Clozapine has serious health consequences

Patients who take clozapine, the most effective antipsychotic drug, have significantly higher rates of metabolic syndrome, according to a first-of-a-kind study by University of Rochester Medical Center researchers.

Metabolic syndrome is a group of conditions that increase the risk for heart disease, stroke and diabetes. The conditions include high blood pressure, excess body fat around the waist, abnormal levels of cholesterol and triglycerides and insulin resistance. Any one of the conditions increases the risk of serious disease. In combination, the risk grows greater.

More than half the clozapine patients studied had metabolic syndrome while only about 20 percent of those in a comparison group did, researchers report in the July issue of The American Journal of Psychiatry.

Patients with metabolic syndrome in this study would be expected to have a two-to-threefold increase in cardiovascular disease mortality, the Medical Center Department of Psychiatry researchers state.

"Clozapine is the last hope for many people," said J. Steven Lamberti, M.D., associate professor of psychiatry and lead author of the journal article. "But there are long-term health implications. This study suggests that patients who need the most effective medication are between a rock and a hard place."

The increased physical health risks must be balanced with the potential benefits of clozapine, the researchers conclude. In addition to its superior efficacy for patients resistant to conventional antipsychotic drugs, clozapine also is the only medication currently approved by the Food and Drug Administration for the treatment of suicidal behavior.

Physicians should monitor closely people who receive clozapine with regular tests for glucose and blood lipid levels, blood pressure and body weight, Lamberti said.

"We need to raise the awareness of physicians about this issue so they monitor their patients and intervene promptly when required to prevent long-term adverse health consequences," Lamberti said.

Lamberti and his fellow researchers studied 93 patients at the Medical Center's Department of Psychiatry who had been receiving clozapine for at least six months. The patients were weighed, measured and tested for diabetes, blood lipids and blood pressure. The researchers then compared the patients to a group of about 2,700 individuals from a national database of health information for thousands of Americans. The comparison group was matched for age, body mass, and race or ethnicity.

The researchers found that 53.8 percent of the clozapine patients had metabolic syndrome. But only 20.7 percent of the comparison group had the same syndrome.

Many studies have shown that clozapine is associated with weight gain, but this is the first study to describe clozapine's link to metabolic syndrome.

"People with schizophrenia are known to exercise less and have poor diets," Lamberti said. "Those factors contribute to metabolic syndrome. We can't say how much clozapine contributes to metabolic syndrome, but we have shown the high prevalence of the syndrome in those who take clozapine."

The National Institutes of Health initiated the Clinical Antipsychotic Trials for Intervention Effectiveness investigation to determine the comparative effectiveness of several drugs.

In one major study, the investigators compared clozapine to new antipsychotic drugs in a group of patients that had not improved with the new drugs. In April, the investigators reported that clozapine was significantly more effective than the new medications. Patients receiving clozapine were less likely to discontinue treatment than those on other drugs.

Because of the findings of this NIH-sponsored study, Lamberti expects a surge in the use of clozapine, a drug he said has been underutilized.

"With any increased use of clozapine, it becomes even more important to point out the need to closely monitor and treat patients who take the drug for metabolic syndrome and its consequences," Lamberti said.