The director of the University of Rochester Alzheimer's Disease Care, Research and Education Program spoke about the need to rethink trial design and Alzheimer neuropsychiatric symptom management.
"If you don’t have neuropsychiatric symptoms, you’re going to develop them at some point during the disease."
Anton P. Porsteinsson, MD, sat with NeurologyLive at the Alzheimer’s Association International Conference on Alzheimer’s Disease (ICAD) in Chicago, Illinois, to talk about the way that the s-CitAD Study, on which he was an author, is going to seek to shift the way that the field thinks about the design and execution of clinical trials.
The director of the University of Rochester Alzheimer's Disease Care, Research and Education Program, noted that the trial of s-Citalopram is going to focus on enrolling patients in a real-world population and to limit the restrictions of the entry criteria, with an ultimate goal of having the trial be truly reflective of how physicians that are treating patients with Alzheimer disease operate clinically. Mainly, Porteinsson said, to focus on the non-pharmacologic, psycho-social interventions for neuropsychiatric symptoms that can be implemented ahead of the pharmacologic treatments.
He detailed that currently, the focus in recent years in the realm of neuropsychiatric symptoms in Alzheimer disease has been on agitation, despite multiple other symptoms impacting patients at an almost universal rate. Symptoms such as apathy and psychosis have become legitimate concerns, and Porteinsson stressed a need for the community to come to a consensus on developing safe, well-tolerated, and most importantly, effective treatments.
The trial itself is building upon the original CitAD trial, which found that racemic citalopram was effective for agitation, with 40% of citalopram-treated participants experiencing substantial clinical improvement compared to 26% given placebo. Although, citalopram was associated with cognitive worsening and prolongation of the electrocardiogram-QTc interval. When analyzing blood concentration models, it was revealed that cognitive and cardiac changes were associated with the R-enantiomer, whereas clinical improvements were primarily associated with the S-enantiomer (escitalopram). The new study seeks to enroll 589 patients and apply an evidence-based, sequential approach to treating agitation in Alzheimer with applicability in real-world settings. Participants not showing clinically significant improvement in agitation after 3 weeks will be randomized to either 15 mg/day escitalopram, or placebo.