Pharmacological and Behavioral Interventions for Fatigue in Parkinson's Disease: A Meta-Analysis of Randomized Controlled Trials

This study aims to evaluate pharmacological and behavioral interventions for the treatment of fatigue in Parkinson's disease (PD) patients.We systematically searched PubMed, PsycINFO, Web of Science, EMBASE, CNKI, Wan fang, and VIP up to July 31, 2022. We used Revman 5.3 software for the meta-analysis. The outcomes included Fatigue Severity Scale (FSS) and Parkinson's Fatigue Scale (PFS). The mean difference (MD) and 95% confidence intervals (CI) were collected or calculated.Thirteen randomized controlled trials (RCTs) with a total of 1758 patients were included. The meta-analysis showed that current clinical treatments reduced FSS (MD: -1.60, 95% CI: -3.14 to -0.05) and PFS (MD: -0.61, 95% CI: -1.17 to -0.05) in patients with PD. Subgroup meta-analysis showed that: (1) neither pharmacological interventions nor behavioral interventions reduced FSS in PD patients; (2) dopaminergic drugs dose-dependently significantly reduced the PFS in patients with PD; (3) behavioral interventions have an almost significant effect (MD: -6.69, 95% CI: -13.71 to 0.33, P = 0.06, I2 = 74%) on alleviating PFS in PD patients; (4) vestibular rehabilitation training significantly reduced the PFS in patients with PD.Current clinical treatments alleviate fatigue in PD patients. Dopaminergic drugs may act a stronger effect than amphetamines. Behavioral interventions, especially vestibular rehabilitation training, may be a promising way for the treatment of fatigue in patients with PD though further evidence is still needed.