The FDA ( Food and Drug Administration ) has required manufacturers of conventional antipsychotic drugs to make safety-related changes to prescribing information, or labeling, to warn about an increased risk of death associated with the off-label use of these drugs to treat behavioral problems in older people with dementia.
In 2005, the FDA announced similar labeling changes for atypical antipsychotic drugs. At that time, Boxed Warnings, the FDA's strongest, were added.
The Boxed Warning will now be added to an older class of drugs known as conventional antipsychotics. The warning for both classes of drugs will say that clinical studies indicate that antipsychotic drugs of both types are associated with an increased risk of death when used in elderly patients treated for dementia-related psychosis.
Antipsychotic drugs commonly are categorized into two classes, the older conventional antipsychotics and the newer atypical antipsychotics. Both classes of drugs are dopamine receptor antagonists that work by blocking the action of naturally occurring dopamine in the brain. They differ primarily in their side effects, with the atypical drugs having a lower incidence of neurological side effects such as involuntary movements or tics.
Neither class of antipsychotic is FDA-approved for use in the treatment of dementia-related symptoms, which can include forgetfulness, poor memory, and an inability to recognize familiar objects, sounds, or people. The drugs are FDA-approved primarily for the treatment of symptoms associated with schizophrenia. The decision to use antipsychotic medications in the treatment of patients with symptoms of dementia is left to the discretion of the physician. Such use is often called off-label use and falls within the practice of medicine.
Recently, two observational epidemiological studies were published that examined the risk of death in elderly patients with dementia who were treated with conventional antipsychotic drugs.
The investigators compared the risk for death with use of an atypical antipsychotic versus either no antipsychotic or the use of a conventional antipsychotic.
These studies have limitations that preclude reaching a definitive conclusion about comparative death rates for atypical and conventional antipsychotic drugs. Nevertheless, the FDA has concluded that these studies, along with the earlier evidence for atypical antipsychotic drugs, suggest that both classes of drugs should be considered to have an increased risk of death when used in elderly patients treated for dementia-related psychosis.
The medications involved in this action are: Compazine ( Prochlorperazine ), Abilify ( Aripiprazole ), Haldol ( Haloperidol ), Clozaril ( Clozapine ), Loxitane ( Loxapine ), FazaClo ( Clozapine ), Mellaril ( Thioridazine ), Geodon ( Ziprasidone ), Moban ( Molindrone ), Invega ( Paliperidone ), Navane ( Thithixene ), Risperdal ( Risperidone ), Orap ( Pimozide ), Seroquel ( Quetiapine ), Prolixin ( Fluphenazine ), Zyprexa ( Olanzapine ), Stelazine ( Trifluoperazine ), Symbyax ( Olanzapine and Fluoxetine ), Thorazine ( Chlorpromazine ), Trilafon ( Perphenazine ).
Source: FDA, 2008