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

​​​​​​​​ 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.