Abstract

ONE PILL, LESS ‘OFF’: OPICAPONE FOR PARKINSON’S MOTOR FLUCTUATIONS – A SYSTEMATIC REVIEW OF RCTS

*Anam Mansoor, Sarfas Naushad, Aswin Suresh Kumar, Asna Nazreen, Mohammad Khalid Hifzur Shaik

Abstract

Parkinson‘s disease (PD) is a progressive neurodegenerative disorder frequently managed with levodopa. However, longterm use of levodopa is often complicated by motor fluctuations, particularly the ―wearing-off‖ phenomenon, where the medication‘s effects diminish before the next dose. To address this, catechol-O-methyltransferase (COMT) inhibitors are used to prolong levodopa‘s duration of action. Among them, Tolcapone was the first to be introduced but was associated with serious hepatotoxicity, leading to limited use. Entacapone, a safer alternative, requires multiple daily doses due to its short half-life, which can affect adherence. Opicapone, a third-generation COMT inhibitor, has emerged as a once- daily option that may improve both efficacy and compliance. This systematic review aimed to evaluate the efficacy and safety of Opicapone compared to other COMT inhibitors—primarily Entacapone and, where relevant, Tolcapone—in patients with PD experiencing motor fluctuations. Following PRISMA guidelines, we identified and analyzed five randomized controlled trials (RCTs) that met inclusion criteria, encompassing a total of 2,396 participants. These studies evaluated changes in ―off‖ time, ―on‖ time, motor scores, and adverse events. Results consistently showed that Opicapone 50 mg significantly reduced daily ―off‖ time compared to placebo, with reductions ranging from approximately 60 to 118.8 minutes. In BIPARK-I, Opicapone was also found to be more effective than Entacapone in reducing ―off‖ time. Common adverse events included dyskinesia, constipation, and dry mouth, with no reports of serious hepatotoxicity. The incidence of adverse events was generally comparable to placebo and Entacapone. Overall, Opicapone appears to be a safe and effective adjunct therapy for PD patients with end-of-dose motor fluctuations. Its once-daily dosing offers a key advantage over Entacapone, potentially improving patient adherence and long-term treatment outcomes. While the current evidence is promising, there is a need for longer-term head-to-head studies, especially comparing Opicapone directly with Tolcapone under controlled safety monitoring. Real-world data would also help clarify its role in routine clinical practice.

Keywords: Parkinson‘s disease, Catechol-O-methyltransferase (COMT) inhibitors, Levodopa, Motor fluctuations, Opicapone.