At least half of Parkinson’s disease patients experience psychosis at some point during the course of their illness, and physicians commonly prescribe antipsychotic drugs, such as quetiapine, to treat the condition. However, a new study by researchers at the Perelman School of Medicine at the University of Pennsylvania, the University of Michigan Medical School, and the Philadelphia and Ann Arbor Veterans Affairs (VA) Medical Centers and suggests that these drugs may do significantly more harm in a subset of patients. The findings will be published in the March 21 issue of JAMA Neurology.

The researchers’ analysis of about 15,000 patient records in a VA database found that Parkinson’s patients who began using antipsychotic drugs were more than twice as likely to die during the following six months, compared to a matched set of Parkinson’s patients who did not use such drugs.

“I think that antipsychotic drugs should not be prescribed to Parkinson’s patients without careful consideration,” said first authorDaniel Weintraub, MD, who is an associate professor of Psychiatryand Neurology at Penn Medicine and a fellow in Penn’s Institute on Aging. Senior author Helen C. Kales, MD, professor of Psychiatry at University of Michigan and a Research Investigator at the VA Center for Clinical Management Research added, “Treatment with antipsychotics should be reserved for those cases where the benefits exceed the risks.”

These findings are not the first to link antipsychotic drugs to increased mortality. Studies dating back to the early 2000s, including a number from Dr. Kales’ group, have found increased mortality with antipsychotic use among patients who have dementia in the general population. Since 2005 the FDA has mandated “black box” warnings on antipsychotic drug packaging, noting the apparently increased risk of death when these drugs are used in dementia patients.

Although most dementia cases are accounted for by Alzheimer’s disease, there are other forms of dementia, including one that eventually emerges in about 80 percent of Parkinson’s patients, usually many years after their Parkinson’s diagnosis. However, a study by Weintraub, Kales and colleagues in 2011 found that the FDA warnings had done little to curb antipsychotic prescriptions for Parkinson’s dementia patients.

For the new study, Weintraub, Kales and colleagues examined the possibility that antipsychotic drug use is associated with higher mortality not just in Parkinson’s dementia patients, but in all Parkinson’s disease patients. Psychosis in Parkinson’s, although it is associated with dementia and later-stage disease, can occur even in the early stages of illness and in the absence of dementia. “It happens not uncommonly earlier in the course of the illness,” Weintraub said.

The underlying causes of psychosis in Parkinson’s are not well understood, but are thought to include the spread of the neurodegenerative disease process to certain brain areas, as well as particular or higher doses of Parkinson’s drugs that enhance dopamine function.

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