FDA Requires Conventional and Atypical Antipsychotics to Warn of Increased Death Risk in Elderly Dementia

Marlene Busko


June 20, 2008

June 20, 2008 — The US Food and Drug Administration (FDA) announced that manufacturers of conventional antipsychotics are now required to add warnings to labels and prescribing information to indicate that these drugs are linked with an increased risk for death in elderly patients with dementia-related behavioral problems.

In 2005, the FDA announced similar labeling changes for atypical antipsychotics. It now requires that both types of antipsychotics carry warnings saying that clinical studies indicate that this increased risk for this use in this patient population applies to both types of antipsychotic drugs.

Two Recent Observational Studies

"It's important to emphasize that this is not a contraindication," Thomas Laughren, MD, the director of the division of psychiatry products at the FDA's Center for Drug Evaluation and Research, said in a press briefing. "Clinicians still have the option of using these drugs to treat this aspect of dementia, at their discretion. However, they are not approved for this indication, and we do want clinicians to be aware of the risks in using drugs in this population if they choose to use them," he said.

A 2005 meta-analysis that the FDA conducted to investigate the use of atypical antipsychotic drugs to treat elderly patients with dementia-related behavior disorders was the basis for the original action, he added, but 2 recent observational studies, although less methodologically rigorous, suggest that this same risk appears to be present for conventional antipsychotics as well.

"Antipsychotic drugs, both atypicals and conventionals, are used primarily to treat major mental illness — in particular, schizophrenia and bipolar disorder," he explained, but they have also been used off-label in other settings, including use for various behavioral symptoms that accompany dementia.

Although the primary symptoms of dementia involve intellectual decline — such as memory loss and impaired judgment and language function — patients with dementia can have psychotic symptoms such as delusions and hallucinations, and they can be agitated, aggressive, and at times, violent, he said. Antipsychotic drugs are sometimes used in treating these behavioral symptoms.

Physicians Should Discuss Risk With Caregivers

"The purpose of this warning is to alert clinicians that there is a risk of excess mortality in using these drugs in this population," he said. Physicians who prescribe antipsychotics to elderly patients with dementia-related psychosis should discuss this risk for increased mortality with their patients and patients' families and caregivers, he added.

In April 2005, the FDA announced results of a meta-analysis of 17 placebo-controlled trials that enrolled 5377 elderly patients. The study found a 1.6- to 1.7-fold increased risk for death in elderly patients with dementia-related psychosis who were treated with atypical antipsychotics compared with those treated with placebo.

The FDA has determined that 2 retrospective cohort studies that were published recently, despite their methodological limitations, provide evidence that conventional antipsychotics share the increased risk for death in elderly patients with dementia-related psychosis that has been observed for atypical antipsychotics (Gill SS et al. Ann Intern Med 2007;146:775-786; Schneeweiss S et al. CMAJ 2007;176:627-632).

People taking antipsychotic drugs should not abruptly stop taking them. Caregivers and patients should talk to the patient's healthcare professionals about any concerns, a press release issued by the FDA states.

Antipsychotic Drugs Involved in the FDA Action

Conventional Atypical
Prochlorperazine (Compazine) Aripiprazole (Abilify)
Haloperidol (Haldol) Clozapine (Clozaril, FazaClo)
Loxapine (Loxitane) Ziprasidone (Geodon)
Thioridazine (Mellaril) Paliperidone (Invega)
Molindrone (Moban) Risperidone (Risperdal)
Thiothixene (Navane) Quetiapine (Seroquel)
Pimozide (Orap) Olanzapine (Zyprexa)
Fluphenazine (Prolixin) Olanzapine and fluoxetine (Symbyax)
Trifluoperazine (Stelazine)  
Chlorpromazine (Thorazine)  
Perphenazine (Trilafon)  



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