NEW YORK (AP) – A schizophrenia drug as well-known for its risk of dangerous side effects as for its effectiveness gets a vote of confidence in a new federally financed study.

Researchers explored a common situation in schizophrenia treatment: If the first drug a patient tries fails to control symptoms adequately, what drug should be tried next?

When patients in that situation were randomly assigned a second drug in the new study, Clozaril emerged as more effective than Risperdal, Seroquel and Zyprexa, said lead author Dr. Joseph McEvoy of the Duke University Medical Center.

That’s not a surprise, he said, because Clozaril “was believed to be the most therapeutically effective drug out there.” But it’s underused because of the risk of side effects that require patients to go through special monitoring, he said.

In a companion analysis of other patients who didn’t want to try Clozaril or who’d abandoned their first medication because of side effects, Risperdal and Zyprexa were found to be more effective than Geodon and Seroquel.

Clozaril is sold by Novartis SA, Risperdal by Janssen Pharmaceutica and Zyprexa by Eli Lilly and Co.

Both papers appear in the April issue of the American Journal of Psychiatry. The work, funded by the National Institute of Mental Health, was the second phase of a government study to seek the most effective way to treat people with this devastating mental disorder.

Schizophrenics struggle with such symptoms as hallucinations, delusions, social withdrawal, and other mental impairments that interfere with a normal lifestyle.

Dr. Darrel Regier, director of the research division of the American Psychiatric Association, said the head-to-head drug comparisons are “a major step forward” that will help doctors make a choice for a second drug to try. Doctors have to consider both effectiveness and side effects of the various drugs in deciding what’s best for each patient, he said.

In fact, McEvoy said if a patient had gotten inadequate response from a first drug other than Zyprexa, he’d recommend trying Zyprexa because it doesn’t have Clozaril’s side effects and the need for special monitoring of patients. But if Zyprexa doesn’t work, he said, he’d recommend Clozaril.

Clozaril’s potential side effects include a loss of disease-fighting white blood cells and a potentially fatal inflammation of heart muscle. The risks make it more complex to use because patients must be closely monitored. For example, users must take weekly blood tests at first.

In the new studies, effectiveness was measured by how long patients stayed with the new drug. In the study that included Clozaril, half the 45 patients on that drug stuck with it for nearly 11 months or more. In the other three medication groups, which contained about 15 patients apiece, the corresponding figure was about three months.

While the difference in that measure between Clozaril and Zyprexa was not significant by statistical criteria, other measures in the study found Clozaril to be superior, McEvoy said.

In the other analysis, which covered more than 300 patients, the results were seven months for Risperdal and six months for Zyprexa, longer than the four months for Seroquel or the three months for Geodon.