Orthostatic hypotension: new frontiers in pharmacotherapeutic management

Orthostatic hypotension remains one of the most disabling manifestations of autonomic failure. Current therapies can improve upright blood pressure and orthostatic tolerance, but treatment is often limited by modest efficacy, short duration of action, and worsening of coexisting supine hypertension.

This review summarizes the contemporary management of orthostatic hypotension in adults with autonomic failure. After briefly reviewing epidemiology, hemodynamic physiology, and major etiologic categories, the discussion focuses on reviewing current non-pharmacological and pharmacological treatments for OH and supine hypertension and explores new emerging therapies for both.

The next phase of the field will likely depend less on identifying a single superior pressor agent and more on treating OH and supine hypertension as a coupled disorder of impaired blood pressure control. Mechanism-based treatment selection, informed by physiological phenotyping, will be increasingly important in explaining therapeutic heterogeneity and matching patients to intervention. Emerging strategies, including norepinephrine transporter inhibition, carbon dioxide-based therapy, continuous positive airway pressure, dynamic mechanical support, passive heat, and neuromodulation, may help expand treatment beyond conventional vasoconstriction.