State-of-the-art pharmacotherapy for autonomic dysfunction in Parkinson’s disease

ABSTRACT

Introduction: Autonomic dysfunction is one of the most frequent and disabling non-motor symptoms of Parkinson’s disease (PD). It includes, among others, orthostatic hypotension (OH), sialorrhea, constipation, erectile dysfunction (ED), urinary dysfunction, and diaphoresis. They are usually under-recognized and suboptimally managed.

Areas covered: Recommended treatments for dysautonomias are summarized with a description of the mechanism of action and observed results. The pathophysiology of each disorder is reviewed to pinpoint possible therapeutic targets. Drugs approved for treating dysautonomia in the general population along with those under development for PD-related dysautonomia are also reviewed. Finally, the key elements of each symptom that should be addressed in clinical trials’ design are considered.

Expert opinion: Midodrine, droxidopa, fludrocortisone, and domperidone may be used for OH treatment. Sialorrhea can be managed with botulin toxin injections and oral glycopyrrolate. Erectile dysfunction can benefit from sildenafil treatment, as urinary dysfunction can from solifenacin. Macrogol, lubiprostone, and probiotics might be effective in treating constipation. Further research is needed to determine adequate treatment for diaphoresis in PD patients. Multidisciplinary management of motor and non-motor symptoms in PD is the best approach for dysautonomias in PD.

KEYWORDS:

• Autonomic nervous system
• dysautonomia
• non-motor symptoms
• Parkinson’s disease
• treatment
• clinical trials
• evidence-based medicine

Article highlights

• Autonomic dysfunction is one of the most frequent non-motor symptoms of Parkinson’s disease

• Dysautonomia is associated with a worse quality of life and a higher demand for health care use.

• Clinical trials for interventions on dysautonomia in PD often suffer from shortcomings, limiting their ability to support clinical recommendations.

• Midodrine, droxidopa, fludrocortisone, and domperidone may be used for OH treatment. Botulin toxin injections and oral glycopyrrolate may be recommended for sialorrhea. Erectile dysfunction can benefit from sildenafil treatment. Urinary dysfunction may be treated by solifenacin. Macrogol, lubiprostone, and probiotics might be effective in treating constipation.

• Further research is warranted to identify safe and effective agents for dysautonomia treatment in PD.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was not funded.