A RESEARCHER’S PERSPECTIVE: What Can We Do When Medicine is Not Enough in the Treatment of Schizophrenia?

Posted: April 6, 2023
A RESEARCHER’S PERSPECTIVE: What Can We Do When Medicine is Not Enough in the Treatment of Schizophrenia?

A RESEARCHER'S PERSPECTIVE - from Brain & Behavior Magazine, April 2023 issue

By Dawn I. Velligan, Ph.D.

Henry B. Dielmann Chair, Department of Psychiatry

Director, Division of Community Recovery, Research, and Training

Department of Psychiatry and Behavioral Sciences

The University of Texas Health Science Center at San Antonio

2016 BBRF Distinguished Investigator

2002 BBRF Independent Investigator

1997 BBRF Young Investigator

Schizophrenia is a common illness, and one with serious impacts that often disable or greatly impair the lives of individuals with this diagnosis. Somewhere between half a percent and one percent of American adults have schizophrenia, according to the most recent studies. It therefore affects over a million American adults, and possibly two or more million.

The illness can be thought of as a constellation of multiple signs and symptoms. First of all, there are what we call the “positive symptoms:” delusions, hallucinations (aspects of psychosis), and disorganized speech and behavior. These are the symptoms that medications are designed to target.

Then there are the symptoms we call “negative symptoms:”, which include the blunting of affect, problems with speech and movement, and trouble with motivation. Importantly, we don’t have good medication choices for negative symptoms.

In addition, there are cognitive impairments in attention, memory, and planning that are present even prior to the positive symptoms of the disorder.

In schizophrenia there are also comorbid conditions involving mood regulation, substance use, and anxiety, all of which need to be addressed when they are identified. Together, all of these symptoms impact how people with schizophrenia get along in the community, how they work and go to school, the kinds of interpersonal relationships they can have, their independent living skills, and whether or not they are going to follow through with medication.


Let’s start with the role of medication, which is important. When people use antipsychotic medicines, they survive longer in the community without a relapse. This is compared with when they discontinue those medications or may be taking a placebo in the context of a clinical trial. We also know that if you don’t take antipsychotic medicine for 11 days, that doubles the risk of hospitalization.

What are the limitations? For one thing, only half of the medications that are prescribed are ever taken by patients. And on average, individuals with schizophrenia have eight to nine relapses in a given 5-year period. Medication followthrough is arguably one of the most modifiable obstacles to clinical stability and relapse prevention. And so it’s something that we often target in our psychosocial treatments and education. Additionally, medications have side effects and are often intolerable for patients, and help explain why adherence is a problem in some cases. Furthermore, while antipsychotic medication might quiet things down, sometimes it doesn’t take everything away. Many individuals on antipsychotics continue to experience delusions or hallucinations. So it’s important to reduce those persistent symptoms and the distress that goes along with them.


For many years, cognitive behavior therapy (CBT) has been an evidence-based treatment for persistent positive symptoms. Some people can hear voices but remain able to do many things. Other people with this problem find it’s very difficult to function. CBT is focused on helping the person come up with alternate explanations for their symptoms. This can help reduce the impact of those symptoms on their behavior.

We also want to focus on changing underlying beliefs. Many people with psychosis develop a worldview while they are growing up that later predisposes them to certain kinds of psychosis. The first thing we do in CBT is to try to normalize the experiences that people have. Addressing distressing or problematic beliefs has to be done carefully. Individuals are used to defending their ideas or being patronized. Confronting them can cause them to have greater conviction in their beliefs. But, it’s important not to agree with these statements. We therapists don’t say things like, “Yeah, I saw the FBI following you, too.” We want to find a fine line in the middle where we’re choosing our words very carefully and really attempting to understand. “Why would the FBI want to follow you? What’s so important or what’s so special about you? I’m confused about that. Do they do this to everyone?” We’re trying to expand the patient’s thinking here. We also want to investigate evidence with the patient. We might ask: How much does it really cost to surveil someone? How big of a team do you need? What kind of devices do you need? And when people realize what it takes, sometimes they begin to have a teeny bit of doubt.

Many famous and successful people have heard voices. Anthony Hopkins. Sigmund Freud. Winston Churchill. It’s important for people to keep in mind that their life is not over because they’re having these experiences.

There’s an organization called voicehearers.org which offers a poster that I give out. The poster summarizes skills for coping with auditory hallucinations. There’s really two basic strategies. One: distracting yourself. For example, wearing earphones that play music that competes with the voices; getting away from things, like going on a picnic. The second method is focusing. You focus on the voices, listen to them, negotiate with them. We encourage people to try a variety of approaches.

A meta-analysis—a study of multiple studies on a topic—that assessed 19 CBT studies for psychosis showed that most of the studies achieved at least a small effect positive impact, and 32% achieved a moderate impact. Does that mean CBT is for everybody? Maybe not, but maybe certain CBT techniques can help many people a least a little bit.


But as I said at the beginning, there’s more to schizophrenia than positive symptoms. There can also be cognitive difficulties in memory, information processing speed, and executive function. This means that individuals have trouble planning, using judgment, and carrying out goal-directed activity. There are also difficulties in social cognition. These faculties underlie our abilities to perceive, interpret, and respond to other people in the world. So if you can’t assess the emotional states of other people, if you can’t understand facial expression and voice tone well, that can cause problems in social relationships. These cognitive difficulties predict how people are going to function socially and at work and to what extent they can live independently.

There are different ways to intervene. One is to directly target cognitive problems such as attention and memory and the ability to plan with cognitive practice. With drills and practice, either on a computer or using pen and paper, you can improve people’s cognitive functioning. This hasn’t been well integrated into clinical treatment overall, and it works best if it’s part of a multimodal program.

There are also a number of programs that look at how to improve cognition in the context of vocational functioning. It’s been found that people in cognitive remediation tend to work longer hours and make more money than people who don’t get cognitive remediation. What you’re expecting here is that cognitive gains are going to generalize into the real world in terms of functional outcomes.


Cognitive Adaptation Training (CAT) was developed at my institution, the University of Texas, decades ago, and we’re still using it to help people to stay out of the hospital and to develop good social and community relationships. CAT relies on what are called automatic processes. Most of what we do every day is automatic. If we paid attention to absolutely everything, it would be impossible, and we wouldn’t get anything done. Environmental cues get us ready to act. Cues are easier to follow than they are to resist. Cues also increase the experience of fluency: they make behavior feel easy to do. Your phone rings, you answer it.

In our practice, we look closely at how people’s environment is set up. Are things set up safely? Are they set up for that fluency, that ease of use? We help patients reorganize belongings in their apartments to decrease the number of steps that it requires to do things.

I do home visits. I see so much clutter that you can’t do anything. Can you imagine trying to get ready for a doctor’s appointment when you open a drawer and there’s SSI papers and potato chips and underwear? Every time you have to do something, there’s a chance that it’s going to take forever. Or, if you do go to the doctor and do pick up your prescription, and then you put your prescription on the dresser, chances are you may not even see it, or you might put the hat on top of it or it might fall somewhere because there’s so much stuff laying around.

So we try to organize things, and then we remind patients where those things are by labeling. I recall a patient who kept their toothbrush and toothpaste in the bottom dresser drawer. Under those circumstances, it’s really unlikely they’re going to use it. So we moved it out of there and we put it in the bathroom where they can see it.

It’s one of the things we do for people whose negative symptoms include apathy, those who have trouble starting things. They’re laying in bed, thinking, “Oh man, I got to get up. I got to walk all the way over there and get my clothes. I got to do this, I got to do that.” And pretty soon it’s too much. So we put a clothing rack at the foot of the bed. And then on every hangar there’s a shirt, pants, underwear, and socks. I try to reduce the number of steps. Everything is right there. We set this up together. Next, you can set an alarm that says, in effect, that it is time to get dressed Whatever the person’s recovery goal, you can tie that to how important it is to get dressed. You try to make this automatic, something you do every day.


Repetition with verbal and visual cues also increases familiarity. For example, you have a voice alarm that tells you it’s two o’clock, it’s time to take my medicine. And that happens every day at two, it starts to have that sense of truth. If you repeat the same behavior at the same time every day it starts to become automatic.

For problems with memory and organization, we use a huge calendar. We put it on the wall and attach a sharpie marker with yarn. If we don’t attach a sharpie marker, nothing ever gets written on the calendar. A lot of people forget to check their phone but if they can see the calendar from across the room, they know that their next appointment is going to be in a day or two. We teach patients to check every day off, so they always know what day it is.

Similarly, if you put a sign on your door, you will not be able to leave your house without taking your medication. And that will work for a while. And then we can change the color or the wording or whatever is going to capture that person’s attention over and over.

We also use pill containers. For people who take more pills than they need, we’ll pack them in separate compartments representing the days of the week so that there’s no cue to open extra compartments. We also put bottles of water and the medicine for evening by the bed, so that all one has to do is reach over. Again, it’s decreasing number of steps, making things easier. We use a lot of checklists. People feel good when they check things off.

In addition to calendars, we also use blank daily schedules. Tell me how you spend your day. For people with negative symptoms, this is really a visual aid. The truth is, if you spend all the week not focusing on how you spend the hours, some people will say that’s fine, that’s what they want. But then, we tell them, if you don’t do anything different this week, next week is going to be the same and the week after that. Is this how you want things to be next year or in five years? Because if we don’t do something different today, there’s not as much hope that things are going to change. So we try and we’re a little bit pushy. We often do things and engage in activities to get people going and doing.

We find that there are pretty good outcomes with cognitive adaptation training. In a study that tested PharmCAT, which is CAT that focuses on taking medicine and making it to your doctor’s appointments and treatment, and compared it with what happens when patients are not in such a program, we found people were only taking about 60% of their medication unless they were in CAT and PharmCAT. We also found that when we stopped making weekly home visits, the habit that we created continued.

People function at a much higher level when they have full CAT. The full CAT program is really necessary to get enough of a boost that it makes a difference in your social and occupational functioning. And you can see that without booster sessions, functioning starts to decline. We also find that people in PharmCAT and CAT were able to stay out of the hospital for longer periods of time.


But what about when negative symptoms persist? Negative symptoms are defined as the absence or reduction of behaviors that are normally there. These include things like anhedonia, difficulty feeling pleasure. People don’t socialize as much. They don’t decide to do things, they don’t plan things, they’re not interested in social or work activities. Their affect can be blunted. They don’t talk much.

At the onset and in the maintenance of negative symptoms, there is a neurodevelopmental issue, but there’s also a protective issue. We see in a lot of early-onset psychosis that people shut down, they’re overstimulated, they withdraw, and that’s protective for them at the beginning of their psychosis. But this can lead to the development of negative symptoms. And it has consequences in the world. Such patients don’t have as many activities or interests that they can discuss with others. So it affects how much others want to talk to them. There’s also a lack of external positive reinforcement. They’re not getting any goodies from the world because they’ve withdrawn from it, and they might lose skills that they used to have. If they were pretty decent conversationalists without practice, some of those skills can weaken. And then they don’t plan things for tomorrow. So tomorrow looks just like today, and then this becomes a behavior pattern that repeats in a loop.


With this problem in mind, we developed an approach we call MOVE, which is a kitchen-sink kind of approach. It involves five components of treatment, ideas we borrowed from others that have been shown to work, including the practices of CAT. We work on how to get people up, moving, doing. We use an intervention for anticipatory pleasure where we ask people, “All right, how fun do you think it’s going to be to go to the zoo?” And then we go to the zoo, have a good time, take pictures, and record their impressions. The next time someone mentions the zoo they might not anticipate that it might be fun. But if we can show them that it was, they can remember. And this is going to help them with anticipatory pleasure because research shows people with a psychotic illness have a capacity to enjoy things—it’s just that they don’t anticipate it.

We have patients do a lot of the training from SCIT, social cognition interaction training, where they look at certain parts of the face so they can identify emotions. And we have them practice things in front of a mirror and on a recorder so that they’re more likely to show affect in their voice and face.

The fourth component is CBT. People have these defeatist beliefs of how they’re going to do, “people aren’t going to like me,” etc. We borrow from one researcher a very simple approach when it comes to unhelpful thoughts: catch it, check it, change it. So you can take an unhelpful thought, look at the evidence, and then replace it with something more helpful.

We also use skill-building approaches such as social skills training and modeling. How do we cook healthy meals? How do we return a garment at a store? We send text messages while people are interacting to remind them to smile at other people and do other activities.

In a study that was funded by BBRF and the NIH, we noted a moderate positive effect size on the negative symptoms scores with MOVE compared with treatment as usual. However, MOVE is labor intensive, requires knowledge of a lot of therapies, and is difficult to recruit therapists for.

There are many other evidence-based interventions for psychosis. Peer-topeer programs are awesome. The clubhouse model where people come to the clubhouse to work and make their resumes is very helpful. We have one in San Antonio. Intensive care management is very effective. We have a number of programs where we work with “high utilizers,” individuals who go to the hospital a lot, and we work to keep them out using multiple approaches.


As patients and families, you have to advocate for yourself and search for what’s available. And unfortunately in some areas you have to pay for “extras,” i.e., attention that involves more than “treatment as usual.” We have really good programs here in the United States that I would encourage people to request their Managed Care Organizations to cover and reimburse for. We therapists only get paid if we keep people out of the hospital, and it’s on the basis of the number of days we keep them out. We use that money flexibly to help people get engaged in activities in the community. That can really change the face of treatment. Certainly, patients and their loved ones can talk to those working in mental health at universities. They would be the people who would most likely be doing studies or be aware of the best treatments and approaches. I urge you not to give up. Keep looking!

We want more people to take advantage of evidence-based interventions of the kind I have described here. They’re not widely adopted a lot of times by agencies that see the greatest number of people with psychosis. We need to increase the first-episode of psychosis programs and recent schizophrenia-onset programs to keep people working and in school, to prevent disability. Keeping people in their school and work life is the very best thing that we can do. We also need to ensure that these models are applied with fidelity. It’s not enough to train people. You really need to make sure they’re doing what they’ve been trained to do. And of course, we need to increase funding for mental health to ensure that these evidence-based programs are adopted alongside the best medical treatments.

Written By Peter Tarr, Ph.D.

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