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Managing “OFF” Symptoms of Parkinson’s Disease
Matthew Swan, MD, Assistant Professor of Neurology, Icahn School of Medicine, Mount Sinai, New York, New York, discussed MD discussed wearing-off symptoms of Parkinson’s Disease, the use of catechol-O-methyltransferase (COMT) inhibitors as adjunctive therapy, and patient communication during a virtual presentation at Neurology Week.
Dr Swan described early treatment for Parkinson’s disease, a chronic neurodegenerative disorder, as a “honeymoon period.” After which, motor complications make managing and treating Parkinson’s disease more difficult.
Complications include wearing off, which is a waning effect on medications prior to the next dose, also known as an OFF period; delayed onset of medication working; sudden OFF where symptoms re-emerge in the middle of dosing interval; dyskinesia; early morning off periods before medication is taken; as well as dose failure.
The mean duration from disease onset to onset of motor complications was found to be 6-7 years in a recent study.
Other research suggests long-duration responses decay over time, so patients experience shorter duration responses and subsequent fluctuations.
“Early PD can initially be managed using levodopa, dopaminergic agonists, or monoamine oxidase type B (MAO B) inhibitors; however, over time patients begin to experience periodic reemergence of motor symptoms, regardless of treatment, which are believed to be the result of the progressive pathophysiology of PD and long-term levodopa treatment,” Dr Swan said.
OFF periods can cause nonmotor fluctuations such as cognitive changes, pain, and autonomic disorders, in addition to fluctuations of mood, anxiety, urinary dysfunction, and more.
The burden of non-motor symptoms and fluctuations increases over time with disease progression. Patients experiencing OFF periods often also report worse quality of life. Fluctuations are reported as one of the most difficult symptoms in patients with Parkinson’s disease for 6 years or more.
Dr Swan highlighted scales and screening tools to assess motor fluctuations, including the Wearing-Off Questionnaire-32 (WOQ-32) as well shortened version (WOQ-19, WOQ-9).
The presentation highlighted management approaches to wearing-off including adjusting dosing intervals of levodopa, reducing pulsatile stimulations, adding adjunctive medications, and deep brain stimulation, but focused on the addition of COMT inhibitors as an adjunctive treatment.
COMT inhibitors increase levodopa bioavailability in the central nervous system. Dr Swan walked through the treatment landscape over the last two decades of 1st, 2nd and 3rd generation options, entacapone, tolcapone, and opicapone, respectively.
The presentation included possible patient cases and considerations for determining the right treatment approach.
“In my practice I see that many patients are burdened by planning their day around medication,” noted Dr Swan.
Patient communication is critical to determining the best treatment option to better manage OFF periods. Dr Swan recommended asking patients:
- What symptoms and fluctuations bothered them the most? Such as OFF time or dyskinesia? Motor OFFs or nonmotor OFFs?
- What are specific challenges of treatment impacting their quality of life? Such as high dosing frequency, pill burden or expense?
“Effective management of wearing-off and motor fluctuations requires collaboration with patients – the best approach must incorporate a patient’s treatment goals,” Dr Swan concluded. —Erin McGuinness and Kaitlyn Manasterski
Swan, M. Moving “OFF” Time to “ON” Time: A Focus on COMT Inhibitors for Parkinson’s Disease “OFF” Symptoms. Presented at Neurology Week 2021; July 14-18. Virtual.
