Treatment of autonomic dysfunction in Parkinson disease and other synucleinopathies

Abstract

Dysfunction of the autonomic nervous system afflicts most patients with Parkinson disease and other synucleinopathies such as dementia with Lewy bodies, multiple system atrophy, and pure autonomic failure, reducing quality of life and increasing mortality. For example, gastrointestinal dysfunction can lead to impaired drug pharmacodynamics causing a worsening in motor symptoms, and neurogenic orthostatic hypotension can cause syncope, falls, and fractures. When recognized, autonomic problems can be treated, sometimes successfully. Discontinuation of potentially causative/aggravating drugs, patient education, and nonpharmacological approaches are useful and should be tried first. Pathophysiology-based pharmacological treatments that have shown efficacy in controlled trials of patients with synucleinopathies have been approved in many countries and are key to an effective management. Here, we review the treatment of autonomic dysfunction in patients with Parkinson disease and other synucleinopathies, summarize the nonpharmacological and current pharmacological therapeutic strategies including recently approved drugs, and provide practical advice and management algorithms for clinicians, with focus on neurogenic orthostatic hypotension, supine hypertension, dysphagia, sialorrhea, gastroparesis, constipation, neurogenic overactive bladder, underactive bladder, and sexual dysfunction. © 2018 International Parkinson and Movement Disorder Society.

Update on treatments for nonmotor symptoms of Parkinson's disease—an evidence‐based medicine review

“…Although there is insufficient evidence for the efficacy of fludrocortisone and midodrine for the treatment of OH in PD, it is considered to be “possibly useful” because of its proven efficacy outside of PD with some signals of efficacy detected in the PD trials . Recently, the norepinephrine transporter blocker atomoxetine has been shown to increase standing blood pressure and reduce the burden of OH symptoms when compared with placebo in mixed cohorts of patients with neurogenic OH …”

“…Even when nonpharmacological methods 57,157,158 are performed properly, many patients still require pharmacological treatment to improve symptomatic OH. 157 Droxidopa is "clinically useful" for the short-term treatment of OH, whereas no data from RCTs in PD are available for longer treatment times. Although there is insufficient evidence for the efficacy of fludrocortisone and midodrine for the treatment of OH in PD, it is considered to be "possibly useful" because of its proven efficacy outside of PD with some signals of efficacy detected in the PD trials.…”

“…2 Recently, the norepinephrine transporter blocker atomoxetine has been shown to increase standing blood pressure and reduce the burden of OH symptoms when compared with placebo in mixed cohorts of patients with neurogenic OH. 157 Before attempting any treatment for lower urinary tract symptoms, urinary tract infections, prostate disease in men, and pelvic floor disease in women should be ruled out. Solifenacin, a type 3 muscarinic receptor antagonist, is considered "possibly useful" in PD, whereas there are no level I data available in PD patients for other muscarinic receptor antagonists or the selective β3-adrenoceptor agonist mirabegron.…”

Digestive Symptoms of Autonomic Dysfunction in Parkinson’s Disease Patients

“…autonomic dysfunction is also a common complication of Parkinson's disease (88.46% of the patients) (2). symptoms of autonomic nervous system (ans) dysfunction in PD (cardiovascular, thermoregulatory, gastrointestinal, urinary, sexual) are reported among the most debilitating (3). gastrointestinal symptoms in PD include dysphagia, nausea, constipation, and defecatory dysfunction.…”

Dysautonomia in the synucleinopathies: not just orthostatic hypotension

“…Among the best-known and better described features of synuclein-mediated autonomic failure is neurogenic orthostatic hypotension (nOH), which results from inappropriate norepinephrine release from efferent sympathetic postganglionic fibers innervating the blood vessels when standing up. The increasing attention to nOH is well deserved given its significant morbidity and the availability of FDA-approved therapies [10]. Autonomic failure in the synucleinopathies, though, affects organs and systems other than the blood vessels, including the heart, the skin and sweat glands, and the gastrointestinal and genitourinary systems.…”