- As far as disclosures,
I have no financial
conflicts of interests here.
Another thing that we like to disclose
is are we going to talk about
non-FDA uses of medications?
And for the psychiatric
symptoms of Parkinson's,
yes, we will be addressing those.
I will do my best in general
to use both the generic and
trade names of medicine.
You know, that is always confusing
and every medicine has two names.
I'll try to make sure you
know what I'm talking about.
For brevity in the slides,
I've abbreviated
Parkinson's Disease as PD.
And I wanna thank my many colleagues
in psychiatry, neurology,
and geriatric medicine,
and my patients, for helping me
learn all that I have learned,
and hopefully I can impart
that knowledge to you as well.
And we have, we're
actually very fortunate,
University of Michigan, to have a very
large group of geriatric psychiatrists.
So the route to geriatric
psychiatry is fairly long.
It's four years of undergrad,
four years of medical school,
four years of residency, plus one to two
years of a fellowship as well.
There are only 1400 of us in the country.
We only graduate about
55 fellows per year.
And so, we're very fortunate,
between the university and VA,
to have 14 to 15 board certified
geriatric psychiatrists on faculty.
And today, as far as objectives,
I want to, I think number one,
help you open up a dialogue
with your Parkinson's care provider
on these symptoms I'm
gonna talk about today.
And you'll be able to identify
what we call neuropsychiatric
or behavioral symptoms
that we will see in Parkinson's.
And also know the treatments that are
available for these non-motor symptoms.
And so, the first description
of Parkinson's was in this
1817 Essay on the Shaking
Palsy by James Parkinson.
And in it, already that long ago,
I guess, what, we had
the 200th anniversary,
that it was a disorder that
affected multiple symptoms.
We know that it affects
the motor symptoms,
which is what we focused on earlier today.
But also, even 200 years ago,
we knew that it impacted mood,
perceptions, and cognition.
So again, it's more than
just a motor illness.
The neuropsychiatric symptoms
that we can see in Parkinson's
span a wide variety, including depression,
anxiety, apathy, compulsions, psychosis,
and cognitive impairment or dementia.
And we'll be talking about
different aspects of these.
And this is a gross oversimplification,
I'm sure Dr. Wyatt would agree with that.
But what, you know, we wanna think,
as we think of these
neuropsychiatric symptoms,
we can explain why they
happen biologically.
It's not a personal failure or a weakness.
It is due to neurotransmitter
changes in the brain.
Basically, decreased neurotransmitters
increase psychiatric symptoms.
So we have dopamine depletion and these
Lewy bodies that come into play.
Now I wanna kind of approach this,
I think it's always helpful as we
talk about some of these things
that we don't often like to talk about,
kind of through a kind of an amalgam
of patients that I have
worked with over the years
put together into Mr. F.
And so, Mr. F, this fictional patient,
had Parkinson's for 10 years.
And he was actually, the motor symptoms
were fairly well-controlled
for a number of years,
just on Sinemet, or the
carbidopa/levodopa combination.
He did always worry, though, about,
you know, could this get worse?
He had a brother about five
or 10 years older than him
who actually had a very aggressive
course with his Parkinson's Disease.
His primary care doctor
had referred him to me
because he was depressed,
anxious, tearful, and withdrawn,
which was a big change for him.
So, having that as our backdrop,
that will launch us into a discussion
of depression in Parkinson's Disease.
And so I really hate this word depression,
'cause we use it all the time.
I'm depressed, I'm this, I'm that.
And I think it's hard to understand
what a syndrome of major depression is,
so I'd like to go over that next.
So major depression is defined by having
one of these two cardinal symptoms.
Either a sad mood,
but not necessarily, you
don't have to feel sad,
or what's called anhedonia,
which is a loss of pleasure
or interest in activities.
So, plus to meet criteria for the full
major depressive episode,
for a course of two weeks
having one of those two cardinal symptoms.
Plus changes in appetite.
So you might actually, most
people tend to eat less
but a few people, with
an atypical depression,
may crave carbohydrates and eat more.
Sleep changes.
Often times insomnia,
trouble falling asleep,
trouble staying asleep,
or waking up early.
And a few people have the hypersomnia,
just kinda sleeping all day.
Oftentimes too there are motor changes,
changes in activity level with depression,
what we call psychomotor agitation.
Thinking of this as, you know,
the hand-wringing and pacing.
Or the opposite, psychomotor retardation,
I like to think of a couch potato,
you know, which is a change
from someone's baseline.
And then, the feelings
that go along with this.
Feelings of guilt, feeling hopeless,
feeling helpless or worthless
or a burden to those around them.
People with depression also have trouble
concentrating or trouble making decisions.
So it may be harder to read
or kind of give up on reading.
Or even things that usually come easily,
like what should I wear today
or what should I make for dinner,
become a very difficult decision.
And a fatigue and loss of energy.
And also, recurrent thoughts
that life isn't worth living,
I'd be better off dead,
wishing I'd die in my sleep
so I don't have to face tomorrow,
or looking into options for suicide.
And so, five or more of those plus either
the sad mood or loss of
interest over two weeks
makes up the diagnosis
of major depression.
But something to keep in mind
as one of those two symptoms,
and what makes it really
hard to discuss depression,
is half of older adults with
depression don't feel sad.
So again, many times we'll
see a mass depression
where just a lot of worry.
Some older adults don't have depression,
you know, they didn't
grow up with that term,
they don't know what it means.
It doesn't have meaning to them.
So again, looking for the constellation
of all those symptoms,
but sadness does not
have to be one of those things.
But then you're saying, hmm,
a lot of those symptoms
that she just said,
aren't they some of the
things we see in Parkinson's?
And so, would you agree?
Yeah.
So we know that sleep
disturbances can happen.
Right?
Appetite changes happen.
Constipation is something else that we see
both in depression and with Parkinson's.
The fatigue factor, the slowed movements.
Changes in focus, memory,
and concentration.
Changes in sex drive.
What about facial reactivity?
We think when people are depressed
they don't smile as much,
but we know that also,
one of the motor changes in Parkinson's
is that, what we call masked facies,
or it's more difficult to
have facial expressions.
And social withdrawal.
There may be many reasons for this.
There might be the mobility issues.
There might be concerns about how one
might appear if there are tremors.
Would I go out to a
restaurant if I have a tremor?
What if I drink coffee?
What if I can't cut my food?
Will I go to the store if
I have to write a check
and it's really hard for me?
Or if I have dyschezia, what
will people think of me?
But the things that aren't there
are the feelings of guilt, hopelessness,
helplessness, worthlessness,
or feeling like a burden.
And we oftentimes, if we have those
and some of these overlap
symptoms, we do treat.
And so, how often do we see
depression occurring in Parkinson's?
Actually the depressive symptoms,
even the non-overlap
symptoms, are quite common.
About 50 percent of
persons with Parkinson's
will have some of those
depression symptoms,
and about 20 percent of people at any time
will meet all those criteria
for major depression.
In one study a while ago, though,
only one percent of
persons with Parkinson's
had mentioned that to
their treating clinician.
And so, especially in Parkinson's,
depression can be not
recognized and not treated.
And I believe that a lot of
people may not think that
I'm going for my Parkinson's appointment,
should I mention my mood?
It may not occur.
And another study had
shown that it's actually,
when there's depression with Parkinson's,
it actually had more
impact on quality of life
than either the motor symptoms,
the severity of Parkinson's,
or the medications used for Parkinson's.
So again, it does have real
implications in function.
Again, a very oversimplification
of why does this happen.
We know that, in Parkinson's,
neurotransmitter levels decrease
due to the neurodegeneration
and changes in the brain.
We know that the neurotransmitters
dopamine, serotonin, and norepinephrine
are involved with mood and anxiety.
So if we have less of
these brain chemicals,
it does make sense that we are
gonna see changes to mood
and changes to anxiety.
However, that's not
just the whole picture.
Changes in the brain effect
these brain circuits as well.
It's not just the overall level,
but what's the highways, you know,
the off-ramps, the on-ramps.
And those get hijacked in Parkinson's
due to the changes in the brain,
again, impacting depression and anxiety.
It's kind of like a freeway lane closure.
I guess up here, what, 696 has been,
one side has been closed, and you can see
that really has a ripple impact effect.
So, just, I wanna bring that up,
that there is a biologic basis
for these symptoms that we see.
We also know that oftentimes anxiety
and depression kinda go hand in hand,
as do the treatments for
anxiety and depression.
And anxiety is another one of those things
that feels a little
different for everyone.
You know, sometimes it's this restless,
tensed up, feeling on edge,
feeling like something bad's gonna happen,
can't relaxe, feeling
nerved up or keyed up.
And I always like to work with people
and find out, how do they
describe their anxiety?
So I know, when I see them back,
I can ask, how is that symptom doing?
Are we doing what we need
to do to help with that?
And anxiety is very common.
43 percent of people with Parkinson's
also meet criteria for one
of the anxiety disorders.
And it seems like it happens more often
in persons with an early age
of onset with Parkinson's.
The people that have more
severe motor fluctuations,
the off-on periods, and more often with
dystonia in some of the studies.
Again, we don't have a lot
of research in these areas.
These are the signals that are coming out.
And what I've noticed
in my clinical practice,
since I guess I've been
doing this since 1999,
so a while, is that
we'll see some of these
subsyndromal depression and
anxiety symptoms coming up.
So they might see me as
a geriatric psychiatrist
for those before the Parkinson's
actually declares itself
several years later.
We know those brain changes take place
before we see the physical manifestations.
And so, what do we do about
depression and anxiety?
Do we just say, well, it
happens, and that's it?
No, I don't advocate for that at all.
I want to give you the
way that I think about
patients with symptoms
that have Parkinson's.
And when you go to your
Parkinson's provider,
how can you have language
and give them information
to better inform how
to treat your symptoms?
When I see someone in
clinic, I like to ask them,
when was your last Parkinson's medicine?
And I want to know, what's
the duration of action?
How long do your motor
symptoms usually respond?
How long does it take, for example,
your carbidopa or levodopa to work?
And when does it kind of wear off?
And where am I seeing
you in that spectrum?
And then, you know, how severe
are the motor changes to your Parkinson's
when your medicine's working
and when it wears off?
And then, getting to mood and anxiety,
is there any fluctuation
with the timing of your motor symptoms
or response to medicines
to the mood or anxiety?
I find a number of people that get
those off periods pretty quickly,
the anxiety's pretty high.
And then, and so I think that's a very
helpful thing to think about when you're,
you know, if you're noticing
depression or anxiety,
see, does it have any relation
to the timing of your medicine?
I always like to ask about sleep.
How's your sleep doing?
Also ask if there are any of that
acting out of dreams or what
we call REM Behavior Disorder.
'Cause that might be a different treatment
than someone that has insomnia
due to depression alone.
We always wanna ask about falls
and a number of other things
that we'll get to as well.
So if we see depression only
occurring in off periods,
we wanna work with the
Parkinson's provider
on what can we do to optimize
the treatment of Parkinson's?
Could it be going up on a dose
of the Parkinson's medicine
or decreasing the interval between doses?
And that oftentimes will help
the depression or anxiety.
And again, I think maybe you'll kind of
get the impression that I don't wanna
give medicines unless they're needed.
Everyone has enough medicines,
and I wanna look at ways, how
can we minimize medicine use
but certainly use it and
use it well when we do?
If it seems like the mood
or anxiety is unrelated
to the motor fluctuations, if it's mild,
we might wanna try
non-medication approaches.
What can we do to learn
about depression and anxiety?
There are counseling strategies.
There's also cognitive behavioral therapy.
So I don't know if you
can see this picture here.
It's a gentleman with a dog face,
you can teach an old dog new tricks.
Kinda corny, but it's true.
So again, there's no one
that's too old for counseling.
And that can be very helpful
for milder, mild to moderate
depression or anxiety.
But if it's moderate to severe
and impacting function
and quality of life,
yes, we do wanna treat.
There are a variety of medications,
and we'll talk about some
general classes of those today.
And also, for severe psychotic
or life-threatening depression,
then we may even consider
electroconvulsive therapy or ECT.
And I can, I have a whole
slide on that as well.
So what do we know about
medicines for depression?
Again, there have not
been many studies done
in people with Parkinson's.
The largest clinical trial to
date has been 115 patients.
Is that very many?
No.
So we do the best with
the data that we have.
But what we do know from the studies
is that people that have the full
major depressive syndrome seem to respond
better to medicines than people
that have just a few of the symptoms,
with some depressive symptoms
but don't meet that whole constellation.
Also, that treatment, you know,
even placebo, even a
sugar pill is treatment.
Right?
So, to some degree, it may
not be an active medicine,
but you are interacting
with someone regularly,
you know, getting evaluated, checking in.
There's a large placebo response
in these studies as well.
So let's say, okay we've determined that,
yes, we probably should use the medicine.
What are the medicines that we use?
Oftentimes we, you know, there have been
studies about different classes,
I don't think they're large enough
to say one's better than
the other across the board.
We often, for safety,
efficacy, and ease of use,
will start with medicines that are
the selective serotonin
reuptake inhibitors,
which are SSRIs.
They first came out in about 1988 or so.
Prozac is the prototypical one.
But we tend not to use that regularly
if we're starting someone
in a geriatric practice.
The sertraline or Zoloft
or escitalopram or Lexapro
are the ones that I would tend to use.
However, if someone's
been on another medicine
and has done really well,
like a paroxetine or Paxil,
citalopram or Celexa,
or Prozac or fluoxetine,
yeah, we'll keep you on
that, if it does well,
and we just need to tweak the dose.
And they have indications
for major depression
and for anxiety disorders.
Don't have a rich, robust database
for Parkinson's, but they do have
the FDA indications for the depression.
The tricyclics are
things that are good for
depression, sleep and
pain, for neuropathic pain.
And these are what I like to think of
as the oldies but goodies.
These are the ones that were
developed in the '50s and '60s.
And they tend to have more
potential side effects with them,
sedation and what we call anticholinergic.
So the two that I have here,
nortriptyline or Pamelor and desipramine,
which I believe is Norpramin, are the ones
that have the least
anticholinergic burden.
And they actually may have had
some signal of preferential response
in persons with Parkinson's.
Surprisingly well tolerated, but again,
they do have some cardiac
things that we would
wanna coordinate with
a primary care doctor
and monitor if there
was any cardiac issue.
But again, they can be used.
I would not say, probably
nowadays, first line.
The third category here, SNRI,
serotonin norepinephrine
reuptake inhibitors.
So they work on two
different neurotransmitters,
both serotonin and norepinephrine,
and also have FDA indications
for anxiety, depression.
And the duloxetine or Cymbalta
has some indications for
different types of pain as well,
like diabetic neuropathy,
other pain syndromes.
And the venlafaxine or Effexor,
in some studies, has
looked quite good as well.
And then there are more
kind of subtle differences.
All medicines work about the same.
About 70 percent of people will get
a benefit with a medication.
And then we kinda fine tune more based on,
you know, what are the
person's specific symptoms.
So someone who maybe has that,
what we call an atypical depression,
kind of very sleepy, kind
of couch potato-like,
we might wanna do something
a little more energizing.
Bupropion or Wellbutrin dosed
in the morning might be that.
If someone's really not sleeping well,
highly anxious and has been losing weight,
we might think of mirtazapine or Remeron.
A medicine that can be used
that neurologists sometimes will use
is a monoamine oxidase inhibitor,
a couple of them, but rasagiline is one
that has been used that
looks like there was
an improvement in people
with Parkinson's in mood.
And there's been also a little bit
of literature on pramipexole,
a dopamine agonist, also
helping mood symptoms.
So there's a variety of
things that we can do.
So when you take an antidepressant,
I think it's also important to understand.
Why is it important?
You know, why should I
be taking another pill?
We wanna be clear, you know,
what are we expecting it to help with,
and when you come back to see me,
what questions am I gonna ask to know
if it's helping with the
symptoms that you're impacted by?
And looking at quality of life,
functional status, those things,
treating depression helps with that.
How long will it take to work?
That's also a very important question,
because there are some
medicines out there,
a category of anxiolytic
called benzodiazepines,
they snuff out anxiety really quickly.
Antidepressants don't work like that.
They're kind of like,
I guess the, you know,
kind of the tortoise and the hare.
The tortoise works slowly
but then kinda treats the symptoms
versus just putting a
quick bandaid on symptoms.
So again, it will take
maybe seven, 10, 12 weeks
to have its full effect of daily dosing.
And you know, we hope
you feel better tomorrow,
we hope it's like a light switch,
but I'm not worried if it
isn't, it's several weeks.
And what are the possible side effects?
Notice I did not say
guaranteed side effects.
Right?
So again, thinking about side effects,
and I think especially with medicines
to treat mood or anxiety,
people anticipate,
oh, it's gonna make me a zombie,
oh it's gonna, you know, be negative.
My goal is never to make anyone a zombie.
My goal is to resume someone
to feeling good again
and enjoying their life.
So, again, zombie is not
part of the equation here.
But what are the possible side effects?
What do we look for?
With most of the medicines,
they'll all say they could
perhaps have an upset stomach,
perhaps have diarrhea or constipation,
most of them say both as options.
Sometimes dry mouth,
sometimes a little bit of disequilibrium.
And again, those would
be very time-limited,
just in a few days, and there are ways
that we can approach that to minimize
the chance of that happening.
How long do you stay on treatment?
And you wanna right out the directions,
'cause a whole lot of information
comes in at a doctor's appointment.
It's hard to keep track of that,
especially if someone like me says,
well we're gonna start a little bit
and then we're gonna gradually
build it up over time.
Over what time is that?
I'll write it out for you.
And I was really worried at
the, you know, back in 1999.
Oh my gosh, am I gonna make
someone's motor symptoms worse?
And I found, in general, really,
antidepressants rarely make
the motor symptoms worse.
But we can really improve someone's mood,
decrease their anxiety, and
improve their quality of life.
So, how do we start the medicine?
We wanna start low, go slow,
but we don't wanna stop and usually
we can get to near younger adult
regular doses for treatment.
So start at a quarter to half
of the usual starting dose,
take it on up as tolerated,
and then be patient.
Again, mood disorders,
usually about seven weeks
is where we see a separation
from placebo pills.
Sometimes the anxiety symptoms actually
require little higher doses and a longer
waiting period to see the improvement.
How long do we treat?
We want to treat at
minimum six to nine months
from a complete resolution of symptoms.
One of the things that can be really tough
is like, well, okay, you know,
it's two months in and I'm feeling great,
I wanna stop this stuff.
And what we find is that
if we don't treat for an
adequate period of time,
the depression's more likely to come back,
usually a few months out.
And then it becomes more
resistant to treatment.
So if it previously responded to one dose,
we might have to go up or change.
So again, being at an adequate
dose for an adequate duration.
Another thing about
practicing in Michigan,
I rarely like to do an
antidepressant taper
this time of year.
We're looking at, you
know, these short days,
gray days, and with ice and
snow and troubles with mobility,
people tend to be more housebound.
I prefer to taper in the early springtime
when we have more outdoors things
and, you know, where it's
safer to go out under foot.
For some people, though,
some people have a history
of recurrent depressive episodes.
Some people may have had poor
function for months to years.
Or very severe psychotic symptoms,
delusional, guilt, ruminations,
seeing or hearing things.
We know that for that type of depression,
if it's happened three or more times,
has been very very functionally impairing,
90 percent chance of that coming back
if the medicines were stopped.
So we also know that the dose
that gets you well keeps you well.
So we'll work with you to say,
you know, kind of looking back at this,
we recommend maintenance
treatment for that.
And has anyone ever heard
of ECT shock therapy?
Electroconvulsive therapy.
Yeah.
And what is its general reputation?
Yeah, its general reputation is like this,
and I think that the movie One
Flew Over the Cuckoo's Nest
probably had a lot to do with that,
as well as the old techniques
of how it was practiced.
However, it's not like that anymore.
The treatment is done in conjunction
with an anesthesiologist
and a psychiatrist.
It's done in a, usually a
post-anesthesia recovery area.
People are given a very
short course of anesthesia,
just a couple of minutes,
and a muscle relaxant,
during the treatment.
And then, then they are monitored
while they come out of the treatment.
And so, again, it's not the barbaric
treatment that it used to be,
and it's actually the
safest, most effective,
most rapid response treatment
that we have for depression.
And there's no upper age limit.
97 is the oldest that we've
treated at Michigan medicine.
We've treated people with
cardiac defibrillators,
people with pacemakers, people with
Parkinson's deep brain stimulators.
So again, very few medical
reasons that we couldn't use it.
It's one of the safest, it's
actually the safest treatment
for women in pregnancy
with peripartum depression.
And we get up to an 85 percent
response rate with ECT.
Usually we would start treatments
in an inpatient setting,
to make sure that the medical monitoring
and all the medical workups happen.
Usual response is about
six to 12 treatments
given two to three times a week.
We do have a very large
outpatient treatment practice
at Michigan medicine as well.
And this is my ideal time of year,
if someone comes in very
depressed this time of year,
I can say and pretty much with confidence,
I can have you better by Thanksgiving.
I can't do that with medicine
if you think of the starting,
tapering, switching,
and, you know, two to three months
of waiting for a response.
So again, it can be a very
rapid and effective treatment.
We have some people,
several of our patients
that we co-manage with our neurologists,
have had monthly maintenance
ECT treatments as well.
So that's been very helpful.
The indication for ECT is
a failure of medicines,
intolerance of medicines,
would be the two main ones.
Or if we, someone has such severe symptoms
or such severe suicidal thoughts
that we just can't wait
for medicines to work,
or a psychotic depression,
and we'll talk a little bit about
that category of medicines later,
where it'd be hard to get to a dose
that would be therapeutic.
Mortality rate is one in 10,000,
usually a cardiac mortality,
and rarely things happen.
And the way it works is
the electrodes induce
a seizure in the brain.
We don't exactly know how it works.
I like to think it kind of
shuffles up the brain chemicals
and lets them resettle at a normal level.
So going back to Mr. F,
we'll bring him back in now.
So he started an SSRI medicine,
kind of a medium dose,
and tended to do well.
And his wife said, and he
said, "I'm not crying anymore."
"I'm kind of enjoying things again."
But then she said "But
he just sits there."
"He still sits around."
And so this gets into another core symptom
that's becoming more recognized
in some of the neurodegenerative illnesses
like Parkinson's, is this apathy,
this lack of motivation and interest
in goal-directed behavior.
Can leave the list, come back
and the list is still there.
Not sad, not depressed, just not doing.
And it's emerging as a
common symptom in depression,
or in Parkinson's, and it doesn't
necessarily track along with depression.
Again, you know, I'm happy to do things,
but I just don't do them,
and when I do them I'm fine.
But you don't feel guilty, hopeless,
helpless, or not wanna live.
And this is really really hard
on the care partners as well,
because someone may seem entitled or lazy,
or just that, you know,
they're unempathetic.
You know, they're doing
this just to bug me.
But again, thinking of those circuits,
there are motivation circuits as well.
And again, we can think
of this biologically,
and that can also be helpful,
understanding it's a core
symptom of the illness.
And remember, it's the
changes from the illness,
it's not the person
doing this intentionally.
So what do we do about it?
Medicines haven't been
overall that effective.
But do you remember Julie,
the cruise director from Love Boat?
Yeah, how many remember The Love Boat?
Okay.
Yeah, so Julie was always
the activities director,
always perky, always
happy, always matchmaking,
kind of getting people
to go outside their box
and do things that they
normally wouldn't do.
And this is what we need for apathy.
Or, you know, I think someone
had the question about,
you know, kind of, 21st Century,
what can we do with computer assistance?
We need a computerized
or a robotic Julie here.
You know, so there are some medicines,
we try things like the stimulants,
like methylphenidate or Ritalin,
or sometimes the medicines we use
for sleepiness with sleep
apnea, like modafinil.
For some people they
work, most they don't.
Antidepressants I haven't
found to be that helpful.
But we need active coaching on,
it's not a choice, do you
want to do this or not,
it's like, which do you wanna do?
Or let's go, not do you wanna go or not.
Just don't make no an option.
How do you encourage and then
kind of stick to a schedule?
It's a lot easier said than done.
But that's one of the
ways to overcome apathy,
that active coaching.
Okay, so Mr. F's wife was working
a little bit more with the coaching.
They were doing more things
as long as she initiated.
You know, called up his friend,
why don't you take him
out to go do this or that.
But then, she saw him exposing
himself out the window,
and then she did a
little bit more searching
and then she yanked that computer
out of the wall and smashed it.
And so this is something
that we know can occur
with, sometimes the Parkinson's,
sometimes the Parkinson's medicines,
are these impulsive and compulsive
symptoms in Parkinson's.
And again, that's something that
people would not wanna talk about,
really, necessarily
with medical providers.
You might not think of that
as something that could
be related to Parkinson's.
But it can be.
And so, the impulse control disorders.
We see things, gambling,
like hypersexuality,
buying or binge-eating,
and it seems like about 14 percent
of people with Parkinson's
may have these symptoms,
about five percent in
any of those categories.
And then there are some
compulsive behaviors,
so hobbyism, getting
really involved in hobbies,
or what's called punding.
Kind of, you know, just kind of
repetitively playing with
your collection of things
and sorting and resorting.
Usually harmless but it can be,
care partners sometimes find it,
like, why are you doing that?
And then, something also in the spectrum
is the dopamine dysregulation syndrome,
which is kind of somewhat
like a, you know,
overusing the dopamine medicine
kind of in a somewhat addictive way.
And all these kind of fall
under a similar category,
and there is a checklist
that Dan Weintraub has developed as well.
So again, if these symptoms are happening,
be sure to let your
Parkinson's care provider know.
So the approaches to that,
we know that it seems like
the dopamine agonist medicines
seem to be more associated with that.
So for Mr. F, took him off of that,
and continued on the carbidopa/levodopa,
and that got better, but he still had
this belief that his
wife was having affairs.
You know, if the friend
came to pick him up,
you know, "Hi Mrs. F, how
are you?" and give her a hug,
that was, there's
something going on there.
And sometimes it's like,
well I saw you flashing porch lights,
I know you have a signal going
'cause you have something going on.
And, you know, pulling out
the high school yearbooks
and kind of looking for things,
reading things into the little notes
that are written in high school yearbooks.
And so this launches us into
a discussion about psychotic symptoms
that we can see in Parkinson's as well.
And again, I want to help normalize these,
and help you feel comfortable talking
with your provider about these.
Or seeking treatment with
a geriatric psychiatrist.
We know at some point in the illness,
about 50 percent with Parkinson's
will have some sort of
psychotic symptoms emerge.
20 to 30 percent of people
will have hallucinations,
and hallucinations are having,
like seeing things that aren't there,
hearing things that aren't there,
feeling things that aren't there,
tasting things that aren't there.
Or sensations in the mouth.
Had one person that had this sensation
of razorblades or shards of
glass or wires in their mouth.
Again, so it's a feeling, you know,
a sensory experience without
a stimulus causing that.
And delusions are fixed false beliefs.
So again, it's not seeing
or hearing something,
but it's believing something.
You know, my wife is replaced,
you know, you're not my real wife,
you're an impostor pretending to be her.
Where were you born?
What was your mother's maiden name?
Kind of questioning like that.
Oh, there's someone in the basement,
or they're coming in and
taking my things when I'm out,
I need to change the locks.
Those would be examples of delusions.
And about 50 percent will have
more mild symptoms of hallucinations,
things like what we call
presence or passage hallucinations,
kind of the flitty, shadowing things
that you're not quite sure
if they were there or not,
but it seemed like maybe
something ran across.
And there can be a whole
variety of how this might look.
You know, so again, this might
be an example of an illusion.
Looking out and perhaps seeing a bush
that actually might look like an animal.
Seems like around here, the two things
that outdoor things look like are deer,
probably 'cause we have a
lot of deer in the area,
or construction equipment.
Those seem to be a couple
of the common things,
what we would call illusions.
An indoor illusion that
we see quite commonly
might be a coatrack with a coat on it
that looks like a person in the room.
And that can be very frightening.
You can have what we
call Capgras Syndrome,
feeling that someone's been
replaced by an impostor.
Fregoli Syndrome, where there's one person
that puts on lots of different
disguises as different people.
And lilliputianism, so
visual hallucinations,
usually of little children,
sometimes animals or
bugs, can happen as well.
And we already talked about the
types of psychotic symptoms,
and it's very interesting that
sometimes people will know, yes,
those are absolutely not real,
or if I turn on the light they go away.
Some people, you know, they seem so real
that it can't be reasoned with.
No, I know I saw that.
And there are some people that say
I know they're not real,
but I still made them tea.
So again, kind of this mixed insight.
So again, treatment of
Parkinson's psychosis.
What do we do about it?
And again, you don't see me saying
let's do meds first.
We wanna do simple things first.
So, if there are things,
so we know that, because Parkinson's
is a dopamine depleting illness,
many of our treatments increase dopamine.
Increasing dopamine is the same
mechanism of action as
hallucinogenic drugs.
So we have to find that balance,
it's always this balance of, you know,
still getting optimal motor
control of Parkinson's
while not causing these
other hallucinations
or psychotic type experiences.
We wanna correct for sensory impairment,
so the glasses up there.
We know that if we have,
if we're not taking things in accurately,
so if we aren't hearing things right
or seeing things correctly,
we're more likely to have our brain
fill in a backstory to make that up.
So again, and usually they tend to be
not negative or happy things.
You know, it's like, someone's
stealing things from me
or you said something negative about me.
So we wanna correct that.
We also wanna always think,
is there something medical going on?
Because sometimes we'll see these
types of psychotic symptoms, let's say,
only if someone has a UTI
or what we call a bladder infection.
They may not have any other physical
symptoms that younger adults have,
but we'll notice some of
these symptoms coming up.
Dehydration, other types of
infection like pneumonia,
and sometimes with folks that
have some cognitive issues,
constipation, if they're really backed up,
it seems like these symptoms get worse
and after a bowel movement,
then then get better.
We wanna look in to make sure
we aren't missing any cognitive issues.
What can we do to modify the environment?
So if there is that illusion
of someone scary in the
corner that's a coatrack,
should I be giving you a medicine?
Or what else could we do?
Move the coatrack, okay.
So again, be creative.
You know, we want low-tech
interventions whenever possible.
And, you know, educate.
So do we have to treat
a happy hallucination.
Let's say a person loves cats,
and there's this lovely little furry cat
that comes in and makes you happy.
Do we need to give a pill for that?
No.
No, not if it's, you know,
if you're terrified of cats
or if it's something really scary,
yes, then we may want to,
but if that's a happy hallucination,
we educate the caregiver, you know,
there are risks and benefits to treating,
and right now I don't think
that benefit is there.
And it's okay, we know
that these symptoms happen.
And we wanna minimize
aggravating medicines.
We wanna reduce the doses of medicines
if we think something's happening,
if they're what we call highly
anticholinergic medicines,
we know that they can be helpful
with some Parkinson's symptoms,
not very commonly used,
but sometimes they will be
and a lot of medicines have these effects.
I also like to think, you know,
they dry the mouth, dry the
bowels, and dry the brain.
Make thinking kind of cloudy.
And then, you know, if
there's pain issues as well,
you know, if someone can take Tylenol
or non-steroidal anti-inflammatory,
then we wanna treat pain,
'cause these things are
less likely to happen.
And so, what else can
we do before we get to
medicines targeting the
antipsychotic medicines.
Sometimes the
acetylcholinesterase inhibitors,
the medicines that are used
for memory difficulties
that increase acetylcholine levels,
can actually help with some
of these psychotic symptoms.
There's one of these medicines
called rivastigmine or
the Exelon patch version,
can be quite helpful,
it has indications for
Parkinson's dementia, but it seems
like it can actually help with
the individual hallucinations as well,
so that would be something
to go to first, perhaps.
Sometimes antidepressants
can help a little bit.
And in Lewy body illness,
some little study on memantine or Namenda.
And when we think,
though, if we are facing
when do we have to use an
antipsychotic medicine,
we wanna think about
what are the potential side effects?
And here that risk/benefit is
we need to think more,
there's a difference
in that compared to antidepressants.
We know the antipsychotic
group of medicines
tend to have metabolic effects.
So they can increase blood sugars,
cause more trouble with cholesterol,
and maybe induce diabetes.
So we wanna think about that.
They have a black box warning
of increased mortality risk.
When you take all the studies together,
the ones that were published,
the ones that weren't,
comparing placebo to active medication,
1.6 time risk of mortality
compared with the placebo.
Some of our work by Helen Kales has shown
that actually, different
medicines have different risks.
There's quite a variability in that.
But again, antipsychotic medicines,
they work by decreasing dopamine,
so what's that gonna do,
most of them, there are
a couple exceptions,
so what happens, then, to
our Parkinson motor symptoms
when we treat with an antipsychotic?
There's a chance for worsening
by decreasing the dopamine.
And the risk of this worsening
of Parkinson's is not equal.
So there are two agents that really are
motor neutral for Parkinson's,
an older medicine called
clozapine, trade-named Clozaril,
which does not have any impact
though it does not have an FDA indication,
and then this newer medicine
that came out in 2016
called, Nuplazid is its
trade name, or pimavanserin.
And that one is very unusual,
that it does not work at
all on the dopamine system.
It works on, through an
inverse agonist method
on some serotonin receptor subtypes.
Then this quetiapine or Seroquel
is the one we would most commonly
start with in clinical practice.
And then there are a number of other ones
that really have more dopamine blockade,
so we tend not to use the in Parkinson's.
And that's just more detail
about the black box warning.
So clozapine, for years and years,
decades, was the most
atypical antipsychotic.
It's been tested and improves
visual hallucinations
without worsening motor symptoms.
We don't know as much if there's,
the dementia in Parkinson's,
how does it work,
'cause it's only been treated
in people without the dementia.
However, it's a wonderful medicine
but it has its own baggage
that comes along with it.
It has the risk to decrease
white blood cell counts
that fight infection.
So, to start it, and it also
can drop blood pressure,
which we know can already
be one of the symptoms of Parkinson's.
So it start it we need to start
at tiny, tiny doses and work it up.
And we have to monitor blood
counts weekly for six months,
then every two weeks
for another six months,
then monthly thereafter,
to make sure that there's no drop
in the white blood cell and
increased risk of infection.
The other antipsychotics,
this quetiapine or Seroquel
has the least extrapyramidal side effects
of the medicines that are easier to use.
There are some open-label reports
that have been promising in
Parkinson's psychotic symptoms,
but some placebo-controlled have not been.
And then these other agents really
not as well with the motor symptoms.
And this Nuplazid or pimavenserin
is a serotonin inverse agonist
that has no impact on dopamine whatsoever,
so neutral as far as
Parkinson's motor symptoms.
And approved for Parkinson's psychosis,
hallucinations and delusions.
It can be very costly out of pocket.
It's one of these brand
new drugs, not generic.
Maybe about 2000 dollars per month.
The company does have a
generous patient support plan.
It only is for Parkinson's diagnosis,
I have not found them to accept it for
a Lewy body illness type diagnosis.
So again, as we were talking with
start low, go slow, don't
stop with antidepressants,
the very same is true but we're even more
careful with the antipsychotic medicines.
We always wanna make sure that, you know,
the risk and benefit is balanced.
So if someone is going
to lose their placement
or is in extreme distress
or if they're reacting to a hallucination
by getting up at night, running around,
driving the car, wielding the knife,
that's where we really think
where that risk/benefit comes out.
Happy hallucinations, I don't think
that risk or benefit is there.
So again, clozapine for someone with
a more psychotic illness
like schizophrenia,
people will take 500 or
600 milligrams a day.
We're gonna start with 6.25 milligrams
and work it on up to maybe
somewhere between 50 and 150 milligrams.
Seroquel or quetiapine,
people with bipolar illness
or schizophrenia would
be taking 800 milligrams.
We're gonna start with
12-and-a-half milligrams
and usually be under 200 milligrams,
usually well under that, for
the Parkinson's psychosis.
And this Nuplazid, they say start with
and stay with 34 milligrams.
I have a little clinical experience,
I am not usually that gutsy,
that's just not in me.
I usually start lower and then
work it up over several weeks,
and it has really made a difference
in a few folks that I've worked with
in their ability to not have troubling,
you know, violent hallucinations
that frighten them,
and now they're traveling to
see their grandkids out of state.
So summary, that the
neuropsychiatric symptoms
are common in Parkinson's,
they make up three of
the four core symptoms
that were described 200 years ago
and are a leading cause of
disability in Parkinson's.
We know there's these overlap symptoms,
but we also talked about the
symptoms that don't overlap,
and weighing the risk of
treatment versus not treatment.
And we know that there's
a biological basis
to all these symptoms
that we discussed today.
You should not feel ashamed or guilty.
And I do want you to talk
with your care provider
if you are having any of these symptoms.
And the treatments are available.
And they can make quality of
life and functioning better.
So thank you very much.
