Response, Remission, and Recovery in Schizophrenia

John Lauriello, M.D.

“So what is Greg’s prognosis?” asked his parents. It had not been the first or even second question they had asked. In fact, it took several weeks for them to begin to accept the possibility that their son had schizophrenia. It seems like a straightforward question to ask, but the answer is rather complicated. My usual answer is that schizophrenia is a treatable illness, and recovery is possible. Having treated patients for over 20 years, I know that Greg could respond well enough to be a working member of society, even have a family of his own. However, I also know that there is a chance he could be plagued by overwhelmingly disabling, and possibly lifelong, symptoms.

Response

When patients with cancer show improvement, they are said to have had a response to treatment, but only when they have no more detectable cancer cells in their body have they achieved remission. This does not mean that patients are “cured” or without relapse risk. In fact, patients may be asked to continue some form of chemotherapy to maintain their remitted state. A full recovery usually requires a specified time free of cancer (for example, five years) and return to previous functioning.

In contrast, in pharmaceutical industry-sponsored clinical trials for schizophrenia, response is often defined as a 20 percent reduction in positive and negative symptoms. These scores, though useful for approval of new medications by government regulatory agencies, inadequately capture all symptom domains, especially cognitive and social functioning.

For the last 50 years, most clinicians would say that response is a meaningful reduction in psychosis, a compliant patient, and few, if any, rehospitalizations. Getting to remission was deemed a luxury that a few lucky patients might achieve. Cynically, some would even say that getting to remission is rare, and those who recover did not have schizophrenia in the first place.

Remission in Three Steps

Believing a patient can achieve remission is step 1. Defining what we mean by remission is step 2, and getting the patient to remission is step 3. Many of us clinicians believe the bar has been raised to expect and strive for remission, so let’s assume we have made the first step. Defining remission is then necessary.

There have been several attempts over the last 15 years to define remission in schizophrenia, using sets of criteria that quantify clinically meaningful improvement and a time criterion to demonstrate sustained improvement. A recent example of usable remission criteria was proposed by the Remission in Schizophrenia Working Group, a group assembled to create a consensus operational definition that could be used both retrospectively, when evaluating older studies, and prospectively for future studies. It requires that patients maintain scores of mild or less in three dimensions (psychoticism, disorganization, and negative symptoms) for at least six months.

Getting to remission is challenging and merits a few “warnings” along the way. First, do not let the pursuit of symptom control be your “Moby Dick.” Just as Captain Ahab was obsessed to the ruin of his ship, eradicating psychosis at all costs can be to the detriment of the patient. If the cost includes unbearable side effects (extrapyramidal side effects, sialorrhea, sexual dysfunction) or long-term morbidity (tardive dyskinesia or obesity), it may not be worth eliminating every hallucination. Instead, alleviating symptoms to a mild level may adequately allow the patient to better tolerate the medication. Second, don’t expect medication alone to get patients to remission. This often requires adjunctive case management and family, social, and vocational therapies.

Finally, don’t expect things to stay the same once remission is achieved. There are multiple reasons why a patient may become symptomatic again. These include, but are not limited to, noncompliance or partial compliance with medications or other treatment modalities, substance use, and worsening of underlying psychopathology. An analogy I often use for the last is the following: You have a very nice beach house, and in front of your home you have a four-foot wall. For many years, the wall provides protection against rain and high tides. But one year, a hurricane hits and the four-foot wall is inadequate to hold the water from rushing into your home.

So, too, we often prescribe patients doses of medication that appear to keep them relatively stable, and to our surprise, despite being treatment adherent, the patient worsens. Symptoms can be like storms, unpredictable and severe. At that time, the medication regimen may need to be adjusted but can eventually return to the lower, more tolerable maintenance dose.

Recovery

t is useful to think of recovery as the next level after remission. Not only are symptoms controlled, there are sustained gains/or maintenance in cognitive, social, and vocational functioning over a longer period. With this considered, we include the UCLA criteria developed by Lieberman and colleagues as a recovery measurement. The UCLA criteria seek to provide a “multimodal normative inventory of personal assets and freedom from psychotic symptoms.” The UCLA criteria include sustained improvement for at least two years in four domains: symptom remission, appropriate role function, ability to perform day-to-day living tasks without supervision, and social interactions. The developers also delineated several factors predicting recovery: good premorbid functioning, intact cognitive performance, a short duration of untreated psychosis, robust response to antipsychotic medications, a supportive social network, and access to psychiatric care.

A common question is, “How many patients with schizophrenia can recover (remember Greg’s parents’ question)?” It has long been believed that early diagnosis and treatment of schizophrenia should provide the best outcome and greatest chance for recovery. In a group of patients with a first episode of schizophrenia studied by Robinson and colleagues, full recovery rates were found to be low, with only one-eighth of those in the study meeting criteria for two or more years.

Although recovery was rare, several predictors of recovery were identified, including better cognitive performance, shorter period of psychotic symptoms prior to enrollment in the study, and more normal cerebral asymmetry. The finding of length of history of psychosis as a predictor suggests that the longer patients are psychotic and untreated, the lower the chance for recovery. This finding underscores how vital it is that patients with their first break of psychosis be brought for evaluation and treatment as soon as possible.

So we can amend our answer to Greg’s parents’ question: “What is his prognosis?” It depends partly on how quickly we have identified the illness and whether we can get him to remission. Remission is possible. It requires reasonable control of psychotic symptoms, and a new focus on cognitive and negative symptoms leading to better functional outcomes. While challenging, sustained remission is the only way functional recovery can be attained. ■