Background and purpose:The monoamine oxidase type B inhibitors plus channel blockers (MAO-BIs plus) are a new class of antiparkinsonian drug with additional mechanisms of action for their property as ion channel blockers. The present study aimed to compare the efficacy and safety of MAO-BIs plus and conventional MAO-BIs, as well as their corresponding doses, as adjuvant therapy to levodopa in the treatment of Parkinson's disease (PD).Method: Randomized controlled trials enrolling PD patients treated with selegiline, rasagiline, safinamide or zonisamide as adjuvant therapy to levodopa were identified.Bayesian network meta-analysis was conducted.Results: Thirty-one randomized controlled trials comprising 7142 PD patients were included. Compared with levodopa monotherapy, the combination therapy of MAO-BIs and levodopa was significantly more effective, with a mean difference of 2. 74 (1.26-4.18) on the Unified Parkinson's Disease Rating Scale (UPDRS) III score change for selegiline, 2.67 (1.45-3.87) for safinamide, 2.2 (0.98-3.64) for zonisamide and 2.04 (1.24-2.87) for rasagiline. No significant difference was detected amongst MAO-BIs. The surface under the cumulative ranking results showed that safinamide 100 mg and rasagiline 1 mg ranked first in improving UPDRS III and UPDRS II, respectively. Zonisamide 100 mg ranked first in reducing OFF time. For safety outcomes, rasagiline was associated with a higher incidence of adverse events than placebo and safinamide. MAO-BIs plus had a higher probability of being safer agents compared to conventional MAO-BIs.Conclusions: Monoamine oxidase type B inhibitors plus, conventional MAO-BIs and the corresponding doses are similar in efficacy in PD treatment. MAO-BIs plus might be safer than conventional MAO-BIs. Head-to-head comparisons are needed for further investigation.

BackgroundLower urinary tract symptoms (LUTS) are common non-motor symptoms but are often overlooked in Parkinson's disease (PD). The prevalence of LUTS in PD is inconsistent among different studies.ObjectiveTo estimate the prevalence of LUTS, urinary incontinence, and urinary retention in PD patients, then, investigate potential sources of inconsistency in prevalence estimation.MethodsWe searched PubMed, EMBASE, and Web of Science databases from inception to May 2022. Studies reporting the prevalence of LUTS or LUTS subtypes in PD were included. Pooled prevalence of LUTS, LUTS subtypes, urinary incontinence, and urinary retention was calculated via random-effects models. Meta-regression and subgroup analyses were performed.ResultsOf 7,358 studies after duplicate removal, a total of 73 studies comprising 14,937 PD patients were included. The pooled prevalence of LUTS was 61% (95% CI 53–69; 27 studies; n = 5,179), while the pooled prevalence of storage symptoms and voiding symptoms was 59% (44–73; 9 studies; n = 798) and 24% (14–33; 11 studies; n = 886), respectively. The pooled prevalence of urinary incontinence, retention and post-void residual (PVR) volume ≥ 100 ml were 30% (95% CI 22–39; 21 studies; n = 6,054), 27% (17–37; 14 studies; n = 1,991), and 4% (1–7; 5 studies; n = 439), respectively. The prevalence of LUTS, urinary incontinence, or urinary retention was significantly associated with diagnostic methods.ConclusionLUTS and its subtypes present in a significant proportion of PD patients. It is necessary to use standardized and validated methods to detect and screen LUTS and its subtypes.Systematic review registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022311233, Identifier: CRD42022311233.

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