NEW WARNING! Risk Of Stroke When The Antipsychotic Risperidone (RISPERDAL) Is Prescribed For Dementia

The manufacturer of the antipsychotic drug risperidone (RISPERDAL), announced on April 16, 2003, that an important new warning had been added to the professional product labeling, or package insert, for the drug concerning cerebrovascular adverse effects, including stroke and transient ischemic attack (temporary reduction of blood flow to the head), when the drug is used to treat elderly patients for dementia. In some of these cases the result was death. Risperidone is produced by Janssen Pharmaceutica Inc. of Titusville, NJ.

The full text of the new warning appears at the end of this article.

The use of risperidone to treat dementia is not approved by the Food and Drug Administration (FDA), and the drug’s only approved use is in the treatment of schizophrenia. When the use of a drug is not approved by the FDA it is referred to as an “off-label” use because only uses of a drug that have been shown to be safe and effective after FDA review can be listed on a drug’s approved product labeling.

In many instances, new warnings are added to drug labels as a result of voluntary reports of adverse reactions submitted to pharmaceutical companies and the FDA by health professionals and patients. Voluntary reports are not ironclad proof that a drug has caused an adverse reaction, though they are extremely important evidence that the drug may be the cause of serious adverse effects.

In the case of risperidone the new warning comes as the result of four controlled clinical trials. Controlled clinical trials are the best type of evidence for establishing a cause and effect relationship. The four clinical trials that compared risperidone to a placebo lasted between one and three months and involved more than 1,200 patients with Alzheimer’s disease or vascular dementia. Adverse cerebrovascular events were twice as common in those patients treated with risperidone (4%) compared to placebo (2%).

Canadian healthcare professionals were warned on October 11, 2002, six months before Americans were, about the cerebrovascular adverse effects of risperidone. In this communication, Canadian authorities indicated that worldwide there had been 37 cases of cerebrovascular adverse events associated with the use of risperidone.

The exact number of cerebrovascular adverse events associated with the use of risperidone is unknown. The FDA estimates that only between 1-in-100 and 1-in10 serious adverse drug reactions are ever reported to the agency. The adverse reaction reporting system is voluntary and there are no laws or regulations that require health professionals to report serious adverse effects to the authorities.

Dementia places a tremendous burden on all involved: patients and the family members of patients who are their caregivers. But, the decision to use an antipsychotic drug to manage the symptoms of dementia must be made carefully. The new warning for risperidone is clear, the drug “has not been shown to be safe or effective in the treatment of patients with dementia-related psychosis.” Currently, the relative safety and effectiveness of other antipsychotic drugs such haloperidol (HALDOL), olanzapine (ZYPREXA), clozapine (CLOZARIL), or quetiapine (SEROQUEL) in the management of dementia is similarly unknown.

If the decision is made to use an antipsychotic drug, family members of patients with dementia must inform themselves of the risks of drug treatment. The antipsychotic drugs can create serious problems for patients with cardiovascular disease, including a previous heart attack or chest pain (angina), cerebrovascular disease, or electrical conduction abnormalities of the heart. Patients taking these drugs should be watched closely for excessive sedation, low blood pressure (especially if they are already taking blood pressure lowering drugs), movement disorders, and cerebrovascular adverse reactions. Patients must also be monitored for neuroleptic malignant syndrome, a potentially fatal symptom complex that includes a high temperature, muscle rigidity, altered mental status and evidence of an irregular pulse or blood pressure, fast heart rate, sweating, and heart rhythm disturbances.

What You Can Do

If a family member is currently receiving risperidone to manage dementia, you should discuss the drug’s new cerebrovascular warning with the prescribing physician. If the decision is made to try another drug, you should learn about the drug’s risks before the drug is given to your family member.

You can report serious adverse reactions to the FDA MedWatch program by phone (1-800-FDA-1088), by fax (1-800-FDA-0178), or by email(www.fda.gov/medwatch ).