The latest generation of antipsychotic drugs appears to be twice as likely to cause sudden cardiac failure and death in users compared to nonusers, according to a new study published in this week’s New England Journal of Medicine.

 

The drugs followed in the study are said to be atypical: Seroquel (quetiapine), made by AstraZeneca PLC, Zyprexa (olanzapine), made by Eli Lilly & Co., Risperdal (risperidone), made by Johnson & Johnson, and Clozaril, made by Novartis AG. These drugs came on the market about 15 years ago as safer, gentler alternatives to the older ones for schizophrenia known to raise health risks. Zyprexa, Risperdal and Seroquel are among the 10 most commonly prescribed medications in the world, with annual sales estimated at $14.5 billion.

Older, typical medications for schizophrenia such as Haldol (haloperidol) and Thorazine (chlorpromazine) made many users doze, drool, and twitch.

 

These antipsychotics, both typical and atypical, are often prescribed for bipolar disorder, anxiety, depression and attention deficit hyperactivity disorder as well, even though their use for those purposes is not cleared by the Food and Drug Administration.

 

For the study, study lead author Wayne Ray, director of the Vanderbilt University School of Medicine’s Division of Pharmacoepidemiology, and colleagues examined the medical records of 44,218 patients who used the older antipsychotic drugs and 46,089 patients who used the newer ones. Also, the researchers looked at the records of 186,000 people who did not use antipsychotic medication. The medical records covered a period of 15 years, from 1990 (when the atypical antipsychotics entered the market) through 2005.

 

They found that patients taking either conventional or atypical antipsychotics 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. The risk — equivalent to 3 deaths for every 1,000 patients taking the drugs for a year — was about the same whether people used one version of the drugs or another.

 

What does that mean? The researchers said the study’s findings do not mean patients should stop taking antipsychotics. Sometimes, these drugs are the only alternative for patients suffering from schizophrenia. However, “the implication of this study is that physicians need to do a very careful cardiovascular evaluation prior to prescribing these drugs. Then, if they’re used, to pay careful attention to using the lowest possible dose,” Dr. Ray said.

 

Also, people suffering from other conditions such as bipolar disorder could consider mood stabilizers, a different class of drugs that includes lithium and valproic acid, instead of antipsychotics.

 

The study’s findings made Drs. Sebastian Schneeweiss and Jerry Avorn of Harvard Medical School urge doctors, in an editorial accompanying the study, to limit their prescribing of antipsychotic drugs, especially to children and elderly patients, who can be highly susceptible to the drugs’ side effects.