD pharmacology or 80 HD treatment
07:12is just that the experiences with
07:14the patients and the trainees.
07:16Really affects the research and
07:18then the research also affects the
07:21care of the patients and hopefully
07:23the education of the trainees and
07:25that it's sort of a circle.
07:27I guess I would also say that I'm a
07:29father of three kids and and I picked up
07:32two dogs in the family during the pandemic,
07:35so I apologize if they make any noise
07:38and I I guess I also should think Angie,
07:41for if it's quiet you should think energy
07:43could she'll be responsible for that,
07:45will hope it continues along.
07:47And
07:48then just again, the main
07:50purpose of this talk is to
07:52discuss that utility of clinical research
07:54and meta analysis and improving the
07:56care of patients and then also to just
07:58demonstrate how clinical exposure and
08:00teaching actually informs the research.
08:02And I'll be talking through that today.
08:06Really, where we're going?
08:07I guess there are three main points
08:09and I'm going to kind of have 3A2 cases
08:12that involve really three aspects of
08:14research that we've done in the lab.
08:16The block lab over the last few years
08:19really to demonstrate three things.
08:21The first one I want to demonstrate
08:23to people is that your risk of being
08:25diagnosed and treated with 80HD is
08:27related to your astrological form.
08:29That's the first thing I intend
08:31to prove to people.
08:32The second one is just to talk about common.
08:36Understanding of the treatments of
08:37the efficacy of common treatments for
08:40ADHD and also examine the effects of
08:42particularly doses of psychostimulants
08:43on the efficacy of medications for
08:46ADHD and the last thing I really want
08:48to talk about is just the important of
08:51race and racism and racial bias in the
08:54treatment of ADHD and other psychiatric
08:56conditions that we've also been doing.
08:59Research in the training program in
09:01the lab on this and I think doing
09:04an evidence based presentation on.
09:0680 HD ADHD pharmacology and and
09:08trying to psychiatry in general.
09:10It's also important to highlight
09:12these findings.
09:15So the first part of this
09:16talk will just be about.
09:20The risk of ADHD and its Association with
09:23birth date and this is research
09:26that's done primarily by a couple of.
09:29Trainees in lab. Jose Flores, who's now
09:32in his addiction fellowship here at Yale,
09:34soon hopefully to be involved in
09:37a child Psychiatry fellowship.
09:38And Victor, who's visiting scholar
09:40here in the Child Study Center.
09:42Ann, if you're looking at 80 HD
09:45as hopefully all of you know,
09:47being involved in the Child study center,
09:49ADHD is really associated with
09:51three core symptoms in extension
09:53and then hyperactivity impulsive
09:55ITI to get the diagnosis.
09:56You have to have an age of onset prior to.
10:00Well and you have to have
10:02symptoms in multiple settings
10:04and it needs to cause impairment.
10:06Other things that you may or may not
10:10know about 80 HD is that it's if you
10:13look at twin and molecular studies,
10:15it's as heritable or more
10:17heritable than any psyche.
10:19And then other psychiatric
10:21conditions that are currently around.
10:23It's has a similar heritability
10:25in twin studies to autism,
10:27schizophrenia,
10:27bipolar disorder,
10:28and in both twin and molecular studies.
10:30It has a much greater heritability
10:33estimate than things like.
10:35Depression and anxiety disorders.
10:37It also really has a pretty
10:40clear neuroscience.
10:41Neural biological mark marker of
10:448080 where it's really delayed
10:47development of the prefrontal cortex
10:50that's important in modulating
10:53cognitive control processes like.
10:56Attention and motor planning.
10:58So it's a disorder that has clear
11:01heritability and also has a clear
11:04neurological signal associated with it.
11:09I'm now going to convince you
11:12that it's associated with
11:13astrological sign and birth date,
11:15so I'm generally using my kids as
11:17examples of these things rather than
11:20the patients I'm singing clinic
11:22just 'cause it's easier for me
11:24to keep track of their names and
11:26not commit any HIPAA violations.
11:28So this patient I'm actually
11:30going to talk about would fit well
11:32with one of my sons, Paul,
11:34but also is actually very germane to.
11:38Patient Amalia was seeing a fairly
11:41recently in the clinic that I I
11:43took over when she left for Brown.
11:45So Paul is in now eight years old.
11:48He's in second grade.
11:50His plans are to have his own YouTube
11:53channel where he's going to be a star.
11:56Hasn't quite figured out what he's
11:58gonna do on his YouTube channel yet.
12:00He likes legos.
12:01He likes racing Matchbox cars
12:03watching and playing Minecraft videos.
12:05He likes cooking that can be really kind
12:08of disastrous thing if unsupervised.
12:10And he likes unboxing present,
12:12so I think if he had his say,
12:14and what is YouTube channel would be he
12:17would unbox presents that someone gave them.
12:20Another thing to say about Sam and
12:23Paul is that they're Twins and.
12:27And. And they were actually born.
12:33December 13th, 2012.
12:35And this is actually a picture of
12:38when the boys were in Phyllis Bodel,
12:40so when they were in kindergarten here
12:43and had a wonderful experience here.
12:46But Paul's experience in kindergarten
12:48at Bodel was at least initially
12:50quite rocky for him when he,
12:53when he started out kindergarten here,
12:55he kind of not really stay on the
12:58rug in class and he and he not be
13:02happy to go in every day and he said.
13:06You know the this is much harder
13:08for me than the other kids.
13:10The other kids are are smarter than me.
13:13They are able to do things I can't
13:15and he said this when he was starting
13:18kindergarten.
13:19Ann and I think this was probably
13:21an accurate perception of.
13:23So, uh, this initial kindergarten experience.
13:25If Odell, that he was behind the other kids.
13:30So one important thing to know about
13:33kindergarten in school in Connecticut is
13:35that it has a January 1st cut off date.
13:39So all the kids that are born.
13:43Set the cutoff for going into
13:45the next rate is January 1st,
13:47so we actually did a meta analysis.
13:50Looking at whether this sort of.
13:53Being behind in kindergarten,
13:55I was very interested in how
13:57this affected kids academically,
13:59'cause I was very interested for my own kids,
14:02but also that just the effect was so
14:05obviously large in in the Twins lives
14:08and so we actually did a meta analysis.
14:11Jose, Victor and I and Adam and a bunch
14:15of other people looking at 14 studies
14:17that looked at the Association between
14:20birth date and and diagnosis of 80 HD.
14:23The studies involved over 3,000,000 children
14:26involving nine different countries,
14:27and we stratified the studies based on when
14:31the cut off for school was in the area.
14:34So this is a graph looking at the
14:37odds of being diagnosed or treated
14:40for 80 HD as a function of when your
14:43birth month was and this was for
14:46studies that had a January 1st cut
14:48off like Connecticut and you can see
14:51that the lowest odds ratio occurs in.
14:54For the kids born in January and then
14:56there's a fairly steady increase
14:58up until the end of the year.
15:00And with the largest odds ratio being
15:02in October, November and December.
15:04If you look separately at schools,
15:08that locations which had a September
15:101st cut off for an end of August cut
15:14off for for going into kindergarten.
15:18You saw a a different relationship
15:20with birthday that the
15:22highest the highest rate of diagnosis of
15:26diagnosis and treatment for ADHD was in
15:29July and August and lowest
15:31was right after the school cut
15:34off in September and October. And
15:38if you overlay the two time periods and put
15:41the cut off in a common place, you get a
15:45fairly similar trends where kids
15:47are at much lower risk when they
15:50are relatively old for their grade
15:52and are at a much higher risk of
15:55getting diagnosed for ADHD if they're
15:57young for their their school age.
16:00And this is in another way of looking
16:03at a comparing the odds of being
16:06diagnosed or treated for ADHD.
16:09In the 120 days before the school
16:11cut off versus 120 days after the
16:14school cut off and at least your
16:17odds of being diagnosed or treated
16:19for ADHD was about 40% higher.
16:22If you were born right before the school,
16:25cut off as opposed to afterwards an you
16:28can actually take this data and look
16:31at changing when the actual cut off
16:34time is and you see that if you only
16:37look at the 30 days before and after.
16:41So the school cut off.
16:43The kids are at about a 50% increased
16:46risk of being diagnosed and or treated
16:50for ADHD if they are born in the month
16:54before the school cut off as opposed
16:57to the month after this welcome.
17:00So it has a pretty profound effect.
17:03Anne Anne this really?
17:06Has a really profound implications
17:08for a number of things.
17:09So the first thing is the bottom
17:12line is that the month of birth is
17:15strongly associated with the risk of
17:17being diagnosed and treated for ADHD.
17:19It's related to the school entrance
17:22cut off date for the location.
17:24It seems like the effect decreases
17:26with increasing age and the effect
17:28is quite substantial.
17:29Really.
17:30A 50% increased risk of being
17:32born in December in Connecticut
17:34as of four supposed to be.
17:37Being born in January and this really
17:39probably has pretty important impacts,
17:42especially for studies in early childhood
17:45that look at ADHD risk that it's not
17:48only your risk of ADHD compared to your
17:52actual Chronicle chronological age,
17:54but it's probably equally or more
17:57important the your risk of ADHD
18:00compared to what your expected age is,
18:03what your grade in school is.
18:06It also has implications for both
18:08public policy in early education.
18:10I mean with Paul,
18:11he's doing great.
18:13He's now eight years old in the second grade,
18:16which probably gave away what
18:18we did with Paul,
18:19which is we had him repeat kid in
18:22kindergarten when he went into spring Glen,
18:24but but this has a significant
18:26financial implications,
18:27and we're we're we're quite privileged
18:29to have the economic ability to
18:31have our kids repeat kindergarten.
18:33My estimate when we were doing the
18:36finances for making this decision
18:38was it was going to cost us about.
18:40$32,000 for the year to hold the
18:43Twins back a year in school for the
18:45both of them so that most families
18:48don't have $32,000 to spend on this.
18:51And I think that really made
18:53me think a lot about this.
19:00Moving on to the assessment
19:03and treatment of ADHD.
19:05We're treating kids with ADHD in the clinic.
19:08I think the one thing that I really
19:10want people to take home is the
19:13importance of using rating scales that
19:15rating scales given to the caregivers,
19:17and the teachers are much more
19:20sensitive to change than just
19:22sort of asking how kids are doing.
19:24And I think people a lot of times in
19:27judging improvement in 80 HD don't really
19:30recognize how much better kids can get.
19:32And it's not just having them be
19:35significantly improved, its to.
19:36The goal should be.
19:38Permission and the nice thing about
19:40these rating scales for ADHD is
19:43that they are freely available,
19:45so I'm I'm a big fan of the ADHD rating
19:48scale for which is publicly available
19:51on lines and 18 question survey given
19:54to parents or teachers that scores ADHD
19:57symptoms from never happening to very off.
20:00Thing,
20:01and it's freely available online.
20:03Here's a web link to it.
20:05Ascentia Lee.
20:06The kids that come in for ADHD in the clinic.
20:10This is what they give them or similar
20:13things like this snap or the Vanderbilt
20:17in terms of treating families with
20:19children with ADHD in the clinic.
20:22Really,
20:22Psychoeducation is the first things
20:25involved in treating these kids
20:27racking just helping them recognize
20:29the important symptoms and.
20:31Cognitive common impairments
20:32associated with ADHD.
20:34Obviously the typical stuff like inattention,
20:36hyperactivity,
20:37and impulsive ITI,
20:38but the other things that are really
20:41important to talk about with families is
20:44just the organizational difficulties.
20:46Many of these kids have also the common
20:50comorbidities that are associated with ADHD.
20:53You could call them
20:54oppositional defiant disorder,
20:56conduct disorder,
20:57but I would say that there it's really.
21:01Kind of the main problems are aggression,
21:03irritability and emotional
21:04abilities is sort of, if we're not.
21:06If we're going to get into common
21:08language and just understanding
21:09these things and treating them,
21:11the other thing really to talk
21:13about with families, just.
21:15Will talk about the people very often.
21:18Focus on the risks of what the medications
21:22are on the treatments for ADHD,
21:25but I think it's also important
21:28to recognize what the risks are.
21:30Not treating ADHD properly and that
21:33ADHD is associated with significant
21:35impairment impairment in in school,
21:38poor school performance,
21:39increased risk of dot dropout,
21:41and and suspension.
21:43It's associated with social impairments,
21:45difficulties with friendships
21:47and recreational activities.
21:49It's associated with the problems
21:51went in familial relationships,
21:53so also associated with a lot of
21:56safety issues that so children
21:58with ADHD and and going on to
22:01adulthood with 88 fear associated
22:03with increased risk of accidents.
22:06Whether it's physical accidents in childhood
22:08or traffic accidents and adulthood,
22:10increased risk of substance
22:12abuse and other risky behaviors,
22:14most of these things actually improved
22:17significantly with successful treatments.
22:21Behavioral treatments are also important
22:24that children with ADHD establishing
22:26clearer routines encourageing
22:28structure in their daily set schedule,
22:31setting, clear expectations,
22:32possibly setting up a reward system
22:35for good behavior, avoiding harsh
22:37punishment as much as possible,
22:40promoting exercise, sleep,
22:41hygiene, good nutrition,
22:43and then promoting things to strengthen
22:46the parent child relationship.
22:49There are also a lot of things you can
22:52do in school to help kids with ADHD,
22:55so there are a lot of
22:56things listed on this slide,
22:58but essentially having the kids sit
23:00in a place in the classroom where
23:02they're free from distractions,
23:04breaking up the big assignments
23:05into smaller pieces and then also
23:07writing down in organizing things
23:09for kids as much as possible,
23:11and then probably the last thing again,
23:13is having a reward system in
23:16school with a behavioral plan that
23:18praises them for good behavior.
23:20So when looking at the other six commonly
23:24used treatment for ADHD is medication,
23:27so I really if you look at all the big
23:32NIH clinical trials in psychiatry.
23:37MTA,
23:37so the multimodal treatment study of
23:40ADHD was the first one that was done
23:43and I think was the one that got a
23:46lot of the trials funded for other
23:49disorders looking at practical clinical
23:51trials about treatment and the MTA study.
23:54The design was quite simple,
23:56involved 580 kids 7 to 10 years
23:58old with combined type ADHD.
24:00They were randomized to 14 months so
24:03it's incredibly long randomized trial.
24:05They were either randomized
24:07to medication management.
24:08Behavioral treatment in this behavioral
24:10treatment arm was really probably
24:12behavioral treatment on steroids
24:13compared to what we what the best thing
24:16I can possibly offer a kid in the clinic.
24:1935 sessions of parent management
24:20training an 8 week child focused
24:23summer camp in ADHD where the kids
24:25would go if they were in the study
24:28and then there was a school based
24:30intervention where they work with
24:31the teachers in the profession.
24:33Paraprofessional,
24:33the same counselors kind of did
24:36all these treatments in the study.
24:37You had the combination treatment
24:39of both the medication management.
24:42And the behavioral therapy and
24:44then 'cause they couldn't use
24:46placebo controls for 14 months.
24:48They had a community care condition
24:51where patients were randomized to
24:53treatment in the community where they
24:55would most of the patients got medications.
24:58Actually similar medications to the ones
25:01used in the medication management condition.
25:05And the primary result of
25:07the clinical trial was this,
25:09essentially,
25:09what mattered in MTA over the 14 months
25:12of treatment was whether you were in
25:16the medication management condition.
25:18So the medication management condition
25:20and the combined Freeman condition
25:22did statistically equivalent,
25:23which was significantly better than
25:26the behavioral treatment alone or the
25:28Community care for core ADHD symptoms.
25:31And it's important to note
25:33that the medication management.
25:35That the combined treatment so
25:37that the addition of behavioral
25:38therapy didn't significantly improve
25:40outcome to the medications alone,
25:43at least in the core ADHD symptoms
25:45it did for some of the comorbid
25:48behavioral disorders and anxiety,
25:50but there was no St statistically
25:53significance there.
25:54So the bottom line is that medications
25:56are even over a fairly long period of
26:00time are the most effective treatment
26:02we have for the core symptoms of ADHD.
26:06And we really in terms of psychopharmacology,
26:09we really have two types of medications,
26:12methylphenidate derivatives
26:12and amphetamine derivatives,
26:14to the psychostimulant medications.
26:15And there is a huge
26:17variety of medications now,
26:19but they all essentially work on
26:21these two active ingredients.
26:23Just the pharmacokinetics of the number
26:26of times you need to take him a day
26:29when they're in your system differs.
26:32And then there are none.
26:34Psychostimulant medications
26:35like atomoxetine bupropion.
26:36A2 agonist like 115 in funding.
26:39An if you look at the efficacy
26:42of ADHD medications,
26:43really the message is quite
26:45simple so the so this is a network
26:48meta analysis that looked at the
26:51comparative efficacy of treatments
26:52and the bottom line was that the
26:55stimulants worked much better,
26:57so this is looking at response rates that
27:00the response rates compared to placebo
27:03were much higher for stimulants
27:05for methylphenidate amphetamine
27:06derivatives compared to any of the
27:08non stimulant ADHD medication.
27:10So the. So the response rate was
27:13about 40 to 50% worse for non
27:17stimulant medications compared to
27:18stimulant medications for ADHD.
27:22It's also important to say that
27:24the stimulants work much faster,
27:26so you can see the effects
27:28of stimulants within a week,
27:30whereas most of the non stimulant ADHD
27:33medications take a couple months before
27:35you see the full efficacy of them.
27:38So then the next thing we looked at,
27:41and this was done with Jose and Victor again,
27:45and also a now a PhD student at that
27:48time of Louisa Medical student from
27:51Brazil looking at does dosing affect the
27:54efficacies of stimulants for childhood ADHD?
27:58And I'm going to talk about a girl.
28:02I will call her Rachel rub.
28:04This is not will use Rachel loosely.
28:06So Rachel when she presented to the
28:09clinic was a 9 year old girl who was in
28:123rd grade carrying a diagnosis of ADHD.
28:15She was actually referred to the thread,
28:17so seedy clinic 'cause she had
28:19some skin picking symptoms.
28:21But the big issues was she was at least
28:23two grades behind for math and reading
28:26and she was getting getting frequently
28:28in trouble for school for issues
28:31with hyperactivity and impulsive ITI.
28:33And when I met her for initially
28:35for the evaluation,
28:37this is back in the time where
28:39we actually saw people in person.
28:41She really couldn't even sit for
28:43half the 60 minute interview.
28:45I plan to do with the family and she
28:48was on 10 milligrams of Adderall
28:50and she was eventually referred.
28:51Because was the Adderall making
28:53the skin picking worse?
28:54That was a fairly similar.
28:57People question to the answer.
28:59The first answer is probably their case.
29:01Report level data that the stimulants
29:03can be associated with skin picking,
29:05but there isn't any data from
29:07controlled studies, and even if it was,
29:10making the skin picking worse,
29:11the issues in fool falling behind
29:13in the behavioral issues were much
29:16more significant and so the basic
29:18clinical question is are higher doses
29:20of stimulants more effective for ADHD
29:22and would they affect the care of this child?
29:27So the thing
29:28I didn't talk about in the
29:30MTA study when it's revisited,
29:32is why was the medication management
29:34condition more effective than
29:36the Community care condition?
29:38Actually, in this graph,
29:39we stratify the community care conditions
29:42by whether or not they were medicated
29:46in the medicated Community care.
29:48Kids did significantly better
29:50than the unmedicated ones,
29:51but they did significantly worse
29:53than the kids in the medication
29:56management condition and.
29:58These kids were started
29:59on the same medications.
30:00So about 86% of them were on
30:03methylphenidate and almost every other
30:05kid was on an amphetamine derivative.
30:08And the big difference was probably
30:11one thought to be one of those
30:14that the kids in the in medication
30:17management condition on average
30:19received most of methylphenidate.
30:21That was about 40% higher than those
30:24in the Community care condition.
30:27It was 37.1 milligrams per day
30:30of short acting methylphenidate,
30:31versus a little under 23. So we actually
30:37looked at this in a large meta analysis,
30:41so we took all randomized
30:43placebo controlled studies of
30:45stimulants for childhood ADHD.
30:4725 studies involving 70
30:49treatment arms over 5000 kids. We
30:52excluded trials that wouldn't really be
30:55clinically relevant.
30:56Crossover trials trials which had
30:58the participants selected for
31:00a particular dose of methylphenidate
31:03or doing well on stimulants.
31:06The median length of the
31:07trial was four weeks and we
31:09really looked at two things.
31:12Wait, what was the dose response
31:13relationship in in 80 HD medications in
31:16general and then versus methylphenidate
31:19amphetamine derivatives and also the
31:21differences in fixed inflexible dose
31:23trials and just so people get the
31:25difference between fixed those trials,
31:27inflexible those trials.
31:28A fixed dose trial is a trial
31:31where the patient is assigned to a
31:34particular dose of the medication
31:36and they can either take that meta
31:39dose of the medicine or drop out.
31:41So they they have side effects,
31:43they still have to stay on
31:45that dose of the medicine,
31:46whereas in a flexible dose
31:48trial you can adjust the dose of
31:50medications related to side effects.
31:51So if you're on a particular dose
31:53of stimulants, inflexible dose trial,
31:55you could go down on the dose,
31:57whereas in if you were fixed those trial,
31:59you could either continue on
32:00that dose or drop out.
32:02That's the big difference
32:03between the two trial designs.
32:06And if you're looking at efficacy,
32:08the improvement in ADHD symptoms,
32:10the first important point is
32:13if you look at medications.
32:15Overall, as you increase the
32:17dose of of stimulant medications,
32:19and so these are in methylphenidate
32:23equivalents and a basic ways.
32:25Generally the Adderall derivatives have
32:28twice the potency of methylphenidate,
32:30so 60 milligrams of methylphenidate people
32:32to 30 milligrams of Adderall derivatives.
32:35Essentially,
32:35there was a overall in the studies.
32:38You saw a fairly substantial benefit
32:41of increasing the dose of stimulants.
32:43Really throughout the dose range,
32:46but particularly up to 30 milligrams.
32:48And when you looked at the
32:51flicks fixed versus flexible,
32:52those studies,
32:53if you looked at the fixed those studies.
32:57Where children had to take
32:59the dose they were assigned.
33:02It seemed like the dose response
33:04relationship was was fairly substantial,
33:07up to about 20 or 30 milliequivalents and
33:11then really leveled off at a dose after
33:153030 milligram milliliter equivalent.
33:18So essentially,
33:19if you were on a dose of methylphenidate
33:21up and you were increasing,
33:23it is generally always made.
33:25It sends up to 30 milligrams.
33:27If you could adjust the dose and
33:29if you went higher on the dose and
33:31you couldn't have just said it was
33:34a relatively neutral proposition.
33:35Whereas if you look at the
33:37flexible dose studies in orange,
33:39there is
33:40a fairly linear relationship between the dose
33:42and the efficacy of the medication.
33:44That is even going up to the
33:47higher doses were better.
33:48Uh, when you were able to adjust
33:50the dose down due to tolerability?
33:56In terms of side effect,
33:58dropouts, not surprisingly.
34:01There you are.
34:02Higher rates of side effects,
34:04dropouts with psychostimulant medications.
34:06As you got to a higher dose,
34:09the effects were great greater,
34:10so the dropouts due to side effects were
34:14hiring the fix those studies is compared
34:16to the flexibel those studies and.
34:20And the and the risk of side effects
34:23and the relationship between dose
34:25and dropouts to the side effects was
34:28fairly similar between methylphenidate
34:31and amphetamine derivatives.
34:33And if you looked at acceptability
34:35across all the studies,
34:37the the likelihood of all cause
34:40dropouts of people leaving the
34:42study was actually lower the higher
34:44you got on stimulant medication.
34:46So subjects were less likely
34:48to drop out of these studies.
34:51The higher dose
34:52of stimulant medications
34:53you put them on, and.
34:56And not surprisingly,
34:58this was a greater effect, inflexible.
35:00Those studies where you could
35:03decrease the dose of the
35:05medication due to side effects.
35:07And again, there was not much
35:10difference between methylphenidate
35:11and amphetamine derivatives
35:12in terms of these outcomes.
35:17So the bottom line is, well, when
35:20you can pause or just a dose of
35:23stimulants to the side effects
35:25similar to flexible dosing trials,
35:28and almost always makes sense to
35:30try at least try titrating up to
35:33higher doses of stimulants that it's
35:36associated with the greater treatment
35:38efficacy and its associated with the.
35:41Actually, greater,
35:42better acceptability among patients
35:43and medications work better,
35:45and this outweighs any side effects.
35:47They have an when you have
35:50side effects in these trials,
35:52either clinically or in
35:53actual clinical trials,
35:55you can quickly adjust the
35:57dose down so it so it leads
35:59to less dropouts and and this.
36:05Again, really backs up the findings
36:07of the original MTA study, and then I
36:11think it's really important clinically,
36:13so I put a graph up from actually a
36:16article that was published in the
36:19Orange Journal this past month,
36:21and this was a study that looked at treating
36:24kids with ADHD and comorbid aggression,
36:27and essentially kids were put in this study.
36:30If they had both,
36:32significant if they had qualified
36:34for diagnosis of ADHD. And
36:36then had a significant aggressive symptoms,
36:38as judged by a threshold an aggression,
36:41rating skill and all the kids were.
36:44Initially optimized on stimulant
36:46medication so they were put on
36:49stimulant medication and then if they
36:51did not respond to stimulant medication
36:54then they were randomized to
36:56receive either Depa Co Risperdal
36:58and placebo and they had about.
37:02150 kids that started
37:04this study and 63% of them when the
37:08dose of the stimulant was optimized
37:11for ADHD no longer met the aggression
37:14criteria of being in the trial.
37:17So essentially it seems like
37:19Risperdal and Deppe coat.
37:23Seem like they were a
37:24little better than placebo,
37:25though not statistically significant
37:27'cause they lost most of their
37:28sample in the open phase.
37:32But most of the kids who were really
37:35being enrolled in this trial for
37:38aggression, who had comorbid ADHD
37:40symptoms actually optimizing
37:41the stimulant led to substantial
37:44improvement in these patients.
37:45An really, at least as a clinician,
37:49makes me wonder how
37:50many kids are created with
37:53this load open the stimulant
37:55plus Risperdal or Deppe code
37:57and and whether we should.
37:59We should really be optimizing
38:01the dose of stimulants first.
38:06So Rachel's story continued. So Rachel's roll
38:10call her was. Was increased
38:14to a dose of Concerta. 54
38:16milligrams in the clinic.
38:19We switched her from Adderall to
38:21Concerta, just 'cause the
38:23pharmacokinetics made more sense.
38:25Is now advancing school.
38:28She's on grade levels.
38:30She's excelling in school made honor,
38:33roll, receiving excellent behavioral
38:35out valuations from school or ADHD.
38:38Symptoms are now minimum minimal. The mom
38:43came in to see me last
38:46week. It wasn't last week was a
38:48couple weeks ago in the clinic and
38:51and I see her every month just
38:53to kind of manage the medications
38:56and the real Rachel in the clinic.
38:59Mom said since rate rachels
39:01ADHD is improved in school,
39:03no one's pushing her like they should.
39:06She's not being challenged and they're
39:08letting her off easy on his assignments,
39:11keeping in place educational.
39:12Supports if they probably shouldn't.
39:15I hate to bring up race,
39:17but is she being treated
39:19differently because she's black?
39:21So Rachel in real clinic life is
39:24a black patient with ADHD and.
39:27This question really kind
39:29of stopped me in my tracks,
39:32'cause I think the answer is clearly yes.
39:36It's quite possible she's being
39:39treated differently with her
39:41ADHD in school and both in the
39:45clinic because of her her race.
39:48And that's the basic clinical question,
39:50and if you look at the literature on 80
39:53E, this was a study published in Pediatrics
39:56that involved in nationally represented
39:58sample of over 17,000 kids with 88.
40:00The fall to 8th grade an looked at
40:04outcomes were essentially diagnosis
40:06or assessment for ADHD and whether
40:09they were taking medications or not.
40:11And if you were black or Hispanic,
40:15you are much less likely
40:17to be diagnosed with ADHD.
40:19And if you looked among.
40:23Black and Hispanic children in school.
40:26The kids who did have ADHD at 5th grade
40:29were much less likely to be receiving
40:32pharmacological treatment
40:34for ADHD. So again, this
40:37the pharmacological treatment is is
40:39again the most effective treatment
40:40we know about for ADHD symptoms,
40:42and it's clear it's quite a bit less.
40:45I have also done some work in
40:48the past, I guess looking at
40:50the MTA cohort. So again, this
40:52these were the, you know,
40:54the kids with ADHD that were in the
40:57big NIH DOT study comparing behavioral
40:59treatments to stimulants over 14 months,
41:01and we looked at they actually filed
41:03these kids up to adulthood now.
41:06But we looked at the eight year follow
41:09up data and looked at really did a
41:12bunch of analysis looking at data
41:14driven predictors of the likelihood
41:16of receiving school discipline.
41:18So being suspended or expelled
41:20from school in the Co work and what
41:23in kids with ADHD predicts who's
41:25going to get suspended
41:26or expelled from school.
41:28And if you look at this cohort and
41:31essentially our main philosophies
41:33in these data driven approaches is
41:35throw everything at the kitchens.
41:38Except the kitchen sink at them
41:40and then see what comes out
41:43as being important and the best
41:46predictor of in this cohort.
41:48So kids who actually receive the
41:51evidence base the similar pharmacological
41:54treatments and behavioral treatments
41:56for ADHD. If you identified his black,
41:59you were 62% more likely to have been
42:03received school discipline. So over
42:05the eight year follow up, period.
42:09And and this is an Ann, I
42:11think at the time when I did this,
42:14when we publish this about five years ago,
42:17this was astonishing to me.
42:18I will say it's not astonishing to
42:21me anymore, but it was amazing to me.
42:24That raised was a better predictor
42:26of receiving significant different
42:27discipline in school than your
42:29initial response to medications.
42:30How bad your ADHD symptoms were,
42:33what your gender was, when you had,
42:36whether you had any comorbid diagnosis.
42:39At initial baseline.
42:40So basically everything.
42:41I felt like I was trained to
42:43look at as a psychiatrist.
42:46With less important than race and
42:50looking at really school disciplines
42:52and outcomes and and and then
42:55the other issue is our racial. The.
43:02You are racial implicit associations are
43:04are are how we treat patients of different
43:08races important in the in the diagnosis
43:11and treatment of different conditions.
43:14And although this is not
43:16directly related to ADHD,
43:18this was something that came out of.
43:21This study came out of a discussion
43:24with Malia, who I think from
43:26the audience today, and Jerome,
43:29who's now an assistant professor at Penn.
43:32Some also recently got his K award,
43:35and it's doing really well and it
43:38was just really came out of the
43:41observation of when we're talking
43:43that mostly the adult clinics,
43:45but also the child clinics.
43:47If you looked at the patients
43:50we treated in the OCD clinic,
43:52we rarely ever treated a black
43:55patient in that clinic,
43:56and if you looked at the patients
43:59we were treating for schizophrenia,
44:01they were primarily by PAC individuals.
44:04That was just something that's
44:06been striking in my training
44:07and my observation that yell,
44:09and I think it's true to some
44:11extent in the in the general clinics
44:13and the specialty clinics too.
44:15But I would say little less so in children.
44:20So we wanted to know like what's
44:23what's driving this effect?
44:25What's causing this?
44:26And the first important thing to note
44:29is that there are definitely racial
44:32diagnostic treatment disparities in track in
44:34psychiatry. So prior studies have
44:37suggested that individuals black
44:39individuals are three to five times
44:41more likely to be diagnosed with
44:43schizophrenia compared to white patients,
44:45despite evidence suggesting a
44:47similar prevalence across racial
44:49groups. So we wanted to examine
44:51implicit associations or attitudes.
44:53Uh, basically appraisals that are made
44:56automatically and unconsciously and may
44:59contribute to health care disparity and
45:02prior research is really conceptualized.
45:05Implicit bias ease as a
45:07form of indirect racism,
45:09and really we had two study
45:13questions and this trial do
45:15psychiatrist and trainees have
45:17racial implicit associations were
45:19related to psychiatric diagnosis,
45:21treatment and compliance an.
45:24And what Democrats demographic factors
45:26predict racial implicit associations of any.
45:28And so I don't know how many
45:31of you have taken the.
45:35You can look on Project
45:37Implicit's website and
45:38take any one of a number of them. There
45:41will also and show you another
45:43study you can do at the end
45:45looking at child mental health,
45:47but essentially these tasks. You care.
45:52Black and white faces with different words.
45:55So in the first Test you were pairing
45:58them with mood disorders and psychosis.
46:02The second task, compliance versus
46:04noncompliance, and the third test.
46:06We look at pharmacological outcomes,
46:08antidepressants and
46:09anti said antipsychotic medications.
46:11This involved around 300
46:13psychiatrists and medical
46:14students. Quite diverse,
46:16sample only a little.
46:18Over half of them were
46:21identified as white.
46:22Very good stratification of
46:24different training levels.
46:25Lots of medical students and roses.
46:27In the mean outcome was D scores,
46:31so the strength
46:32of Association between how fast
46:34and how many errors you made when
46:37comparing black versus white faces
46:39and the categories of words in this
46:43case can find versus non compliant
46:45psychotic versus mood disorder and
46:48antipsychotics versus antidepressants.
46:50And basically, participants who
46:53categorised white faces more
46:55quickly and with fewer errors
46:58when their parents have.
47:02Greater implicit pro
47:04white anti black bias so.
47:09Associating whitefaces with compliance.
47:12Or the other outcomes and this is
47:16just a way of looking at the histogram
47:19of the outcome and so we went when
47:23we looked at this in the sample,
47:25I think the first thing was it was striking,
47:29but not particularly surprising was
47:31that most psychiatric providers
47:33associated faces of black
47:35individuals with psychosis
47:36noncompliance an antipsychotic words.
47:38And for any of these three outcomes, about
47:4140% of the sample had.
47:43Moderate are greater.
47:46Association of Black faces with.
47:51With psychosis or the OR the other outcomes,
47:53and if you looked in the other direction,
47:56so the. It was about 5%, so they
47:59were, so they are eight
48:01times more likely to have.
48:04Associations of these providers of
48:06black individuals with psychosis
48:08noncompliance and antipsychotics.
48:09Then we looked at the
48:11characteristics of our sample,
48:13and we looked at two things.
48:16Provider race and the Big Thing was that.
48:21Black providers did not show this same
48:25implicit bias as other populations,
48:27and then the other big thing was it seemed
48:31like your amount of implicit bias got
48:34worse as you increased level of training,
48:38and this was true for psychosis
48:40and antipsychotic medication words,
48:42but not necessarily,
48:44but was not true of compliance,
48:47so it seems almost like it's possible that
48:50these implicit biases get trained into.
48:53Your potential medical
48:55education was really striking, so the
48:58conclusions that psychiatrist and
49:00trainees have racial implicit biases
49:02related to psychiatric diagnosis,
49:04treatment, and compliance.
49:06Clinician race and training seem
49:08like they're predictive of these
49:11racial implicit bias ease.
49:13We have additional data
49:14that Victor is writing up at
49:17the moment, suggesting that
49:19greater Self reported childhood
49:21exposure to black intervention.
49:23Individuals is actually associated
49:25with decreasing racial implicit bias
49:28even after controlling for race.
49:31And then I think it's important.
49:34I'm also emphasized that although
49:36we just looked it implicit,
49:38bias in these studies that there are
49:41additional factors that I wish we
49:44looked at more in this study that
49:46are really important than that we're
49:49including in future studies that
49:51explicit racism import is important.
49:53Also, structural, systemic, race,
49:55racism are also really important factors.
49:58And then negative mental health care
50:01outcomes experienced by many black patients.
50:04If you're looking at what the
50:07application is, I think the first thing
50:10is just education education about racism and
50:13racial implicit bias is imperative to
50:16reducing racism and psychiatric care
50:18that it seems like racial diversity
50:21and psychiatric providers may mitigate
50:23some of these effects of implicit bias.
50:26And then I think the thing we're working
50:29on now is, are there similar racial,
50:32implicit, and explicit biases
50:34among. Child, mental health
50:36providers and then hopefully doing
50:38teachers and school workers.
50:42And then the next step for
50:45research is just really developing
50:47interventions and curriculums that
50:48reduce racism and implicit bias.
50:50Then I think another important
50:52thing is just measuring the
50:54efficacy of these interventions.
50:56So I think there going to be a lot of
50:59interventions that are coming along,
51:02but it would be really great to
51:05have better measures of racism,
51:07explicit racism and implicit racism.
51:09Look at how well this actually
51:11improved outcomes within provided.
51:13Within systems and then the
51:15last thing is to look at kids.
51:19And so here is the.
51:22Applied for the current study we're doing.
51:25Looking at external Ising behaviors
51:27and and racing kids and just trying
51:30to get a similar sample in child
51:32psychiatric providers and other mental
51:35health professionals to look at whether
51:37they're similar biases in that population.
51:42Alright,
51:42take home points 80.
51:44HD causes significant impairments for
51:46kids and adults pharmacotherapies
51:48most effective treatment for core
51:51ADHD symptoms across the lifespan.
51:53Higher doses of stimulant medications
51:56have greater efficacy and there actually
51:59associated with improved acceptability.
52:02They mitigate about against
52:04many poor outcomes in children,
52:06and then I think it's important
52:09in any evidence based presentation
52:11about treatment of ADHD in kids.
52:14Just to mention that there is racial
52:17in equities are really profound factor
52:20and in the current care and outcome
52:23over Dalton with ADHD and then this
52:26goes along side of any research.
52:29Optimizing stimulant medications
52:30is also to improve the outcomes.
52:33Of all of our patients with ADHD.
52:36Spectar, particularly the black ones,
52:38and so thank you,
52:40I will leave it open for questions.
52:55There were two questions in the chat.
53:01Any of the chatters want to?
53:06Ask your question, I think. Justin.
53:11Jose, did you raise your hand? Go for it.
53:15Thank you doctor black.
53:17Great talk. I had a question
53:19specifically about the testing for ADHD.
53:21I do know that I don't know
53:24if you're familiar with Robert
53:26Williams and how he showed that
53:28some of the IQ tests were also,
53:31you know, they scored differently
53:32for Caucasian or white patients
53:34versus black children in particular.
53:37Have you seen anything like
53:39that with the ADHD testing like
53:41the Vanderbilt or. They the the
53:44ADHD four that you know that it
53:46also shows any racial bias. So
53:49I'm I'm by no means an expert in this.
53:52I sort of came about it in a data
53:56driven way after blocker muted.
53:59You did know you're good, you're good, OK?
54:05I think there's a lot of complexities too.
54:11The diagnosis and treatment of
54:13ADHD by race and ethnicity,
54:15and I don't think it's a simple story.
54:17I think they're probably different cut
54:19points on assessments and informants.
54:21It affects the outcome.
54:23I don't know the literature that well.
54:25I would also say it's I think I've
54:28it's a great under simplification
54:31of what I've said regarding.
54:33I think it would be too much of
54:36a take home message just to say.
54:39You know Bipac children or underdiagnosed
54:41or treated for ADHD that clearly the
54:44assessment and treatment of in all this
54:47is going to be much more complex than that.
54:50I also really worried about the proper
54:54assessment of comorbid disorders.
54:57You know I,
54:58I just worry that this is more of a
55:00circle surrogate for less mental health care,
55:03psychiatric care in general,
55:04and that it's not only that the kids
55:06are being left diagnosed with ADHD,
55:08but that we're also missing
55:10other other factors.
55:11And and I think that was one
55:13thing that was really hard.
55:14And, you know,
55:16I completely ducked the question
55:18of how I'm going to deal with
55:20this in the family other than.
55:22Affirming that the Moms concern
55:24is probably well validated.
55:28But I don't know. I think there's a lot
55:33of research to be done in the area,
55:35and what I can say is it's probably
55:37a fairly large effect and I I don't.
55:40I don't pretend to understand how it all
55:42works and how it should be measured,
55:44but I think that's something that our our
55:46field and really needs to start focusing on,
55:49'cause at least in the data driven
55:51approaches, it's as important is how well
55:53you respond to stimulants, which, again,
55:55stimulants work better than any other
55:57medication I know of for any condition.