FDA Expands Mortality Warnings on Antipsychotic Drugs

The FDA has requested that boxed warnings about an increased risk of death in older people with dementia be added to a class of “conventional” antipsychotic drugs.

Prescribing antipsychotic drugs to treat behavioral problems in older people with dementia is an off-label use, but physicians may do so even with the new safety warning, which is “not a contraindication,” Thomas Laughren, director of CDER’s Division of Psychiatry Products, said in a conference call with reporters.

The agency has the authority to request that manufacturers add this warning under the FDA Amendments Act of 2007. Drugmakers must submit the new boxed warning language to the FDA within 30 days or provide a reason why they do not believe it is necessary.

In 2005, the FDA announced similar labeling changes for “atypical” antipsychotic drugs, such as Bristol-Myers Squibb’s Abilify (aripiprazole) and Eli Lilly’s Zyprexa (olanzapine). At the time, the agency did not have enough evidence to include conventional antipsychotics in the warning, and the quality of the evidence gathered from two observational epidemiological studies since then “is not ideal,” Laughren said.

However, the FDA decided to err on the side of caution by adding the boxed warning for the conventional class of antipsychotic drugs and slightly revising the language for the atypical class. There are 11 conventional antipsychotics in the class, including Thorazine (chlorpromazine) and Haldol (haloperidol).

Both conventional and atypical antipsychotics are dopamine receptor antagonists that block the action of naturally occurring dopamine in the brain and are primarily indicated for the treatment of symptoms associated with schizophrenia. They differ primarily in their side effects; the atypical drugs have a lower incidence of neurological side effects such as involuntary movements or “tics.”