The patients were in their late 70s, on average.
The University of Southern California's Lon Schneider, MD, and colleagues randomly split the patients into four groups, giving each group a different drug.
One group received Zyprexa. Another group got Seroquel. A third group took Risperdal. For comparison, the fourth group got pills containing no medicine (placebo).
Drug doses were adjusted as needed.
The researchers tracked how long patients stayed on their assigned drug.
Eighty-two percent of the patients discontinued their assigned drug during the study.
Patients in all four groups stayed on their drugs (including the placebo) for a similar average amount of time: five to eight weeks, the study shows.
Between 16% and 24% of patients taking any of the antipsychotic drugs stopped taking those drugs due to adverse events -- such as sedation, tremors, or movement problems -- compared with 5% of those taking placebo.
The four groups also included similar percentages of patients who showed symptom improvements (26% to 32% of those taking antipsychotic drugs and 21% of the placebo group).
"Adverse effects offset advantages in the efficacy of atypical antipsychotic drugs for the treatment of psychosis, aggression, or agitation in patients with," the researchers write.
By "atypical antipsychotics," they mean newer antipsychotic drugs, which include those used in this study.
Full Results to Come
The option to switch to another drug might have led some patients to discontinue their assigned drug, the researchers note.
The results posted in The New England Journal of Medicine are just the first phase of a five-year study. So there are more findings to come from the study's later phases.
"Although the differences among the groups may have been significant in a larger trial, our findings suggest that there is no large clinical benefit of treatment with atypical antipsychotic medications as compared with placebo," the researchers write.
Prescribing Antipsychotics After 'Deliberation'
"We thought overall the drugs would show their effectiveness," Schneider says in a University of Southern California news release.
"The answer is yes, they are somewhat effective, but overall the efficacy is offset by adverse events that resulted in discontinuing the medication," Schneider continues.
"It was a surprise, in that the expert opinion which drove this study was that these drugs are particularly useful in treating these difficult symptoms," Schneider says.
"The findings here look at the time to discontinuation for the antipsychotics versus the placebo, and that time difference reflects the overall effectiveness of the medication. By that measure, the medications were not better than placebo," he says.
"The results suggest that antipsychotic drugs should be prescribed only with some deliberation," Schneider says.
The journal also includes an editorial by Jason Karlawish, MD, of the University of Pennsylvania's Alzheimer's Disease Center.
The findings "suggest that these drugs have a limited, but at time necessary, role in the care of patients with Alzheimer's disease," Karlawish writes.
"They are perhaps best prescribed in systems of care that can provide the skills and expertise needed to ensure that the risks associated with the drugs are justified by the potential benefits," Karlawish continues.
The study was funded by the National Institute of Mental Health. The drugs were supplied by the drugs' makers.
Schneider and colleagues report various financial ties to drug companies including the drugs' makers. Karlawish reports no such financial ties.
Zyprexa is made by Eli Lilly and Company. Seroquel is made by AstraZeneca. Risperdal is made by Janssen Pharmaceutica. Lilly and AstraZeneca are WebMD sponsors.