The effect of monoamine oxidase-B inhibitors on the alleviation of depressive symptoms in Parkinson's disease: meta-analysis of randomized controlled trials

Abstract

Background: Depression is a major nonmotor symptom of Parkinson's disease (PD). However, few treatments exist for PD depression. Monoamine oxidase-B inhibitors (MAOB-Is) provide symptomatic relief for the motor symptoms of PD and exert antidepressive effects. The present meta-analysis of randomized controlled trials (RCTs) investigated the effects of MAOB-Is on depressive symptoms in patients with PD.

Methods: Articles on PD-management-related RCTs using one of three MAOB-Is approved by the US Food and Drug Administration, that is, selegiline, rasagiline, and safinamide, were identified. The primary outcomes were the benefits of MAOB-Is for depressive symptoms. Subgroup analysis included the effects of MAOB-Is on patients in the early versus middle-to-late stages of PD and the effect of short-term versus long-term treatment.

Results: Overall, six studies were included, four of which were conducted on patients with early stage PD. Overall, MAOB-Is significantly reduced the severity of depressive symptoms [standardized mean difference (SMD): -0.14, 95% confidence interval (CI): -0.21 to -0.06, p < 0.001]. Subgroup analysis indicated that the positive effect of MAOB-Is was significant in patients with early stage PD (SMD: -0.20, 95% CI: -0.31 to -0.09, p < 0.001), but not in those with middle-to-late-stage PD (SMD: -0.07, 95% CI: -0.17 to 0.03, p = 0.18). The antidepressive effect was significant for short-term treatment, that is, 90-120 days (SMD: -0.23, 95% CI: -0.35 to -0.10, p < 0.001), but not long-term treatment, that is, 24 weeks to 18 months (SMD: -0.08, 95% CI: -0.18 to 0.01, p = 0.09).

Conclusion: In addition to the treatment of PD motor symptoms, MAOB-Is may help reduce the severity of depressive symptoms in PD, especially in patients with early stage PD. Considering the tolerability and simultaneous benefits of MAOB-Is, further RCTs are warranted to confirm their therapeutic effects in moderate-to-severe PD depression.

Keywords: Parkinson’s disease; depressive symptoms; monoamine oxidase-B inhibitors.

Figure 1.

Flowchart of study selection.

Figure 2.

Effect of MAOB-Is on the depressive symptoms in patients with PD. (a) Forest plots of the meta-analysis result for the overall effect of MAOB-Is on depressive symptoms in patients with PD; (b) funnel plot with pseudo 95% confidence limit of the overall effect of MAOB-Is on depressive symptoms in patients with PD. CI, confidence interval; df, degrees of freedom; MAOB-I, monoamine oxidase-B inhibitor; PD, Parkinson’s disease; SD, standard deviation; SE, standard error; SMD, standard mean difference.

Figure 3.

Subgroup analysis of the effect of MAOB-Is on depressive symptoms in patients with (a) early stage and (b) middle-to-late stage PD. CI, confidence interval; df, degrees of freedom; MAOB-I, monoamine oxidase-B inhibitor; PD, Parkinson’s disease; SD, standard deviation.

Figure 4.

Subgroup analysis of the effect of MAOB-Is on depressive symptoms in patients with treatment duration of (a) <24 weeks and (b) ⩾24 weeks. CI, confidence interval; df, degrees of freedom; MAOB-I, monoamine oxidase-B inhibitor; SD, standard deviation.