TCPR: Dr. Ongur, I know you’ve been interested in creative ways of helping patients with psychosis function well in the community. Are we not doing very well as a field in improving the functioning of our schizophrenic patients?
Dr. Ongur: We actually do very well when using antipsychotics to treat positive symptoms, whether those are symptoms of schizophrenia or manic episodes. We can take patients who are psychotic, put them on an antipsychotic, and over the ensuing weeks most of the positive symptoms will come under control. If they are hearing voices, we can quiet the voices, and we can improve their delusional thinking so that they can do reality testing. And for patients who are manic, we can treat grandiosity and excessive activity.
TCPR: And isn’t that enough to improve patients’ functioning in the community?
Dr. Ongur: There are a couple of lines of research showing that treating the positive symptoms is not sufficient. The first line of research has focused on the relationship between positive symptoms and functioning in the community, broadly defined as living on your own, holding down a job, and having meaningful relationships. As it turns out, the positive and manic symptoms are not directly related to these abilities. In other words, some patients are free of these positive symptoms and yet not able to live independently, and then other patients have significant positive symptoms and can function very well. What does seem to predict functioning, however, is cognitive functioning and negative symptoms.
TCPR: Can you give us some examples?
Dr. Ongur: For example, a patient may be treated with antipsychotics and be free of hallucinations and delusions, but if he has cognitive impairment, he will have a hard time with an entry-level job. He may be working at a grocery store, bagging groceries and holding a gallon of milk, but then he can’t remember if he scanned the milk. “Did I just scan this or not?” This is an example of impaired working memory. By contrast, you might have a patient who hears voices and who is concerned that he may be in danger because of being monitored by the CIA, but he is cognitively preserved. That person could get a job—he might be quite vigilant about his environment, but he can work.
TCPR: How solid is the research showing no relationship between positive symptoms and functioning?
Dr. Ongur: Very solid and well-established. In the late 1990s and 2000s, [Duke University psychology professor] Richard Keefe, PhD, and others did much work on this topic (for example, see Keefe RS, J Clin Psychiatry 2007;68 Suppl 14:8–13). He looked at cross-sectional studies, studies in which researchers collected data on symptoms and data on community functioning. These studies inevitably found that the positive symptoms have no relationship with how the patient is functioning, whether he or she is living independently, has friendships, etc. Instead, it is the negative symptoms and cognitive impairment that are correlated with functioning.
TCPR: As psychiatrists, what can we do to improve functioning? Are there certain medications that treat negative symptoms and cognitive impairment better than others?
Dr. Ongur: There is no strong evidence that any one of the antipsychotic medications improves negative symptoms and cognitive deficits better than the others. The more recent research actually shows that medications may impede community functioning. In one study done in the Netherlands, researchers recruited about 400 patients with first episode psychosis (Wunderink L et al, JAMA Psychiatry 2013;70(9):913–920). These patients ranged in age from 18 to 25 years old, and they were all treated with standard doses of antipsychotics (both first and second generation antipsychotics), and were followed for two years. Most of them did well, in terms of reductions in positive symptoms. Then, at the two-year mark, these patients were randomized into two different arms. One group stayed on the same dose of medication (the maintenance treatment or MT group), and the other group attempted to decrease or discontinue their medications (the dose reduction or DR group).
TCPR: Was this a double-blind study?
Dr. Ongur: No, the patients were randomly assigned but they knew which condition they were in, as did their doctors.
TCPR: Were patients able to get off of their medications?
Dr. Ongur: Many were—40% of the patients in the DR group completely discontinued the medication. The remaining 60% ended up on lower doses. On average these patients ended up on about 2 mg risperidone dose equivalents. The patients in the maintenance group ended up on 4 mg risperidone dose equivalents. As you might expect, there was a higher relapse rate in the DR group—43% vs. 21% in the MT group. But then the patients were followed for another five years, and interestingly, the patients in the DR group were more than twice as likely to recover (40% in the DR group vs. 18% in the MT group). “Recovery” meant that they were functioning well and had no psychotic symptoms.
TCPR: This is an interesting result. Basically if you’re willing to pay the price of some extra symptoms of psychosis in the short run, you might do much better in the long run by lowering the dose or discontinuing antipsychotics.
Dr. Ongur: Yes, it appears that tapering or discontinuing meds might yield a long-term benefit of helping patients get out into the community and function normally.
TCPR: Does this imply that medications can actually be harming patients in the long run?
Dr. Ongur: There is that possibility. We’ve always known that medications can cause significant morbidity by virtue of side effects. For example, sedation, weight gain, and psychomotor slowing can all impede functioning.
TCPR: So what are the clinical implications of the Wunderink study?
Dr. Ongur: Well, first of all, it’s important to emphasize that this was only a single study and it needs to be replicated. In fact, we are hoping to do a study such as this at McLean Hospital. But the results of this study imply that when possible, we should try for the lowest dose in patients. Let’s say you have a patient who is on a high dose of antipsychotics and is no longer hearing voices and no longer having delusions. But all he’s doing is sitting on the couch and never leaving home—he’s having negative symptoms. So you decrease the dose and now he starts hearing some voices again. At this point the typical decision would be, “The patient is now having symptoms and we need to increase the dose back to where it was.” But given the results of this study, you might want to say to the patient, “Now you are on a moderate dose and let’s see if you can live with some of these symptoms in order to help you get out of the house and living on your own.”
TCPR: How do we decide which patients can tolerate dose reduction?
Dr. Ongur: That’s very hard to know. Patients who are better candidates for dose reduction have higher premorbid functioning. For example, they may been above-average students who did not have many other problems before they developed a psychotic disorder. Another good candidate would be a patient in whom you have treated the positive symptoms very well, but he still has significant negative symptoms. On the other hand, the patients who may not be good candidates for this are patients who have a long history of having serious decompensations when they decrease their medications, who end up in the hospital, or who end up becoming violent. Regardless of the patient, you will generally want to see them more frequently after any trial of dose reduction. And reduce the dose very gradually.
TCPR: In addition to dose reduction, what can we be doing in terms of therapy or other measures to help these patients be successful in the community?
Dr. Ongur: There are several techniques. You can use cognitive behavioral therapy techniques to help patients develop their own coping mechanisms. One method is “compartmentalizing” the symptoms. For example, you might say to your patient, “When you go to work, you don’t have to listen to the voices. Listen to them only when you come home.” Another technique is talking back to voices. For example, I had a patient who was really tortured by voices that represented a struggle between good and evil. I asked her “What can you say to those voices that will help you cope with them?” And what she came up with was saying to the voices, “This battle doesn’t concern me, you figure this out amongst yourselves!” And she has found this to be a very effective strategy.
TCPR: Are there other techniques?
Dr. Ongur: Another technique is to enlist a support network to help. For example, a young man with schizophrenia was overwhelmed by delusions of reference. Every time he would walk down the street he would interpret every gesture or remark by strangers as if they were about him. To deal with this, he picked some friends who were “safe people” who he could go to as a reality check. So he would be in his class and he would see people moving around and would wonder if they were sending messages about him. So he would go to one of his friends and say, “Are these people moving around because of something I’m doing?” And his friends would say, “No this is just people moving around, it has nothing to do with you.” Of course, these were people who knew what his condition was and were willing participants. But it worked very well for him. These approaches do not work for everyone but they are worth trying.
It is the negative symptoms and cognitive impairment that are correlated with functioning.
~ Dost Onger, MD, PhD
TCPR: What about rehabilitation programs? As psychiatrists, we often hear about these and may refer patients, but how do they actually function?
Dr. Ongur: Occupational rehabilitation programs are often state-run and they work on several principles. One is that people can tolerate some voices and other positive symptoms in the service of getting into a work environment, which we’ve already talked about. The second principle is hope and recovery. This is often called “strength-based approaches” as opposed to “symptom-based approaches.” Rather than focusing on patients’ diagnoses, symptoms, and their history of hospitalization, these patients are asked questions such as, “What can you do? What are your skills? Are you good with computers? What are your interpersonal skills?” The answers guide the occupational placement. The third principle is that the occupational environment should be a competitive work environment—meaning it is not an artificial sheltered environment (Gold PB et al, J Behav Health Serv Res 2014;epub ahead of print). The term often used in the field is “meaningful role performance,” and the theory is that patients will do better and feel more competent if they are placed in a real job with wages and real world expectations, rather than in a workshop funded primarily by a public entity. And finally, the fourth principle is that recovery is not linear and that there can always be setbacks but a setback doesn’t mean that a patient failed.
TCPR: How can office-based psychiatrists take advantage of these rehabilitation programs?
Dr. Ongur: The overall message is that treating someone with schizophrenia is a team effort. Psychiatrists should always consider referring such patients to community rehabilitation programs where the patient can develop a hopeful and recovery-oriented attitude to their illness and take control of their own treatment. Many such programs exist in Massachusetts and throughout the country and the state mental health services are often a good place to start looking for them.