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New Developments in the Management of Neurogenic Orthostatic Hypotension

  • Hypertension (W White, Section Editor)
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Abstract

Orthostatic hypotension (OH) is defined as a sustained reduction of ≥20 mmHg systolic blood pressure or ≥10 mmHg diastolic blood pressure upon standing for ≤3 min. Orthostatic hypotension is commonly associated with hypertension, and its prevalence is highest in those with uncontrolled hypertension compared to those with controlled hypertension or normotensive community elderly subjects. Orthostatic hypotension can cause significant disability, with patients experiencing dizziness, lightheadedness or syncope, and other problems that potentially have a profound negative impact on activities of daily living that require standing or walking. Furthermore, OH increases the risk of falls and, importantly, is an independent risk factor of mortality. Despite its importance, there is a paucity of treatment options for this condition. Most of the advances in treatment options have relied on small studies of repurposed drugs done in patients with severe OH due to rare neurodegenerative conditions. Midodrine, an oral prodrug converted to the selective α1-adrenoceptor agonist desglymidodrine, was approved by the FDA for the treatment of OH in 1996. For almost two decades, no other pharmacotherapy was developed specifically for the treatment of OH until 2014, when droxidopa was approved by the FDA for the treatment of neurogenic OH associated with primary autonomic neuropathies including Parkinson disease, multiple system atrophy, and pure autonomic failure. These are neurodegenerative diseases ultimately characterized by failure of the autonomic nervous system to generate norepinephrine responses appropriate to postural challenge. Droxidopa is a synthetic amino acid that is converted to norepinephrine by dopa-decarboxylase, the same enzyme that converts levodopa into dopamine in the treatment of Parkinson disease. We will review this and other advances in the treatment of OH in an attempt to provide a practical guide to its management.

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Acknowledgments

Dr. Biaggioni is supported by the National Institutes of Health grants RO1 NS055670, PO1 HL56693, UL1 TR000445-06 (Clinical and Translational Science Award) and the Paden Dysautonomia Center.

Compliance with Ethics Guidelines

Compliance with Ethics Guidelines

Conflict of Interest

Dr. Biaggioni was a consultant for Chelsea Therapeutics, Inc. during the development of droxidopa.

Human and Animal Rights and Informed Consent

This article does not report any studies in human or animal subjects performed by the author.

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  1. Division of Clinical Pharmacology, Department of Medicine, and the Autonomic Dysfunction Center, 560 RRB, Vanderbilt University, Nashville, TN, 37232, USA

    Italo Biaggioni

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  1. Italo Biaggioni
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Correspondence to Italo Biaggioni.

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Biaggioni, I. New Developments in the Management of Neurogenic Orthostatic Hypotension. Curr Cardiol Rep 16, 542 (2014). https://doi.org/10.1007/s11886-014-0542-z

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