Newer antipsychotic drugs nearly double the odds of sudden death from a heart problem and may be riskier than older medicines, researchers say.

The newer "atypical" antipsychotics are approved for schizophrenia. The drugs are among the best selling in the world, and are also prescribed for unapproved purposes such as treatment of dementia in the elderly, attention-deficit hyperactivity disorder, anxiety and depression. 

'To me, three per thousand [deaths] is frequent enough [that] I would take it into account for a family member or friend.' — Dr. Wayne Ray

In Thursday’s New England Journal of Medicine, federally funded researchers in the U.S. studied Medicaid records of nearly 44,000 people in Tennessee for the 15 years ending in 2005.

Those studied included 44,000 people taking older antipsychotic drugs such as haloperidol, 46,000 users of the newer atypicals and 186,000 who were not taking antipsychotics but shared similar age, heart risks and other characteristics with those taking the medications.

The newer drugs studied included: 

  • Clozapine, made generically.
  • Johnson & Johnson's Risperdal or risperidone.
  • Eli Lilly and Co's Zyprexa, known generically as olanzapine.
  • AstraZeneca's Seroquel, also sold generically as quetiapine.

"Increased risk was seen for current users of atypical antipsychotic drugs, who had a rate of sudden cardiac death that was more than twice that for nonusers," said the study's authors, Dr. Wayne Ray of the Vanderbilt University School of Medicine and colleagues.

The overall rate among drug users was about three deaths per year for every 1,000 patients.

"To me, three per thousand is frequent enough [that] I would take it into account for a family member or friend," said Ray.

Those taking the highest dose of atypicals had the greatest risk for a fatal heart attack, and the risk appeared to fade once the medications were stopped, said Ray.

Over the course of the 15-year study, 1,900 people died of sudden cardiac death. The drugs can interfere with the flow of potassium that is needed for proper functioning of the heart.

The researchers reported that the current users of typical antipyschotics showed 1.99 times the rate of sudden cardiac death compared with non users. Among atypical users, the rate was 2.26 times greater than for nonusers, and 1.14 times greater than for those taking older antipsychotic drugs.

Less support for use in children, elderly

Patients should not stop taking the medications without talking to their doctor, he stressed.

Since people with schizophrenia have few alternatives to antipsychotics, the researchers suggested that they get heart tests such as an electrocardiogram or EKG before starting the medications.

In a journal commentary, Drs. Sebastian Schneeweiss and Jerry Avorn of Brigham and Women's Hospital in Boston said there was much less evidence that the drugs work for unapproved purposes, particularly for children and in the elderly with dementia.

"For these patients, the use of antipsychotic medications should be reduced sharply," they wrote.

Three atypicals — Zyprexa, Risperdal and Seroquel — are among the 10 top-selling drugs worldwide, with a combined sales volume of $14.5 billion US in 2007, the editorial noted.

With files from the Associated Press