Pharmacological Interventions for Orthostatic Hypotension: A Systematic Review.

Orthostatic hypotension (OH), defined as a sustained drop in systolic (≥20 mmHg) or diastolic (≥10 mmHg) blood pressure upon standing, is a debilitating condition prevalent in older adults and individuals with neurodegenerative disorders. It significantly impacts quality of life, leading to dizziness, falls, and syncope, and is associated with increased morbidity and mortality. This systematic review evaluates the efficacy and safety of pharmacological treatments for OH. Following the PRISMA 2020 guidelines, 25 studies, including randomized (RCTs) and non-randomized controlled trials (NRCTs), were analyzed. Study quality was assessed using the Cochrane Risk of Bias 2 (ROB 2) tool, the Joanna Briggs Institute (JBI) Checklist, and the Newcastle-Ottawa Scale (NOS). The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework was applied to evaluate the certainty of evidence across key outcomes. Drugs approved by the U.S. Food and Drug Administration (FDA), such as droxidopa and midodrine, consistently improve orthostatic symptoms and are recommended as first-line therapies. Atomoxetine and fludrocortisone showed moderate efficacy, while pyridostigmine in combination therapies provided additional benefits. Octreotide demonstrated potential for refractory OH but lacked robust evidence. Adverse effects, including supine hypertension, dizziness, gastrointestinal disturbances, and fatigue, highlight the need for personalized therapy to balance efficacy and tolerability. While pharmacological treatments show promise, further comparative and long-term studies are necessary to refine therapeutic strategies and improve patient outcomes.