Understanding schizophrenia: Key clinical considerations and treatment trends

Shoemaker, Blake   0:01

All right, good afternoon or good morning to my West Coasters for joining us today for our quarterly Genoa webinar for our partners, as well as our community workers out in the field. We're going to give it just a few minutes for everybody to kind of load into the system. I can see more people dropping in here.

We have had a big request on these webinars. I know historically we talk about drugs specifically, but we've had a lot of feedback from the field wanting to know more about specific disease states as opposed to, you know, specific drugs. So this is the very first one of these that we have done, and it's going to be centered around schizophrenia, some of the clinical considerations that we have, and as well as some of those treatment trends that are in place.
So we're going to let just a few more people drop in here. But I want to thank you for taking the time to join us today. I know you guys are very busy in the field, seeing patients, providing prescriptions, providing care for our patients. And I'm looking at the names dropping into the chat. Some of you I know through work. Some of the names I actually recognize from NatCon. Thank you for stopping in our booth at NatCon if you're one of those people.
But yeah, we're very excited to talk about this today and kind of get everybody up to speed on the latest guidelines around schizophrenia. So without further ado, I think everybody is loading in now, so we will go ahead and get started.
So first off, a little about me. My name is Blake Shoemaker. I'm A PharmD by background. I serve as Genoa Healthcare Senior Manager of Pharmacy Product. I have actually worked in a pharmacy setting since I was 16 years old and been in it for a minute now. I graduated from Sanderford University back in 2008 with my pharmacy degree.

And as far as my history with Genoa, I've been with Genoa since 2020. I originally started as the site manager at our Fort Wood site here in downtown Chattanooga, Tennessee, where I live today.

So as we start the topic of schizophrenia, let's talk about some individual impacts. We have some statistics here that really jumped out at me. So one in 300 worldwide have a diagnosis of schizophrenia or have schizophrenia. To kind of compare that to some of the other conditions that you might see in your community settings, we have about one in 500.
that would have eating disorders. We have about one in 200 that deal with bipolar disorder. If we're talking about things like substance use disorder, self-harm, that's closer to one in 100. Depressive disorder is more prevalent, one in about 25. And then when we look at all mental health diagnoses rolled into one, you're looking at about one in four.
globally. The next number is 28 and a half. That is the average potential life loss for individuals with schizophrenia. Now, that loss of life is for many reasons, including both disease state and comorbid considerations. But one thing I wanted to call out is that schizophrenia is a disease state that is really complicated, right? We don't understand it fully from time to time.
really hard to learn unless you're exposed to it on the regular. But I know that there's a perception out there that a lot of this life lost are, you know, these patients being involved in suicide attempts or drug overdoses or crime. You know, you see these people who don't have stable housing out on the street that have this very complicated diagnosis and the public perception is, you know, oh, these
these misfits out in society, like causing trouble, you know, they probably lost their lives, something like that. But the vast majority of the time, these main causes are physical. It's going to be cardiovascular, it's going to be metabolic, it's going to be the most loss of life there. Speaking of loss of life, the biggest number of all, 4.9% is the suicide.
rate in people with schizophrenia. Now, when we look at our global suicide rates in 2021, your global suicide rate was about 9 per every 100,000 people in the world. If that 100,000 people were only people who suffered from schizophrenia, you're looking at 4,900 per 100,000. So that's definitely eye-popping that that's over 250 times the normal suicide rate.
rate for a patient with this diagnosis. And then finally, 0.7%. That's the loss of brain matter that we see after one psychotic episode that can progressively worsen and gets worse each time thereafter. Now, when we talk about brain matter, what brain matter? It could be gray matter. It can be white matter as well. And research on scans suggests that this can be as much as up to
two teaspoonfuls of brain matter that can be permanently damaged per episode. So every time you have a break, it is progress that you lose that you may not necessarily be able to get back. The average brain is about 1400 cubic centimeters in mass. So that 0.7% is how we figured that. And it can be as much as 3% of the cortical gray matter. So it really underscores the importance of recognizing the diagnosis.
and getting the patient on adequate treatment as quickly as possible because this is progress that you lose every time.
So while those are the individual impacts, I want to really stress that schizophrenia, even though it has individual impacts, it is not an individual disease. As we look at these economic impacts, the estimated economic impact in 2019 alone was over $342 billion.
counting both direct and indirect costs. And that was from a study done by the Journal of Clinical Psychiatry in 2022. There were a couple of things that I wanted to point out. Look at this cost for law enforcement. Law enforcement was $26.1 billion in 2022. And when we talk about law enforcement, we talk about the cost of police protection.
legal services, judicial services, the cost of housing and taking care of these inmates if they become incarcerated. It's almost as much as inpatient care. Inpatient hospital stays were $30.2 billion and law enforcement not far behind with $26.1. But you'll notice that looking at the direct and indirect
health care costs, the indirect outside health care costs make up the majority. Unemployment brought on a cost of $54.2 billion. Patients with schizophrenia are from 15 to 30 times more likely to be unemployed with rates that can vary from 75 to 90% year to year.
when your general population rate is only 3 to 6% these days. And schizophrenia is in the top 15 causes in the United States for disability, which would allow these patients to not hold jobs. Also, you notice caregiving, $112.3 billion. Caregivers on average provide about 36 hours a week.
week of care. So this is certainly a full-time job for them, but they spend about $1,800 monthly on daily needs for these patients and nearly $3,900 annually on significant life events, which can be doctors' visits, hospitalizations, things like that. And those costs often aren't reimbursable by insurance plans. So
It's really hard to find people who can caretake and those who are having to pay out of pocket for a lot of these things.
So one thing I wanted to cover with schizophrenia is exactly what it is and then the difference between positive and negative symptoms, because we do get a lot of questions about the differences between the two, how they respond to treatment, stuff like that. So schizophrenia, by definition, is going to be altered brain structure and chemistry that's primarily associated by increases of
dopamine and serotonin in the brain. And so when you have your symptoms, they're categorized into positive, negative, and cognitive. So we're gonna start with positive. So the best way to remember this, positive addition, negative subtraction. Okay, so positive symptoms, when you have your normal baseline of mental functioning,
Positive symptoms are going to be things that are added on top of normal functioning. Okay. They're often episodic and they are responsive to treatment. So these are things that will respond to medication therapies that you see. So some of your examples of positive symptoms are going to be things like delusions. What are delusions? So delusions are
false fixed beliefs that persist even though there's evidence to the contrary. They can vary a lot, but a few examples of those can be paranoid delusions or delusions of persecution. So for example, they say that they think the FBI is following them or they feel like their spouse is trying to poison them, that paranoid.
So that's an example of those. You can also have grandiose delusions where they have this inflated sense of self and importance and ability. They view themselves as a famous figure, some kind of a unique mission that was given to them. You know, God gave me this mission to burn my house down. You know, things like that where, you know, they have this grandiose delusion. There are also delusions of reference.
where they say that ordinary events that are ordinary to everybody else have a specific purpose to them. So they might watch the news every day because they say that there's a secret message only for them on the news. So those are some examples of delusions you might see. In addition to delusions, you might also have hallucinations. So hallucinations are perceptions that you have without external stimuli.
The most common ones of those are going to be the auditory ones, right? They report, they hear voices, they hear things that are not there. But you can also have visual hallucinations. You can have tactile hallucinations where they have feelings like of touch and then also ones of smell, olfactory hallucinations as well. We also have disorganized speech or disorganized speech.
thinking. So it's impairment through organization. It is not a language deficit per se. The best way I can describe it is word salad, right? They ramble, you know, from one topic to the next with no guardrails and they frequently kind of derail, they forget what they're talking about, but the talking just never stops, right?
So that disorganized word salad is kind of a hallmark type thing as well. And then grossly disorganized or catatonic behavior. So they can have disorganization that interferes with their daily functioning from moment to moment. Bizarre or purposeless behavior, poor self-care, not taking care of themselves, inappropriate emotional responses,
things along that line. So those are all going to be your positive symptoms.
So we get to negative symptoms. So same example, we have our normal mental functioning. These are things that subtract from that, that take away. Okay. So loss of normal emotional and behavioral functions. They're often persistent. These are your symptoms that most often lead to disability. Okay. They're associated with worse outcomes.
and they are less responsive to treatment. So these do not respond to medications nearly as well as your positive symptoms do. These are more common in men, and surprisingly, they're often associated with a much higher rate of substance use disorder as well. So something to keep an eye on there. Some examples of negative symptoms. So affective flattening.
which is just a reduced emotional response. So their face is really flat. They don't show emotion. They talk in a monotone. They don't get part of, they are really bad about making eye contact, things like that that you might notice. Allogia is another thing, which is a decrease in speech output. Abolition, which is a decreased motivation for goals, difficulty starting or sustaining activities.
get them excited about some new activity and then they just can't keep themselves motivated to stay involved in it. Anhedonia is another thing as well. Reduced ability to experience pleasure, decreased interest in previously enjoyable activities. So that could be another sign as well. And then asociality, a social withdrawal.
as well. So those are all the negatives that kind of take away from that patient's life. And then we have our third category down here at the bottom left, our cognitive symptoms, poor memory, difficulty with decisions, poor insight, concentration, and impaired sensory perception.
So those are the negatives. So how do we diagnose? So this is the latest DSM-5 criteria, and we just have these five points here. So number one, obviously your symptoms. You have to have two or more symptoms during a one month period, and one of the two symptoms has to be delusions, hallucinations, or the disorganized speech that I talked about.
Number 2 is going to be your duration. You have to have a continuous disturbance for at least six months to meet the criteria. Number 3, function. So a decline in one or more major areas of life. So that's going to include work. That's going to include interpersonal relationships. It's going to involve self-care.
care, even academic functioning. If they're in school, if they're in college, a decrease in academic functioning could qualify for this as well. Number 4, any childhood history. Prominent delusions or hallucinations after a diagnosis of autism spectrum disorder, or you could even have communication disorder that is established and meeting all the other criteria as well.
And then finally, #5, the biggie, differential diagnosis, right? Because you have to rule out other things. These symptoms are not exclusive to schizophrenia. You have to rule out other medical conditions that can actually cause those psychotic features. So, you know, other things can cause hallucinations, delusions, disorganized thinking. So #1 that comes to mind for me, substance use disorder.
right? Psychosis from drugs, very easily seen. Major depressive order, sometimes. You can have psychotic symptoms with mood disturbances of certain kinds. Bipolar disorder is another common thing that you can see. And then you can also have schizophreniform and schizoaffective that can really muddy the waters even more. So what am I talking about? So here's a visual.
that I think is really good to see. So when you have a diagnosis of schizophrenia, the blue line is represented by these schizophrenia symptoms. And then the red line is the symptoms of mood disorder. So with schizophrenia, you're going to have the schizophrenia symptoms that kind of run the show, right? And then you're going to have these symptoms of mood disorder that can show up in the background, but they're not playing the leading role.
in the situation. Mood disorder, it's kind of a flip on that, right? The mood disorder is what you see most of the time. And then you have schizophrenia symptoms that can kind of peek their head out during or after the mood symptoms. But where it gets really complicated is schizoaffective because you have equally prominent schizophrenia symptoms and equally prominent mood symptoms as well.
So definitely something you got to be careful when you get the right diagnosis. So let's talk about treatments. And I know this is going to sound funny when it's a pharmacist teaching a presentation for Genoa Pharmacy, but your number one intervention is going to be psychosocial. Why psychosocial and not medication first? Well, medications alone are very much insufficient.
Medications are effective for positive symptoms, as I mentioned, but it's not perfect and the negative symptoms often don't respond very well to the medications. So you have negative symptoms, cognitive dysfunction, functional outcomes not really addressed by medication. And the latest data I was able to find, it suggested that only about 29% of patients with psychosis
receive actual specialty mental health care that they would need in addition to medication to be adequately treated. So 29% is certainly a number that we can improve on and need to improve on. So I have some of the interventions listed here. CBTP, which is cognitive behavioral therapy for psychosis, is a big one.
That is the principle that thoughts, emotions, and behaviors are interconnected by examining the beliefs behind the hallucinations or the delusions and improving coping strategies by using insight into that. This is really useful in your patients who have no insight into their condition and with symptoms despite medications. But again, this doesn't have a whole lot of impact on negative symptoms. So it's not your best choice for negative symptoms. Family
education is another biggie. That is one of the strongest evidence-based interventions we have. That's basically providing family training on the illness, communication, problem solving, and recognizing early signs of relapse in these patients. These outcomes are associated with a much stronger reduction.
in relapse and hospitalizations, and improvement in medication adherence, and reduce caregiver burden and stress. So that is one that I highly recommend as well. We also have social skills training or SST. Those are behavioral interventions with role-playing, modeling, and feedback. Those help to improve social competence and community functioning.
as well. Supported employment and education. We spoke to unemployment just a bit ago. This can be helped for employment placement and ongoing job support. Actually, unemployment status is one of the strongest predictors of recovery. So that is something you can really do to do that. And then CRT, or cognitive remediation therapy,
is cognitive training for attention, memory, processing speed, and executive function.
So that's your first line treatment. Your next line is going to be your antipsychotic treatment. Now, it's important to call out that there's no singular medication here that is a recommended drug of choice here. The rule of thumb is that you want to use the lowest, most effective dose. You need to trial these with
confirmed, underscore confirmed adherence for at least six weeks to access efficacy. You need to make sure that these patients are taking their medications on the regular, greater than 80% of the time, you know, at worst case, for at least six weeks to make the call on whether it's the right therapy. Generally, you do want to use a second generation antipsychotic.
instead of a first generation due to a lower risk of extrapyramidal symptoms or EPS, which we'll talk more about here in just a bit. First generations typically focus on blocking just dopamine while your second generation antipsychotics are going to focus more on dopamine and serotonin. So you have a cleaner side effect profile and less risk for things like tardive dyskinesia and EPS.
I.
Patient considerations.
So some of the things that we want to look at here.
At initial assessment, you want to look at vital signs. You want to look at BMI, blood count, blood chemistries. Why do we want to do all of this? So we want to do this for sure, because some of these medications side effects include things like weight gain, increased blood sugar, increased cholesterol. So we do want to get a good baseline on these medications to know where they are.
and then watch where they go after they start the medication. You also want to include a pregnancy test if there's childbearing potential as well, because some of these medications are contraindicated in pregnancy. And then as indicated, labs in that right column, you know, you have blood sugar, cholesterol, heart rhythm, prolactin, involuntary movement assessments, things along that line.
as well. And then when they do their follow-ups, you're going to recheck to see the trends. You're going to see if things stay the same, things increase, things decrease, and then make the call whether or not you need to adjust the therapy based on that. So let's talk a little bit about treatment resistance, okay? So treatment resistance is defined as failure of at least two
adequate trials, and by adequate, I mean that we know they are absolutely taking medication greater than 80% of the time with two different drug profiles and documented adherence that we can prove, where we have a caretaker that is watching them take the medication or some other similar method to be able to make sure that they take the medicine.
We need to have at least two adequate six week or longer trials, different mechanism of action, documented adherence, and we're still seeing symptoms that can be defined as treatment resistance. So some of the things I have outlined here on the screen could be false indicators of treatment resistance that aren't really. So having the incorrect diagnosis, they might not be responding to the medication because they don't have the right diagnosis to start with.
Inadequate dose, you may need to adjust to a higher dose to make sure that the patient's not responding. Inadequate duration, we talked about six weeks at least on the therapy.
Poor adherence is another thing that we're going to talk about. Great backer of selecting a long-acting injectable therapy, and we'll talk more about that here in just a bit to make sure that they have the medications on board. Or it could be a comorbid medical condition that makes you think that they're not responding to the treatment when they actually are. Or they could be
you know, doing things like abusing substances and having these breakthrough symptoms that are attributed to the substance itself and not the diagnosis originally. So if you do have a patient who is treatment resistant, what is the way to go there? So some of your ideas that you can use, you can use clozapine. Clozapine has a very broad mechanism of action that's great for treatment resistance. It's also
very active for patients who have suicide risk and aggression. Another path that you can take is you can use a combination of a first generation antipsychotic along with a second generation antipsychotic. That's another path you can take as well. And then of course, if you haven't used a long-acting injectable, you can certainly give that a try as well to make sure that adherence is not giving you bad information on your end.
So when we look at our treatment selection, here are some of the main safety concerns that we see, as well as some of the usual suspects that can cause them. So side effects are a huge reason for non-adherence in these patients. I know sometimes we get it in our heads that, you know, a patient just doesn't want to take their medication, so they're just not going to do it. Or the patient forgets to take their medication, and that's the main problem. But you would be surprised just how many patients report that they stop it because
They went from one bad thing, you know, having a diagnosis of schizophrenia, to taking a medication and suddenly they're having these terrible side effects that make them feel like now they have two bad things. So they're going to stop taking the medication. So these are some of the safety concerns you can see and then some of the medications that might cause them that you might want to adjust. So EPS or extrapyramidal symptoms, these are higher risk in your first generation antipsychotic.
Some of the common things you'll see with that are dystonias, which are really painful muscle contractions. They're more common in men, so you can have neck twisting, back arching, where they might be sitting in the office and their neck is turned and they're kind of arched back in the chair like this. Those dystonias can be really painful and can be a big reason for discontinuation of medication.
You can also have restlessness in these patients, which is, you know, pacing, constantly shifting in their chair, can't sit still. That's often mistaken for anxiety or agitation. When it's not really anxiety or agitation, it could just be the restlessness as a side effect. So be careful with that. Parkinsonism, drug-induced Parkinsonism is a big.
Those are going to be those really slow, rigid movements. You can even see tremors like in the hands and the extremities. We do get a lot of questions about the difference between drug-induced Parkinsonism and tardive dyskinesia because they're both involuntary movements and how we can tell the difference between them. What I often tell people on that is in Parkinsonism, the movements are going to be much more slow.
much more rigid. You're going to see that tremor, but a lot of the things that you can see are very rhythmic in nature. Like you can watch it and you can see a very constant rhythm throughout. Whereas tardive dyskinesia is very fluid movements. You know, they may, you know, not be able to sit still. You got a lot of mouth, jaw, tongue involvement where they...
you know, just can't sit still. They feel like they can't catch their breath or whatever. So those movements are more fluid. They're much more chaotic. There's no rhyme or reason or rhythm to them. So that's a big way that you can kind of tell the difference between those two.
So we also have metabolic changes listed here. So metabolic changes can be things like rapid weight gain, elevated blood sugars, elevated cholesterol, things like that. So those are, how are we going to tell? Exactly what we talked about in the slide before. We're going to take those baseline labs and we're going to do the repeat draws to make sure we can catch those things before they become a larger problem.
as well.
We also have QT prolongation. This is the hardest one to spot because a lot of the time it's very asymptomatic. QT prolongation is simply an extended interval, just in fractions of a second, between the heart contracting and relaxing. So you often don't have signs or symptoms that patients can present this as saying that it feels like their heart is racing,
They feel lightheaded, they feel like they're going to faint. So that could be an early sign that that could be going on. So those are the right questions to ask on that, to ask if they ever feel like they're lightheaded or their heart is racing. Hyperprolactinemia is another one. Now in females, this can present as fewer or no menstrual periods.
But in men, it can also present as decreased libido, infertility, erectile dysfunction. This is very high up the list of side effects that will immediately make a patient want to stop taking the medication because now they're having these sexual side effects. They, you know, they're already having trouble experiencing, you know, pleasure from activities and now we're causing infertility and erectile dysfunction. So again, they
stop the medication. So again, asking those right questions about noting if there have been any problems in that department as well. And then final thing I have here is anticholinergic symptoms. So that's going to be things like constipation, dry mouth, urinary retention, blurry vision, things along that line. Now, I will call out that this can
contribute to cognitive impairment and falls in the elderly population. So you notice a lot of these drugs here like chlorpromazine, thyriazine, trifluprazine, clozapine, lanzapine. A lot of these are first generation medications and we often don't like to use these in older patients because they can contribute to confusion and falls in the elderly. So something else to think about.
So I did want to include this. I thought this was a really cool chart. This is a data analysis from the schizophrenia guidelines project. Nurses basically conducted clinical interviews with patients who were not taking their antipsychotic as prescribed. And these were the reasons that were given back to them, the specific barriers that were listed. And you'll notice that number one on the list
is not things like being in denial about their illness or not trusting their doctor or being struggling with difficulty with the regimen. Number one was stigma, which blew me away when I saw that. Now, stigma in this study was defined as having embarrassment or shame about taking medication, having concern about others seeing them take medication and feeling judged.
or even fear of being just simply labeled mentally ill. So the stigma surrounding it was the number one thing reported by patients. And right there at #2, adverse drug reactions. That's why it's so important to have the conversation about not just leaving it, are you taking your medication, talking to them about what life has been like since they started taking that medication so that you can identify any of the other issues that could lead to discontinuation.
homelessness, forgetfulness, lack of social support. All of these things up here can be handled by those social interventions that we talked about. And that's why those first line treatments, before you even get to the medication, are going to be things like this to kind of help with.
So I mentioned LAIs, and if you know me, you knew we were eventually going to get to LAIs, but here we are. So what are LAIs? So LAIs are long-acting injectables. And what these are, are they're injectable forms of the same exact medications that you would choose right now as a first oral option, but they're just injectable therapies.
They are not only dinosaur drugs. And that is a big perception that's out there that we're trying to change. The example I always like to use, I love medical shows. Like, I'm big on The Pit. If you haven't watched The Pit, you need to watch it. It's amazing. But before Noel Ali did The Pit, he did another big medical show, ER, and I loved ER. I watched ER so many times through.
It's ridiculous. But what happens on ER? You see a patient rolled into the ER on a stretcher. They're currently having some kind of a psychotic break. They're striking at people. They're throwing things all over the place. And what does the doctor say? I need 10 milligrams of Haldol stat. And, you know, they load that syringe and they inject the patient. And what happens to the patient? They just...
you know, they're out, they're down for the count. And I think that, you know, for those who may not have a lot of exposure to LAIs or what they're doing, you know, that perception is, oh, if I use a psychiatric injection, that's what they think of. And they think of patients losing, you know, autonomy. They think of patients just lying around on the bed all day, not being able to function.
when again, these are the exact same medications you would choose as an oral therapy that are current generation medications. They're just in an injectable form so that the patient doesn't have to take a pill every day. And they remove one of the largest barriers to any therapy, especially behavioral health, and that is non-adherence. I would argue that the hardest part of any prescriber's job
especially in mental health, is having a patient return to clinic. They're still having the symptoms that we were trying to treat, and you're not sure if you should change that therapy because you're unsure if it's the medication not working or the patient not taking the medication the way they're supposed to. If we gave them an injection at that last visit, and that's all.
off the table as far as adherence goes, and we know they're still having symptoms, you can quickly and confidently make those changes and get the patient where they need to be in a much shorter time frame. And with all of those episodes causing that brain damage that we talked about, the quicker we get them there, the better.
LAIs use different designs and chemistries to achieve an extended release from the injection site to achieve and maintain effective drug concentrations. For your older ones, a lot of those are suspended in an oil, like sesame oil, that slowly release the base drug out of it once you inject. There are others that are crystalline, where the crystals are different sizes and they break down at different rates.
so that they provide the medication over time. And then we have others that are depot where you give them the shot and then you actually feel the knot where the medication is and kind of lives as the bloodstream kind of picks it up as it goes by. So really interesting methodology behind that.
So I did want to go over this chart really quick.
And I think this is a good example because the dynamics and the pharmacokinetics of these drugs are a little complicated. So this chart, really simple, right? So the bottom axis is going to be time. This is going to be the time since the medication was taken. And the vertical arrow is going to be the concentration of drug in the system. But the most important line on this chart
is this blue dotted line in the middle, which is the MEC, or what we call the minimum effective concentration. What does that mean? The minimum effective concentration is the concentration that you need to reach in the patient's system to treat the symptom that you're looking to treat. If the concentration is below that line, the medication is in the system, but it's not treating adequately. And if it's over that line, you're at a point where the drug concentration
is at a point where it treats the symptom. So perfect example, let's say I wake up this morning and I wake up with a headache. I'm going to reach for that Advil in the medicine cabinet, right? And so when I take that Advil, the concentration is going to rise. And then once it hits this line is when I'm going to start to feel that headache start to fade a little bit. And then for the four hours or so that it's over this line,
I'm going to have that pain relief. And then once it drops below this line, I'm going to start to feel that headache start to come back. You know, if the headache is still there, I'll start to feel it come back at that moment. And then I'll need to make the decision whether or not I want to take another dose. Or maybe the headache has passed since this time and the drug continues to wash out of the system until it's completely gone. Unfortunately, it's not that simple for antipsychotics because antipsychotics take days, if not weeks.
to reach an adequate concentration in the system. So this curve is more like this. You're going to take day one, wash out, day two, day three, day four, day five, and you're just going to be on this upward curve until eventually you get above this, you know, just kind of a rough estimate here, and then you'll stay above it at the rest of the time. But
You're counted on every single day to push this curve a little bit higher. And if the patient takes the medication every single day, you'll eventually get to this line. But the whole time that you're below this line, however many days this is, you're still going to have those breakthrough symptoms. The problem is, is that what happens when the patient takes day one?
day two, day three, and then they miss a day.
And then they take day four and then they miss a day. And then day five, day six, day seven. You see how we're kind of moving away from this line? It's giving them more and more time below this line where those symptoms are not going to be treated. So you're going to think that the medication's not working when in effect the medication is not at a level that it needs to be. So that's why it's so important that patients take their medications every day.
so that we can efficiently get to this line and stay above this line. LAIs take the guesswork out because the LAIs normally have a pretty quick onset of action. And then when it starts to wash out, you have kind of this plateau effect where it does kind of wash out of the system, but you notice that it's very, very slow. And what's happening?
every single day, they're staying above this line, which means that the symptoms are still going to be treated. Now, you still have this area over here where you could still have some breakthrough symptoms while you're waiting on it to kick in. And these are cases in which that you might have to do an oral lead-in on therapy. Depending on the drug, depending on the strength, that will often be in the package insert to let you know.
But some drugs have day one loading doses where you give them maybe the maintenance dose and a loading dose on day one, and it basically puts them therapeutic within 24 hours. There are other older medications where you may have to take oral medication along with that shot for up to three weeks before you get to a therapeutic level. So just be aware of that and make sure that you read your package indication to know that whether or not you need to do.
and orally then and if that needs to be the case.
So some of the drugs we have available as options for this. So you're going to have your first generation antipsychotics. That's going to be your Flufenazine and your Haldol. Haldol is still the most commonly used typical antipsychotic to this day. That then has been in tablet form since the 60s and has been an LAI in our toolbox since the 80s. But your second generation ones you have listed there, you have your Risperdal-Consta.
You have your own vagus astena. You have your Zaprexa-Relprev. That is 1 I want to call out because we don't see a lot of use of it. And the reason that we don't see a lot of Zaprexa-Relprev is because it's actually associated with the REMS program. The REMS program is that you have to basically have the prescriber register.
the pharmacy register and all of those patients register because you have a risk of post-injection delirium or sedation syndrome, or PDSS for short. So for that reason, not only do all of those agencies have to be registered every time you dispense, you actually have to observe the patient for three full hours after the injection to make sure that they're not going to have this side effect.
So I did want to call that out. It's an option, but it's not a great option at the moment. There is a new olanzapine containing LAI that's supposed to be coming out later this year pending approval that is not supposed to have those restrictions on it. So be on the lookout for that sometime in Q4.
We also have our Abilify maintenna and our Aristata. Our Aristata is the first one that was starting to push the envelope as far as dosing interval, beyond four weeks to six and even 8 weeks as well. You've got Proseris. Proseris is on the process of going off the market, so that won't be around much longer. But Yuzeti is available.
It contains Risperidone, so it can replace the Proceris pretty easily. And the USEDI is also available in one to two month forms as well. And then we have our Zofri. And then your final category, you have your extended interval LAIs. So those are going to be your Invega Trenza that lasts three months. You have your Invega Hafiera that lasts six months.
your Abilify Asimptify last two months. And I know for the purposes of this presentation, we're not talking about this, but do know that there are LAIs in other drug categories as well. We do have them for substance use disorder, as well as both the prevention and treatment of HIV. If that is something that you're interested in learning more about, we will have an email at the end of this presentation. You can feel free to email us for more information.
So why LAIs? So we've already talked about medications are always on board and that it's easier to make your therapy decisions or adjustments that are going to lead to better outcomes. There was a 2020 study in the Annals of General Psychiatry that looked at about 75,000 patients in a 10-year period from 2008 to 2017. And what they saw when they compared LAIs
directly to their oral counterparts is that there was a reduction in readmission rate of 29% compared to the oral medication in real world settings. Even more impressive is when we looked at the use of LAIs in patients who had repeated readmissions, that readmission rate was reduced by up to 58%. So the data is
Very solid on that. Secondly, reduced cost to the healthcare system. A lot of those numbers that I quoted way back on one of those early slides, medication non-adherence can lead to those poor outcomes and those significant costs. So if we're able to get them on an LAI sooner, then we don't have those added up costs that come down the road. And then finally, I wanted to reiterate, these are current generation medications, not just the old ones.
They're the same medications that you would pick as your first choice today, just as an injectable form. So all that said, let's take a look at your typical treatment journey. This is really important. This is based off of a Lancet study that happened in 2021. It looked at 18 years worth of data containing randomized controlled trials, cohorts, and pre-post studies looking at the benefit of LAIs
versus oral equivalents. The total number of patients was about 397,000. The total number of studies was 137 studies. So that's how we came up with this treatment journey. And some of the numbers that I'm going to fill in here momentarily are directly from that study.
So first off, you have a patient that presents with undiagnosed symptoms. Some of these hallucinations, delusions, they show up. They don't know what's going on. They show up with these symptoms. What is the median age? What's the symptoms start to present? It's going to be in the 20s to 30s. More early will show up in men. Typically in men, it's in the late teens to early 20s.
In women, it's often the late 20s to the early 30s, but that median mark is going to be in that 20 to 30 year range. So step two, we've got to start treating these symptoms without having a final or definitive diagnosis because we have to rule out some of these other things that can overlap. So you've got to rule out things like personality disorders.
mood disorders that may happen, psych features, delusional disorder, substance use disorder, even some physical things. Sometimes you might have a brain tumor that can be causing some of these things or certain STDs like neurosyphilis can cause this. So you've got to treat the symptoms. You've got to start ruling things out. How long does it typically take to rule those things out? This study showed that it takes about a year.
About a year of kind of ruling things out one or two at a time until you get things where they need to be. So then you finally arrive at your diagnosis of schizophrenia. Okay? So you get your schizophrenia diagnosis, you start the first oral antipsychotic regimen, and then you enter what I refer to as the spin cycle, where you have
all of these episodes of oral antipsychotic regimen switches. So you send them out with their first month of therapy, and then you let them try for a month or two, and then they come back in, and then you're not convinced that they took their medication, right? So then you talk with their caretaker to watch them take their medication, and then they take their medication, and then you decide the medication's not working, so you up the strength and you go through this whole cycle. What this study showed that on average is that
four different oral antipsychotic regimens, not counting strengths, were started before suggesting their very first LAI. So the question becomes, looking at this data, how long is it taking us to get from a diagnosis of schizophrenia to their first LAI antipsychotic recommendation? And the shocking news on this,
Knowing how effective LAIs are is that this study, 397,000 patients across nearly two decades, showed that it's taking almost 10 years to recommend their first LAI. This is 10 years of repeated office visits. This is 10 years of hospitalizations. This is 10 years of progress lost.
brain damage that we can't get back. So we need to shorten this gap. We need to start getting to that LAI recommendation sooner than we currently are. Because even though we're diagnosing them in their 20s and 30s, on average, the average age for an LAI start is 38 years old. And that's something that we can certainly do a better job of.
So we see all of this. Why aren't we using LAIs? Why is this the treatment story? So number one, they're specialty medications. You can't always fill or bill them at a retail level. You might send these to a big chain pharmacy down the street and the pharmacy tries to process it and they get a rejection that says pharmacy not contracted.
or, you know, drug out of network. And it's not a situation where you have to do a prior authorization. It's just they are not licensed to handle these kinds of vacation. So you think, you know, the only way you can get them is to use some kind of a mail order pharmacy. But what I want to say is that Genoa is dual license, not just for long term care, but also specialty.
So you're not going to run into this issue with your local Genoa. If you send this to Genoa, we can typically get these taken care of you no problem and get these delivered to your office based on preference. Number 2, PA process is a pain. No fear, no phrase strikes fear into the heart of a medical practice faster than you have to do a prior authorization.
right? We hate them. They take forever to do. They're often difficult to navigate. And the tools have made it a little bit easier. I know CoverMyMeds is a big one that everybody uses and it's made things a little bit less burdensome. But do know that Genoa can help you with that as well. It's very common for our pharmacies to partner, not just with our internal clinic partners, but also our external partners as well, as long as we can
science and paperwork with you for you to provide us the information. Our pharmacies are very well equipped to help you with those prior authorizations. So that's one less thing that you have to do that we can kind of take off your plate as well. And then the final thing I have listed here is doctor can't access the medications or you don't have the space for the staff to administer. So what am I talking about?
access. Well, this is a medication that often when we fill it at our pharmacy, we don't want to hand to a patient, right? Why would we not want to hand these to the patient? Well, number one, you don't want the patient to try to self-administer because some of these medications can be, it can be a problem if the patient tries to administer and they administer correctly, or administer incorrectly rather.
Another thing is the product integrity. So if a patient picks up the medication and they're going to bring it to your office, I can't tell what happened to that medication between the time it left my pharmacy and the time that it got to you, right? Did they leave it in a hot car? Did it sit somewhere, you know, outside of temperature range? Because you're not going to be able to open that box and look at it and tell that something's wrong with it.
So how do we access these medications? So we provide free delivery or free mailing of medications, either to the office where it's being administered, or if it's an oral medication, we do that for all of our oral medications as well to the patient. Depending on the situation, we're happy to do that. I'm also proud to say that we have a pharmacist-led administrator.
program for those practices that would love to use LAIs, but they don't have the time, the space, or the staff to actually do the administration. That's something that we can do as well. We can administer in 47 out of the 48 states that we operate in, the only exception right now being New Jersey, just because of the laws in that state. And we're trying to work to advocate for change on that. But in the other 47 states that we operate in,
there is a path for us to do that. Sometimes it's as simple as you sending us a prescription and a note giving us permission to do the administration, and then we would do it and send you a copy of the record once it's done. Some states it's a little more complicated. We might need to sign a collaborative practice agreement, but we're happy to draft those documents and get you to sign those as well. But there is a path.
forward in most of the states that we're in. Because you know as well as anybody that those resources, that time, the space, the staff that you have available in the office is a priceless resource. And if you don't have the time to provide, we can certainly help step in and take the burden off your plate.
So how can our pharmacy team help? Just to kind of summarize, your Genoa Pharmacy can coordinate with the mental health team. We have onsite pharmacies that are embedded in community mental health centers, and we have direct pharmacist coordination among psychiatrists, case managers, social workers, everybody. So we are very involved. So if you have a Genoa in your building, you know.
It's a lot easier to see if a patient is having problems with their medications when you can just walk down the hall and have a conversation with one of us at the window instead of trying to pick up the phone and getting voicemail and can't get through on the phone system. Number 2, I did want to speak to our specialty packaging as well. We do have bubble packs. We do have dose by time of day organizers as well, and we do have mailing delivery.
as well. That mailing never costs anything. So if we are mailing or delivering to your office, that's not going to cost you a thing. If we are mailing traditional medications of any kind to your patients, those patients never pay for delivery or mailing as well. That is a cost that we absorb to make that happen to make sure that the patients are on their medications. And then the final thing I have is LAI administration and navigating state laws.
As I mentioned, we have 47 states active out of 48 that can administer at this time. And we're working on number 48. So we'll see where that goes. But we're also keeping an eye on states for changes because some states only allow us to administer certain categories of medications. So Florida is an example I'll use. Florida allows us to administer mental health medications.
but they don't allow us to do HIV or substance use disorder. But on the other side of the spectrum, where I'm at in Tennessee, our state board has stated that as long as we have a valid prescription and permission from the prescriber, we can do all categories. So it does vary a little bit from state to state. So if you're curious about what your state offers on that and how
you know, big the lift would be on our part to make that happen, please don't hesitate to reach out and let us know. We're happy to take a look at that for you and see.
And these are the references that I used today. And I failed to mention at the beginning of the presentation that I wanted to leave time here at the end for Q&A. So if anybody has any questions, any comments, you know, anything related to Genoa, feel free to use that chat feature. Feel free to use that Q&A as well. I will take a peek.
here, giving you guys a few moments to do that.
Don't see anything in the Q&A, so I'll move over to the chat.
Yes, I have my counterpart, Megan, answering some questions in the chat. This webinar recording is going to be sent to everybody who registered. So if you're here today, you're going to get an email with the link to the recording. If you want to watch this back again later, or if you have other people that you want to share it with, that will certainly be available hopefully in the next week.
That answers the question about on-demand.
Will it be a recording? Yes, we have the recording.
Perfect.
Send the references. So yes, we will have the references available. I'll run it back to this slide if you want to do a capture of it. And we'll also have that available in the recording that we will have available as well.
I have some clients who are interested in LAIs but haven't done an oral challenge. What are your recommendations with that? That is an excellent question. So obviously you do want to do an oral trial with these medications because we don't want to give them a month of the medication at one time via injection when we don't know if they'll tolerate the medication. Either if it will work or if they'll have a reaction to it, right? So we don't want that.
The recommendations for how long they have to be on that therapy are very gray. Typically, the rule of thumb on most of these medications is that you're going to use them for at least a few days to account for initial exposure, like if there's an initial exposure type allergy, and then a couple of extra days would account for a repeat exposure type allergy.
But typically, you will have made sure that they're going to have the correct response to these medications to at least dull some of the symptoms that you're seeing before you jump in with an LAI. So you do want to try at least a few days worth of the dosing before jumping in with an LAI. But I would recommend watching for some symptomatic response. So maybe giving them a month.
to see how they do on it. And then if you're seeing some symptom resolution, but not quite what you want to see, and there's still upward movement for the dosing, then maybe you jump over to the LAI because then you take the dosing, then you take the compliance off the table, and then you can play with your dosing within the LAI itself. So that's a great question.
A...
Very complimentary group. Thank you for all the compliments.
So, we'll get it, I'll check Q&A again.
Are you aware of any LAIs in the pipeline for teens? That's another really good question. So right now, all FDA indications on the entire LAI category are 18 and above only. There has been no movement that I have seen to this point getting the indication changed to younger than 18.
However, that said, I know that there are some prescribers that have used them off-label. The one in particular that comes to mind is Risperdal Consta. I've seen used a couple of times. The Risperdal Consta is an every two-week LAI. So it doesn't stay in the system as long. It can be a little bit lower doses.
So I know it's still like, you know, 2 doses a month when we have all of these monthly options available. But I have seen some off-label use of that, even though there's no official indication. But I will warn you, if that is something you want to do, be sure that the patient's insurance is going to cover that. When I still worked at my single pharmacy, we had a couple of patients where they wanted to try it on 16 or 17 year olds.
And that's fine. I mean, you have the ability to do that off label if you choose, you know, with all the documentation and stuff. But when we tried to run it on the patient's insurance, the insurance was actually tied into the FDA indication. So they wouldn't pay for the drug itself because they said they wouldn't pay a claim for anybody under the age of 18. So consider that, making sure that the claim will actually get paid.
No official indication and no movement to change it to younger than 18, but you certainly have the ability to do it off label if you think the risk out, the benefit outweighs the risk.
Right. Looking, looking, looking. We'll give it a couple more minutes because I left plenty of time here at the end. I wasn't sure how many questions we would have. So.
And as we kind of begin to wrap up for the day, I want to thank everybody for being here. I know that you are very busy in the field, seeing patients, taking care of patients, and as your pharmacy partner, in a lot of cases, or prospective pharmacy partner, if you're just now learning about Genoa and what we do,
you know, we want to take, we want to do all that we can do so that you can focus on what only you can do. And that is taking care of your patients face to face. Whether that means, you know, helping with prior authorizations, whether that means helping with administration of medication, whatever it takes, we're happy to step in and be an active partner in that.
And I know that those of you who have worked with us can really kind of speak to the level of service that Genoa provides you and your patients. We are going to send out this recording of the presentation out. It will be available on our YouTube channel as well. If there's any questions that come up later that you didn't think of now, maybe you're watching this recording later and you're somebody who
couldn't participate in the live Q&A, we do have that email address there, clinical services at genoahealthcare.com. That's a shared inbox on Genoa side that one of us can certainly be able to jump in and answer the question or set up a call with you to see what we can do to help. Is it possible to have the PowerPoint? I don't think we can share the actual PowerPoint file.
But we are going to have the recording up so that anything that you wanted to kind of screen capture from the presentation to kind of use as a reference point, you could certainly do that as well.
So...
But with that, I think we'll go ahead and draw it to a close. I want to thank you again so much for taking the time to join us today. It's probably one of the highest numbers we've ever seen on a webinar. And again, our very first one focused on a disease state. So if you have other disease states that you want to learn more about, you can certainly hit us up.