The time to discontinuation because of lack of efficacy was longer for active medicines (ie, beneficial), said Sultzer, one of the lead investigators in the CATIE-AD trial.
“So if the rationale for change was that they didn’t seem to be working well enough, antipsychotics won, but when the change was due to adverse effects, placebo won, so when you add them together, it was essentially a wash,” he said.
More recently, the CATIE-AD study group published a paper exploring possible antipsychotic treatment effects on distinct symptoms.3 Sultzer, director of the Gero/Neuropsychiatry Division of the VA Greater Los Angeles Healthcare System, was the first author.
“Our goal was to try to understand whether there was a particular kind of symptom that may respond better to antipsychotics compared to placebo,” Sultzer explained.
If you looked at a global symptom measure, there was a significant effect of risperidone(Drug information on risperidone) and olanzapine(Drug information on olanzapine) treatment over placebo, based on rating scale scores at the time that initial phase ended, he said. Symptoms of hostility, aggression, anger, and paranoia responded best to antipsychotic treatment, although the improvement was modest on average, and many patients still had symptoms.
The differences between the 3 antipsychotics were fairly small, partly because the overall effects were mild. Sultzer added that from a research design standpoint, distinguishing between the medications was challenging.
Quetiapine did not do as well, but that may be related to a dosing issue, because the doses of quetiapine(Drug information on quetiapine) were relatively low, although there were some adverse effects, he said. But between olanzapine and risperidone, “there were few differences.”
In relation to placebo, the last observation in phase 1 of CATIE-AD showed greater improvement with olanzapine or risperidone on the Neuropsychiatric Inventory total score, and improvement with risperidone on the CGIC. Patients treated with risperidone or olanzapine showed improvement on the Brief Psychiatric Rating Scale (BPRS) hostile suspiciousness factor. The BPRS psychosis factor also improved with risperidone.
However, “antipsychotic treatment effects on the BPRS agitation factor score, which includes excitability, tension, and anxiety were not as robust,” according to Sultzer and his coauthors.
Nor were beneficial effects apparent on measures of functional abilities, quality of life, or time needed for care giving.
“The olanzapine group actually did a little worse than the other antipsychotics and placebo for outcomes such as patients’ functional abilities and rating of blunted affect and emotional withdrawal,” said Sultzer.
In CATIE-AD when the clinician felt that the original medication was less than ideal, he or she could move to phase 2 and prescribe one of the other 2 antipsychotics not used in phase 1, or citalopram(Drug information on citalopram) (Celexa).
“The data for phase 2 of CATIE-AD have not yet been published,” Sultzer said. “At this stage it looks like the overall difference between antipsychotics and citalopram is not significant.”
In addition, Sultzer said, we are continuing to work with the CATIE data set, looking specifically at whether we can predict who is more likely to respond to treatment or who might be at greater risk.
The CATIE-AD researchers emphasized the need for additional studies to better understand the risk-benefit profile and effectiveness of specific treatments in individual patients. One such study is looking at the adverse effects of newer antipsychotics in older adults.