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Heart risk cited in newer antipsychotic drugs

Zyprexa, Risperdal and Seroquel, among the 10 most commonly prescribed medications, are just as likely as older antipsychotic drugs to cause a fatal heart attack, a study finds.

January 15, 2009|Thomas H. Maugh II

A widely used class of antipsychotic drugs that includes bestsellers Zyprexa, Risperdal and Seroquel is just as likely -- perhaps even more likely -- to cause a fatal heart attack as older antipsychotic drugs like haloperidol, researchers reported today.

The findings, which run contrary to a long-standing belief, add to a growing drumbeat of criticism about this class of drugs, known as atypical antipsychotics. Zyprexa, Risperdal and Seroquel are among the 10 most commonly prescribed medications in the world, with annual sales estimated at $14.5 billion.

Researchers are especially concerned about the rising use of atypical antipsychotics in the elderly and the young -- both groups that are fragile and more susceptible to adverse effects of powerful medications.

Last week British researchers reported in the journal Lancet Neurology that Alzheimer's patients given the drugs to control aggression were nearly twice as likely to die from any cause as patients who did not receive them.

Some studies have shown that as many as 40% of Alzheimer's patients in nursing homes receive the drugs for unapproved use.

The number of prescriptions for the drugs written for children and adolescents doubled to 4.4 million from 2003 to 2006, in part because of increases in diagnoses of bipolar disorder. Their efficacy in children and Alzheimer's patients has never been demonstrated, experts said.

Eli Lilly & Co., the manufacturer of Zyprexa, is expected to settle a lawsuit with the federal government as early as today, paying a record $1.4 billion in civil and criminal charges to resolve complaints about the marketing of Zyprexa for unapproved uses. The company has already paid nearly $1.3 billion to states and consumers to settle other complaints about marketing and side effects.

"I am, and have been, very concerned about these drugs," said Dr. Ian Cook, a psychiatrist at UCLA's Geffen School of Medicine who was not involved in the new study. "These are powerful medications that affect the brain and the body, and we need to be very thoughtful in their use."

No one, however, is urging abandonment of the atypical antipsychotics. The nub of the matter is that there are no other drugs with the same beneficial effects.

"The antipsychotics are a godsend," said Dr. Alan Manevitz, a psychiatrist at Lenox Hill Hospital in New York who was not involved in the study. "They have taken people and unchained them from walls. . . . We don't want to throw out the baby with the bathwater."

The drugs are approved only for treatment of schizophrenia and bipolar disorder in the general population. But their use has been expanding to treat aggression in young people and dementia in the elderly.

"We use them because they are somewhat useful in some patients . . . and because we have no alternative," said Dr. Dilip V. Jeste of UC San Diego.

Researchers already knew that atypical antipsychotics could produce excessive weight gain, increase the risk of diabetes and induce strokes and heart problems in the elderly. The Food and Drug Administration requires both conventional and atypical antipsychotics to carry a so-called black-box warning -- the strongest warning possible -- informing patients and physicians that the drugs are associated with increased risk of death in elderly patients treated for dementia.

In their federally funded study, published in the New England Journal of Medicine, the researchers analyzed Tennessee Medicaid records for the 15 years ending in 2005. They identified 44,000 users of conventional antipsychotics and 46,000 of atypical antipsychotics. They compared them with 186,600 matched patients taking neither.

The scientists found that patients taking either type of drug were about twice as likely to die of a heart attack as those not taking the drugs, with the risk of death increasing with dose and the length of time on the medication. There were about 3.3 excess deaths per year for every 1,000 patients taking the drugs.

The prescribing of drugs "is a balancing of risks and benefits. Our study gives more information on the risk side of things," said study leader Dr. Wayne A. Ray of the Vanderbilt University School of Medicine.

Conventional antipsychotics, such as haloperidol (Haldol) and chlorpromazine (Thorazine), were stumbled on by chance in the 1950s and were found to have a powerful calming effect on psychotic patients, but also a number of side effects. Among the most disturbing was tardive dyskinesia, characterized by tremors and other movement disorders that are often irreversible.

The atypical antipsychotics, which also include Clozaril, Geodon and Abilify, were designed to avoid tardive dyskinesia, which is why they were perceived as safer, Ray said. "Today, nearly all people taking antipsychotics are taking the atypical ones," he said.

In an editorial accompanying the paper, Dr. Sebastian Schneeweiss and Dr. Jerry Avorn of Brigham and Women's Hospital in Boston argue that the danger can be mitigated by assessing patients' cardiovascular risk before treatment and after a month on the drugs. Patients with a heightened risk could be counseled on ways to lower it, such as modifications of diet and exercise.

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thomas.maugh@latimes.com

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