Diagnosing and treating neurogenic orthostatic hypotension in primary care

Abstract

In response to a change in posture from supine or sitting to standing, autonomic reflexes normally maintain blood pressure (BP) by selective increases in arteriovenous resistance and by increased cardiac output, ensuring continued perfusion of the central nervous system. In neurogenic orthostatic hypotension (NOH), inadequate vasoconstriction and cardiac output cause BP to drop excessively, resulting in inadequate perfusion, with predictable symptoms such as dizziness, lightheadedness and falls. The condition may represent a central failure of baroreceptor signals to modulate cardiovascular function, a peripheral failure of norepinephrine release from cardiovascular sympathetic nerve endings, or both. Symptomatic patients may benefit from both non-pharmacologic and pharmacologic interventions. Among the latter, two pressor agents have been approved by the US Food and Drug Administration: the sympathomimetic prodrug midodrine, approved in 1996 for symptomatic orthostatic hypotension, and the norepinephrine prodrug droxidopa, approved in 2014, which is indicated for the treatment of symptomatic neurogenic orthostatic hypotension caused by primary autonomic failure (Parkinson’s disease, multiple system atrophy and pure autonomic failure). A wide variety of off-label options also have been described (e.g. the synthetic mineralocorticoid fludrocortisone). Because pressor agents may promote supine hypertension, NOH management requires monitoring of supine BP and also lifestyle measures to minimize supine BP increases (e.g. head-of-bed elevation). However, NOH has been associated with cognitive impairment and increases a patient’s risk of syncope and falls, with the potential for serious consequences. Hence, concerns about supine hypertension – for which the long-term prognosis in patients with NOH is yet to be established – must sometimes be balanced by the need to address a patient’s immediate risks.

Keywords :

• Neurogenic orthostatic hypotension
• supine blood pressure
• supine hypertension
• reduction of falls

Declaration of interest

This review was funded by Lundbeck LLC. Editorial assistance in developing this manuscript was provided by The Curry Rockefeller Group, LLC, which was funded by Lundbeck LLC. L Kuritzky has received consultancy fees from Lundbeck LLC and is a member of the speakers’ bureau for Lundbeck LLC. AJ Espay is supported by the K23 career development award (NIMH, 1K23MH092735); has received grant support from CleveMed/Great Lakes Neurotechnologies, and the Michael J Fox Foundation; personal compensation as a consultant/scientific advisory board member for AbbVie, Chelsea Therapeutics (now Lundbeck NA Ltd), Teva, Impax, Merz, Pfizer, Acadia, Cynapsus, Solstice Neurosciences, Eli Lilly, Lundbeck LLC and USWorldMeds; royalties from Lippincott Williams & Wilkins and Cambridge University Press; and honoraria from UCB, Teva, the American Academy of Neurology and the Movement Disorders Society. He serves as Associate Editor of Movement Disorders, Frontiers in Movement Disorders and Journal of Clinical Movement Disorders, and serves on the editorial boards of Parkinsonism and Related Disorders and The European Neurological Journal. R Payne is an employee and CEO of North Coast Family Medical Group. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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