A preprint posted to medRxiv on June 4, 2026, describes methods to reduce the placebo response seen in clinical trials of agitation in Alzheimer's disease, a problem the paper's authors call a major obstacle to developing new treatments for the symptom. The paper reports that high placebo response, meaning large apparent improvement among patients assigned to inactive treatment, has repeatedly complicated the interpretation of agitation trials, making it hard to separate a drug's true effect from improvement that would have happened anyway. The authors set out to build models of placebo response that can be applied prospectively, using only information available at a trial's screening or baseline visit, and to identify design strategies that reduce placebo response without also blunting the ability to detect a real drug effect. Agitation in Alzheimer's disease, sometimes grouped with behavioral and psychological symptoms of dementia, affects a large share of people living with the condition and is a leading reason for nursing home placement, which is part of why the field has continued searching for reliable ways to test new drugs against it. The stakes are current: brexpiprazole, approved for Alzheimer's agitation, carries a boxed warning about increased mortality risk in older adults with dementia-related psychosis, and a newly approved dextromethorphan-bupropion combination has not closed the unmet need for safer, more effective options, leaving trial methodology itself as a bottleneck to bringing forward the next generation of candidates. Independent reviews of past agitation trials have separately found that most studies made little or no attempt to address placebo response in their design, a gap the new preprint's models and strategies are aimed at closing.