Newer antipsychotics pose risk of death

Marketed under names such as Risperdal, Seroquel, and Zyprexa, they are among the world's 10 top-selling drugs. For the last 20 years or so, these "newer" antipsychotics were considered safer than the older drugs they were meant to replace. But a new study has cast these drugs in a harsher light.

The study, in the January 15 issue of the New England Journal of Medicine found that clozapine, risperidone (Risperdal), quetiapine (Seroquel), and olanzapine (Zyprexa), similar to the first generation of antipsychotic medications, can cause sudden cardiac death. The study also found that higher dosages increased that risk.

Consumer Reports has long tagged those medications as problematic, given their many and serious side effects (see below); the expense of the newer drugs, which are not typically available in generic versions; and the likelihood that patients will stop using them because of their intolerability. A number of recent studies have now shown they are generally no more (or less) effective than the older antipsychotic drugs.

Today's news adds another, and deep, wrinkle, and here's why: A 2006 study found that two-thirds of prescriptions written for antipsychotics were for conditions that are not approved indications by the Food and Drug Administration, such as stroke-related dementia, anxiety, obsessive-compulsive disorders, post-traumatic stress disorder and personality disorder. A recent analysis has shown that these drugs hold no advantages over drugs actually approved to treat those disorders.

Such off-label prescribing is perfectly legal. Another 2006 study found that, for all prescriptions, about one in five are written for disorders other than the one for which they were approved. At the present time, to give you a sense of what's in store, studies are now under way to test if some of the newer antipsychotics can treat conditions as diverse as irritable bowel syndrome, anorexia, and fibromyalgia. Today, these medications are only approved to treat bipolar disorder and schizophrenia.

With today's study release, doctors will have a new risk—death—to tip the scales in their risk/benefit analysis. Our medical advisers strongly agree with the NEJM editorial authors, who urged doctors to stop prescribing these drugs so often for off-label use, particularly in children and the very old, where the evidence that they work is marginal or nonexistent.

CR's Take: If you, your child, or a very old person in your care is faced with the prospect of taking an antipsychotic medication, make sure that the drug is being used for the FDA-approved indications of bipolar disorder or schizophrenia. Don't be afraid to get a second and even third opinion, if the diagnosis is in doubt. Pay close attention to the information about side effects, which include abnormal menstruation, blurred vision, constipation, drowsiness, lack of coordination, muscle weakness, seizures, slurred speech, tremors, and weight gain.

Patients who have a history of, or who are being treated for, a heart rhythm abnormality, should probably avoid these drugs, if at all possible. Electrocardiograms, looking for a specific abnormality known as prolongation of the QT interval (the time it takes the heart to discharge and recharge on an EKG) taken prior to, and at intervals after starting the drug, should be done. If that abnormality is present, the drug should be stopped or not started.

—Lisa Gill, producer and writer, Consumer Reports Best Buy Drugs

See our FREE Consumer Reports Best Buy Drugs report on Schizophrenia and Bipolar Disorder for a more detailed analysis of the risks, benefits, and costs of antipsychotic medications.