With two on-label agents now available, the panel turns to what actually drives the choice between them, noting how recently this was not the case: treatment was entirely off-label, clinical benefit was uncertain, and clinicians were taking on real risk without established evidence to support it. Having two studied, FDA-approved options changes that calculus meaningfully across every specialty caring for these patients.

Comorbidities and overall risk profile emerge as the leading factor in choosing between the two therapies. Patients already at elevated risk for falls, tardive dyskinesia, or existing metabolic and cardiovascular disease tend to steer the panel toward the non-antipsychotic combination first, reserving the antipsychotic option for patients who genuinely need it. Active psychosis moves the decision in the opposite direction, since the non-antipsychotic combination is not designed for that presentation; a patient who is easily activated, or who has a history of hypomania, mania, or activation on other psychotropic medications, similarly points toward the antipsychotic option, sometimes paired with an off-label anticonvulsant.

Long-term care introduces its own complicating layer. Having both agents available is described as a genuine game changer, since facility five-star quality ratings can be penalized by antipsychotic use, making it historically difficult to use an antipsychotic even in patients with psychosis who clearly needed one. Yet the panel is candid that this benefit cuts both ways: administrators and directors of nursing still apply real pressure to use the non-antipsychotic combination instead, purely because it does not affect the facility rating, even in a psychotic patient who may genuinely need an antipsychotic. The panel closes by noting that this dynamic, while still a live tension in long-term care today, is beginning to shift as comfort with both options grows.

Our next episode, "Shared Decision-Making for Agitation in Specialty Care and Disease Trajectory," turns to how shared decision-making plays out in specialty psychiatric care.