Consequences of Relapses in Schizophrenia

John M. Kane, MD: One of the challenges we have is that not all of our patients have good insight into their illness, and sometimes, when people feel better, they don’t necessarily see the need for medication. And unfortunately, or fortunately, when people stop their medications they don’t always see the effect of that right away. And so, they need to understand the concept of prevention or prophylaxis, and they also need to understand the consequences of relapse. How would you present that to a patient, in terms of thinking about the consequences of relapse?

T. Scott Stroup, MD, MPH: I think there are 2 kinds of consequences. One is the disruption it might have on your job or your housing, or to your relationships. And that can hit home pretty readily. There’s this other sort of biological thing—psychosis. Being psychotic is bad for your brain too. And so there may be disease progression, if that’s the way we think about it. But you know, I really try to use more of the motivational interviewing kind of approach to say, “You know, there are things you want to do, like work or have relationships or maintain housing, and medications may be one way to help you maintain those things.”

John M. Kane, MD: And the irony is that when people are lulled into a false sense of security that they’re doing well, they actually have a lot to lose.

T. Scott Stroup, MD, MPH: Right.

John M. Kane, MD: And sometimes it’s hard for them to really see that. I think it’s a very challenging part of the therapeutic relationship to try and instill, in a young person who’s experiencing the onset of this illness, the right kind of information and the right kind of motivation without scaring them too much. You also want them to have a sense of optimism and hope about the future. So it can be a real challenge.

T. Scott Stroup, MD, MPH: People have an acute illness model. They took the medicine and, “I’m better. I’m done.” And trying to draw that link between the medicine; “I’m feeling better because of the medicine.” We think it’s obvious, but it’s not obvious to others.

John M. Kane, MD: Absolutely. And you referenced the potential changes in brain physiology or brain function. Jeffrey, what do you think? There’s been a lot of interesting discussion, data, controversies about the effects of medication over the long term and the effects of being psychotic on the brain. So how would you characterize them?

Jeffrey A. Lieberman, MD: I characterize it this way. Only in psychiatry would you have a situation over half a century from the discovery of a major advance in therapeutics and with a countless number of studies demonstrating acute and prophylactic efficacy of a class of medications, would you still have people questioning the effectiveness of these medicines, either overtly or subtly encouraging people to avoid the use of antipsychotic medications. I think that it’s a double standard, it’s wrong-minded, and it’s destructive.

So the specific arguments Scott began to describe are: If you risk discontinuing medicine, even if it’s done in a rational and deliberate way, you will be vulnerable to have symptoms recur. And if symptoms recur, there’s immediately some disruption to your life. There’s also the potential for complications such as suicide, such as violence, such as homelessness. But there’s also the possibility that there is some progression of the illness, and don’t forget, schizophrenia was originally identified by Emil Kraepelin at the latter part of the 19th century not because of its symptoms, which Eugen Bleuler focused on, but because of the deterioration that individuals experienced over the course of their illness.

So this is a characteristic of schizophrenia. It seems to be tied to the process of having psychotic episodes, and then with the advent of imaging, it was associated with the possibility that the progression is reflected by some structural brain changes in the form of a reduction of volume of certain regions in the brain, and particularly in the gray matter.

Now, the countervailing line of evidence that individuals will site as cautionary, is the studies that suggest that people who get more antipsychotic medication may lose more volume in brain gray matter. And then there were some studies done in monkeys that compared placebo versus different antipsychotic drugs that showed this atrophy in the brain. The problem with those studies though was that these animal studies were normal monkeys. They weren’t individuals who had schizophrenia. So if you were to do the unethical, impossible-to-do study where you took first-episode patients and you randomized them to placebo, or you randomized them to treatment, and you took healthy controls and you just followed them, what I predict you would see is a decline in brain volume in specific regions in the untreated illness group, and you would see less of a decline in the treated group. So this is the flaw, in not having definitive evidence.

So in essence, although there are these different ways of construing the evidence, it seems to me that to not use medication for fear of long-term effects is completely wrong and that the long-term benefits clearly outweigh the potential risks. And then the other thing that you were alluding to, John, is the comorbid medical conditions which shorten longevity. Individuals who have greater adherence to medicine over the course of their lives do tend to live longer than those who don’t.

Transcript edited for clarity.