Predictors of Relapse in Schizophrenia

John M. Kane, MD: Jeff, what about the causes and predictors of relapse?

Jeffrey A. Lieberman, MD: The predictors of relapse, in part, depend on a lot of the causes, in the sense that the causal factors really are the things that are inducing an individual’s vulnerability to relapse. At the beginning, contrary to historically what was a pretty pessimistic view of the therapeutic prospects, when we began doing studies of people with schizophrenia with the antipsychotic drugs who were in an earlier stage of the illness it was appreciated that they had a pretty good symptom response to treatment, in terms of achieving a reduction or even a remission of their symptoms.

As numerous studies have demonstrated, after you have an acute response, continuing treatment prevents the likelihood of recurrence. And then the question was, how long do you sustain treatment? I believe that the sum of all of the maintenance treatment studies have shown that you’re never really safe. If you stop treatment, there’s a higher rate or risk of relapse than if you remain on treatment, by a lot. So the prudent course of treatment would be to sustain medication on an ongoing basis at the lowest effective dose that is tolerable.

What happens that leads people to relapse is that many don’t want to stay on medication and they’re not adherent. They can be nonadherent because their adverse effects aren’t addressed adequately, they don’t like the idea of taking medication because it’s somehow stigmatizing, or they think they can just do without it. And if they stop, it’s essentially a matter of time, in most cases, until they have a recurrence.

In addition, things can even overcome the prophylactic effects of medication in preventing relapse. Stress, for example. If somebody experiences massive stress in their life, whether it’s intrafamilial, or whether it’s a change in the treatment providers or something. And then there’s the ubiquitous problem of recreational drug use. And it’s not all recreational drugs. Alcohol is not necessarily so bad, but stimulants and cannabis are really bad.

And then some people’s illness may be severe enough that just the cyclicity of the illness can break through maintenance treatment. So those are the main causes, and therefore the predictors, apart from the symptoms beginning to return, are if individuals have past history of nonadherence, past history of substance abuse, or past history of recurrences even in the presence of maintenance antipsychotic drug treatment.

John M. Kane, MD: One of the factors you mentioned that’s very important is nonadherence, and we know that’s a challenge in any chronic illness. Many of the studies suggest that rates of relapse among patients who are nonadherent are pretty striking, and you certainly reported on some of those results.

T. Scott Stroup, MD, MPH: Right. It goes back to Gerard Hogarty in the 1970s. In people stabilized on antipsychotics who stopped in placebo-controlled trials, the relapse rates are 3 times higher over 2 or 3 years. So we know that staying on medications helps prevent relapse, at least over that period of time.

John M. Kane, MD: Absolutely. I think one of the meta-analyses that Stefan Leucht, MD, published suggested that the number needed to treat when you’re comparing relapse rates on drug and placebo was 3 to 4. That’s a very powerful effect. So I think one of the challenges that we have to face is helping patients to understand the need for medication and accept the need for medication. Jeffrey, what would you say in terms of discussing with patients the signs of relapse? How would you approach that conversation?

Jeffrey A. Lieberman, MD: Well first, I think people who have schizophrenia, or are diagnosed with schizophrenia, and their families should be apprised of the nature of the illness. There was actually a form of a psychosocial adjunct to treatment called psychoeducation, which is not that often practiced, but the intent of it was to provide some semiformal kind of didactic information to patients and families, particularly if they’re in the early phase of the illness where they don’t know from experience what’s in front of them, and that this is not a one-time deal. It’s not like you know you have chicken pox and then you’re immunized for life. It is potentially a recurrent illness that’s chronic and can be disabling.

And then, in addition, a discussion about the benefits and risks of medication is warranted. It’s more than just, “Well, the medication helps you, your symptoms, be reduced, and there are some adverse effects that you could experience.” It’s really, what are the benefits and risks for extended treatment, or taking it for a long period of time? And in that context, there are longer-term adverse effects, which used to be more of a problem with the first-generation drugs, in terms of tardive dyskinesia. But for the second-generation drugs, there’s the potential for weight and metabolic effects.

And then there’s the issue about whether there’s the potential for progression of the illness if individuals sustain recurrent episodes. Any patient-doctor relationship should have a mutuality which allows for shared decision-making. But for the patients and the family to be able to express an informed opinion, they need to understand information about the illness and what the consequences are. And then, if they want to take their chances off medicine, then do so.

But the reality is that all of the evidence points to the fact that a treatment is effective, and sustained treatment mitigates the likelihood of people having recurrences, and therefore, the possibility that the illness can progress and complications can develop.

T. Scott Stroup, MD, MPH: I think you’re right. If you can teach people about what the illness is like, and that it’s recurrent, or can recur, people, or family members in particular, might notice if someone’s becoming more withdrawn, or sleeping less, or is not taking their medications, or is abusing substances.

Jeffrey A. Lieberman, MD: There’s a common criticism that’s leveled at us: That we’re pill pushers and we’re trying to just push medications on people. There may be some individuals who are a little too excessive, but most physicians are trying to use medication judiciously. When you take medicines for hypertension, diabetes, asthma, or use statins, nobody blinks an eye for taking it on an ongoing basis. But when it comes to psychotropic drugs, uh oh, you’re taking it unnecessarily.

Transcript edited for clarity.