Many studies have previously shown that antipsychotic medication increases the risk of death in patients with dementia, but researchers recently discovered that some drugs may be riskier than others.

In 2008 the U.S. Food and Drug Administration issued a black box warning on all old and new antipsychotics describing the increased mortality risk in elderly patients treated for dementia-related psychosis, but the latest study discovered that the death risk varies significantly from drug to drug and increases with higher doses.

Researchers said that haloperidol doubled the risk of death in patients compared to risperidone, and patients treated with quetiapine were significantly less likely to die compared to risperidone patients. Researchers said that there were no significant differences between other types of antipsychotics and risperidone, which was used as a reference drug because it was the most commonly used drug in the study population.

The study examined data from 75,445 participants who were all older than 65 years old and who started treatment with an antipsychotic drug during a stay in a nursing home from 2001 to 2005. Researchers examined the effects of haloperidol, aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone, and excluded the other antipsychotic drugs because they were used by too few patients.

Researchers said a total of 6,598 patients had died within the six month study from non-cancer related causes during the first 180 days after the start of treatment, and the death risk appeared greatest in patients receiving the highest doses, and appeared to increase as dosage increased.

“The evidence accumulated so far implies that use of haloperidol in this vulnerable population cannot be justified because of the excess harm. Quetiapine might be somewhat safer than other atypical drugs, but these findings will require replication in other studies,” the authors concluded.

The study was published on Thursday in the journal BMJ.

Antipsychotics are commonly used agitation or disruptive behaviors in dementia patients, and study author Krista Huybrechts of Harvard Medical School wrote despite FDA warnings in 2005 and in 2008, the use of “the use of these drugs is likely to continue because of the continued growth of the dementia population" and the need for some type of intervention,” according to a news release.

Dr. McCleery from the Oxford NHS Foundation Trust argued in an accompanying editorial that future research should work on identifying the effectiveness of non-drug based interventions and how these alternatives can be implemented in dementia treatment.