Pharmacology and Evidence-Based Strategies for Current and Emerging Treatments for OFF Periods in Parkinson Disease

After several years, patients with Parkinson disease often experience OFF episodes, or periods each day when medication efficacy “wears off.” How can you increase their ON time? In this CME activity, follow along as 2 experts review evidence on treatment.


Parkinson disease (PD) is a progressive neurodegenerative disease characterized by motor symptoms such as rigidity, resting tremor, and slowed movement in addition to nonmotor symptoms. As the disease advances and a patient’s response duration to a levodopa dose is shortened, OFF episodes become more prevalent, negatively impacting their quality of life. Clinicians may employ a variety of therapeutic strategies to reduce OFF time, such as altering the levodopa dose or initiating adjuvant therapy. Medications to treat daily OFF time include dopamine agonists, MAO-B inhibitors, COMT inhibitors, amantadine ER, and adenosine A2A antagonists; as-needed rescue therapies include subcutaneous apomorphine, apomorphine sublingual film, and orally inhaled levodopa; and, when necessary, advanced therapies such as carbidopa/levodopa enteral suspension or DBS may be indicated.

From the Series: Recognizing and Managing OFF Periods in Patients with Parkinson Disease

To cite: Isaacson S, Pahwa R. Pharmacology and evidence-based strategies for current and emerging treatments for OFF periods in Parkinson disease. J Clin Psychiatry. 2021;82(1):SU19004BR2C.

To share:

© Copyright 2020 Physicians Postgraduate Press, Inc. 

Target Audience

Neurologists, nurse practitioners & physician assistants, and other clinicians who specialize in movement disorders and treating patients with PD

Learning Objectives

  • Incorporate an understanding of Parkinson disease (PD) treatment mechanisms into care for OFF episodes
  • Provide evidence-based treatment for OFF periods in patients with PD
Activity summary
Available credit: 
  • 1.50 AMA PRA Category 1 Credit™
  • 1.50 Participation
Activity opens: 
Activity expires: 

Support Statement

Supported by an educational grant from Sunovion Pharmaceuticals Inc.

Learning Objective

After completing this educational activity, you should be able to:

  • Incorporate an understanding of Parkinson Disease (PD) treatment mechanisms into care for OFF episodes
  • Provide evidence-based treatment for OFF periods in patients with PD

Release, Review, and Expiration Dates

This brief report activity was published in November 2020 and is eligible for AMA PRA Category 1 Credit™ through November 30, 2022. The latest review of this material was October 2020.

Statement of Need and Purpose

Physicians and patients are not communicating clearly about OFF episodes, and detection through clinical evaluation alone is less accurate than if an assessment tool is used. Neurologists, therefore, need education on the use of assessment tools, facilitating good communication with patients and care partners, and risk factors for OFF periods. Because therapeutic strategies for OFF episodes have expanded, and guidelines were recently updated, clinicians also need education from experts about new treatment strategies for OFF episodes and current guidelines. This activity was designed to meet the needs of participants in CME activities provided by the CME Institute of Physicians Postgraduate Press, Inc., who have requested information on Parkinson disease.

Disclosure of Off-Label Usage

The authors have determined that, to the best of their knowledge, amantadine ER is not approved by the US Food and Drug Administration for the treatment of OFF periods in patients with Parkinson disease..

Review Process

The faculty members agreed to provide a balanced and evidence-based presentation and discussed the topics and CME objectives during the planning sessions. The faculty’s submitted content was validated by CME Institute staff, and the activity was evaluated for accuracy, use of evidence, and fair balance by the Chair and a peer reviewer who is without conflict of interest.


This activity is derived from the teleconference series “Recognizing and Managing OFF Periods in Patients With Parkinson Disease,” which was held in May–July 2020 and supported by an educational grant from Sunovion Pharmaceuticals Inc. The opinions expressed herein are those of the faculty and do not necessarily reflect the opinions of the CME provider and publisher or the commercial supporter.

Faculty Affiliation

Rajesh Pahwa, MD
The University of Kansas Medical Center, Kansas City

Stuart H. Isaacson, MD
Parkinson’s Disease and Movement Disorders Center of Boca Raton, Florida

Financial Disclosure

The faculty for this CME activity and the CME Institute staff were asked to complete a statement regarding all relevant personal and financial relationships between themselves or their spouse/partner and any commercial interest. The Accreditation Council for Continuing Medical Education (ACCME) defines a commercial interest as any entity producing, marketing, re-selling, or distributing health care goods or services consumed by, or used on, patients. The ACCME defines relevant financial relationships as financial relationships in any amount occurring within the past 12 months that create a conflict of interest. The CME Institute has resolved any conflicts of interest that were identified. No member of the CME Institute staff reported any relevant personal financial relationships. Faculty financial disclosures are as follows:

Dr Isaacson is a consultant for, has received grant/research support from, has received honorarium from, and is on the speakers/advisory boards for AbbVie, Acadia, Acorda, Adams, Addex, Allergan,  Amarantus BioScience, Axovant, Benevolent AI, Biogen, Britannia Pharmaceuticals, Cerecor, Eli Lilly, Enterin, GE Healthcare, Global Kinetics, Impax, Intec Pharma, Ipsen, Jazz, Kyowa, Lundbeck, Michael J. Fox Foundation, Neurocrine, Neuroderm, Parkinson Study Group, Pharma2B, Roche, Sanofi, Sunovion, Teva, Thereavance, UCB, US WorldMeds, and Zambon.

The Chair for this activity, Rajesh Pahwa, MD, is a consultant for Abbott, AbbVie, Acadia, Acorda, Amneal, CalaHealth, Global Kinetics, Impel Neuropharma, Kyowa, Lundbeck, Mitsubishi, Neurocrine, Prilenia, Sunovion, and US WorldMeds; has received grant/research support and honoraria from, and is a member of the speakers/advisory boards for Abbott, AbbVie, Addex, Biogen, Biohaven, Boston Scientific, EIP, Global Kinetics, Impax, Initec, Lilly, Neuroderm, Neuraly, Parkinson’s Foundation, Pharma2B, Prelinia, Roche, SIS Labs, Sun Pharma, Sunovion, Theranexus, Theravance, US WorldMeds, and Voyager.

Accreditation Statement

The CME Institute of Physicians Postgraduate Press, Inc., is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.



Credit Designation

The CME Institute of Physicians Postgraduate Press, Inc., designates this enduring material for a maximum of 1.5 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Note: The American Nurses Credentialing Center (ANCC) and the American Academy of Physician Assistants (AAPA) accept certificates of participation for educational activities certified for AMA PRA Category 1 Credit™ from organizations accredited by the ACCME.

To obtain credit for this activity, study the material and complete the CME Posttest and Evaluation.

MOC Approval Statement

Through the American Board of Medical Specialties (“ABMS”) ongoing commitment to increase access to practice relevant Continuing Certification Activities through the ABMS Continuing Certification DirectoryPharmacology and Evidence-Based Strategies for Current and Emerging Treatments for OFF Periods in Parkinson Disease has met the requirements as a MOC Part II CME Activity (apply toward general CME requirement) for the following ABMS Member Boards:

MOC Part II CME Activity

Psychiatry and Neurology

Available Credit

  • 1.50 AMA PRA Category 1 Credit™
  • 1.50 Participation


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