PhD student The University of Manitoba Winnipeg, Canada
Background: Safinamide and zonisamide are novel mixed monoamine oxidase-B (MAO-B) inhibitors, which have beneficial effects in the treatment of motor fluctuations, as add-on therapy, in Parkinson’s disease (PD). However, the effect of these drugs on quality of life (QoL) and cognitive function (CF) were not examined in recent meta-analyses.
Objectives: To examine the efficacy, safety, QoL and CF of safinamide and zonisamide in treating PD patients, compared to placebo, with focus on motor and non-motor outcomes.
Methods: We searched MEDLINE, EMBASE, Cochrane Central, Scopus, PsycINFO, and trials registries up to December 2022 for randomized trials of adults with PD published in English. Primary outcomes were change from baseline in Unified Parkinson’s Disease Rating Scale section III (UPDRS-III) and any serious adverse events. Secondary outcomes included any change from baseline in OFF-time, Parkinson’s Disease Questionnaire 39 (PDQ-39), and Mini-mental state Examination (MMSE). Random effect models were used to calculate the pooled mean differences (MD) and risk ratios (RR) with 95% confidence intervals (CI). We assessed the risk of bias of each trial and publication bias.
Results: Of 3148 screened citations, 11 trials met the inclusion criteria (4,284 PD patients). UPDRS Part III scores were significantly lower with mixed MAO-B inhibitors than with placebo (MD -2.21, 95% CI -2.21 to -1.43; I2 65%). Subgroup analysis showed a significant improvement in UPDRS-III in both safinamide (MD -2.06, 95% CI -3.16 to -0.96; I2= 72%) and zonisamide (MD -2.43, 95% CI -3.66 to -1.20; I2= 61%) compared to placebo. Similarly, subgroup analysis by doses showed an improvement in UPDRS-III at the safinamide 50 mg (MD -2.22, 95% CI -4.19 to -0.25; I2=82%) and 100 mg (MD -2.25, 95% CI -3.54 to -0.97; I2=70%) and zonisamide 25mg (MD -2.29, 95% CI -4.06 to -0.51) and 50 mg (MD -2.60, 95% CI -3.56 to -1.63, I2=75%). MAO-B inhibitors significantly decreased OFF-time compared with placebo (MD -0.94, 95% CI -1.39 to -0.48; I2=16%). No significant differences in MMSE (MD -0.15, 95% CI -0.53 to 0.23; I2=28%) and PDQ-39 (MD -4.64, 95% CI -10.19 to 0.23) scores were observed. All examined doses of zonisamide and safinamide were well tolerated, with no significant difference in incidence rates of serious adverse events when compared to placebo. Sensitivity analyses showed that the results were stable.
Conclusions: Evidence suggests that mixed MAO-B Inhibitors as adjunct therapy are effective for motor symptoms and well-tolerated among adults with PD. However, there was no evidence of additional benefit in non-motor symptoms nor improvement of CF and QOL. Further trials examining the possible pharmacological activity of mixed MAO-B inhibitors on non-motor symptoms are needed.
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