FDA Orders Older Antipsychotic Drugs To Carry Increased Warning Of Death Risks

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Main Category: Regulatory Affairs / Drug Approvals
Also Included In: Alzheimer's / Dementia;  Schizophrenia;  Seniors / Aging
Article Date: 17 Jun 2008 - 3:00 PDT

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The US Food and Drug Administration (FDA) flexed its new muscles yesterday, 16th June, and "ordered" manufacturers of older conventional antipsychotic drugs to strengthen the label so it warns about increased risk of death when the drugs are used off-label to treat older people with dementia. Under new powers granted in the Food and Drug Administration Amendments Act of 2007 (FDAAA), the agency can now order, rather than ask, the manufacturers to do this.

This action brings older conventional antipsychotic drugs in line with changes made in 2005, where Boxed Warnings, the strongest class of FDA warning a drug can have, were introduced for atypical antipsychotic drugs.

The FDA has sent letters to the manufacturers of both types of drug, under its new FDAAA powers, giving them notice to change the drug labels so they all carry the same type of warning. The manufacturers have 30 days in which to submit the new wording to the FDA, or to explain, if they do, why they don't think the changes are necessary. Under the new FDAAA rules, there is a strictly timed resolution process, and if that fails, the federal authority can enforce the changes.

According to the FDA's announcement, the Boxed Warnings for both types of drug will carry words to the effect 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".

Director of the FDA's Division of Psychiatry Products in the Center for Drug Evaluation and Research (CDER), Dr Thomas Laughren, said:

"It is important that health care professionals and consumers have the most up-to-date drug safety information."

"The prescribing information for all antipsychotic drugs will be updated to describe the risk of death in elderly patients being treated for symptoms associated with dementia," he added.

There are two common types of antipsychotic drugs, the older "conventional" antipsychotics and the newer "atypical" antipsychotics, both of which block the action of naturally occuring dopamine in the brain (they are dopamine receptor antagonists). The main difference between them is that the atypical antipsychotics have fewer neurological side effects, such as "tics" (involuntary movements).

The FDA has approved neither the older conventional nor the newer atypical antipsychotics for the treatment of dementia-related symptoms, such as forgetfulness, poor memory, and failure to recognize familiar objects, sounds, or people. They are federally approved primarily for treating symptoms of schizophrenia, but doctors can use drugs "off-label" if they have good reasons, and it is common practice for them to use drugs approved for one disease to treat another, at their discretion.

The FDA's action is based on two recently published observational epidemiological studies where an atypical antipsychotic was compared with no antipsychotic or a conventional antipsychotic. However, due to the limitations of the research it was not possible to make conclusions about the death rates of atypical versus conventional antipsychotic drugs, but the FDA decided that the results, along with some earlier research, was enough to lead them to conclude that both types of drug should be considered as posing an increased death risk to elderly patients being treated for dementia-related psychosis.

People who are taking antipsychotic drugs should not suddenly stop taking them, said the FDA, and their doctors should address any concerns they may have by talking to them.

The following table lists all the drugs covered by this latest FDA action:

Conventional Antipsychotic Drugs	Atypical Antipsychotic Drugs
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)

The FDA is sending a letter to all health professionals explaining the research data and giving treatment advice. This can be viewed here.

Click here for FDA.

Source: FDA.

Written by: Catharine Paddock, PhD
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today