Efficacy and safety of combination therapy with pramipexole and levodopa vs levodopa monotherapy in patients with Parkinson disease: A systematic review and meta-analysis

Abstract

Background: Pramipexole (P) or levodopa (L) treatment has been suggested as a therapeutic method for Parkinson disease (PD) in many clinical studies. Nonetheless, the combined effects of 2 drugs for PD patients are not completely understood.The aim of this research was to evaluate the clinical efficacy and safety of P plus L (P+L) combination therapy in the treatment of PD compared to that of L monotherapy, in order to confer a reference for clinical practice.

Methods: Randomized controlled trials (RCTs) of P+L for PD published up to April, 2020 were retrieved. Standardized mean difference (SMD), odds ratio (OR), and 95% confidence interval (CI) were calculated and heterogeneity was measured with the I2 test. Sensitivity analysis was also carried out. The outcomes of interest were as follows: the efficacy, unified Parkinson disease rating scale (UPDRS) scores, Hamilton depression rating scale score or adverse events.

Results: Twenty-four RCTs with 2171 participants were included. Clinical efficacy of P+L combination therapy was significantly better than L monotherapy (9 trials; OR 4.29, 95% CI 2.78 to 6.64, P < .00001). Compared with L monotherapy, the pooled effects of P+L combination therapy on UPDRS score were (22 trials; SMD -1.31, 95% CI -1.57 to -1.04, P < .00001) for motor UPDRS score, (16 trials; SMD -1.26, 95% CI -1.49 to -1.03, P < .00001) for activities of daily living UPDRS score, (12 trials; SMD -1.02, 95% CI -1.27 to -0.77, P < .00001) for mental UPDRS score, (10 trials; SMD -1.54, 95% CI -1.93 to -1.15, P < .00001) for complication UPDRS score. The Hamilton depression rating scale score showed significant decrease in the P+L combination therapy compared to L monotherapy (12 trials; SMD -1.56, 95% CI -1.90 to -1.22, P < .00001). In contrast to L monotherapy, P+L combination therapy reduced the number of any adverse events obviously in PD patients (16 trials; OR 0.36, 95% CI 0.27 to 0.50, P < .00001).

Conclusions: P+L combination therapy is superior to L monotherapy for improvement of clinical symptoms in PD patients. Moreover, the safety profile of P+L combination therapy is better than that of L monotherapy. Further well-designed, multicenter RCTs needed to identify these findings.

Figure 1

Flowchart of study selection in the meta-analysis.

Figure 2

Comparison of P+L combination therapy and L monotherapy in the clinical efficacy for Parkinson disease. L = levodopa; P = pramipexole.

Figure 3

Comparison of P+L combination therapy and L monotherapy in the motor UPDRS score (A) and ADL UPDRS score (B) for Parkinson disease. ADL = activities of daily living; L = levodopa; P = pramipexole, UPDRS = unified Parkinson disease rating scale.

Figure 4

Comparison of P+L combination therapy and L monotherapy in the mental UPDRS score (A), complication UPDRS score (B), and HAMD score (C) for Parkinson disease. HAMD = Hamilton depression rating scale; L = levodopa; P = pramipexole; UPDRS = unified Parkinson disease rating scale.

Figure 5

Comparison of P+L combination therapy and L monotherapy in the any adverse events for Parkinson disease. L = levodopa; P = pramipexole.

Figure 6

Funnel plot for estimation of potential publication bias.