May 5, 2022
Transcript:
0:05
Good afternoon.
0:06
We’ll give folks just a few minutes to get into the Zoom room, then we’ll get started.
0:23
Oh, hello.
0:23
My name is Michelle Wagner and I’m with NAMI, New Hampshire working on the first episode, Psychosis Early Serious Mental Illness Initiative.
0:32
Thank you for joining us today for our Webinar titled Tardive Dyskinesia Recognition and Treatment.
0:40
Today’s presentation is being recorded and you’ll be able to find it on the education page of the Onwardnh.org website.
0:50
Though we aren’t offering formal CEU’s, we will be providing a certificate of attendance.
0:56
You’ll receive that automatically when you complete the evaluation after today’s presentation.
1:02
This is a Zoom Webinar, which means your camera and microphone are off.
1:07
The chat and Q&A features are working, so please enter any questions you have there.
1:13
Emily Huff is providing technical assistance for us today, so together we’ll work to get those questions answered.
1:21
And joining us today is Dr. Jeffrey Reed,
1:25
and rather than read his bio, we’ll have Dr. Reed.
1:30
Go ahead and introduce himself.
1:32
Jeff.
1:34
Thank you very much, Michelle.
1:36
So, yeah, I’m, I’m, I’m Jeffrey Reed.
1:38
I’m one of the faculty psychiatrist at Dartmouth Hitchcock Medical Center in Geisel School of Medicine.
1:45
I am teaching faculty for the Resident for the Resident program here at DH and teach 2nd, 3rd, and 4th year students both at the medical school and on the units here at the main hospital.
2:01
Much of my background is has been in psychosis, did research as an undergrad, moved over to the National Institutes of Mental Health after I graduated college to do a research fellowship in schizophrenia, and then subsequently moved to MGH after that, prior to going to medical school.
2:21
During medical school, I worked,
2:23
sorry,
2:23
During my residency, I worked closely with,
2:24
Dr. Douglas Nordsey, who was one of our more resident experts in psychosis who’s now at Stanford.
2:35
and, I’ve pretty much kind of followed in his footsteps here at DH.
2:38
So, very happy with the job I’m doing.
2:41
I, I, do have some of my time, I did spend at West Central Behavioral Hall which is Community Health Center in Lebanon, NH, formerly work the Serve community treatment team, and now work the community support team where I largely work outpatient with folks with severe mental illness as well.
2:59
Okay.
3:02
Great.
3:02
Thank you, Dr. Reed.
3:04
So, now you will go ahead and share your screen.
3:07
We’ll have definitely take the opening screen down and we’ll listen to this important presentation.
3:15
All right.
3:16
Let me get things squared away like we did before.
3:20
Portion of screen.
3:22
Yeah, Portion of screen and then.
3:37
Good.
3:37
All right.
3:37
Can, can, Michelle, can you see everything?
3:40
Is it, is it.
3:42
All right, Perfect.
3:43
Good.
3:44
Today we’re going to be speaking about a condition called Tardive Dyskinesia.
3:48
Tardive Dyskinesia, I’ll describe more in detail what that is, is sort of a one of many neurological conditions that can arise from the use of neuroleptic medications, right?
4:03
We have several others they’re and they fall within a class of things called extra paramidal side effects.
4:08
So, it’s a series of movement disorders that could include not only this condition but also tardive, dystonia, parkinsonism, akathisia a lot of different conditions that are more neurologically based but also caused by the medications that we we use.
4:25
In fact, tardive dyskinesia is largely a medication induced condition and and and not as often seen spontaneously or organically in in neurological medicine.
4:36
All right, good.
4:43
So, I’m going to play a little video here.
4:45
This is probably the the fanciest part of what I got to show you about what Dyskinesia looks like okay and this is from the JAMA network.
4:56
This is sometimes what we’ll often see with folks who have, ah, Tardive Dyskinesia.
5:00
Let me bring this up and get it planned.
5:01
Here we go,
5:03
So, tardive symptoms are neurologically based conditions that develop over long periods of time and, the product of chronic treatment was like what we call dopamine receptor blockers, okay.
5:12
So, if you think about medications that we use to treat schizophrenia or even bipolar disorder, those medications work primarily through blocking dopamine in the brain, OK.
5:23
and, we try to target as best we can just blocking dopaminergic brain activity.
5:29
However, it does include other areas.
5:32
What you’re seeing here actually in this slot in in this video is what we know to be Ora Facial Dyskinesia.
5:42
Now dyskinesias are broken down really well.
5:46
Movement disorders are broken down in two different classes.
5:49
Okay, there’s Hypokinetic and Hyperkinetic, whereas Hypokinetic movement disorders present with notable slowing of body movements.
5:56
So Display to Kinesia or Parkinsonism.
6:00
The Hyperkinetic movement disorders include Dyskinesia, carry and form movements and, and, actually show up.
6:09
It’s almost purposeful movements that include multiple muscle groups.
6:12
So, as you saw in the video, you could see, let me see if I can play it again.
6:16
I might not be able to.
6:19
You can see sort of this, this chewing active, this chewing action, this rhythmic movement of the of the lips so you can get a thing called lip smacking.
6:28
People will sometimes accidentally bite their tongue because of this automatically.
6:33
Now, these are not movements that a person can control, all right?
6:36
This can sometimes be affect other muscles other than the facial muscles.
6:41
So, things like what we call the Paraspinal muscles can help affect the muscles of the of the pelvis and and also the extremities.
6:51
So, you can see similar kind of muscle activity in those other areas and those who and and sometimes for those who may be on these Dopamine blocking medications over long periods of time, they may start to show, they may not show evidence of of a Dyskinesia where you can, you know someone outside of themselves can really see it.
7:11
They may notice themselves or a burning sensation or an irritation in their mouth.
7:15
OK,
7:16
So, it means when you when we’re seeing people clinically that’ll be something we may ask about hey, do you sometimes bite your tongue do you find yourself noticing sort of a like an uncomfortable feeling in in in in your lips or run around your tongue or even swallowing And that can be early evidence of, of a, of a, Dyskinesia okay.
7:35
So, Tardive Dyskinesia is actually also highly correlated with the poor quality of life we’ve seen which further underscores the importance of you know developing effective treatments for develop for managing this condition.
7:47
Sadly, only about 13% of patients who develop Tardive Dyskinesia from their antipsychotic medications experience full resolution of the condition and full cessation of of of someone.
8:01
Even after you discontinue a medication that can cause something like this, it, it, you know very rarely, I mean that that’s actually about 13% of those folks in.
8:13
So, ultimately even to get a resolution of those symptoms in that 13% it takes over 2 years, it can be close to 2 1/2 years for those symptoms resolved.
8:21
So, they even when you saw the medication along for a long time, some people as you might imagine it lasts forever okay, it does not go away.
8:31
So, you are targeting treatments that might be able to to address is really, really, very important and improve people’s quality of life quite a bit, Okay.
8:44
So, I want to go through a little bit of a background why these things may develop.
8:50
So, in order to understand Tardive Syndrome we really need to start to understand the basic under underlying through Neurophysiology or Neuropharmacology as well as brain circuits that are related to schizophrenia as well as the treatment of Schizophrenia.
9:06
So, what we know to be a large part associated with the condition is, is through dopamine, okay.
9:16
So, Dopamine is a major excitatory neurotransmitter in the brain, and neurotransmitters are chemicals in the brain that communicate between cells called neurons, and they also can communicate between brain areas.
9:28
So, you get these long circuits that can go from one area to the brain to the other and it’s these chemicals that allow for that communication.
9:35
and, we think of illnesses such as Schizophrenia, we first need to understand that dopamine plays a significant, though not exclusive role in the condition.
9:43
and, the condition is also associated with sort of heightened dopamine activity in some regions of the brain, which are associated with things like hallucinations or delusions.
9:53
and, in other parts of the brain, it can actually be sort of seen in, in as sort of under active.
9:59
So, certain areas of rain, there’s less dopamine activity.
10:01
In other areas of the range, heightened dopamine activity, which can be very characteristic of the condition.
10:06
That’s why you see start to see all those different symptoms, which I, you know more of like a syndrome that we know is Schizophrenia.
10:14
Now, there are 4 main pathways of the of the brain that we know to be related to dopamine.
10:19
Okay.
10:20
I’m going to start to go through some of those here.
10:21
One of those particular pathways is more associated with the movement disorder of Tardive Dyskinesia.
10:31
So, the first being the mesolimpic pathway.
10:35
So, the mesolimpic pathway is that that’s associated with what we know is in terms of positive symptoms of Schizophrenic things like auditory invisible hallucinations and delusions.
10:45
The next pathway is known as the mesocortical pathway, which is associated with learning and memory.
10:51
And, then there’s the nigrastriadal pathway, which is associated with the control motor movements.
10:55
It’s this Nigra striatal pathway that’s actually associated with what we know is Tartite Dyskinesia and, it’s having to do with altering the tone of dopamine in that pathway that leads to this condition.
11:09
The other path that we do we also know is affected not only in in people who take these medications but is, is part of the the the three other pathways that are largely dominergic.
11:23
It’s a tumor, tumor infundibular pathway and this largely has to do with your brain, so your brain and ability to regulate hormones throughout the body.
11:35
So, hormones being similar to the kind of like neurotransmitters, they communicate chemically with other parts body far away from where this the source of where the communication starts.
11:46
OK.
11:48
When we think about Tardive Dyskinesia, it’s the nigostrile pathway that we are in that that we really focus on and it’s that pathway that’s adversely affected by the Med same medications that we use to treat Schizophrenia.
11:59
It can actually affect that particular, that particular pathway and causing the movement disorders that we see because of the medications.
12:07
So, tardive movement disorders originally in the central nervous systems and specifically in the basal ganglia within the Nigra Striola Pathway and that includes the striatum, which is the Caudate and Butamben, the Globus Pallidus and Turner and the Substantial Nigra.
12:24
These all these regions are really heavily sort of communicated with them in terms of with with dopamine and dope and and enact dopamine 2 receptors and allow for that transmission conditions such as tardive dyskinesia developed from for this extensive blocking of dopamine 2 receptors in that region.
12:44
Now, we still don’t know exactly the mechanism at least this condition.
12:48
It’s long been proposed that dopamine 2 receptor blockade in this circuit results in sort of reflexive upregulation of dopamine 2 receptors to normalize the dopaminergic safe.
12:58
So, basically if you’ve got a medication that they’re taking to treat their illness right and it’s effective in treating your illness well, it doesn’t just affect that one pathway that treats your illness, it affects all these other pathways.
13:10
So, if you block dopamine and Nigra Striano Pathway, what happens is it’s presumed that there’s an increase in the number of receptors on cells that receive dopamine transmission.
13:21
And as a result, what happens is if you were to discontinue the medication, you get a huge flux of dopamine active activates all those new receptors which can actually worsen Tardive Dyskinesia at which point you want to treat it.
13:37
So, we can go over how we best address that our it’s because of this upper regulation of these dopamine 2 receptors that we believe we developed this movement disorder from those medications okay, all right.
13:55
So, in individuals living with severe Mental Illnesses such as get your finger by port or antipsychotics may be used to treat both acute and chronic psychotic conditions.
14:03
They can treat bipolar mania.
14:05
They can treat bipolar depression and also serve as an augmenting drug for the treatment of major such conditions like Major Depressive Disorder, Obsessive Compulsive Disorder and even PTSD.
14:17
Now whereas Tardite Dyskinesia was largely seen in individuals with Schizophrenia, it can be found in a broader population due to the prescribing practice that we see for these other conditions.
14:26
So, you know you can have a condition like schizoaffective disorder, schizophrenia to be treated with these medications.
14:32
You develop tardive dyskinesia that and it’s largely because of medications.
14:37
Well, if you have major depressive disorder or bipolar disorder and you have to start these medications, you could develop that as well Okay.
14:43
So, it’s not just we see a lot of patients with Schizophrenia and these Primary Psychotic Disorders.
14:48
However, it’s because of the medication, not because of the illness itself, Okay.
14:55
And what we find though is there’s certain medication classes that are more likely to cause Tardive Dyskinesia, that movement, this, this really severe movement disorder that does develop over time due to long term use of these meds.
15:06
So, what we find is that with first generation antipsychotics such as Haloperidol, Fluphenazine or Chlorpromazine, these medications carry a high risk of causing Tardive Dyskinesia with their chronic use and are associated with a high affinity for domine receptor blocking in the brain.
15:23
So, what’s interesting about those first generation medications, the older medications is a they more heavily blocked the D2 receptors not only in the areas that treat a Schizophrenia, but also in the areas that are responsible for movement, for hormone balance and even for cognition Okay.
15:41
So, these medications not only can help the condition, but worse than others conditions like movement disorder or cause these movement disorders.
15:48
And the reason that’s the case is the case is because these medications were very strongly blocking D2.
15:55
Now the newer medications like the second generation drugs, things like quetiapine, also the Seroquel, Clozapine, which is the most effective medication we have for treating schizophrenia and alanzapine is like Praxa, they’re less dopamine blocking, so they don’t have as much of a blocking capacity at D2 receptors.
16:14
Therefore, they’re less likely to cause things like tardite dyskinesia or these other neurological conditions are due to these medications.
16:24
What I what you see here is domine receptor blocking.
16:27
You’re going to see this a lot in the presentation.
16:29
Domine receptor blocking means these are these medications, you know make it an able for the cells in the brain to communicate with domine between those two cells okay.
16:42
And that’s what a lot of these medications do.
16:45
The third generation agents which are things like aeropiprazole I think brexperizole and those kind of meds, not only are they dope mean blocking, but they’re also dope mean activating.
16:59
So, what they do is because that don’t mean activating action is less likely to cause these these different conditions.
17:08
However, they’re still a little bit dopamine blocking.
17:11
Therefore they can still cause tardive dyskinesia in some people, but it’s less likely, it’s less far and and and these medications are far more tolerable over time, especially longer you take them and these medications because they both block and activate dopamine 2 receptors, that’s why they’re called partial Agnes Okay.
17:32
That’s that’s where that comes from.
17:35
OK, now the early studies investigating the impact of of these dopamine blocking drugs found that target dystonia actually occurred on average between 20 and 30% of all patients who take them.
17:47
OK, recent and a recent meta-analysis of about 41 studies reveal an average risk overall of 25% in all treatment groups.
17:54
This regardless of believe of first generation, second generation, third generation drugs.
17:59
OK, though they did find however that in the of those who are taking first generation in psychotics like Haloperidol or Fluphenazine or even Chlorpromazine, roughly 30% of those folks developed Tardive Dyskinesia.
18:14
Now compared to those who are taking things like Zyprexa or Seroquel or or Abilify, about 20% of people developed Tardive Dyskinesia.
18:25
So, that’s not a big difference.
18:27
I mean this risk is still very high in the second generation drugs where they’re supposed to be less likely to cause it.
18:33
They’re they’re pretty much still the same OK.
18:38
Though in in many people and especially clinically I’ve seen it occur less in in less severity and be much more manageable once it does happen.
18:47
So, let’s see here.
18:49
OK,
18:49
All right,
18:50
So, you know the ongoing mainstream in for first generation age and the risk of TD was about 32% over time.
18:57
So, when we think about the longest one stays on medication, the more likely they’re to develop the condition.
19:02
If you remain on a first generation medication like Haldol or Fluphenazine, the risk of TD when it was about 32%, about five years of treatment, it goes up to 57% at 15 years of treatment.
19:16
And then after 25 years of being on a medication like that, 68% of people who take that medication develop Tardive Dyskinesia.
19:23
OK, alright.
19:30
So, not just one of the things that we also want to remember too is yeah these medications do cause Tardive Dyskinesia and put people at higher risk for developing it.
19:38
There are actually certain conditions that you can you have control of or you don’t have control of that may contribute to your, your your risk of developing it once you start these medications.
19:48
OK,
19:48
So, we call these non modifiable risk factors.
19:51
So, a couple of things that increase your risk for Tardive Dyskinesia is older adulthood, female sex, white and African American descent.
20:01
Intellectual disability is another, another state in which you know you put you at higher risk of developing this condition.
20:09
And also the cooccurrence.
20:11
If you have Schizophrenia, having something like a major depressive disorder, or having a history of bipolar maniac, those if you have a cooccurring mood disorder like those, it puts you at higher risk of developing Tardive Dyskinesia, especially when you start these medications.
20:26
Now the the risk factors that you can control if you’re on these medications are one, as a doctor it can you know the the type of medication you use and the doses of medication that you use really strongly predicts if someone’s going to develop Tardive Dyskinesia.
20:43
So, we really encourage, especially when I’m training the Med students and the residents start at the lowest dose necessary to start and only increase it to a dose that they were.
20:52
They really need to treat their their condition and do not go any higher.
20:56
And, if at some opportunity you can reduce the dose back down, you’re welcome to do that.
21:00
OK.
21:01
And, I would very much encourage it and if people were to develop more of these, these ,sorts of, signs of Tardive Dyskinesia or or even other movement disorders like like a destonic reaction, it gives you you have reason to either decrease the dose, find a different medication, it’s.
21:19
So, part of this is going to be through physician dependent okay in terms of what we can do to control and prevent this condition.
21:26
The other thing is if a patient has a prior dystonic reaction, So what that really is, you know prior prior history of developing real significant muscle stiffness only it’s painful muscle stiffness, muscle spasms, things of that nature or have a neurological condition that can lead to a dystonic reaction that can also contribute to someone that’s just developing Tardive Dyskinesia especially when start on these kind of medications and then the use of tobacco, alcohol and other substances also increases one’s risk of Tardive Dyskinesia.
21:57
So, we, we, always as we would in any mental health or medical condition work really hard with people to help with smoking cessation, helping with reducing alcohol use and even finding treatments that are meant to to address those or prevent those from from worse than okay.
22:12
Because just by virtue of the fact that you’re engaging in that substance use, it does increase your risk of developing the Tardive Dyskinesia.
22:21
So, prevention and management.
22:22
So, first and foremost we want to focus on the early signs of Tardive Dyskinesia and and doing so through evidence-based screening.
22:30
The long standing standard of practice is the use of the what we call the abnormal involuntary movement scale.
22:34
Something we do often in the hospital, something I do in my outpatient in in my outpatient practice is you have a standard screen you sit with someone for about 5 or 10 minutes.
22:44
You can go through it and it gives you a it gives you a measure, it gives you a number and you can track that number over time when they’re on these medications.
22:52
I’ll typically do a baseline screen when someone comes in and then every you know 6 to 12 months based on what’s currently the APA recommendations for monitoring with with when someone’s on these medications and also depending on their risk factors, I will continue to to to monitor based on this scale, right.
23:08
So, that’s one way.
23:09
So, if you start to see their aim score gradually change over time, increase particular, then you want to start to look at I, you know, is this because of the medication?
23:20
Are there certain things are doing, are they smoking more, are they drinking more?
23:25
Those kind of things you want to pay very close attention to because then you can start to address it before want it gets so bad that it really starts to affect their life or they start to notice it and also such that you catch it running up.
23:38
So ,it’s maybe reversible and it’s not a permanent neurological condition going forward we want to use so again we want to use medications when when we’re when we’re prescribing for people are lowest risk for causing Tardive Dyskinesia.
23:51
So, those being Clozapine, Quetiapine, Olanzapine are lower risk Aripiprazole which is Abilify as low risk but not not necessarily the best compared to Clozapine.
24:01
Clozapine is the best agent and quetiapine the best agents and and and folks who may have had dystonic reactions or Dyskinesia in the past and need to be on antipsychotic or medication that you want to use to prevent it.
24:16
All right.
24:16
So, we, we, do focus on those medications as as as good options.
24:20
You want to implement treatments that may reduce the presence and severity of tardive dyskinesia.
24:24
OK.
24:25
If someone develops it.
24:26
We do have treatments that we’ll we’ll start to discuss here shortly that that may be helpful in reducing or even eliminating it and also educating you know doctors and training and other providers on the on the proper use of drug, sorry, dopamine receptor blocking agents, right.
24:41
Well, I see these medications overuse on average for conditions that they were not meant to be to be used.
24:48
OK.
24:48
Things like someone with a depression or irritability, things like that that could be otherwise addressed with other interventions that are not likely to cause this condition.
24:59
All right.
24:59
So, what you see here is actually ah I, I, found this to be really helpful in, in, in my practice Ah, and a graphic from an article back in 2020 by Bashir and Yankovic.
25:14
All right.
25:15
And, it goes through sort of different treatments and also their level of evidence in, in the, in the management of Tardive Dyskinesia.
25:23
OK.
25:24
So, in the event that someone develops tardive dyskinesia, all right, one of the things that you want to do first is looking if you can do modification to their medication, OK, can you reduce your dose?
25:35
Can you maybe look at another medication that could be equally as effective and helpful to them without the risk of developing tardive dyskinesia.
25:46
If finding other options, reducing the dose, making maybe making lifestyle modifications like reducing smoking, reducing alcohol use, if those things are not are not fully effective in reducing tardive dyskinesia, how do we do it?
26:04
So, if you got a patient who comes in, they’ve got a chronic mental illness, they have their Schizophrenia, they’ve had it for, they’ve been diagnosed for 20 years.
26:11
They’ve been on Fluphenazine for the entire time and all of a sudden they’re developing Tardive Dyskinesia.
26:17
OK,
26:18
But every time you reduce a dose, so, you try to stop it or you switch to something else, they, they, they, they notice a real increase in their symptoms.
26:25
They may end up getting hospitalized.
26:27
Well, guess what, Maybe you can’t decrease the dose, maybe you can’t change the Med.
26:31
So, what do you do?
26:32
Right.
26:32
That’s where we start to look at these interventions medications natural supplements in some cases will involve neurology to to get involved to help out with this process because in people who you can’t stop their meds otherwise it really does forever impact their their mental health and their personal life and their quality of life.
26:55
We start to move into these new meds and So what this table does Okay is look at the different options that we have things like VMAT 2 inhibitors I’ll go into those in more detail.
27:07
Clonazepam which is Benzodiazepine Cycloloma which is a natural supplement that will soft and see people using not only for for this condition but as an antioxidant for other for for other conditions in mental health.
27:19
It’s this and then there’s also the treatment of sexual dysfunction due to antidepressants will, will, use that same the same medication.
27:27
There’s Amantadine and there’s also brain stimulus that will in very severe forms will use botulinum toxin, which is Botox in certain muscle groups where they’re finding the Tardive Dyskinesia And also an alternative, 1st and 2nd generation met antipsychotics.
27:43
And then in way down below we’re talking about medications are really not shown to have much, much evidence to support them.
27:51
Do you look as you look at this here, the level of evidence, what Level A means or sort of level?
27:57
Yeah.
27:58
So, level A largely being their love sort of the the amount of support and evidence that supports are used.
28:04
So, Level A basically means there is data, there is evidence that it does improve Tardive Dyskinesia Level C our medications are possibly affected.
28:14
So, there may be some evidence, but it’s not conclusive, right and maybe not enough really to provide an FDA indication for the for these medications.
28:23
Level B is and what what that means is these probably are very these probably are effective in treating Tardive Dyskinesia, but not first line of not first choice necessarily because they are not as effective as a Level A and level use shows is basically in insufficient evidence to support their use in the in treatment of tardive dyskinesia.
28:44
All right.
28:49
So, the first class okay that we were talking about.
28:51
So, these are level A.
28:54
These are preferred agents for someone who needs treatment for Tardive Dyskinesia or vesicular monoammy 2 transport inhibitors.
29:01
That is a long and it’s been a reasonably complicated, so V mats are broken down, we call them V mats.
29:07
V mats are broken down to two forms, There’s a V mat one and a V mat two.
29:10
So V mat one is found, you know, both in the central and peripheral nervous system.
29:16
V mat two is found only in the central nervous system, right.
29:18
So, basically the brain and spine we want to, we don’t want a medication that’s going to affect all the other you know, systems in your body like your blood pressure, so your cardiovascular system, your skeletal muscle system and things like that.
29:30
We only want to you know target the areas that are located in your brain that cause Tardive Dyskinesia.
29:36
So, what inhibition to what these do is they’re inhibitors.
29:40
So, in inhibition of a V mat depletes dopamine and the neurotransmission of dopamine which is believed to play a major role in development of Tardive Dyskinesia like we discussed previously.
29:50
So, given the current hypothesis that TD arises from up regulation of post synaptic dopamine receptors and and causes what we call Dopaminergic Hypersensitivity.
29:58
So, they’re much more sensitive to if there’s dopamine present, they’re, they’re, more likely to receive that dopamine transmission and also and because of that cause Tardive Dyskinesia.
30:10
These medications reduce the risk of the progression of tardive dyskinesia once it becomes present by reducing this dopaminergic transmission without further blocking domine receptors or you have dopamine receptor blockers, but then you got these D mass that prevent the release of dopamine into the into the space that where it can be transferred to other cells.
30:30
Now we have 3 different VMS that are currently available to us okay and then they’re and they’re actually available to us in the United States.
30:36
They’re not available necessarily all over the world.
30:39
And, there are two, only two really that are FDA approved for the use of Tardive Dyskinesia.
30:43
So, I’ll go over those right now one that’s been come fairly common and you’ll often find this in in folks who develop Tardive Dyskinesia is valbenazine, it’s also known as INGREZZA.
30:54
It’s approved by the FDA for this solely for the treatment of Tardive Dyskinesia with two supporting double-blind Laceva controlled trials called they were called the connect two and connect three trials showing significant advocacy in the reduction of drop in reducing AIM scores.
31:09
So, remember when I was talking about the scale that I use inpatient out outpatient to assess for Tardive Dyskinesia and other movement disorders.
31:19
This is this medication when added to their their antipsychotic treatment can reduce that AIM score for someone who’s developed tardive dyskinesia.
31:29
So, it can reduce the severity of that condition.
31:32
OK.
31:33
And, and that’s over about a period of six weeks, not one year follow up.
31:37
The data actually demonstrated longterm showed good longterm advocacy and safety and also tolerability in the treatment target dyslenee.
31:44
So, basically after one year being on the medication, it was a safe drug and continue to provide people benefit and relief.
31:52
However, here’s the issue, these meds are not cheap.
31:55
This medication by itself for 30 days is about $7200 a month.
31:59
That’s big.
32:00
OK.
32:02
It’s still on patent, it’s still branded.
32:05
So, this is very expensive met and just to get it covered we have to do quite a bit of of of working with insurance companies and outside providers to get this covered.
32:15
It is a very effective medication.
32:17
So, it, it, I find it’s well worth the effort.
32:20
The other medication that we’ve got.
32:22
The other thing is so what’s nice about this, it’s a medication that lasts up to 22 hours in your system, right.
32:28
It’s basically a once a day met right?
32:30
Or you can at least dose it once a day and right now we dose it between 40 and 80 milligrams every day.
32:36
The biggest side effects we find is, you know either largely sedation, people can develop headaches they can and and quite a bit of daytime fatigue.
32:43
OK.
32:46
So, Tetrabenazine is another medication that was actually first approved for the treatment of Huntington’s Chorea and Tardive Dyskinesia somewhere around 2017 and actually followed and this was falling two very successful double-blind multi center randomized trials and it sort of underscoring is is effectiveness and basically is effectiveness and this is a medication because right here you can see it’s, it’s you know it pretty much lasts in your body about 10 hours right.
33:18
That’s it kind of it peaks and then starts to metabolize.
33:21
So, it’s a twice a day medication.
33:23
So, it’s not as easy necessarily to treat to, to take as Valbenzine, which is once a day as you have to do around twice a day.
33:30
and, the recommended dosing for treating tardive dyskinesia between 6 and 48 milligrams daily.
33:36
Really the biggest side effects of this tend to be sedation and insomnia.
33:40
However, when you look at the risk of sedation, insomnia and people who take it compared to placebo, the rates are just the same.
33:47
So, actually it’s nowhere simplicity in terms of cause and side effects.
33:51
Now, Tetrabenazine, actually this medication, just to give you a sense of prices from around $6200 a month, depending on those between 42 and $6200 monthly.
34:02
Tetrabenazine is the third medication, but it’s not.
34:06
It does not have an FDA indication for its use in Tardive Dyskinesia, at least not yet.
34:10
It was first developed in the 1950s as an antipsychotic, so, it was meant to treat Schizophrenia, Schizoaffective disorder.
34:17
However, over time we’ve come to discover it’s actually quite effective in in in managing things like Huntington Disease and Tardive Dyskinesia.
34:26
It’s a shorter acting medication that lasts about five to seven hours.
34:29
You’re going to find yourself taking it at least twice a day, if not three times a day, what their current recommendations are around 100 milligrams, three times a day.
34:37
That’s what they were using in the studies that were showing that there was, you know, sort of showing efficacy with the medication Okay.
34:47
Now the medications that have a I believe a level B in support, so good evidence to support it though it’s not so good that you know we would just consider first line are benzodiazepine specifically Clonazepam.
35:03
Now benzodiazepines are what we know as gamma, gamma amino, butyric acid agonist, so basically gamma GABA agonist okay.
35:14
So, they’re very sedating.
35:16
They,
35:16
I mean you can use medications like these for treatment of epilepsy or other seizure disorders.
35:23
You can also use it as angularlytics.
35:25
That’s where we see it most often used in mental health as or as an anti anxiety drug.
35:29
However, the biggest issue we have with it is addiction intolerance, right.
35:34
So, we do find that people can become very dependent on these medications and it’s very difficult to get them off of it.
35:41
There’s a lot of different benzodiazepines, right?
35:43
and, but in a lot of being used for tardive acnesia, though probably incorrectly.
35:51
The only medication that we have that has some evidence to support it really is I mean at least sufficient evidence to support uses Clonazepam which is a longer acting longer onset of duration benzodiazepine.
36:05
And this one has been studied in a 12 week double-blind randomized crossover trial and only 19 patients by the way.
36:12
So, it’s not a big study who developed Tardive Dyskinesia and taking also these antipsychotics or high dopamine blocking drugs where they were able to find that there’s about 37% reduction in Dyskinesia compared to baseline over that 12 week.
36:27
So, they do work but there’s not a lot of evidence to support their use.
36:30
In fact the the, the the study I’m talking to you about is actually the one that I have you know pasted here as being one.
36:38
I think probably that was out of the out of the APAI believe believe it was the APA that publishes a number of years back another medication that also has some some evidence of support in treating tardive dyskinesias, ginkgo biloba.
36:59
Now it’s interesting because, you know, this is one of those one medications that you see often.
37:03
You see it like the coop is any grocery store to find it.
37:06
And there’s like, you know, natural, natural whole, health food stores, things like that.
37:14
And it’s based in sort of more traditional Chinese medicine.
37:19
It’s one of the most widely distributed medicinal plants in the world.
37:23
and, often times I ask you why they take it.
37:25
They don’t often know why, but they find a boost.
37:28
but, it’s largely an antioxidant and we’ll often initiate this treatment in in and it does show to have some effect in treating antidepressant induced sexual dysfunction and there is some research supporting its use.
37:42
but, it’s also been shown to be effective in the treatment of Tardive Dyskinesia in a in a double-blind randomized placebo-controlled study of 157 patients with both Tardive Dyskinesia and Schizophrenia, it showed to reduce significantly reduce those AIMS scores.
37:57
So, again that that that scale that I will often do to measure for Tardive Dysmusia, these other movement source by around an average about two point, about two, two points compared to a placebo not as great.
38:12
You’re going to find some of the other options things like clonazepam or even the the V mat 2 inhibitors.
38:21
However, there can be a benefit and for someone who you may have an addiction but you know attention, or may have a history of addiction to alcohol or benzodiazepines or maybe otherwise, so there’s a contraindication to use something like Clonazepam, this is not a bad option.
38:39
It falls within the same evidence class as the Clonazepam, but without all those concerns in terms of addiction or independence.
38:47
OK, so I I would not rule this out.
38:48
and, the dose for this would be about 240 milligrams a day for folks who developed part of Dyskinesia with their medication.
38:57
I’m going to try to, I don’t have too many more slides because I do want to finish apply within the next 5 minutes to, you know, start to answer questions.
39:06
So, another medication that we use, or we and I’ve actually used this here at the hospital has been Amanta D, which is what we call an NMDA receptor antagonist.
39:16
So, what, what, in what is known as to be anti gluta maturgic?
39:19
So, glutamate is one of the major if not the major excitatory neurotransverse in the brain.
39:24
So, when we think about movement disorders we think about over excitation.
39:29
Well, that’s what that’s what this helps treat is this sort of over excitation, right.
39:34
It was initially developed as an antiviral which was meant really to treat influenza A however now commonly used in treating Parkinsonism in Parkinson’s and in what we call levodopa induced Dyskinesia.
39:47
So, levodopa is a medication that increases the amount of dopamine in the brain in people with Parkinson’s disease who have low levels of dopamine in the brain.
39:57
And, if you increase dopamine in the brain, guess what, much like we found with the dopamine model, Schizophrenia and what happens when you you have longterm treatment with a domine receptor blocker, you end up increasing.
40:13
Basically Dopaminergic, so, um.
40:15
So, you wanted to sort of tone that down.
40:17
This is a medication that’ll help do that.
40:20
It was originally the study in about 1971 for the for in in people with Tardive Dyskinesia and actually then later followed up the two, you know, major double-blind crossover studies showing significantly lower AIM scores compared to compared to placebo, right.
40:37
and, there’s like this is more of a crossover where they did Amantadine for a while and then they crossed over to placebo and vice versa and found that the during the Amantadine treatment arm people did quite well reducing their Tardive Dyskinesia.
40:50
OK.
40:53
So, I was quickly able to wrap up, but I want to have some opportunity to answer questions because there’s a lot, there’s a lot to do with try Dyskinesia because one of the issues is we don’t really understand it that well, right.
41:08
We only have a proposed mechanism that’s not been widely understood nor has it been really, you know, significantly supported in the literature.
41:16
We just really have a hypothesis and based on the medications that we prescribed and by due to the fact that we started, we do see an improvement with these medications.
41:26
It gives us some sense of what the mechanism mechanism maybe and it is largely associated with dopaminergic tone in the brain, specifically in areas related to to to movement in movement disorders, which is the, the Nitro Striatal pathway in the brain, which is also related to Parkinson’s disease by the way.
41:48
So, that allows us some ability to get a sense of what may be happening to cause this condition.
41:53
Now this is not the only condition that arises with longstanding use of high domain blocking drugs.
42:02
OK, this is one of many in in.
42:06
I think every other condition could probably be its own lecture.
42:10
Things like Tardive Dystonia, things like Parkinsonism, things like Akathisia, they all have their own.
42:18
They’re all these conditions that can arise from longstanding use of these meds, and many of them have different ways of treating them, right.
42:25
So, this is just one of these side effects from the medications over time that can develop.
42:31
So, there’s a lot more to discuss on the matter now what I focus just on tardive dyskinesia for the purposes of our our discussion this afternoon.
42:39
So, Michelle, I don’t know.
42:41
I can’t see anyone right now.
42:43
So, I don’t know what’s happening.
42:44
So, if you want to stop sharing screen, Jeff.
42:47
Yeah, I’ll do that.
42:49
That was we figure out how to do it on chair.
42:56
All right.
42:57
OK.
42:57
Stop.
42:57
Wait.
42:57
Stop sharing.
42:58
That’s it.
42:59
There we go.
43:00
Now we’re good.
43:01
Now we’re good.
43:01
That was wonderful.
43:02
It was a immense amount of information and really important and good information.
43:09
So, I working at NAMI, New Hampshire.
43:13
I’m always thinking about the family and individual perspective, right?
43:18
I’m the, I’m a community educator with them.
43:20
I’m also the peer services coordinator.
43:24
So, I think about how this impacts people who are taking these medications.
43:29
I also have worked in the medical field.
43:31
So, I come at it from that perspective as well.
43:34
and, I some of the statistics were just staggering and and I tried to write them down.
43:40
I don’t know that I got them correct, but I think you were talking with the first generation antipsychotics that if if folks have taken it for 15 years, they have like a 57% chance of developing Tardive Dyskinesia.
43:57
So, what do we say to people who are young and this medication could benefit them yet there are these really significant side effects.
44:12
You’re right, Michelle and actually the reason I so as we’re talking about Pearls, right in the First Episode Program and Early Intervention Program, there was a great chapter written by Doug Nordsey and and his trainee that reviewed this a couple years ago.
44:28
We wrote a textbook together looking at these interventions.
44:33
As it turns out, when you look at the medications that are currently recommended for young people with first episode psychosis.
44:38
So, we’re talking about people maybe in their late teens, early to mid 20s.
44:43
It’s within the first like maybe two years of of having their first psychotic episode.
44:49
All those first generation agents, student are not listed as preferred agents, right?
44:53
So, Haldol is no longer preferred agent.
44:55
So, Phenazine, Profenamine, Thorazine no longer preferred agents.
45:00
What they are now is Clozapine, which is not my favorite by the way.
45:03
We can talk about that, but Olanzapine or Risperidone, Aripiprazole which is the partial dopamine D2 and D3 agonist and also Quetiapine Seroquel.
45:18
So of those, remember when we were going through like the low risk drugs, three of those are low risk drugs, risperidone higher risk, OK, but there’s three or three out, four of those are low risk, right.
45:30
So, it gives you a sense that we do not start with those medications any longer though as you know they can still develop.
45:36
So, the big thing and and I think this is something that you can really, you know you you can really speak, speak more to you is like is that not only is it early intervention but early education.
45:48
Because, I would tell you when we have someone on the unit who needs to start these medications, it makes my job a lot easier if they know what problems can arise from it because they know what to look for okay.
45:59
So, often times I find that, you know, either they may not remember or they may never been taught what these medications can do and how they can affect you, like weight gain with some of these.
46:11
But also the movement is worse.
46:12
Hey, by the way, if you’re noticing that you’re biting your tongue or your mouth is kind of chewing on its own without you actually doing anything, or you’re noticing that, you know, your hands kind of doing its own thing, like kind of a rolling move, that’s not normal.
46:26
And that’s probably because your medication, you should let someone know because that can be treated and prevented.
46:32
It’s really just that simple conversation about what the side effects look like that allow you to do way less work.
46:40
I have, I mean I work way less when someone knows what’s going on, right.
46:44
And so there’s that.
46:46
The same thing with risperidone, right.
46:47
Well, what happens with Risperidone?
46:49
Well, guess what, some patients will develop what we call Galactorrhea.
46:52
So, then those, they’re lactating.
46:54
Why are they lactating?
46:55
They’re not pregnant, right.
46:56
They don’t have a kid and you know they’re not pro Sprint, you know they’re not.
46:59
They’re, they’re not, not postnatal, but they’re lactating.
47:02
Why would and again, why would a 19-year-old male, you know, Natural male be lactating?
47:10
That’s not a normal thing.
47:12
So, and I’ve had people say, oh, it’s been happening for two years and I’ve noticing my chest is developing but I don’t know why, like it’s your meds.
47:19
Did anyone talk to you about your medication could do that?
47:22
We need to stop it.
47:23
Like Oh no, I didn’t know.
47:24
Well, it’s education, right?
47:27
and, and what I have seen is that folks seem to be caught between a rock and a hard place.
47:34
There are patients who need medications in order to function in the world, so they don’t end up back in the hospital.
47:42
Yet these medications have serious side effects.
47:45
And I do wonder how effective we are in communicating those side effects to patients.
47:52
That balancing act between this can happen, yet it’s helpful for you to take it.
47:59
That’s a really hard position to be in and a lot of medication options now because there’s like 3 different antipsychotics I have to choose from, I don’t have.
48:10
I mean, I got a toolbox.
48:11
It’s massive, right?
48:12
So, I can choose any of them.
48:13
and, it makes it easier too that there’s probably 3 medications that are going to be good for someone as a first drug, as a first try.
48:20
and, then I just kind of hand to them like choose one and let’s talk about that one based on what you want to do.
48:27
and, it takes again, it’s way less work on my part because they’re choosing the medication.
48:32
They’re going to feel more confident having chosen that medication.
48:35
and, then once they choose it, then I can have more of an indepth conversation like, well, these are the problems with this one compared to the other one.
48:42
Are you okay with it?
48:43
Let’s move forward now, that kind of thing.
48:46
an,d Doctor Reed, I believe that you are telling people about those potential side effects.
48:53
Oh yeah.
48:54
and, I’m not sure that everyone is, I’m not sure prescribers are giving people the the true picture of the seriousness of the potential side effects.
49:05
and, and if you look at the SOSOI inhibitors are Abilify as the most prescribed antipsychotic in primary care.
49:13
Now why is a primary care doctor prescribing Abilify?
49:18
I, I don’t know.
49:19
I got to tell you though that the marketing behind Abilify and the drug reps did a really good job.
49:27
but, most of the patients that people are who take that medication don’t have Schizophrenia or bipolar disorder.
49:34
So, it’s like, it’s like, and often times like why?
49:37
Why would a primary care doctor know the side effects?
49:40
Because they’re not.
49:41
I mean, that’s all I did.
49:43
Like, I, I, I operate in a very narrow range of treating people with mental health conditions, right?
49:49
So, I know those things, But Med students don’t know those things.
49:53
Primary care is not likely to know those things.
49:55
and, my residents barely know those things, right?
49:57
That’s why they’re here.
49:58
So, yeah, it’s.
50:00
So, that’s when someone comes in, the hospital sees me outpatient.
50:03
Like we would do a Med review and say, oh, do you know what all this is?
50:07
and, then we do the education part and then they’re like, OK, I get it now.
50:10
So, it is helpful.
50:12
but, you’re right there.
50:14
Not everyone knows.
50:15
and, now I know.
50:16
So, they if they don’t know that, how can they educate people?
50:19
Right.
50:20
Right.
50:20
We have enough ethical obligation to let people know the side effects of the medications that they’re taking so they can make an informed decision.
50:28
Yeah, yeah.
50:30
and, I, and I, I try to look like very kindly upon it because like I told you earlier, just, just to to review Tardive Dyskinesia that took eight hours easily of just research just on this one movement disorder related to medications.
50:47
They’ve got all these other movement disorders right with other treatments.
50:51
So, it’s very complex and the neurobiology is very complex.
50:56
Absolutely.
50:57
I don’t expect everyone to know.
50:58
I just want people to be more careful when they start to select these meds, like you said, right, and to have patients know what to look for and family members as well.
51:07
I know for myself, I have a family member.
51:11
I have two family members who are taking antipsychotics, second generation.
51:16
and, on a different second-generation Med, one of my family members started to do facial grimacing.
51:25
Yeah, that’s right.
51:25
Yep, right.
51:27
So, I have a medical background.
51:28
So, the minute I see that, I’m paying attention to that.
51:31
Is this something with his meds?
51:34
but, not everybody is aware.
51:35
They’re not sure what to look for.
51:38
Yeah,
51:38
and, then it gets more complicated.
51:39
I mean, what?
51:40
What’s nice working with younger people, too.
51:43
They still have family members involved.
51:46
If you meet someone in their 40s or their 50s and they’ve had the illness for 30 years, they may no longer have contacts with the people who may have been supporting them before.
51:55
And, so they’re by themselves.
51:57
So, you’re really like your community mental Health Center or your or your primary care are basically the people who are going to identify because they may actually be kind of your family, right.
52:07
So not, I mean, I, so it’s been the benefit of like educating families at the first early in the illness.
52:14
But, also like as we go forward especially with the Pearls program, everything like educating like the different providers in community, mental health and in primary care what this looks like because they may not have anyone else to pick up on it.
52:27
Absolutely.
52:29
So, you talked about people being on medications longterm and the statistics go up dramatically.
52:37
I think 68% at 25 years is what you’ve said.
52:43
Do we tell people don’t take these drugs, they may harm you.
52:47
I, I tell people they will improve your quality of life significantly.
52:53
They will make you, they will often help you feel safe.
52:57
They will often allow you to get back to living a lifestyle that you may once known and you may seek to get back to.
53:05
However, everything that you put in your body has consequences.
53:09
It’s smoking, it’s taking cannabis, it’s the food that you eat.
53:14
It’s the medication to take.
53:15
Everything carries a risk.
53:17
You have to balance that risk.
53:19
What are you willing to what?
53:20
What, what do you value and what are you going to accept as a risk?
53:25
And, then you make a Med choice from there.
53:27
Right.
53:27
So if someone says, yeah, you know what, I get a little bit of a tremor.
53:31
I have a little bit of a sort of a sort of a grimace.
53:36
But, they said I know no other medication that works to keep me safe.
53:40
I need to be on Haldol.
53:41
Right.
53:41
OK.
53:42
So, we’ll start then we’ll start valbenazine, right or something like that.
53:47
I will start these medicine folks, right.
53:49
But, it’s a matter of being recognizing what their, their, their risk factors are that modifiable or not modifiable but also like what’s the current recommendations based on the APA and and and you know what we know in the literature and by and now it’s yeah, some people need to be on this first-generation meds.
54:10
I get it.
54:11
We’ll sometimes use them in the short term in a hospitalization to keep them safe here in the hospital but, not necessarily prescribed an outpatient.
54:17
We’ll switch them to a second generation medication prior to going right or not have that as a permanent option, start them on something second generation, but have a backup of the first generation to help with agitation here.
54:30
It’s in the invoices and seeing people, those kind of things while here while starting a newer Med that may take a number of weeks if not months to really kick in.
54:42
That first generation medication can be there for the short term.
54:46
And, if it’s in there for short term, they’re not on it for five years, they’re on it for maybe six months and they’re less likely to develop those side effects.
54:53
So, that’s where, that’s why I use those medications.
54:56
Now when you were talking about the medications that can treat TD, the cost of those prescription medications is outrageous and they’re and they’re and they’re like the standard of care by the way.
55:13
So, again underscores how how important it is for you to identify early switch to a different Med if you can do it.
55:25
Basically you have to have a lot of good reason, evidence to go to insurance companies say that they need to start a Med like this.
55:30
You don’t just start it when you start the Med.
55:33
No, it’s not how it’s going to work with them.
55:37
They’re going to ask you did you try five of these other meds first before you went to this?
55:42
Understandably so.
55:43
Right.
55:45
So, that’s why I’ve not, I don’t often start these meds.
55:48
I, I’ve never started an inpatient I’ll tell you that right now.
55:53
So, it, it, it’s something that there’s a lot of other things you can do before you move to that $7200 a month Med, right.
56:01
And, I think that’s what’s important because we think about healthcare costs.
56:05
Do you have to factor that in?
56:06
Because yeah, Medicare and Medicaid is not going to cover that without a fight.
56:11
You know, it was good reason too, by the way.
56:15
Like, we need to be diligent before we get to that.
56:17
Absolutely.
56:18
Rather than throwing more medication on top of it.
56:22
Yeah.
56:22
So, Ginkgo biloba sounds like it’s definitely, I never use it with people, but it’s not a bad option.
56:31
I’ll go with that before Clonopin any day of the week.
56:36
Yeah.
56:36
Particularly for those with substance use.
56:38
Yeah, exactly.
56:39
Or, or, they may also be, you know, on a stable maintenance regimen of Suboxone for managing opioid use disorder.
56:47
Well, you don’t want to start them on Klonopin at the same time, right, because then that can make them, that’s a dangerous combination.
56:53
So, then why not get COCA Lola.
56:56
So, and I’m just taking a quick look in the chat and Q&A and I think we’re all set for questions.
57:04
You did a fabulous job.
57:07
Any last words for us?
57:09
No, I, you know, I’m excited to keep you know work more and more with you as I’m, I’m moving forward with the Pearls program or early intervention program as we’re moving towards getting that going in the next year hopefully.
57:22
And so, I, I’m hoping to be a bit more present as my schedule gets a little bit easier and and and more accessible.
57:29
I’m hoping to be more accessible.
57:31
Maybe that’s the goal for the next 12 months, more accessible.
57:34
So, I appreciate you also appreciate you reaching out and and asking me to do this because it helps me quite a bit reviewing these things because it’s been a while.
57:43
Yeah.
57:44
And this is important information for individuals and families to have and for providers to be reminded of and for them to hold up on their their education around this condition.
57:56
So, Doctor Reed, we look forward to seeing you again.
58:00
And just a reminder to folks, there will be a recording of today’s presentation that will be posted on the Onwardnh.org education page that will be up within a couple of days.
58:12
You’ll also receive an e-mail after this presentation which includes a link to the website and a certificate of attendance for today’s event.
58:21
Emily, that evaluation link, if you could just pop that in the chat really quickly so that folks can do the evaluation so, we can improve our programming.
58:34
And also I’m happy to answer any questions you have.
58:38
You can reach me at m.wagner@naminh.org and we look forward to seeing you next time.
58:46
Thank you very much.
58:47
Take care.