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January 15, 2009

Study Finds Drug Risks With Newer Antipsychotics


The popular drugs known as atypical antipsychotics, prescribed for an array of conditions, including schizophrenia, autism and dementia, double patients’ risk of dying from sudden heart failure, a study has found.

The finding is the latest in a succession of recent reports contradicting the long-held assumption that the new drugs, which include Risperdal, Zyprexa and Seroquel, are safer than the older and much less expensive medications that they replaced.

The risk of death from the drugs is not high, on average about 3 percent in a person being treated at least 10 years, according to the study, published Thursday in The New England Journal of Medicine. Nor was the risk different from that of the older antipsychotic drugs.

But it was significant enough that an accompanying editorial urged doctors to limit their prescribing of antipsychotic drugs, especially to children and elderly patients, who can be highly susceptible to the drugs’ side effects, including rapid weight gain.

In recent years, the newer drugs, which account for about 90 percent of the market, have become increasingly controversial, as prescription rates to children and elderly people have soared. Doctors use the drugs to settle outbursts related to a host of psychiatric disorders, including attention deficit disorder and Alzheimer’s disease. Most are not approved for such use. After an analysis of study data, the Food and Drug Administration required that all antipsychotics’ labels contain a warning that the drugs were associated with a heightened risk of heart failure in elderly patients.

The new study, an analysis of more than 250,000 Medicaid records, is the first to rigorously document that risk for the newer drugs in adults over 30 without previous heart problems.

In the study, researchers at Vanderbilt University and the Nashville Veterans Affairs Medical Center analyzed Tennessee Medicaid records for 276,907 people ages 30 to 74. About a third of them began taking an antipsychotic medication in the period studied, from 1990 to 2005, either a newer atypical or an older drug. Two-thirds made up a control group. The researchers excluded patients with heart disease or other problems that might put them at higher risk of cardiac failure. Antipsychotic drugs can affect heart rhythm in some vulnerable people.

They found 478 sudden cardiac deaths among those taking the drugs, about twice the rate of the control group. The risk — equivalent to 3 deaths for every 1,000 patients taking the drugs for a year — was about the same whether people took the newer or older medications. The higher the dose of the drug, the study found, the higher the risk of sudden death.

“The implication of this study is that physicians need to do a very careful cardiovascular evaluation prior to prescribing these drugs,” especially if there are alternative treatments, said the lead author, Wayne A. Ray, a professor of preventive medicine at Vanderbilt and the Nashville veterans’ hospital. “Then, if they’re used, to pay careful attention to using the lowest possible dose.”

Dr. Ray’s co-authors were Dr. Cecilia P. Chung, Dr. Katherine T. Murray, Kathi Hall, and C. Michael Stein, all of Vanderbilt.

In 2005, government-sponsored researchers reported that three of four new antipsychotic drugs tested were no more effective than an older, far less expensive drug in treating schizophrenia — the disorder for which they were originally approved.

In 2006, doctors working on the same large study reported that the drugs were no more effective than placebos for most elderly patients being treated for dementia-related psychosis. Since then, several review articles have come to similar conclusions, and raised concern about a far more common side effect: weight gain.

“When it comes to treating kids, these cardiac events are going to be rare,” said Dr. Jon McClellan, a psychiatrist at the University of Washington. “But heart problems due to obesity are not rare, and the public-health implications of kids on these drugs gaining 10 to 15 pounds are much greater.”