Yale Psychiatry Grand Rounds: February 4, 2022

February 04, 2022

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"Addressing the Epidemic of Alzheimer's Dementia With Population Health Informed Collaborative Models of Care"

Brent Forester, MD, Chief, Division of Geriatric Psychiatry, McLean Hospital

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00:00I'm Chris Van **** and I direct
00:04our department's division of
00:07aging and geriatric psychiatry.
00:09This is the first grand rounds that
00:12our division has hosted in some time
00:15and I I'd like to say I think we're
00:18resuming in very fine style with
00:20today's speaker doctor Brent Forrester.
00:23Now Brent is the chief of the division
00:25of Geriatric Psychiatry at McLean and
00:28Medical Director for Dementia care
00:30and behavioral and mental health.
00:32Population health management
00:34at Mass General Brigham.
00:38He is associate professor of psychiatry
00:40at Harvard Medical School and has
00:42several other titles that I won't list.
00:45But of special note is that Brent is
00:48the current president of the American
00:51Association for Geriatric Psychiatry,
00:54which is our national organization.
00:57He specializes in the treatment
00:59of older adults with depression,
01:01bipolar disorder,
01:03and behavioral complications of
01:05Alzheimer's disease and related dementia.
01:09As we'll see.
01:11In his presentation today,
01:13his research focuses on novel treatment
01:16approaches to manage the disabling
01:19behavioral complications of dementia
01:21such as agitation and aggression,
01:23and his presentation today is entitled
01:27addressing the epidemic of Alzheimer's
01:29dementia with evidence based approaches
01:32to treating Neuro psychiatric syndrome,
01:34symptoms of dementia,
01:36and population health informed
01:39collaborative models of care.
01:41So with no further delay,
01:43let me introduce to you
01:45doctor Brent Forrester.
01:48Thank you Chris for that kind
01:50introduction and really great to see
01:52many of you on the screen who I know
01:54who have been friends and colleagues
01:55of mine for quite so many years.
01:57I will say that Yale holds a special
01:59place in my heart because as Michelle
02:01and Kirsten know during the annual
02:04meeting I become A at least a
02:06member of your family by going out
02:07to a dinner with the Yale folks.
02:09So that's always a highlight
02:11of the year for me,
02:12and it's a real pleasure to
02:14speak to you today about a topic
02:15that's dear to my heart.
02:16Which is Alzheimer's disease?
02:18So I'm going to share my screen.
02:33And Chris, give me the
02:35thumbs up if that looks good.
02:37That looks good, alright, excellent.
02:39Alright, by the way,
02:41I should say the building on the left,
02:45the old print there is the original
02:47campus of the McLean Asylum and well,
02:49it says Somerville Mass.
02:50Some people would have call it now.
02:52Charleston Charles Charlestown,
02:53Massachusetts when it was founded in 1811,
02:56it moved to the campus where currently
02:58is in Belmont in 1895 and the buildings
03:01still pretty much look the same
03:03and and the building on the right,
03:05which little fuzzy is a new corporate
03:07structure that mass general Brigham
03:08built a few years ago and has largely
03:10been empty for the past two years.
03:12Because of the pandemic.
03:14But it represents our transformation
03:16from siloed sort of singular
03:18hospitals to a system of care,
03:20and I'm I'm mentioning that now
03:22because I think it's relevant for
03:23the the second part of the talk,
03:25which is more on the population
03:26health side of things.
03:30Alright, so here are some of my disclosures.
03:34So I'm going to talk a bit about
03:35real quickly about epidemiology of
03:37dementia and talk about a case,
03:38really to highlight some of the key
03:40clinical issues I want to address today,
03:41which are really the behavioral symptoms
03:43of dementia that drive the burden of
03:45this disease and give those of you,
03:46especially those of you who, whether you,
03:48whether your geriatric psychiatrist or not.
03:50Most people I realize or not you're going
03:53to be seeing not only an aging population,
03:55but you're going to be seeing an
03:57increasing aging population with
03:58various neurodegenerative illnesses
04:00including Alzheimer's disease.
04:01And knowing more about diagnosis
04:02and treatment approaches is going
04:04to become increasingly important,
04:05so that's what I really want to
04:07focus on today.
04:08And then I'll spend some time at the
04:09end talking about how we've adapted
04:11some of these key principles and
04:13implemented them in a population
04:14based setting in primary care.
04:18So I like to start every talk I give on
04:20Alzheimer's disease with the most recent
04:23facts and figures from the Alzheimer's
04:25Association and every March or so.
04:27So we're about to see another
04:28one of these in in about a month.
04:30The Alzheimer's Association comes
04:31up with their facts and figures
04:33that highlights demographic issues
04:35related to Alzheimer's disease.
04:36And I'll just highlight a few things on
04:38this slide right now in the United States,
04:40there are about 6.2 million
04:42Americans with Alzheimer's disease,
04:44and based on the aging of the population,
04:46that number is supposed to
04:47triple in the next 20 years.
04:48And that's not.
04:49Unique to the United States,
04:50it's true all over the
04:52world with aging adults.
04:54It's the 6th leading cause of death
04:55in the United States and by the way,
04:57the pandemic has been a disaster
04:59for Alzheimer's disease.
05:00The death rate in Alzheimer's dementia
05:01not only because of individuals who are in
05:04more advanced stages and congregate living,
05:06but but independently because of illness
05:09issues related to the illness of Alzheimer's,
05:11or the effect of the virus.
05:12We've seen just a much higher
05:15mortality rate over the past two years.
05:18This is a disease that not only
05:19impacts the person with the illness,
05:21but like many illnesses that we care for.
05:23In psychiatry really impacts the family.
05:25So we estimate there over 11.2 million
05:28Americans providing unpaid caregiving
05:30support to loved ones with dementia.
05:33The total cost of care in the United
05:35States in 2021 was $355 billion,
05:38with an added two $57 billion.
05:43For providing home care,
05:45for example, what's really important,
05:47I think that's become much more clear,
05:50especially in this report from the
05:522021 Alzheimer's Association report,
05:55was the bottom right box,
05:58which is really the disproportionate
06:00impact in underserved populations.
06:02And interestingly,
06:0336% of black Americans,
06:0618% of Hispanic Americans,
06:07in 19% of Asian Americans believe
06:09that discrimination is a barrier,
06:11or would be a barrier to receiving
06:13Alzheimer's care.
06:14And one of the biggest problems that
06:15we have in in the research setting.
06:17It's just ruin all of psychiatry.
06:18But we see this a lot in dementia as well.
06:20Is that we're seeing generally
06:23homogeneous populations being
06:24either volunteering for or being
06:26recruited into clinical trials,
06:28and so there's an increasing worry
06:29that what we're finding in some
06:31of these outcomes are really not
06:32representative of a larger population.
06:34So this is an area that I think
06:36throughout all of medicine,
06:37but but also here and Alzheimer's
06:39disease is a major issue.
06:41So let me start out by a relatively
06:43straightforward case of a gentleman
06:45that I saw a number of years ago,
06:46who at the time was in his late 60s and
06:49I had first seen him a few years earlier.
06:51When he presented with cognitive
06:53issues working as an accountant
06:55unable to do the tax returns and
06:57his partners were concerned,
06:59as was his wife,
07:00we diagnosed him with Alzheimer's
07:02dementia and now a few years
07:03later he had been having
07:04about two months of insomnia, irritability,
07:07physical restlessness and pacing,
07:08especially late in the day and for
07:10about the past week he started to talk
07:13to these imaginary people who were
07:14in his home and he started to look
07:16more confused according to his wife.
07:18He really had no major medical
07:20problems in the past.
07:21It was a very healthy guy.
07:23And we had put him a few years ago and
07:25and episil, or Aricept and Memantine.
07:26And Amanda standard treatments.
07:28Even today in 2022 for Alzheimer's disease.
07:31And he had been on mirtazapine for few years
07:34for anxiety and periods of insomnia as well.
07:37But now he was having some
07:38of these other symptoms.
07:39So what I want you to think about as
07:42we go through this talk is questions
07:44that come out of a case like this
07:46and how you would approach it.
07:48So for example, how?
07:49How would you define or describe
07:50these neuro psychiatric symptoms?
07:52Because they're they range
07:54across a spectrum of mood,
07:55anxiety, sleep,
07:56and then even into psychosis with paranoid
08:00delusions and possibly hallucinations.
08:02Most importantly,
08:03how would you seek the cause
08:04with the etiology of these neuro
08:06psychiatric symptoms and what?
08:07Medical or neurological diagnosis may
08:09help to explain this presentation.
08:12And if you're going to treat this individual,
08:15what target symptoms would you be
08:17going after and then what behavioral
08:19interventions might help and?
08:21And if you were going to use the medicine
08:22to augment treatment that he's currently on,
08:24what would you use and why?
08:25And what is the evidence based for that?
08:27So what I'm going to hopefully
08:28cover in this first part of the
08:30talk is really going through the
08:31systematic approach to assessment,
08:33diagnosis and then and then both
08:36behavioral and pharmacological
08:37management of these of these neuro
08:40psychiatric symptoms of dementia.
08:41So as far as background goes,
08:44if you see somebody with dementia
08:46over the course of their illness,
08:47neuro psychiatric symptoms
08:49are universally prevalent.
08:51In fact,
08:52some studies have shown rates of up
08:54to 100% over the course of illness.
08:56Again,
08:57they could be as mild as worrying or pacing,
08:59or they could be as severe
09:01as physical aggression.
09:02But when you see these symptoms,
09:03the reason they're important is not
09:05only they are disabling to the person
09:07and making them feel lousy and and
09:08concerned about safety concerns,
09:10but they do.
09:11Seem to be associated with a higher
09:13morbidity and even mortality,
09:14and a more rapid functional decline.
09:18Practice guidelines that exist,
09:20including the 2016 APA guidelines
09:22for the use of antipsychotics
09:24and Alzheimer's disease,
09:25recommend antipsychotics as first
09:27line treatment for those patients
09:29with dementia who have agitation
09:31that are associated with psychosis,
09:33so hallucinations or delusions.
09:34But what if you've got somebody who's
09:38physically aggressive or disinhibited
09:40verbally without any provocation,
09:42without any association with
09:44psychosis or or depression?
09:46That's where the even the experts don't
09:47agree on a first line of treatment.
09:49That's where we use combinations of
09:52medications that include antipsychotics
09:53or mood stabilizing
09:55anticonvulsants or SSRI's,
09:56and we'll talk more about this in detail.
09:58And so we have a number of
10:01different acronyms that are used
10:03to describe these syndromes,
10:04one of which is BPSD or the behavioral
10:06and psychological symptoms of dementia.
10:08But we don't have true standards of care.
10:10There is really no true
10:12algorithm or standards of care.
10:13Some have been developed,
10:14but it really has to be thought of
10:17on an individual patient level and
10:18and very importantly which a lot
10:20of people don't understand is that
10:22any drug ever used by any of us to
10:24treat these behavioral symptoms that
10:26dementia is by definition off label.
10:29Because the FDA has yet to approve
10:30a single drug to manage any
10:32behavioral symptoms of dementia,
10:33or the psychosis of dementia.
10:36So I mentioned these definitions,
10:38Dilip, Jeste,
10:39and Sandy Finkle came up with
10:41a psychosis avadi which was a
10:43diagnostic sort of a research
10:45diagnosis that was in the DSM 4
10:47neuro psychiatric symptoms of a D.
10:49This BPSD,
10:50but most importantly is that whatever
10:52the acronym is or the descriptor is,
10:55it's really important to go down into
10:57the nitty gritty and like what are
10:58the symptoms that person is presenting with,
11:00because these acronyms really account
11:02for a whole range of symptoms.
11:04As I mentioned before,
11:05and you can see here on the slide.
11:10The the most important really take
11:12home message from this part of the
11:14talk is that throwing medicines at
11:16patients who present with these symptoms
11:18without figuring out what's driving
11:20these symptoms will lead to problems.
11:22And it sounds so obvious to say.
11:24But when you're dealing with a
11:26fragile brain that's in the context
11:27of a neurodegenerative illness
11:29like Alzheimer's disease,
11:30the therapeutic index,
11:31the window for efficacy and
11:32tolerability is very, very narrow,
11:34and so if we're going to intervene
11:36with medications when appropriate,
11:37we've got to be very careful
11:39that we're actually.
11:39Now we're treating so the three big
11:41buckets of causes of these behavioral
11:44symptoms can be broken down into
11:46environmental precipitants like
11:47interactions with caregivers or time
11:49of day or change in routine or noise,
11:52or even cultural issues.
11:53The way in which a loved one will
11:55speak to their spouse with dementia
11:57and a person with dementia doesn't
11:59understand where they are or or or who
12:02their spouses and they start asking the
12:04same questions over and over again,
12:05and the spouse themselves is feeling
12:07exhausted and burned out and depressed.
12:09And before you know it.
12:09They're having arguments.
12:11Those things don't require necessarily
12:13medications, but a lot of caregivers,
12:14support education, etc.
12:17Medical causes in fact.
12:18The first,
12:19second and third things we look
12:21for when we see a patient like
12:23the one I described is might.
12:25May there be an infection or a new
12:27medication accounting for the side effect?
12:29Or maybe they're drinking
12:30alcohol or some other drugs.
12:31Or maybe they've got an electrolyte
12:33disturbance where their
12:34diabetes isn't well controlled,
12:35so that's what we're looking for in pain.
12:37And during the first wave of this pandemic,
12:40back in the winter of 2020,
12:43we saw a number of older
12:45patients presenting with.
12:47Delirium, agitation,
12:48confusion,
12:48etc superimposed on dementia as the
12:52first manifestation of COVID-19,
12:54which was very interesting.
12:55And we've we've seen and now know a
12:58lot more about the neuro psychiatric
12:59manifestations of this illness.
13:01And then finally, psychiatric.
13:02And the reason I bring this up is 2 fold.
13:05One is,
13:05it's really important to gather
13:07a pre-existing or prior to the
13:09onset of dementia.
13:10Psychiatric history from a family
13:12member or from some collateral source.
13:14Because what you might be seeing is
13:16somebody who's aging with bipolar
13:18disorder who's now got cognitive problems.
13:20Or you might be seeing somebody who
13:22never had a psychiatric problem and
13:24now now is experiencing Alzheimer's
13:25disease with superimpose behavioral
13:27complications and the approach to
13:29treatment may very well be different.
13:31I'll also tell you a little vignette here,
13:33because this story,
13:34which I this was a patient,
13:35I saw very early on in my career
13:37in a nursing home setting,
13:39taught me a lot about the importance of
13:41collateral information and diagnosis.
13:42So I was working at the mental
13:44Health Center of Greater Manchester,
13:46NH on the faculty at Dartmouth,
13:47and I was assigned to work in
13:49this nursing home and.
13:50One of the first days I
13:52actually worked in this
13:52nursing home, I was asked to see this woman.
13:55Who is 53 at the time and she was in a
13:57locked dementia unit and all I knew is
14:00that she had been hospitalized for a week
14:02before in the General Medical Hospital.
14:04After a syncopal episode at home was
14:06found to be dehydrated and and was
14:08admitted to the hospital and now she
14:10was diagnosed with picks disease or
14:12frontal temporal dementia variant and
14:14she wasn't cooperative with anything.
14:17She wasn't eating drinking,
14:19not cooperating with activities.
14:21So I saw her.
14:22She's standing in the hallway and
14:23she was first of all about 30
14:25years younger than everyone else.
14:26Which I thought was strange.
14:28I walked up to her and she had
14:30absolutely no facial expression.
14:32She was completely mute and when I
14:34went in the hallway to do a brief
14:37neurological exam on her and I did some
14:40assessment of upper extremity mobility.
14:42She left her hand up like this.
14:44She was catalepsy.
14:45I thought maybe you know this is unusual.
14:48Neurological manifestation of catatonia,
14:50but there's no psych history in her chart,
14:53so I called her husband and I said,
14:54Bob, what's going on with your wife?
14:56And he said, well,
14:57we've been married for 30 years,
14:58and she's got bipolar disorder,
14:59and she was doing pretty well
15:00until a few weeks ago, when she?
15:02Started but I thought was getting
15:04depressed and wasn't talking to us
15:05much and wasn't eating or drinking
15:07very well and she passed out one
15:09day and now they tell me she has
15:10end stage dementia and she's at
15:11the end of her life and I said,
15:13well you know Bob,
15:14it may be a manifestation of
15:15bipolar disorder we call catatonia,
15:17and so we had our hospitalized
15:20and she had ECT.
15:21And and she became my outpatient
15:22for the next five years because she
15:24went back to her normal baseline,
15:26which was essentially euthymic
15:28without catatonia,
15:29with some mild executive dysfunction
15:31and some delayed recall problems,
15:32which improved with prompting.
15:34But she certainly didn't have
15:36advanced frontal temporal dementia.
15:38I learned a lot from this case.
15:39One thing was which you read in
15:40a medical record is what you read
15:42in a medical record.
15:43And even with emr's these days,
15:44we know how those cannot be complete.
15:46It's not that they're wrong necessarily,
15:48but they're just not complete all the time,
15:50and there's really nothing that
15:51substitutes getting a really good
15:53history from a family member.
15:54And then finally,
15:55people with acute psychiatric
15:57illness like this woman had.
15:59It's impossible to know what their
16:01baseline cognitive functioning is.
16:02And until you treat that you
16:04don't really know what they're
16:06what the underlying baseline.
16:08A cognitive functioning maybe.
16:09So those are the three buckets of causes
16:11and keep that in mind as we go through
16:12some of the treatment approaches.
16:14So our colleagues,
16:15Helen Cals and others at the University
16:17of Michigan developed this dice approach,
16:19which was now published a few years ago
16:21in Jags. And this.
16:22This approach is really
16:23what I just told you about.
16:25It's like a it's just a systematic way
16:27of assessing describing the behavior
16:28you're seeing when it's happening,
16:30where what's provoking it,
16:32investigating the etiology,
16:33and you can see on the slide.
16:34There are many things,
16:36many of which I mentioned.
16:37Constipation, pain,
16:38medical problems, etc.
16:40And then create a treatment plan and that
16:42could be both behavioral and pharmacological.
16:44And very importantly,
16:45this is something we're not good at.
16:47In psychiatry is collecting
16:48objective data on symptom, severity,
16:51frequency and impact on caregivers,
16:53and then see how our treatment
16:55interventions actually impact outcomes.
16:57So there are a number of measures
16:58that we can use to assess
17:00behavioral symptoms in dementia.
17:01The one that's most widely
17:03used now in clinical trials.
17:05And we're trying to implement
17:06now in population settings,
17:07is the neuro psychiatric inventory.
17:09There's a version of it called the NPIQ,
17:11which is shorter, but it's burdensome.
17:14It takes a little time,
17:15but what's nice about the NPIQ is
17:17you're assessing 12 domains of behavior,
17:20mood, psychosis,
17:21etc,
17:22and the impact of this behavior
17:24on on the caregivers.
17:26Well being so that that is a
17:29really useful instrument.
17:30But implementing this in in
17:32traditional clinical care is
17:34is way easier said than done.
17:36This is not a talk where I'm
17:38going to go through an exhaustive
17:40series of studies on behavioral.
17:41You know interventions for or non
17:44pharmacological interventions
17:45for patients with dementia
17:47and behavioral symptoms,
17:48but I really want to call this out
17:50because before we intervene with
17:52medicines and let's unless it's an
17:53acute crisis with safety concerns,
17:55we need to intervene first
17:57with behavioral interventions,
17:59and those could be and the way I think
18:00about it is you've got to be creative.
18:02It's got to be individualized.
18:04Every study that's looked at this is said.
18:06It's not one size fits all.
18:07It's very.
18:07Individualized,
18:08and then if you look at the literature,
18:10you'll be disappointed because you'll see
18:12some studies that are not well designed.
18:14It's hard to have a control
18:16group and they're not that large,
18:17but they've been published
18:18in some good journals.
18:19Actually,
18:20the two areas that I really
18:23wanted to highlight here.
18:25Our are the activities and the exercise,
18:28so exercise,
18:29exercise and incredibly helpful
18:31intervention that might not only help
18:33us with our own brains as we age in
18:35terms of reducing the risk of Alzheimer's,
18:36but may also ameliorate some
18:38of the agitation anxiety that
18:41goes along with with dementia.
18:43And then there's the impact that
18:44you can have on caregivers because
18:46a lot of these precipitants to
18:49behavioral outbursts are often
18:50driven by the environment,
18:52which may be the caregivers,
18:53could be nurses and long.
18:54Long term care facilities nurses aides.
18:56It could be family members at home, etc.
18:58So,
18:58but there's a ton of need for
19:01good research in this area,
19:03and every guideline that you will
19:05read will say before you do anything
19:07with medicine you want to do non
19:09pharmacological interventions.
19:11So the the the next main part of this
19:13talk is really to focus on evidence
19:15based pharmacotherapy and then I'll
19:16talk a little bit about some of the work
19:18we're doing for some of the symptoms
19:20that are more difficult to treat.
19:22Now focus mostly here on the NSA koteks.
19:25And primarily because they're.
19:26They're the best studied.
19:28Frankly, class of drugs,
19:29and they're there's tremendous
19:31controversy with their use.
19:33It may be the most controversial thing
19:34that we have in geriatric psychiatry
19:36is that when to use and when not to
19:38use antipsychotics and older adults,
19:39but specifically in dementia.
19:40So I want to give you a sense of
19:43what the data shows first of all,
19:44with the limitations are what
19:45we can learn from it,
19:47how we apply it in clinical practice,
19:48and then the warnings that
19:50the FDA put out now in 2005.
19:51And I'll talk a little bit about some
19:53of the other classes in particular the.
19:55Antidepressants.
19:58So this is such a basic statement.
20:00I hate to mention it to this crowd,
20:01but it's something that happens
20:02all the time in psychiatry.
20:03You know, it's a Mrs.
20:04Jones has psychosis or the Mrs.
20:06Jones is psychotic.
20:06Well,
20:07what does that even mean?
20:08It's like saying where she has
20:09a psychotic disorder.
20:10It's like saying that Mrs.
20:11Jones has a cough disorder and it could be.
20:13It could be cancer,
20:14or you've got something stuck in your throat,
20:16or you've got an allergic reaction and
20:18the approach is totally different.
20:19So in older adults,
20:20although we may describe how someone
20:23is doing with a variety of symptoms,
20:25we've got to figure out the
20:27underlying diagnosis or we'll get
20:28lost very quickly with treatment.
20:30So we know what the diagnosis of
20:32psychosis is, but it it's a symptom.
20:33It's not a diagnosis,
20:35and in older adults who develop
20:37psychosis for the first time in
20:39their in in their later years,
20:41it's generally not late onset
20:43schizophrenia at the age of 70 or even
20:45late onset mania and bipolar disorder,
20:47it's usually dementia or it's
20:50delirium superimposed on dementia.
20:53And it may be the first manifestation
20:55of somebody with Alzheimer's disease.
20:57Not always,
20:57but it.
20:58It can be because you know half the
21:00people in the United States with
21:01dementia aren't diagnosed and the
21:03ones who are aren't diagnosed until
21:04they're already in the moderate stages,
21:06which is when you start to see psychosis,
21:09impaired memory from dementia is
21:11is often what is is the what,
21:15what the psychosis is really about,
21:16which is that they they can't remember
21:19where they are or they misidentify
21:21their spouse because they have.
21:23This, you know,
21:24Misidentification syndrome
21:25or Capgras syndrome,
21:27where they think they're like their
21:29caregivers an impostor or their mates,
21:31unfaithful,
21:31which the first patient that
21:34Doctor Alzheimer's saw Augusti.
21:35She actually believed that her
21:37made her spouse was unfaithful.
21:39That was one of her presenting symptoms so,
21:41but if you look at these quote
21:43unquote delusions,
21:44fixed false beliefs,
21:45they're often based on the fact
21:46that the persons having cognitive
21:48impairment and inability to recognize
21:50familiar people or things and then
21:52stories get created around it.
21:54So that's really important to keep in mind,
21:56and then finally the duration of
21:58treatment is often informed by the
22:00actual diagnosis and what I mean by
22:02that is if if this is delusions and
22:04Alisa nations and somebody who's
22:05manic with a history of bipolar
22:07disorder who also now later life,
22:08happens that dementia.
22:09You know they're going to need to
22:11continue to stay on pharmacotherapy,
22:13but if this is somebody with
22:14Alzheimer's disease and all of a
22:15sudden has a UTI and in the setting
22:17of the UTI they see things that
22:18aren't there and get agitated, well,
22:19you can give them a land subpoena or
22:22QT and perhaps a risperidone for a
22:24period of time because they're agitated.
22:26But if you don't treat their
22:28UTI without antibiotics,
22:29you're not going to get very far.
22:30So anyway, it it sounds so obvious,
22:33but this is what I mean about
22:35looking for the underlying cause.
22:38So the older drugs the conventional
22:40antipsychotics like caliper,
22:41it all are still used,
22:42hopefully rarely and there is data on them.
22:45But the reason why we don't use
22:47them much if at all is because of
22:50the toxic side effects and they
22:51really include extrapyramidal side
22:53effects like that are listed here.
22:55Risk of falls orthostasis with a low
22:58potency and psychotics and then the
23:01risk of tardive dyskinesia which.
23:03The risk factors for developing
23:05tardive dyskinesia as you all know,
23:07include advancing age,
23:08and so if you see somebody with
23:10schizophrenia in their 30s and they're
23:13treated with antipsychotic medication,
23:15the risk of developing TD in
23:17the first year is about 5%,
23:19and so about 5% every year.
23:20So after three years, it's about 15%.
23:22Now if that same person in their 70s,
23:25and you give them haloperidol for a year,
23:27it's 28% risk of TD,
23:30and that goes up to nearly
23:312/3 after three years.
23:32So that's one of the main reasons why.
23:34We really try to avoid these,
23:36especially for long term use in older adults.
23:40So I'm not going to go through the
23:42exhaustive literature on the atypical
23:43antipsychotic use in dementia,
23:44but I want to highlight that
23:46these four drugs, risperidone,
23:47olanzapine, Katipunan, aripiprazole.
23:49The reason why there's dosing
23:52ranges listed on the slide is
23:54because it's based on evidence.
23:56It's not just clinical judgment.
23:59There are a lot of studies that were done and
24:01will go through a few examples in a minute,
24:03but risperidone .5 to two?
24:04You'll notice these general doses are low.
24:07You'll notice the quote
24:08typing dose is quite variable,
24:09which is.
24:10One of the challenges with this
24:11drug is how hard it is to figure
24:13out what dose the person needs.
24:15There are a lot of other atypicals
24:16that have come on the market
24:18in the last decade or so with
24:19very little data and clozapine,
24:21which is a much older.
24:22Drugs still has very little data in dementia.
24:24There's a one positive and one negative
24:27brexpiprazole study with the third
24:29trial ongoing and pimavanserin which
24:31was being studied for the psychosis
24:34of or dementia related psychosis.
24:36In April of 2021,
24:39the FDA rejected their application.
24:40So there's more work going on there.
24:43Still to this day no drugs
24:45have been approved by the FDA.
24:47For the psychosis of
24:49Alzheimer's disease now TD,
24:50tardive dyskinesia does not go away
24:52when using an atypical antipsychotic,
24:54but it is much less than in
24:56the older adult population.
24:58On haloperidol, for example.
24:59So it's about 5% or so per year for
25:03risperidone and olanzapine compared
25:05to 28% with the conventional agents.
25:10I want to show you two
25:12studies only two studies,
25:13'cause this is a huge literature,
25:15but they highlight the way in
25:17which this data was collected and
25:20it's really important to remember.
25:23Generalizability of data.
25:24So the first series of studies
25:26that were done essentially in
25:28the 90s in the early 2000s.
25:30We're done in patients who were in
25:33nursing homes who had more advanced
25:35dementia with mini mental status exams
25:37in the single digits or low teens.
25:39Many of them had substantial
25:42medical comorbidity and some
25:44of them had mixed dementias,
25:45not just Alzheimer's disease,
25:47that they already had strokes
25:48and had vascular dementia.
25:50I mentioned that because of some of
25:51the problems with with mortality and
25:53stroke that I'll mention in a minute,
25:55so this was the risperidone trial.
25:56This was the first one published now.
25:59Crazy, it was back in 1999 already,
26:01but there were four different treatment arms,
26:04placebo .51 and two and one of the
26:06primary outcome measures that we looked
26:08at was the psychosis subscale of this
26:11behavioral measure in Alzheimer's disease.
26:14And what they found Ihracat still have
26:16Jesse and Jacobo Mintzer in this study.
26:19Was that once you got to a milligram a
26:21day you saw an improvement in psychosis,
26:24although the effect was modest.
26:26But once you went from one to two,
26:27you got no added benefit
26:30on reducing psychosis.
26:31Instead, what you got was doubling the
26:33rate of extrapyramidal side effects,
26:35and So what you see very clearly
26:36from this study,
26:37which was one of the five
26:39risperidone studies done.
26:40Again, advanced population,
26:41long term care settings,
26:43medical comorbidity.
26:44So if you saw somebody who's younger who's
26:46an outpatient who had a mini mental of 25,
26:48which you still see the same
26:49problems you know we,
26:50we don't have that data as much.
26:54But in the in these studies you
26:55see a lot of extra mental side
26:57effects once you go above 1,
26:58where between one and two this happens.
27:00I'm not sure you have to treat
27:02the individual, of course,
27:03but you're going to see rigidity and
27:05tremor and gait disturbance and so forth.
27:07Once you get above 1,
27:08certainly to 2 milligrams with risperidone.
27:11So there's a little bit of
27:12a therapeutic window there.
27:16Now I want to contrast that kind of study
27:18funded by the Pharmaceutical industry in
27:20the advanced patients and nursing homes.
27:22With the Katie study, most people who
27:24are not geriatric psychiatrist know about
27:26the Katie study because of schizophrenia.
27:29But there happened to be a sister study done
27:31at the same time called Katie Adie and that
27:34was the Alzheimer's sister study of Katie.
27:37And we were involved when I was up
27:39at Dartmouth back in the late 90s.
27:40In this trial we were one of the sites
27:42and it was 42 sites around the country.
27:44It was 421 patients but they were out
27:47patients including assisted living residents
27:48and they had a deal with either psychosis,
27:51aggression or agitation.
27:52Oh, and one thing I didn't mention was
27:54those first studies were only about 6
27:56to 12 weeks interation. These study.
27:59This study was 36 weeks in duration 9 months.
28:02And the individuals in this study
28:04were randomized to one of four arms,
28:06olanzapine, quetiapine, and risperidone,
28:08or placebo and the doses.
28:11The mean dose was based on the dose
28:13at the time that the person was
28:15switched from phase one to phase two.
28:18The way the study was designed is
28:20people were randomized to one of these
28:22four treatment arms and they were
28:24out patients if they had persistent
28:26psychosis and agitation the the
28:27investigators doing the study.
28:29The clinicians,
28:29like I was were really pretty quick.
28:33To switch because we knew that
28:3525% chance they were on placebo
28:37and they were outpatients,
28:38they were safety concerns,
28:39so the doses they got too.
28:40As you can see from the previous slide,
28:43a mean of five of alanza pain is therapeutic,
28:45at least in those earlier studies with
28:47risperidone being a milligram a day.
28:49Also therapeutic in QT app in the
28:52one quetiapine study that showed
28:54efficacy was 200 milligrams a day
28:56and and this may have been under
28:58dosed and then there's placebo.
29:00So at the end of the day the outcome
29:02that they looked at in this study.
29:03It was not symptom reduction.
29:05It was not reduction of psychosis
29:07or aggression on a rating scale.
29:09The outcome they looked at was how
29:10long did it take for the investigator
29:13to make a decision to switch from
29:15drug drug atede rugby and that
29:16decision is of course a balance
29:18of is the drug working or is the
29:20drug not being tolerated or not?
29:22So after the after looking at
29:24this as the primary outcome,
29:26this this effectiveness measure,
29:27there was really no difference in any of
29:29the four groups in terms of time to switch,
29:32and the reason for that was although
29:34there may have been some efficacy
29:36advantages and symptom reduction
29:38tolerability for placebo is way better
29:40and and so if you looked at only
29:44efficacy which is symptom reduction,
29:46psychosis or agitation,
29:47you stayed on risperidone and olanzapine
29:49longer than you did quit typing,
29:51which may have been underdosed or placebo.
29:54So the secondary outcomes were positive,
29:56but but not the primary outcome here.
29:58So when this came out,
29:59by the way which is now 16 years ago,
30:01it's made front page news and the
30:03question was do these drugs even work?
30:05But again, I think it's is this.
30:06It's an efficacy effectiveness difference.
30:11And as I mentioned before,
30:12the tolerability was the issue is
30:14that you know placebo was less often
30:16discontinued because of adverse events.
30:18What's interesting here is that and again,
30:20remember, it's only 421 patients,
30:22but there was no stroke difference.
30:23There was no death difference.
30:25There was no fall difference between these,
30:28you know drugs or or or placebo.
30:32Now Dev Dev Anand is a Colombian colleagues,
30:35tried to answer really important question
30:36a few years ago in this study which is
30:39like if you put somebody on risperidone,
30:40let's say and they've got psychosis
30:43and agitation in dementia.
30:44How long do you keep him on the drug?
30:46You know,
30:46when can you safely stop the drug
30:48and so the the way this study was
30:51designed is they they gave patients
30:5316 weeks of open label risperidone.
30:55And 180 were then randomized to staying
30:58on risperidone or or converting to
31:00placebo tapered off and going on placebo
31:02and what they found is that the relapse
31:05rates after four months of being on
31:07risperidone and now being stable.
31:08If you then take people off the
31:10relapse rates are twice as high and
31:12the next four months on placebo
31:14and then even higher three times
31:16as high over the next four months.
31:19So although all recommendations
31:20including the API guidelines I'm going
31:23to show you in a minute say after.
31:25A period of time attempt to taper
31:28and discontinue the medication.
31:30This was in the New England
31:31Journal of Medicine.
31:31It was a well designed study.
31:32It's it's easier said than done,
31:34so this is a challenge that we have.
31:37So I want to highlight some of the
31:39warnings so when risperidone was
31:41trying to convince the FDA back in the
31:43early 2000s that their drug may may
31:45have safety and efficacy advantages
31:46in this population and they went
31:48to the FDA for approval review.
31:50That's when they first noticed that
31:53there might be a stroke risk issue.
31:55There was one study that showed a
31:56higher risk of stroke like events
31:58and drug versus placebo.
31:59It led to an investigation of
32:01mortality in the in the warning.
32:03So if you just look at the stroke risk OK,
32:05these could be large hemorrhagic,
32:07or embolic strokes.
32:08It could be microvascular ischemic disease
32:10that that caused symptoms like dizziness,
32:13Tia like symptoms.
32:15The the risk of these stroke like
32:18events in drug versus placebo was two
32:20to three fold higher for risperidone,
32:23olanzapine and aripiprazole.
32:25Interestingly, not for quetiapine in fact,
32:28you might even argue that placebo
32:31was worse than than putting in
32:33terms of these risk factors,
32:34but the end was much smaller with
32:36with quote type you know overall
32:38than the others and this is not
32:40a black box warning from the
32:41FDA. This is a warning that's been placed
32:44on some of these atypical antipsychotics.
32:46But not all. This is the problem.
32:49Is this box warning.
32:50This is where the controversy comes
32:52from and it's really important to
32:54understand where the data was from.
32:56This was 17 trials that the FDA reviewed
32:59now 17 years ago with over 5000 patients,
33:022/3 on drug, a third on placebo,
33:05and these were patients who were
33:07studied in those original trials.
33:08Like I showed you with risperidone
33:10where these were end stage
33:11patients in nursing homes.
33:13Lominy mental scores,
33:14lots of medical comorbidity and the risk of
33:17death was four and a half percent on drug,
33:202.6% on placebo.
33:21So there's a higher statistically
33:22significant death. Great.
33:23And one of the big questions
33:25that people ask is, well,
33:26why were people dying on these
33:28drugs and and one of the,
33:29you know,
33:30we don't know for sure 'cause
33:31no autopsies were performed,
33:32but when you look at the cause of
33:34death that were documented by the
33:36clinicians overseeing the trials,
33:37it was either cardiac or infectious.
33:39And so one theory is that these
33:41drugs we know can prolong the QTC
33:43interval and it can cause cardiac
33:44arrhythmia and sudden cardiac death.
33:46So that could be 1 mechanism
33:48the other could be sedation,
33:51leading to aspiration, pneumonia,
33:52infection and and then subsequent deaths.
33:54So we don't know for sure.
33:56Those are two potential mechanisms.
33:58Interestingly,
33:58when the warning first came out in 05,
34:01it was just for the Atypicals,
34:03even though there were studies involving
34:05Haldol and conventional agents,
34:07but they weren't comparable studies,
34:08but they weren't these randomized
34:10well designed trials,
34:11and so eventually,
34:12though,
34:13in 2008,
34:13the FDA broadened the warning to
34:15include all NS psychotics and that's
34:17the warning that exists until today.
34:20So.
34:23Thankfully, our Appa came out with guidelines
34:26in 2016 and and those of us who serve on
34:29various committees at the APPA and AGP.
34:31We were able to inform or at least
34:33give some feedback on these guidelines.
34:35But I think the main the the main take
34:37home points that are on these guidelines
34:39are really what I just went over.
34:40You know, use these antipsychotics
34:42only if benefits outweigh risks.
34:44Start low and go slow.
34:45If there are adverse effects, continue
34:47to monitor risk and benefits of need.
34:51Really importantly, if no response
34:52after four weeks on an adequate dose,
34:55try something else,
34:56taper and discontinue,
34:57and then when there is an adequate response.
34:59If there is a controversial statement
35:01in any of these guidelines,
35:02it's probably this bullet point
35:04based on the Devon on study.
35:06Because if if if if you
35:08follow these guidelines,
35:09they would suggest no matter what tape the
35:11taper them off the drug after four months,
35:13unless you've had previous
35:14experience with a recurrence of
35:17symptoms that are problematic.
35:19And then again,
35:19avoid Haldol as a first line agent,
35:21because if you look at subsequent data,
35:23which really seem to show that
35:24the mortality risk is higher with
35:26the with the conventional agents,
35:28how paradol seems to have a higher
35:30mortality rate than than the atypicals
35:31that we want to avoid haloperidol and
35:33then there's really no data with long
35:35acting injectables in this population.
35:38So what are we supposed to do?
35:40One thing I'll just mention,
35:42which is not.
35:42I don't think I have a slide on this,
35:44but it's important to know is
35:45that these drugs?
35:46These antipsychotic drugs and frank
35:48and in fact all psychiatric drugs,
35:50are heavily regulated by the federal
35:53government in nursing homes in
35:55federally funded nursing homes.
35:56Because of Medicare and Medicaid,
35:58seems highly regulates the use of
35:59these drugs in those facilities.
36:01When can you start? How do you monitor?
36:04What do you have to document, etc.
36:07But the same patient with the
36:08same problems who happens to live
36:10in assisted living or at home.
36:11We can do whatever we want,
36:13so there's got to be a balance between
36:15over regulation and no regulation,
36:17because we do see misuse of these
36:19medications all the time when the
36:21warning first came out in 05,
36:23a lot of our colleagues in nursing home
36:25settings who were non psychiatrists
36:27said well for medical legal reasons,
36:29well, it's avoid alanza Pean.
36:31Let's put them on Ativan instead.
36:33Well,
36:33that's not a good idea because
36:35of tolerability issues.
36:35We'll talk more about in a minute.
36:37And I just say go back to the basics
36:39like we talked about what's causing
36:40these problems in the 1st place.
36:42Always employ these behavioral
36:44interventions first,
36:45and then if we're going to
36:46use antipsychotics,
36:47which sometimes are indicated,
36:49do it with informed consent,
36:51and I've never had a family member say to me.
36:53Well,
36:53don't treat my mom who's wandering
36:55into the street at night because she
36:57sees things outside or she's worried
36:59about people talking behind her back.
37:01But within antipsychotic,
37:01because it may lead to a small risk of
37:04death or mortality when there are safety
37:06issues concerned and the families are.
37:08Caring for their loved ones,
37:09they understand the risk benefit equation,
37:11but we've got to give informed consent.
37:15So that's probably more than you
37:17wanted to know about antipsychotics,
37:18Deppe code or dival proex was
37:20studied in at least four well
37:23designed randomized control trials.
37:24In many case series,
37:26there is evidence for reduction of agitation,
37:29but for whatever reason in in three
37:31of the trials there was no benefit
37:34on the primary outcome measure,
37:35but there was some benefit on a secondary
37:38and then in this ADC S trial which was done,
37:41there was no benefit on any measure.
37:43So since that trial came out,
37:45there's been less use of.
37:46Divalproex,
37:46one of the other issues is tolerability
37:49with gate disturbance tremor,
37:51even delirium.
37:52Some have been using gabapentin
37:54without almost any data,
37:56and there's some interest in doing an
37:59actual randomized trial with gabapentin
38:00because of its anxiolytic and effects.
38:02Perhaps on behavioral disinhibition,
38:04but there really is limited data.
38:07There's good data with the rise
38:09and our colleagues at Hopkins in
38:11Rochester and elsewhere collaborated
38:12on this Itala PRAM trial and
38:15agitation and Alzheimer's disease.
38:17I want to make the important
38:18point that this is for agitation
38:20and also arm is not depression.
38:22Almost all of the antidepressant
38:24trials for depression and dementia
38:26have not been positive trials.
38:28But this one, the sital Apram study,
38:30was for agitation,
38:31a dosing range of 10 to 30 milligrams a day.
38:33The behavioral effects were noted,
38:36and the thing we have to watch out for
38:37in the elderly is the QTC prolongation.
38:39Above 20 milligrams a day,
38:41this is with sital apram.
38:43There's now an escitalopram study going on.
38:46This was called site at the
38:47next one is called S site AD,
38:49and so we'll see what that one shows.
38:51So let me tell you a little bit about
38:53our journey with novel therapeutics
38:54before I go into public health.
38:56So a number of years ago
38:58I was medical Director,
39:00an inpatient geriatric psychiatry unit,
39:0218 beds, all dementia,
39:05all behaviorally disturbed.
39:06All there for two to three
39:09weeks of acute treatment.
39:10And it was a really amazing experience
39:13actually and and still exists.
39:15Today.
39:15We had this woman who came
39:17in at the age of 67.
39:19She had been diagnosed by colleagues
39:20of mine at mass general a decade
39:22earlier with Alzheimer's disease.
39:23She was now 10 years into an illness.
39:25She was essentially minimally
39:27verbally responsive at this point.
39:29She had attribute on her MRI demonstrating
39:31consistency with Alzheimer's,
39:32dementia, and at home with her spouse.
39:34The problem wasn't her her profound
39:37cognitive impairment or lack of speech.
39:39It was physical aggression with her spouse.
39:41Her husband really was overwhelmed
39:42and she had had at that .12
39:45failed medication trials and she
39:46really was not able to go into a
39:48nursing home from that situation
39:49and he couldn't manage her anymore.
39:51So she came in the hospital.
39:54Her name was Louise,
39:56two months in and I tell you her
39:58name because her daughter has
39:59been very public with her story.
40:01So two months into her hospital
40:03course she was really not responding.
40:05We tried every imaginable medication.
40:07She had tolerability concerns
40:08or she didn't respond and my
40:10colleague who I was working with,
40:11Doctor Alex Stoyer, said, well,
40:13what about ECT, and I said, well,
40:15why would you treat somebody
40:16with advanced dementia with ECT?
40:18I mean already she's got cognitive problems.
40:20He's like.
40:21Well, it can't get much worse and
40:22really other than palliative sedation,
40:24I'm not sure we have many options.
40:26Here and there was a small literature at
40:28the time on the use of ECT for patients,
40:30again with refractory agitation.
40:31This was not depression and dementia.
40:33This was aggression and dementia.
40:36So with consent from the caregiver and from.
40:41Appropriate medical clearance with our team.
40:42We treated her with ECT.
40:45She had eight in patient
40:46bilateral treatments.
40:47The profound effect was
40:49remarkable with some evidence.
40:51After the third treatment and
40:52then pretty remarkable improvement
40:54after the 8th when she went home
40:56she was down to two medications,
40:57really only as a talip RAM at that time.
41:00And and what's amazing about this woman
41:03is that she was treated at McLean
41:05Hospital monthly with maintenance ECT.
41:07For the next 10 years.
41:10And then she passed away from
41:12metastatic cancer about six years ago.
41:14So the daughter,
41:16who was very much impacted by her
41:19mom's illness and then became
41:20a big advocate for Alzheimer's
41:21disease research and treatment,
41:23also helped to support our further study
41:26of this one thing I'll say about this case,
41:29which was also amazing is that it
41:31LED us to treat more people like her
41:33with ECT and then collect data on it.
41:36And so we published one study that
41:38was 16 patients retrospective chart
41:40review with very poor data other than us.
41:44Filling out a Pittsburgh agitation
41:46scale based on you know 3 physicians
41:49agreeing to how symptomatic patients were.
41:51And then we decided to collect more data,
41:52but.
41:54One of the questions that's come up is,
41:56well, what about quality of life?
41:57And so this was Louise when in her
41:59earlier days and Karen statement
42:01about her mom and she basically
42:03said that my mom was a petite 5
42:05foot three 115 pound terror winner,
42:07aggression reared, she was uncontrollable,
42:09her medicines were losing efficacy
42:10and it became so dangerous for our
42:12in home aide and my dad and I that
42:14we had no option but to place her at
42:16McLean Hospital on the inpatient unit.
42:18But from that very first, ECT.
42:19The medical teams my father and
42:21I were were rendered speechless.
42:23Walking down the hallway after
42:25that first treatment.
42:25She came at me like she
42:27used to win aggressive,
42:27but this time she reached her arms.
42:29Let's rub my cheek lovingly.
42:30Shanda smile from ear to ear.
42:33And tears rolled down my cheeks.
42:34Her agitation and aggression
42:36nearly disappeared.
42:37She went from 31 medicines to one.
42:39We brought her back home and were
42:40blessed with another 10 years with her.
42:42This gave my mother tremendous quality
42:44of life and quality of care and my
42:46father gave my father, his wife and
42:48me and my mother and without ECT.
42:49She would never have seen me get married.
42:51So Karen was very public about this.
42:53She was on NPR.
42:55She she helped us some.
42:57Like I mentioned with our grant.
43:00Alright, So what about the data?
43:02So we we then realized that the
43:04retrospective chart review is not enough.
43:06Let's try to collect some data that we
43:08could find from doing a prospective study,
43:11and we thought we'd be clever.
43:12We thought we would have two groups.
43:14We would not randomize people,
43:15but for those people who agreed to get ECT.
43:18They would get ECT.
43:19And for those who said no,
43:21we would just follow them naturalistically.
43:22And by the time we actually intervene
43:25with ECT everybody wanted ECT.
43:27So this was the scale that we used
43:29as the primary outcome measure the
43:32Cohen Mansfield agitation inventory.
43:34Patients were in the hospital on
43:35average of four weeks before the 1st
43:37ECT treatment and these were people who
43:39had failed multiple medicine trials.
43:41They had on average 9.4 treatments and
43:43we saw meaningful improvements again.
43:46Open label by the 3rd treatment
43:48that continued to improve through
43:50the 9th treatment.
43:51So we spent many years collecting
43:53data at multiple sites and putting
43:55together this amazing team and
43:57we now have a five year.
43:59R A1 funded in 2018 by the NIH,
44:02where we're randomizing people to to ECT,
44:05which is now right.
44:06Unilateral, brief,
44:07ultra pulse ECT versus simulated ECT,
44:09which is essentially everything
44:12but anesthesia.
44:13We take people down to the ECT suite.
44:16We keep them in a separate room.
44:17They get an Ivy.
44:18They get gel in their scalp
44:20but they do not get anesthesia.
44:22They're PRN.
44:23Medicines can be used in the treatment
44:25team is blind to their allocated group.
44:27This has been a labor of challenge.
44:31We have been having lots of difficulty
44:34with recruitment for a variety of reasons,
44:36not the least of which is this pandemic,
44:38but also it took a year to get an
44:42investigational device exemption
44:43from the FDA,
44:44but I can talk more about this
44:46in the Q&A at the same time I
44:48was working on this unit.
44:49We also were experimenting at the time
44:51with Dronabinol or Marinol because of
44:53its effects on CB1 and CB2 receptors,
44:56but in particular the CB1
44:57receptor that may mediate the
45:00anxiolytic effects of cannabinoids.
45:01And and so again,
45:02for those of you who are maybe
45:04in training and are thinking
45:06about a research career,
45:07the idea of coming up with really
45:10important clinical questions based on
45:11what you're seeing in front of you.
45:12Research questions that could be
45:14addressed through research is really,
45:15really guided by your clinical experience.
45:18So we started using dronabinol
45:19and we wound up publishing.
45:21You know a paper on 40 patients,
45:23but the the theory behind this,
45:25and this was a paper we just published
45:27summarizing some of the literature on
45:29cannabinoids for Alzheimer's disease.
45:30For agitation in particular,
45:32like why would cannabinoids work?
45:34So there's a whole bunch of
45:35mechanisms that are fascinating here,
45:37including neurotransmitter regulation,
45:38but there seems to be neuroprotective
45:40effects as well as reducing
45:43neuroinflammation and oxidative stress.
45:44May help its circadian rhythm disturbances,
45:47a variety of other conditions
45:48like pain and anxiety.
45:50And then of course there may be some
45:52beneficial effects on the vascular system.
45:54In that first study that we published,
45:56it was 40 in patients
45:58with dementia agitation.
45:59We treated them with the mean dose of
46:01TREN abanil up to 7 milligrams a day.
46:03So again we tried to get people
46:05to 10 milligrams a day,
46:06but on average they were on 7.
46:08The primary outcome measure was the PS.
46:11The Pittsburgh Agitation Scale,
46:12which is 4 items of physical
46:14and verbal agitation.
46:16And the side effects were sedation,
46:18delirium and again whether it was related,
46:20unrelated, unclear.
46:21So we use this data and my colleague
46:24Paul Rosenberg and I collaborated
46:26together to write a a narrow
46:28one which got funded in 2016,
46:30and so we're we have a no cost extension.
46:32We're in now.
46:34And we're randomizing people
46:36to 5 milligrams a day for week.
46:38One of tRNA been all up to 10 milligrams
46:40a day. It's a three week trial.
46:43We started inpatient.
46:44We've now expanded to long term care
46:47and outpatient settings as well.
46:50We're looking at Alzheimer's
46:52disease predominantly and severe
46:54agitation using the IPA criteria.
46:56And we do have rescue medicines
46:58and we're allowing people to stay
46:59on their concomitant medications.
47:01And even with all of that,
47:02this is a very hard study to recruit for.
47:04But I guess the good news is we are now
47:07almost 60 patients into our our goal of 80.
47:10You can see our demographics here,
47:13weighted towards around 78 years old,
47:17about 65% women, which is pretty common.
47:19And like unfortunately,
47:20as I mentioned in the beginning,
47:21most of these studies,
47:23despite one of our sites being in
47:25Baltimore and one of our sites being
47:27in Miami where they have a very,
47:29very high Cuban American but
47:31essentially Latino population,
47:33we're still struggling with our
47:35demographics in terms of race and ethnicity.
47:38So hopefully we will have data on
47:40this within the next year or so.
47:42Finally, on the cannabinoid realm of things,
47:45my colleague at McLean, Stacy Gruber,
47:46and I have been collaborating together
47:48on a trial of cannabidiol CBD,
47:51mostly CBD.
47:51This is a plant based compound for
47:54anxiety in Alzheimer's disease,
47:56and again anxiolytic effects of this
47:59drug may be may be helpful specifically
48:02and may not induce psychosis like THC could,
48:07so this is a sublingual solution
48:09that is by weight,
48:11it's you know.
48:13.3% THC so it's predominantly
48:16CBD, 45 milligrams,
48:17with only a milligram of THC,
48:19and so we're now in them,
48:20and this is only an open label.
48:21Proof of concept Spiral Family
48:23Foundation funded study.
48:27So many reasons why not to use
48:30benzodiazepine's, the cholinesterase
48:31inhibitors and memantine do have some
48:34effects on anxiety and agitation.
48:36I'll just mention that the cholinesterase
48:39embitters may specifically address
48:41apathy and visual hallucinations and
48:43memantine may may also address agitation.
48:46But none of those effects are acute.
48:47You're not going to use these drugs and
48:50expect to see a response in a few days.
48:52So if you've got a patient who's mildly
48:54anxious and nonspecifically agitated,
48:56and by the way all of this presumes
48:58an adequate work up like we talked
49:00about and behavioral interventions.
49:01But if you've got a nonspecific
49:04agitation syndrome without aggression,
49:05without psychosis, without depression,
49:07based on the site at trial, you might.
49:10You might consider SSRI's, or,
49:12if they're not sleeping or eating well,
49:13mirtazapine, or if it's only intermittent,
49:16you might consider trazadone.
49:18If, on the other hand,
49:19there on the other side of the spectrum,
49:21they're physically aggressive and agitated.
49:23And they have psychosis.
49:24That's where the experts would agree
49:26that the atypical antipsychotics
49:27are a good first line of treatment.
49:29If they are aggressive and
49:31agitated with depression,
49:32again agitated and aggressive
49:34with depression,
49:35that's where you may want to
49:36start with S rise or rise,
49:37or even mirtazapine.
49:39But it's this fourth group that
49:41really is the challenging group.
49:42This is the group that I think
49:44winds up in hospitals difficult
49:45to treat in nursing homes.
49:47Why family members burnout?
49:48It's when you've got aggression
49:50without psychosis, we often will not.
49:51We don't really have a first line treatment.
49:54This is where we often use
49:56combination therapies,
49:57which may include anticonvulsants
49:59in atypical antipsychotics.
50:01Alright, so the last part of this talk.
50:05Before we do Q&A is I I wanna
50:07bring up the concept that we will
50:10never have enough specialists,
50:12not just in geriatric psychiatry,
50:13but in any psychiatry subspecialty
50:15to treat the mental health
50:17challenges of our population.
50:18And we all know this in our field and
50:20we're seeing it now highlighted by the
50:21pandemic in ways we couldn't have even
50:23imagined a few years ago in some ways.
50:25But some of what's driving the potential
50:27for optimism is really a transformation,
50:30and the way we organize health
50:32care and the way we pay for health
50:34care and so back in the old days,
50:36which is not that old and frankly,
50:38still dominates in many parts
50:39of the country we built,
50:41care around institutional settings,
50:43payments incentivized, more care.
50:45This is very true in our specialty arenas.
50:47You know, the more you do,
50:48the more you build, the more money you make.
50:52And again, this is often driven
50:54by procedural based specialties
50:55and in our old way of doing things
50:57and yesterday's healthcare system.
50:59Traditional fee for service Healthcare
51:00is really what this is is that we were
51:03responsible for getting people better
51:05now is immediate outcomes and we were
51:08grudgingly accepting and increasing costs
51:09which we no longer will do well with.
51:11The Affordable Care Act of 2010 and
51:14and population based approaches which
51:16have been taking hold in certain parts
51:18of the country with risk contracts
51:20where we're basically now being.
51:22Asked to build care around a patient,
51:25not around an institution,
51:27and instead of just trying
51:28to incentivize more care,
51:30we're incentivizing better care so that
51:33the reimbursement isn't just about volume,
51:35it's about value.
51:36It's about quality and addition to just,
51:38you know, doing,
51:39doing what you need to do and
51:41and we're not just responsible
51:42for how someone is doing today,
51:44but also over a longer period of time.
51:45And,
51:46and we're doing this in part because
51:47we just can't sustain the cost burden.
51:50These are the principles of value based care.
51:53And the triple aim of health care
51:55that Don Berwick talked about,
51:57which is trying to improve quality
51:59of care patient outcomes while
52:00reducing overall costs and a very
52:02important fourth part of the game,
52:04which is often not mentioned,
52:05which is our own quality of life, right?
52:07What about the health care?
52:09I mean,
52:09the mental health well being and
52:11the burnout in the health care
52:12providers which we're now seeing.
52:14Of course becoming tremendously challenged.
52:17And for those of you in geriatric psychiatry,
52:20I want you to know that there's a huge
52:22opportunity for us in this population.
52:24Health based landscape.
52:25And I would argue it's true
52:27for all of psychiatry.
52:29If anything value based care,
52:32I think has an opportunity to elevate
52:33psychiatry and to put us in a real
52:36leadership role in healthcare systems.
52:37Because if you really want to improve
52:40quality of life and reduce costs,
52:42you got to,
52:43you got to address mental health care
52:45and luckily we've got two decades of.
52:47Data suggesting that collaborative
52:49care approaches for depression in
52:51primary care incredibly effective,
52:53and we're now starting to see similar
52:55data in terms of Alzheimer's disease
52:57as one model for how geriatric
52:59mental health can be evolved or
53:02involved in a meaningful way in
53:04in this evolving landscape.
53:06This is a very busy slide,
53:08but I want to let you know that we're not
53:10the only ones that are doing this work.
53:12In mass General Brigham I would.
53:14I would point to two groups that
53:15have really three groups that
53:16have really led the way there.
53:18I would say anyone on this slide
53:19has really been leading the way,
53:20but David Rubin at UCLA geriatrician with
53:24his ADC program Alzheimer's Dementia
53:26Care and and the aging Braid Care program.
53:29Chris Callahan and Melos Boustani,
53:31all of these people are geriatricians
53:35and linking in with geriatric
53:36psychiatry is is they,
53:37they realize, is critical.
53:39UCSF developed the care ecosystem model
53:41in their memory and aging center,
53:43and then there are others as well.
53:44So there are a number of these programs
53:46that mind at home program at at Hopkins,
53:48for example, are trying to improve
53:51clinical outcomes like behavioral
53:52symptoms that dementia like caregiver
53:54stress while also reducing cost and
53:57doing it without the traditional,
53:59you know, 11 specialist doctor and one
54:01patient and family in a room together.
54:04So about three years ago we four years ago.
54:07Now we put together a bunch of experts
54:08across our health care system and we said,
54:10well, if we could do something
54:12for dimension primary care,
54:13what would it look like?
54:14How would we assess people who
54:15would be the target population?
54:17What would the model look like?
54:18We eventually decided to implement
54:20David Rubins UCLA model,
54:22which is seen here on the right
54:24side of the slide,
54:25which is pairing a dementia care
54:27manager who's a social worker with a
54:29geriatric NP and a supervising physician
54:32could be a geriatric psychiatrist.
54:33Could be a geriatrician.
54:34But someone who's expert in dementia care?
54:37The patient and the caregiver
54:39in the middle of this.
54:40Diagram and LinkedIn very closely
54:42with the primary care doc and
54:45using all available technology,
54:47including electronic records for developing
54:49registries and following people overtime.
54:51Our goal was to develop this high
54:53quality care program for individuals
54:55with cognitive impairment by
54:57facilitating evidence based assessment
54:59and treatment in primary care over
55:01the entire illness trajectory and for
55:03both the patient and their caregiver.
55:05So we targeted individuals who
55:07were members of our Medicare ACO.
55:10And had a known diagnosis of dementia
55:13based on codes in the EHR or were
55:15suspected to have cognitive impairment
55:18based on the clinician or family concern.
55:21And we have a whole series of
55:23services that we utilize and now
55:24that we've been doing this,
55:26we launched it timing wise about a month
55:28before the pandemic really took off.
55:31But this is essentially an
55:33embedded specialty care model.
55:35It's not very scalable, it's too costly.
55:38The outcomes that we're looking
55:39at now are promising David Rubins
55:41outcomes are very promising,
55:42but to scale it you actually have to
55:44do a lot of fee for service billing,
55:47using care management and E&M codes.
55:50Which is fine,
55:51but it's not going to be paid for alone
55:55by reducing the overall costs of care.
55:59So we then looked into other models
56:01and this is the UCSF model and we
56:03got a grant from the NIH impact
56:05Collaboratory couple years ago,
56:07and the idea here was to take the care
56:12ecosystem model developed at UCSF,
56:14which is originally implemented
56:15not with a nurse and social worker
56:18and and physician team,
56:20but with a health care navigator
56:22who's a non clinician who gets
56:24trained in basic dementia assessment.
56:27Two tools, one for the patient.
56:28For the caregiver and seven protocols
56:30that address the gold standard dementia.
56:33101 principles like medication
56:35deprescribing and reducing
56:36behavioral symptoms of
56:38dementia and supporting caregivers,
56:39and connecting people to
56:41resources and so forth.
56:42And so we decided.
56:44Instead of building a new
56:45siloed program in our system,
56:47we would take nurses who were part
56:49of our high risk care management
56:51program and we're following like
56:53180 patients on their caseload
56:55and we would train 20 of you know,
56:57train 15 nurses in our first
56:59wave and 15 in our second wave.
57:01But train them to manage in this
57:03evidence based way their dementia
57:05population on their care on their caseload,
57:08so maybe 10 or 15 of their
57:10180 would have dementia,
57:11so we're now in the midst of wave
57:13two and I would say my lesson
57:16learned from this is implementation
57:18is very very challenging.
57:19Nurses are overwhelmed with 180 very
57:21complex patients and even though
57:23they knew these dementia patients
57:25had been following them for years,
57:27we then asked them to do more
57:28than they would normally do,
57:30even though it's gold standard care.
57:32And they got quickly overwhelmed,
57:34so we're now trying to figure out
57:36ways to modify their caseload.
57:37So they can give these patients
57:39and caregivers the attention
57:40they need and deserve.
57:41But I do think and we'll be
57:43looking at our data soon it.
57:45I think this is a very interesting model,
57:47though that could potentially be
57:49scaled along with other resources.
57:51So just in summary.
57:54The behavioral symptoms that
57:55dementia part of this talk.
57:57It's really important to remember
57:58that these are symptoms.
57:59They're not diagnosis,
58:00they beg a need then to dig deep and
58:02find the underlying cause that's driving.
58:04The behavioral problem will
58:06always intervene no matter what.
58:07With these non pharmacological
58:09treatments and then,
58:10when needed,
58:11think about various evidence based
58:13pharmacotherapy strategies we
58:15talked about always monitoring,
58:17tolerability and and side effects
58:19and giving informed consent.
58:21At the end of the day,
58:22you know when you've got a really
58:23challenging patient like some
58:24of the ones that I mentioned.
58:25If you break it down to the basics of,
58:28you know what we're trying to do here.
58:29Our goals are pretty much
58:31always aligned with families.
58:32If we break it down to enhancing quality
58:34of life in keeping someone safe.
58:37And sometimes it's very complicated to
58:38figure out the right pathway forward,
58:40but that often will take a lot of
58:42the stress out of the room and
58:44allow people to develop a plan.
58:45And then finally there,
58:46there's going to be a lot more
58:48information about novel integrated
58:49care models, not just for dementia.
58:51But for all sorts of psychiatric
58:53care and primary care settings.
58:54I know many of you do this.
58:56I mean the VA, by the way,
58:57has been doing most of this than
58:58the rest of the health care systems
59:01because they essentially had these
59:03integrated care models going on
59:04way longer than the rest of
59:06traditional health care.
59:07But you're going to be seeing
59:08more and more of this,
59:09and I'm hopeful that it
59:11really allows those of us
59:12in psychiatry to really make a
59:14big impact and take a leadership
59:16role in caring for patients
59:17in primary care settings.
59:19So I'm going to stop there.
59:21And welcome any questions.
59:24So Brent first of all, let me just
59:28thank you for a wonderful talk.
59:30Couldn't couldn't thank you enough.