Traditional Pharmacologic Therapies for Alzheimer's Disease Agitation: Mechanisms, Evidence, and Adverse Events

In this episode, 'Traditional Pharmacologic Therapies for Alzheimer's Disease Agitation: Mechanisms, Evidence, and Adverse Events,' the expert neurologists explored the following questions: What are the traditional therapies such as antipsychotics used in the management of patients with Alzheimer's disease agitation and their respective mechanisms of action?What has the data demonstrated with these therapies? What are the adverse events seen with these therapies? When are you utilizing dose reductions with these therapies? Anton Porsteinsson provided a comprehensive overview of the traditional pharmacologic landscape for Alzheimer's disease agitation, noting that up to half of patients ultimately require pharmacologic treatment and that conventional and atypical antipsychotics including haloperidol, risperidone, olanzapine, and quetiapine remain the most widely used agents despite limited and inconsistent evidence of efficacy. He outlined the significant adverse event burden associated with these agents, including sedation, increased falls, cognitive worsening, Parkinsonian features, gastrointestinal symptoms, and a boxed warning for increased all-cause mortality and cerebrovascular events in elderly patients with dementia. Alireza Atri added that as antipsychotic use has declined over the past decade in response to safety concerns, clinicians have increasingly turned to other off-label options including benzodiazepines, selective serotonin reuptake inhibitors (SSRIs), trazodone, gabapentin, and mood-stabilizing anticonvulsants such as valproate, none of which carry a well-established evidence base for agitation and many of which introduce their own meaningful adverse effect profiles, underscoring the urgent need for the two recently approved agents now available for this indication. Throughout the conversation, the experts provided a comprehensive reflection on the field and the factors that may shape how clinicians approach care moving forward. In the next episode, 'Brexpiprazole and Dextromethorphan-Buproprion: Mechanisms of Action and Key Clinical Trial Data for Approved Alzheimer's Disease Agitation Therapies,' panelists continue their discussion on Alzheimer's disease agitation and highlight the mechanisms of action of brexpiprazole and dextromethorphan-bupropion, the two Food and Drug Administration (FDA)-approved therapies for this indication, and the key safety and efficacy results from their pivotal clinical trials.