- Welcome to Healthy Minds.

I'm Dr. Jeff Borenstein.

Everyone is touched by psychiatric conditions either themselves or a loved one.

Do not suffer in silence.

With help, there is hope.

(gentle piano music) Today on Healthy Minds.

Psychosis and schizophrenia.

What are the early symptoms that a person may experience if they are developing psychosis or schizophrenia?

And what should you do if you are experiencing those symptoms or a loved one is experiencing those symptoms?

Today, I speak with leading expert, Dr. Robert Cotes about the early warning signs and the treatment for psychosis and schizophrenia.

That's today on Healthy Minds.

This program is brought to you in part by the American Psychiatric Association Foundation, the John & Polly Sparks Foundation, and the WoodNext Foundation.

Rob, thank you for joining us today.

- Jeff, it's so great to be here.

Thanks so much for having me.

- I wanna jump right in and talk to you about a topic that you've been very focused on, which is the prodromal syndrome and early psychosis.

Could you first tell us what exactly is that?

- One of the reasons that we've been very interested in the prodrome of psychosis or of schizophrenia is that if you're able to intervene early, you have a great chance on improving the overall outcome of how people with this condition do.

And one of the reasons I got interested in this area is that I was working on the inpatient unit and found that many of our patients had weeks and weeks and weeks of psychosis that was untreated before they actually got to our services.

We really were interested in doing something to help reduce this amount of time that people were treated, that people didn't get treatment.

And it's called the duration of untreated psychosis.

So we are really, really interested in reducing the duration of untreated psychosis to as small as possible as we could.

And there's a lot of reasons why people have a long duration of untreated psychosis.

Sometimes, it's because of stigma, sometimes, it's because people just aren't sure about what's going on.

There's a lot of confusion.

One of the ways that you may be able to reduce the duration of untreated psychosis is to create a program that sees people in what's called the Clinical High Risk for Psychosis category, or sometimes called CHR, or sometimes called CHRP, Clinical High Risk for Psychosis.

And in these programs, we're looking to identify people who are having signs of psychosis that are maybe very, very brief.

We call them attenuated psychosis, attenuated psychosis symptoms.

And sometimes, this means brief auditory hallucinations that are just very, very subtle.

Another common sign of the, common symptom of the prodrome is something called a social withdraw or social isolation.

Sometimes, people can also have mild depressive symptoms during this period.

And it turns out that one third of people who meet this criteria for clinical high risk for psychosis actually go on to develop an episode of psychosis later in their life.

And we think that if we can intervene in this clinical high risk for psychosis area, we may be able to get the duration of untreated psychosis very close to zero.

And that is what we're really going after with these types of programs.

- It's almost as if we're treating the brain as we treat the heart.

For example, if somebody has a little bit of chest pain, we are gonna wanna be proactive, and treat them before they have a full heart attack, to decrease the risk of a heart attack or the severity of it.

So we want to intervene.

If somebody is experiencing some of the symptoms you just described, what should they do?

- I think the first thing is the education about these symptoms is so important.

When someone has an episode of psychosis or when they have brief attenuated types of symptoms, it's often very be bewildering or confusing, and, you know, people aren't really sure of what's going on.

So that's why it's so important that we have conversations like this to really educate about what these signs and symptoms are like.

That way, that if someone does have them, they can reach out, and they can have a conversation with someone who specializes in this to help get them connected to the right kind of care.

- Tell us about what is that care?

What if somebody is experiencing those symptoms gets this diagnosis?

What do you do for them?

How do you help them?

- When someone gets a diagnosis of schizophrenia, which is one of the many causes, which is one of the many underlying illnesses of psychosis, which is also a disconnection from reality, it is something that can be treated and it's something in which people can kind of continue to do the things that they want to do in life.

There are a number of, I think there's over 300 early psychosis programs around the United States.

And these programs specialize, the criteria varies in, you know, from program to program, but usually, it's for young people, you know, say maybe 15, 16 up until 25 or 30.

And these are programs that specialize in working with people who have experienced psychosis for often two years or less.

And in these types of programs, you get wraparound services, coordinated services for all the kind of things that people need in order to be successful early on in the illness.

These programs can provide medication support, they can provide family education, they can provide often peer support.

So somebody else who's actually gone through this can work with that person and share their experience.

They provide individual therapy.

They provide nursing support.

So pretty much everything that anyone would need in that early period, including supported employment or education.

That's really helping get people back to work or getting people back to school.

That might be one of the most important parts of it actually.

And these programs provide all of those services, and they actually talk to each other and coordinate the care.

And we think that this sort of combination of services really helps people to get back on track most quickly and going on to live the lives that they want.

- I think one of the key points you're making is that while medication is a piece of the puzzle is only one piece of the puzzle, there's a lot more that could be put in place to help support the individual.

- Yeah, that's exactly right.

And I think that a lot of the other components of the early psychosis team, you know, like the therapy or like the support, helping get people back to work or school, that really helps to build the trust with the team, and often with the healthcare system.

Again, that might make it possible for people to consider medication.

A lot of times, after people have had an episode of psychosis and maybe if they've had some interaction with the healthcare system, there can sometimes be a lack of trust or maybe something has happened, maybe something traumatic has happened, someone might have to go to the hospital for a little while, and that's not what they were planning on that day.

So I think a lot of these teams really help around sort of restoring trust.

And then once that trust is restored, then it might be a lot easier to consider taking a medication.

- You mentioned peer support as being a part of the treatment.

I want you to speak a little bit about that, because I think it's extremely important when a person who's going through something for the first time gets to speak with another individual who's been there, done that, and have and is doing well, that that could be very helpful to the person going through this.

- Yeah, absolutely.

I think that peer support is really one of the most critical elements.

And what I love about peer support is that it really challenges the hierarchical system that we have oftentimes in medicine and in mental health.

And what I think peer support does is really helps to have everyone sort of on the same plane, on the same level.

We learn from people with lived experience.

We learn from the person that's sitting in front of us.

Everyone is the expert in their own experience.

And I think that this is really one of the most important parts of peer support.

A peer support specialist, particularly one that's experienced psychosis, when they tell their story, that's so much more powerful than a story that say I could tell about like what psychosis is like, or how I understand it or what I've read about it.

So on our teams, we really, really value peer support, and we actually have peer support that a certain kind of peer support also that has been a family member of someone who's experienced a mental health crisis called a peer support parent.

And these are folks that specifically work with the family and talk about what to expect, what might be helpful.

So I think that this combination of both a peer support specialist for the individual person and a peer support specialist for the family can really, really be a nice compliment to the rest of the team.

- I agree with you 100%, and I've seen it in action being very helpful for people.

I wanna shift gears a little bit and speak about medication.

Tell us about the types of medications that are used under these circumstances and what people need to know about that.

- Medication can be an important part of the plan, but again, is is not the only part of the plan.

And medication, the types of medicine that can help people who experience psychosis are called antipsychotic medications.

The most common kind are work on the dopamine receptor.

They're called dopamine-receptor blocking agents or DRBAs.

And then there's a new kind of antipsychotic medication which was just released called xanomeline.

And this works in a different way through muscarinic receptors.

So when we say antipsychotic medication, we're really talking about both of these different types of medications.

The antipsychotic medications that we have, particularly the dopamine receptor blocking agents are really effective at helping with the delusions and the hallucinations that people with psychosis can experience.

They're less helpful at the negative symptoms, which means like lack of motivation, which can mean like a lack of feeling pleasure about things that people normally like to do.

They're not all that helpful with the cognitive or the memory type symptoms of the illness.

And it turns out that the negative symptoms and the cognitive symptoms are actually some of the most troubling symptoms that people with these types of conditions can experience.

So the medications really help with the delusions and the hallucinations.

They're pretty good at that.

You know, in about 75% of people, antipsychotic medications, particularly in the early phase of the illness, can really do a good job of helping with those types of symptoms.

Now, these medications have a number of potential side effects that I think are important to talk about.

So the dopamine receptor blocking agents are antipsychotic medications that can cause sometimes weight gain.

Sometimes, they can cause involuntary movements of the mouth or the face.

Sometimes, they can cause stiffness in the arms or legs.

Sometimes, they can cause tremors, and sometimes, they can make people feel tired.

The good news is that many of these side effects that these medicines can cause can be treated and they can be reduced.

But, you know, these side effects are important to address.

And, you know, if somebody's experiencing these types of side effects, it's very important to talk to, you know, one's prescriber or the rest of the team about that.

- Often, people, while they may benefit from these medicines and many people do, sometimes, people find the medicine as troubling as the illness itself.

So it's very important to speak up about any side effects as you said, and make adjustments, 'cause sometimes changing medicine, certainly treating at a lower dose that still may be effective can make a difference.

I want you to talk about a particular medicine that you have expertise in, which is clozapine.

People have heard of this medicine, it probably isn't used as much as it should be to help people.

I'd like you to tell us about clozapine.

- So clozapine is a really, really important medication that can be helpful for about 20 to 35 to 40% of people who live with schizophrenia.

And this medicine was FDA approved back in 1989, and it's been around for a long time.

And as you mentioned, it's not used as often, maybe as it could be used due to a variety of reasons.

So clozapine has an FDA approval for two things.

Number one, something called treatment resistant schizophrenia, which is poorly named.

But what all it means is that someone has tried two different antipsychotic medications before.

Typically, it's the dopamine receptor blocking agents.

They've tried those medicines at an adequate dose for an adequate amount of time, and despite their best effort, those medicines just haven't really been working to treat particularly those delusions or the hallucinations.

And again, this not responding to two different medicines happens in, you know, about 20 to 40% of people with schizophrenia.

And if this happens, the only medicine that's really expected to work is clozapine for those folks.

So some people would say that maybe these are, you know, people with clozapine responsive schizophrenia, not treatment resistant schizophrenia, 'cause I think that sounds really pessimistic.

I've seen people have remarkable turnarounds and really be able to get their life back many times with clozapine.

We also now know that once someone has failed two different medicines, it's really important to start clozapine as early as you can, because the earlier that it's started, the better it works.

There's a lot of parallels, I think to the early psychosis work that we talked about earlier on.

The earlier you can intervene with clozapine for the appropriate type of person, the more likely it is to work.

Clozapine can cause a side effect called neutropenia.

And what neutropenia means is that's where the blood cells that fight off infection called the neutrophils can become lower than usual.

And in about 4% of people, clozapine can cause neutropenia, which is an absolute neutrophil count, typically less than 1.5.

Now, in less than 1% or around 0.8% of people with schizophrenia who take clozapine, it can cause severe neutropenia, which is an absolute neutrophil count of less than 500.

And once the absolute neutrophil count gets low like that, people can be susceptible to infections.

So patients who start clozapine actually have to have weekly blood work for the first, you know, the package insert recommends the first six months that someone is taking clozapine.

And that can be a big, big barrier.

So the idea of taking a weekly blood test for many people with schizophrenia is just, it's often too much.

You know, in 2025, the FDA actually decided to no longer make the reporting system necessary for people to continue to prescribe clozapine.

So now, it's possible that clinicians and prescribers can have a little bit more flexibility with the monitoring of the neutrophil count with clozapine.

It's still very, very important to monitor, especially for the first 18 weeks because that's when the risk of severe neutropenia is the highest.

And then after the first 18 weeks, the risks goes down over time.

- The benefits of this treatment for many people really makes it worthwhile to take this careful approach in terms of the rare but certainly can occur side effect.

So I think you gave a very good explanation as to how people should be thinking about clozapine.

- The other thing about clozapine that sometimes people forget is it has a second FDA approved indication, which is for people with schizophrenia or schizoaffective disorder who have had suicidal behavior or suicide attempts.

And, you know, people who have schizophrenia are more likely to die by suicide than, you know, those without schizophrenia.

And it's a major problem.

And clozapine is actually the only medication, the only antipsychotic medication that really has any data to show that it may actually help reduce the risk of suicide.

- Yeah, you bring up an important point, which is the issue of suicide prevention.

Whether it be that particular medicine to help with that or other interventions for people who are experiencing early psychosis or schizophrenia later in life, that the risk of suicide can be significantly higher for those people.

- You know, the risk of suicide for people with schizophrenia is often highest early, like right after the diagnosis is made in those early parts, which I think is another big reason that getting into those first episode, those early psychosis programs called coordinated specialty care is so important.

But it also, it's this interesting paradox, because on one hand, you know, people are at greatest risk for suicide early after the diagnosis.

The only medication that really helps to reduce the suicide risk is clozapine, which is often reserved for people who have had, you know, two or more failures of dopamine receptor blocking agents.

You know, I think for people who are particularly high risk for suicide or who have had high risk suicide attempts, considering clozapine early on is a really, really important consideration.

- I wanna ask you about co-occurring conditions, in particular, substance misuse for people with schizophrenia.

Could you talk about that issue?

- So we know that people with schizophrenia are more likely to use substances than people without schizophrenia.

And this is, you know, may be one of the fundamental issues of the illness, and there may be some differences in how people experience reward and some brain circuit mechanisms that might make it more likely for people to use substances.

I think that sometimes, people can get caught up and wonder, you know, is it the substances or is it the schizophrenia, for example?

And it's easy to sort of reduce it down to like this one or the other kind of thing, particularly when people come into emergency services for the first time.

You know, there's a condition called substance-induced psychotic disorder, which may be someone has used cannabis, somebody has used cocaine, and they've, you know, begun to develop symptoms of psychosis.

This is a common reason for presentations to say the emergency room, for example.

But I think that what we've come to understand is that for people who have a history of substance-induced psychosis, they actually may be more likely to go on to develop schizophrenia later on.

We also know that people with schizophrenia just are more likely to use substances.

So the challenge is in our system trying to really work with people on both the mental health issues and the substance use condition at the same time.

Often, what you'll see is someone or a system trying to focus on one of those things first until they can really address the other.

But I think that what we really need to think about is how do we address these things concurrently, because that's how we're going to be most effective.

- You have to treat the whole person.

You can't just treat one part of a person, yeah.

Is there a concern that people who may be at higher risk of developing schizophrenia or early psychosis that by using, let's say marijuana, which has been legalized in so many places, by using that it can increase that risk or tip them over into developing schizophrenia?

- Yeah, I think that that's a possibility.

There's a certain group of people who may be particularly vulnerable to the use of cannabis products during a certain developmental window in, you know, maybe earlier, late adolescence.

It's a very difficult thing to study, but it does look like cannabis use during a specific age range for a specific group of people who might be vulnerable to it may have something to do with the development of psychosis.

- If you are speaking right now to a person who may be experiencing some of these symptoms and their family, what do you say to them?

How do they have hope for themselves to live a full healthy life?

What do you say?

- Well, I would say, first, that hope is possible.

And there are so many examples of people who have done really, really well with this.

And I think that, you know, it's really important to find someone, you know, that has experienced psychosis, that has been able to move forward with their life.

Maybe a peer support specialist, maybe it's somebody on social media, maybe it's someone who's written a book about their experiences, but finding these examples of people who have done this and learning from them about what they've done.

I think that hope is such an important part of this.

And I think that hope is very realistic for people who have had a diagnosis of psychosis.

It's very, very difficult to predict the course of someone who has had a diagnosis of schizophrenia, for example.

We don't really understand, as, you know, I think there needs to be more research done in this area about sort of the different types of trajectories that people may have.

And I think that there's things that people can do to really help, you know, improve their trajectory and to help, you know, live healthy lives.

But I think that hope really is at the cornerstone of it.

And I think that early intervention is really, really a key.

One thing I would also say to individuals and families is that just by the very nature of the way that psychosis occurs, in which our mind has a disconnection from reality, it's really, really important to have people in our corner that we can trust people that we can, you know, sort of gauge like, likes is this, are you noticing this?

And then be able to sort of trust their experience.

It's so hard because this system that we experience the world through, you know, if somebody's been experiencing psychosis, a lot of times, it's been intact for many, many years, and then something happens where it changes and the way that they see the world changes.

And it's so hard, I think to sometimes shift that from the system that they've been using their whole life.

So being able to bounce ideas off of other people, family members that you can trust, I think is also gonna be a really, really important part of that.

- As is the case with so many things in life, having people around you, don't try to do it alone.

Have people that you trust and love that could be helpful to you.

Rob, I wanna thank you for joining us and thank you for the work that you do.

It really makes a big difference in so many people's lives.

So thank you very much.

- Thanks so much for having me, Jeff.

Really appreciate it.

(gentle piano music) - Do not suffer in silence.

With help, there is hope.

This program is brought to you in part by the American Psychiatric Association Foundation, the John & Polly Sparks Foundation, and the WoodNext Foundation.

(gentle piano music)