Four Commonly Used Antipsychotic Drugs Don't Work

CAVANAUGH: Our top story on Midday Edition, doctors treating seniors with behavioral problems associated with dementia now have fewer treatment options. A new study from UC San Diego finds that four antipsychotic drugs being prescribed off-label to dementia patients are ineffective. And worse than that, they also cause side effects. Doctor Dilip Jeste, distinguished professor of psychiatry and neurosciences at UC San Diego. He led the study. Welcome to the program. JESTE: Thank you, Maureen. It's a pleasure to be here. CAVANAUGH: Before we get to your study, let's talk about the problem of older people with dementia. What kind of mood disorder can they develop? JESTE: First of all, the number of people with dementia is substantial. There are estimated to be about 4 million Americans with dementia, most commonly Alzheimer's disease. And that number is expected to increase to 15 million in another 20 years. Half of these people with dementia have psychotic symptoms at some stage of their illness. About 1/3 of them have depression. And very large number, about 90% of them end up having severe agitation sometime during the course of Y illness. CAVANAUGH: Now, when you talk about these problems, these behavioral problems, what kind of behaviors are we talking about? JESTE: The most common behavior problem is agitation. The person gets agitated, annoyed, irritable. When it becomes more severe, it becomes a problem because a person can Hurst himself or other people. Depression is associated with withdrawal from others, not eating well, not sleeping Lsometimes crying. The problem we were most interested in was psychosis. So this includes dilutions that are false beliefs that you cannot change. Or hallucinations in which you experience something, see something or hear something that doesn't exist. And as I said, about half of the people with dementia have psychotic symptoms sometime during the course of illness. They can be mild or severe. When they are severe, they become a real problem. The person may accuse his or her spouse of having an affair with the neighbors or poisoning their food and will stop eating or taking medications, may become agitated and attack the spouse or neighbor or some other person, even start fire, for example. So it does become a problem for the caregivers as well as other people in the surroundings. CAVANAUGH: Now, when we talk about these psychotic dilutions, when we talk about agitation and so forth, these behavioral problems associated with dementia, are we talking exclusively about Alzheimer's disease? JESTE: Usually 1/3 of the patients have Alzheimer's disease. But there is something called vascular dementia, which follows strokes. There are some less common dementia, frontal, temporal dementia, but almost all of them have behavior problems which are similar to those in Alzheimer's. CAVANAUGH: There are currently no drugs that are designed specifically to treat the problems that you were just speaking about in DeMaio; is that right? JESTE: Yes, that's the unfortunate case that at present there are no FDA-approved drugs for treating agitation, aggression, depression, or psychosis in people with DeMaio. CAVANAUGH: Which drugs have been used to treat these symptoms? What are the brand names of the drugs doctors have been using to see whether or not they would be effective on these particular behavioral problems? JESTE: I want to focus on psychosis. Symptoms of psychosis, the commonly used drugs are antipsychotics. But they had some kind of side effects, such as tardy eskinesia. It's a severe movement disorder that persists. If you can think about Huntington's, it can resemble that. CAVANAUGH: I see. JESTE: So that was a serious problem, and that's why these drugs slowly fell out of behavior when the new erantipsychotics became on board. So there was a lot of excitement about these drugs that they were better and caused fewer side effects. Unfortunately over the year, people found out that although they did not cause that disorder, they had other side effects. They could produce diabetes, weight gain, a confluence of symptoms or signs that increase the risk of diabetes, heart disease or stroke. CAVANAUGH: So which drugs did you look at in your study? JESTE: In our study we looked at four most commonly used atypical antipsychotics in this population. They are risperidone (Risperdal), aripiprazole (Abilify). CAVANAUGH: Abilify. JESTE: Quetiapine (Seroquel), and olazapine (Zyprexa). CAVANAUGH: Right. I think especially Abilify, people have probably seen TV commercials for this particular drug. Now, when we say that they have been prescribed by doctors for psychotic symptoms in people who have DeMaio, we say that they have been prescribed offlabel. What do we mean by that? JESTE: That they are not approved by the FDA for that particular indication. Antipsychotics are approved by the FDA for schizophrenia and bipolar disorder primarily. If they are used in any other condition that becomes offlabel use. Offlabel use is not illegal, however it does carry some issues because it is a nonFDA-approved medication. CAVANAUGH: But doctors do that frequently with one drug that is approved for one particular malade, and it shows signs of helping in another direction. JESTE: Yes, and the reason is because there are no FDA-approved treatment for certain conditions. And psychosis and DeMaio is a prime example of that. This is a common problem, and half of the people with DeMaio have it, sometimes it can be really severe, and that leaves the caregivers often to put the patient in a nursing home, for example. So they have to do something. And that's why these drugs as well as other drugs are used in that population. CAVANAUGH: Now, when you and your colleagues decided to look at these four drug, what is it that you wanted to find out? JESTE: What we wanted to find out was how these drugs compare with each other on a long-term basis. There have been several studies of these drugs conducted by the pharmaceutical industry as well as by other investigators, but most of them were short-term study, only for a few weeks. What we wanted to see was what happened to patients who continue on these drugs for a month, as happens commonly in real life. So we wanted to compare these drugs with one another. Not with placebo, but with one another to find out which was the best drug. CAVANAUGH: Did you find any of these drugs effective in moderating the psychotic symptoms of people with DeMaio? JESTE: Unfortunately not. We had two major units, one was how long the patients stay on the drug. If a physician starts a patient on the drug and is the drug is working well, not causing side effects, they usually will continue on the same drug. If it is not working or causing side effects, they will stop the drug. So how long you continue on a drug is a good measure of the usefulness of the drug for the patient. Here we expected that the patients would continue for up to two years, and yet we found most people did not. The average length to stay on the drug was less than six months. CAVANAUGH: Because it wasn't working. JESTE: Either they were not working or they were causing side effects. Because if the patient had been greatly improved, the drugs would be stopped and they wouldn't need any drug. But in these cases, the physician often switched them to another antipsychotic. CAVANAUGH: Did you find any of these four medications that you tested were more effective than the other? JESTE: Unfortunately not. That was actually our expectation, and that was our hope when we started the study, to find out which of these drugs would work better in some patients. The goal was to come up -- the hope was to come up with guidelines that we could say use drug A in this type of patient, in these dosages, and that will work. Use drug B in these other kinds of patients. What we found was rather sobering, that all of the drugs were much more similar than different, and we did not see effectiveness to the extent that we expected or hoped. CAVANAUGH: 28 us about the safety. What kind of side effects did you encounter in patients? JESTE: About 1/3 of the patients developed metabolic syndrome within one year. That means a confluence of symptoms such as blood pressure, blood glucose, body weight, cholesterol. And it becomes a risk factor for diabetes or heart disease or stroke. We found 1/3 of the patients developed metabolic syndrome within a year, much higher than you would expect in the world outside. When patients develop serious adverse events, they are defined by the FDA has death, hospitalization, or emergency room visit for a life-threatening condition. We found that about 1 quarter of the patients developed serious adverse events with these drug, and nonserious adverse events were seen in about half the patients. CAVANAUGH: Okay. So from your study, and from the results that doctors have been having prescribing these medications, and that is really no result except some side effects, what can doctors do now when a patient with DeMaio is exhibiting psychosis in some way? JESTE: I think when the symptoms are severe, they need to be treated. And short-term use of medications is appropriate. CAVANAUGH: What medication though? JESTE: They can use antipsychotics. Our study showed that overall, there is no group effect. However, in an individual patient, some drugs may still work better than others. So the doctor can find out from his or her own experience with the patient which drug might be safer and more effective. It's a trial and error sometimes. But the drug should be tried in low dosages, because there are still side effects. Use the drugs to control the symptoms, and when the symptoms are controlled, think about slowly reducing and then stopping the drug. CAVANAUGH: So in rare instances with individual patients, one or another of these drugs might still be useful for a short period of time? JESTE: Right. I would say more than rare, because unfortunately these are serious problems. And many of these patients do need treatment, and again doctors don't have too many choices. So when the symptoms are severe, they often need to be treated. And what we are concerned about is the long-term use offlabel. Short-term use I think is still justified. CAVANAUGH: Is there any pharmaceutical company working on a drug specifically to modify psychotic behavior in older people with DeMaio? JESTE: Not they know of. At present, most of the interests of the industry in patients with DeMaio is on improving cognition. So these are the cognitive enhancers that are being tried. And one hope is that these drugs may also have some positive behavioral effects. But that remains to be demonstrated. I do hope that happens because then we'll have to use fewer drugs to these these patients, but at some stage, we don't have any cognitive enhancer that effective treats these behavioral problems also. CAVANAUGH: Thank you. It's a complicated subject and I think you've explained it to us very well. Thank you very much, Doctor . JESTE: Thank you, Maureen. My pleasure.