OBJECTIVES : Parkinson’s disease (PD) is a neurodegenerative disorder characterised by movement-related symptoms. Levodopa is widely used as first-line therapy and provides symptomatic control. However, motor complications are likely to develop with long-term use. There are several classes of anti-PD interventions that can be added to levodopa therapy as adjuvant therapy. The aim of the current meta-analysis was to evaluate the comparative efficacy of agents used as adjuvant therapy in PD.

METHODS : A previously conducted Cochrane systematic review (SR) [Stowe, 2010] was updated according to PRISMA guidelines to identify English-language articles published post 2010. The Medline database was interrogated in April 2019 to identify placebo-controlled randomised controlled trials (RCTs) investigating catechol-O-methyltransferase inhibitors, monoamine oxidase-B inhibitors, dopamine agonists (DAs), and amantadine add-on therapy to levodopa in patients with PD. Pair-wise meta-analyses were conducted for OFF time, Unified Parkinson's Disease Rating Scale (UPDRS) II, and UPDRS III scores in RevMan 5.3.

RESULTS : A total of 65 RCTs were eligible for inclusion (20 from the update and 45 from the original SR). The meta-analysis results demonstrate that all active interventions were associated with a statistically significant reduction (improvement) in OFF time (hours/day), UPDRS II, and UPDRS III scores compared with placebo. The meta-analysis results were consistent when conducted at the individual intervention level or drug class level and when conducted regardless of study follow-up (4 weeks to 9 months) and when restricting the data to 8-16 weeks follow-up. Across all outcomes, data suggest that DAs were associated with the largest beneficial effect among all classes of active agents.

CONCLUSIONS : The current study provides a comprehensive meta-analysis of adjuvant treatments of patients with PD. While currently available agents lead to improvement in OFF time, new therapies with novel modes of action are actively required to address the significant unmet need.