Both approved and off-label uses of the drugs decreased, particularly among elderly patients with dementia.
Atypical antipsychotic use among elderly patients with dementia has declined since the April 2005 FDA advisory and subsequent black box warning of an increased mortality risk associated with off-label usage in this patient population. As reported in the January 11 Archives of Internal Medicine, E. Ray Dorsey, MD, and colleagues found that overall use of these medications decreased by 19% in patients with dementia in the year following the warning, and it continued to decrease for all patient populations.
Dr. Dorsey, of the Department of Neurology at the University of Rochester Medical Center in New York, and colleagues reviewed data from the IMS National Disease and Therapeutic Index between January 2003 and December 2008 to examine an office-based use of atypical drugs, such as clozapine, risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, and paliperidone. An interrupted time-series analysis was used to quantify the advisory’s impact on usage in the targeted population of patients ages 65 and older with dementia, as well as all patients, for both approved and off-label uses.
The Rise and Fall of Atypical Antipsychotic Use
Between January 2003 and March 2005, mentions of atypical antipsychotic use increased annually by 34% among all patients and 16% among elderly dementia patients. In 2004, there were 13.6 million mentions of the drugs, 0.8 million of which were for patients with dementia. In the year following the advisory, atypical drug use decreased by 2% overall, and 19% among patients with dementia.
From the time of the advisory to the end of 2008, monthly atypical drug usage declined by more than 50% among elderly patients with dementia. In 2004, 19% of all drug mentions among those with dementia were for an atypical agent, which declined to 9% by 2008. Before and after the advisory, the majority of drug mentions in these patients were for off-label uses with uncertain evidence.
“While the potential benefit of decreased atypical drug use among this population may be large based on epidemiological studies, considerable atypical drug use for dementia continues,” the researchers wrote. “Nearly 10% of prescription drug uses for dementia among elderly patients are for atypical antipsychotics; as of December 2008, there were 8,000 new atypical drug uses each month among patients with dementia, despite the increased risk of death and limited evidence of their efficacy.”
An Unintended Side Effect
The investigators noted that this black box warning was different than many other advisories, because it applied only to off-label usage in elderly patients with dementia, rather than a broader population of prescription drug users. However, the warning was associated with declines across all patient populations and uses.
“Given the decline in use for populations outside the advisory’s target and for FDA-approved indications for which effectiveness has been demonstrated, the observed ‘spill over’ effect is likely unintended and may be detrimental to the public’s health,” the researchers wrote, adding that this effect has been seen after previous black box warnings. “Targeting specific segments of patients and physicians (eg, high prescribers) and further customizing and evaluating the impact of regulatory actions may improve their impact at minimizing the risks associated with select prescription medications.”
—Rebecca K. Abma