Just under one percent of the general population suffers from schizophrenia. The economic burden of the disease was estimated at $33 billion per year in the early 1990s. Much of that cost can be attributed to the consequences of psychotic relapse, which is common among schizophrenic patients.

Past studies of antipsychotic drugs tended to be short-term trials, lasting four to eight weeks. They had shown that second-generation drugs helped reduce psychotic symptoms, but longer-term studies were needed in order to determine their long-term effects on the disorder, especially on relapse.

“Schizophrenia is a chronic, psychiatric illness,” explains John G. Csernansky, M.D., the Gregory B. Couch Professor of Psychiatry at Washington University School of Medicine in St. Louis and the study’s principal investigator. “Relapse is common even under the best of circumstances, with an average patient relapsing at least once every one to two years. Because of the chronic nature of the illness, it is very important to determine whether newer drugs can diminish the relapse rate. Relapse prevention is the most important indicator of therapeutic success over the long term.”

The study involved nearly 400 patients with schizophrenia. They were treated at 40 sites around the United States. All study patients had records of having relapsed within the 24 months prior to the start of the study. Investigators spent two years comparing the rate of relapse in patients taking risperidone, a second-generation antipsychotic medication, to patients taking an older drug, haloperidol. Since its discovery in the 1950s, haloperidol has been one of the most commonly prescribed drugs in patients with schizophrenia and other psychotic disorders.

“At the time this study began, haloperidol was the most commonly used antipsychotic drug in the United States,” says Csernansky. “In any way one could measure it, haloperidol was the industry standard.”

When the study was completed, Csernansky and colleagues found that the one-year rate of relapse for patients on haloperidol was about 50 percent. But the rate of relapse for patients taking risperidone was only about 25 percent, about half of what was observed in patients taking the older drug.

“Reducing the rate of relapse is a tremendous benefit to the patient, but it’s also a benefit for the family and the system of care that has to pay for the hospitalization that often goes along with relapse,” Csernansky says. “Most importantly, however, patients who relapse face many months of difficulty. Hospitalization can last from seven to 21 days, but even after discharge it may take weeks, if not months, to restore work relationships and social relationships a patient had established prior to relapse.”

Haloperidol and other traditional antipsychotic drugs block activity in brain cells at the neuron’s dopamine receptor. Newer drugs like risperidone block the dopamine receptor, but they also act at other receptors, such as the serotonin receptor. Past studies have shown the newer drugs seem to be more effective and cause fewer side effects, at least in the short term. This study, however, followed patients for at least a year — with some participating in the study for two years. The goal was to determine whether psychotic symptoms were controlled and side effects minimized during a longer time period.

Antipsychotic drugs can have side effects on the central nervous system. After years on such drugs, some patients develop symptoms similar to Parkinson’s disease. Over many years, some even develop a chronic movement disorder called tardive dyskinesia, a condition that resembles Huntington’s chorea. The newer drugs, such as risperidone, have fewer neurological side effects.

Despite the dramatic change in rates of relapse, Csernansky says more immediate differences observed in study patients were subtle. “Risperidone had benefits in terms of causing a modest reduction in symptoms and side effects, but it’s interesting that those benefits were relatively small. One wouldn’t necessarily notice a large change in symptoms, at least in the short term,” he says.

Csernansky says more needs to be done to cut relapse rates, but he believes the reduction offered by risperidone is a very positive development. Unfortunately, he says the cost difference between the two drugs may influence some clinicians and managed care plans to continue to favor the older drug, but he says the cost of relapse also must be included in the equation.

“In general, a hospitalization for schizophrenia lasts about two weeks and costs in the neighborhood of $500 per day, so cutting the relapse rate by half could have significant economic benefits,” he says.

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John G. Csernansky, et. al., “A comparison of risperidone and haloperidol for the prevention of relapse in patients with schizophrenia,” New England Journal of Medicine, Jan. 3, 2002.

This research was supported by grants from the Janssen Research Foundation. The investigators also received honoraria for delivering lectures from the Janssen Research Foundation, Eli Lilly, AstraZeneca Pharmaceuticals and Pfizer Pharmaceuticals

The full-time and volunteer faculty of Washington University School of Medicine are the physicians and surgeons of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.

Note: If no author is given, the source is cited instead.

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