Newer antipsychotic medications also pose sudden cardiac death risk

Newer medications designed to treat serious mental illnesses such as schizophrenia and bipolar disorder without troubling side effects pose the same risk of sudden cardiac death as older drugs, a new study shows.

The findings about the newer -- or "atypical" -- drugs spur a call for closer monitoring of the their use, especially when prescribed for other conditions.

People who took atypical antipsychotic drugs, including best-sellers Zyprexa (olanzapine), Risperdal (risperidone), and Seroquel (quetiapine) were at least as likely to suffer a fatal heart rhythm disturbance as people who took older, "typical" antipsychotics such as haloperidol (Haldol) and thioridazine (Mellaril), researchers from Vanderbilt University School of Medicine report in tomorrow's New England Journal of Medicine. A person's risk rose with the amount of the drug they were taking, the large study showed.

Drug specialists from Harvard Medical School urge a sharp reduction in the drug's "off-label" use, which means prescriptions for reasons other than for which the drug has been approved. That was seen as especially important for children and for the elderly with dementia. Screening is recommended for heart problems in patients who have no alternatives, according to an editorial also appearing in the journal.

Researchers have suspected that the newer drugs could increase the risk of sudden cardiac death, based on reports that, like older versions, they also affect the electrical rhythm of the heart. The new study is the first to establish a strong link, one they reached after looking at 15 years of medical records for more than 93,000 Tennessee Medicaid members taking antipsychotic drugs, half on older ones and half on newer ones. They were compared to 186,000 other enrollees with a similar psychiatric illness who were not taking the drugs.

From 1990 through 2005, a total of 1,870 people died of sudden cardiac arrest. The risk was about twice as high for people taking antipsychotic drugs compared to people who weren't. The elevated risk translates into about three deaths per 1,000 people per year.

The increased risk for atypical antipsychotic drugs was slightly higher than for typical antipsychotic drugs, although not statistically significant, according to Wayne A. Ray, director of pharmacoepidemiology at Vanderbilt and the study's lead author.

"Everyone would have hoped they were safer," he said in an interview. "We certainly didn't find that."

Ray said patients should not stop taking their medications without first talking to their doctors about the risks and benefits of the drugs. For people with schizophrenia, there are no alternatives, he said, so cardiac tests for other risk factors and further tests while they take the drug are a good idea.

People with bipolar disorder could consider mood stabilizers, a different class of drugs that includes lithium and valproic acid. When it comes to off-label use, Ray advises caution.

"They should be used very cautiously and sparingly for off-label indications," he said.

Dr. Sebastian Schneeweiss and Dr. Jerry Avorn, both of and Brigham and Women's Hospital, note in their editorial that screening is already required for clozapine, the first atypical antipsychotic drug, because it can wipe out white blood cells that protect people from infections. Its death rate of 0.02 per 1,000 patients per year is much lower than the rate of 3 per 1,000 patients per year that the antipsychotic study found.

"It is time to consider a risk management program for these antipsychotic medications, typical or atypical," Schneeweiss said in an interview.