Table 4.

Studies describing the effects of levodopa and dopamine agonists in patients with RBD.

Authors, Year [Ref]	Study Setting	Type of Study	Main Findings	Level of Evidence (Quality Score)
Strijks et al., 1997 [29]	10 patients diagnosed with PD. Dosage of 200 mg/day. Assessment of motor performance with UPDRS and motor test.	3 months open-label study	Lack of improvement in PD motor symptoms.	II (NA)
Shults et al., 2002 [30]	Eighty subjects with early PD not requiring treatment for their disability. Dosages of 300, 600, or 1200 mg/day Evaluation with the UPDRS at the screening, baseline, and 1-, 4-, 8-, 12-, and 16-month visits. Follow-up of 16 months or until disability requiring treatment with levodopa.	Multicenter, randomized, parallel-group, placebo-controlled, double-blind, dosage-ranging trial.	Significantly lower increase in UPDRS scores during follow-up in patients assigned to CoQ10 therapy, especially with the highest doses.	I (>50%)
Müller et al., 2003 [31]	Twenty-eight treated and stable PD patients. Dosage of 360 mg/day for 4 weeks. Scoring of PD symptoms, and visual function using the Farnsworth–Munsell 100 Hue test (FMT).	Monocenter, parallel-group, placebo-controlled, double-blind trial	Mild symptomatic benefit on PD symptoms in patients assigned to CoQ10 therapy. Better improvement in FMT performance in patients assigned to CoQ10 therapy.	I (>50%)
NINDS NET-PD Investigators 2007 [32]	Seventy-one untreated early PD patients assigned to CoQ10 therapy (2400 mg/day), 71 to GPI-1485, and 71 to placebo. Measurement of change in total UPDRS scores and subscores, Hoehn & Yahr staging, and Schwabb & England scale scores, either at the time requiring symptomatic therapy or at 12 months.	Randomized, double-blind, calibrated futility clinical trial	The primary outcome measure (change in total UPDRS scores over 1 year) did not differ significantly between the 3 treatment groups. Changes in Hoehn & Yahr staging, and Schwabb & England scale scores did not differ significantly between the 3 treatment groups. CoQ10 was well-tolerated. The percentages of withdrawal because of adverse effects were 8%, 11%, and 10%, respectively, for CoQ10, GPI-1485, and placebo.	I (>50%)
Storch et al., 2007 [33]	One hundred thirty-one patients with PD without motor fluctuations and a stable antiparkinsonian treatment. Treatment with placebo or nanoparticular CoQ10 (100 mg 3 times a day, equivalent to 1200 mg/day of standard formulation) for 3 months. The stratification criterion was levodopa treatment. Evaluation with the UPDRS (sum score of parts II and III) at baseline, 1, 2, and 3 months at each visit monthly.	Multicenter, randomized, double-blind, placebo-controlled, stratified, parallel-group, single-dose trial.	The mean changes of the sum UPDRS parts II/III score did not differ significantly between the placebo and CoQ10 groups (−3.69 and −3.33) No secondary outcome measure showed a significant change between the placebo group and the CoQ10 group. The frequency and quality of adverse events are similar in both treatment groups.	I (>50%)
Parkinson Study Group QE3 Investigators [34]	Six hundred patients diagnosed with PD (from 67 hospitals in the USA) in the previous 5 years, free of dopaminergic therapy in the previous 3 months, with Hoehn & Yahr stage of 2.5 or less. Two hundred were assigned to CoQ10 1200 mg/day, 200 to CoQ10 2400 mg/day and 200 to placebo. All patients were taking vitamin E 1200 IU/day. Evaluation at 16 months from baseline or until a disability requiring dopaminergic treatment. The study was powered to detect a 3-point difference between active treatment and placebo.	Phase III randomized, placebo-controlled, double-blind clinical trial	At study termination, both active treatment groups showed slight adverse trends relative to placebo. Adjusted mean changes (worsening) in total UPDRS scores from baseline to final visit did not differ between the 3 study groups. Treatments were well-tolerated with no safety concerns.	I (>50%)
Jie et al., 2014 [35]	Eighty-eight patients diagnosed with PD and treated with levodopa. Forty-four were assigned to CoQ10 375–750 mg/day, and 44 to placebo Evaluation with the Webster Scale at baseline and 3 months	Monocenter, randomized, placebo-controlled, double-blind clinical trial	Significant improvement in UPDRS Webster Scale scores in the group of patients treated with CoQ10. Lack of significant adverse effects.	I (>50%)
Wang et al., 2014 [36]	Thirty-nine patients diagnosed with PD under conventional therapy. Twenty-one were assigned to CoQ10 450 or 1200 mg/day, and 18 to placebo as add-on therapy Evaluation with the UPDRS III and Webster Scale at baseline and 36 weeks	Monocenter, randomized, placebo-controlled, double-blind clinical trial	Significant improvement in UPDRS III and Webster Scale scores in the group of patients treated with CoQ10 1200 mg/day (but not of the patients treated with CoQ10 450 mg/day) compared with the placebo group.	I (>50%)
Li et al., 2015 [37]	Seventy-five patients diagnosed with PD and MCI. Random assignation to treatment with CoQ10 100 mg b.i.d. and creatine 5 mg b.i.d. or to placebo. Evaluation with the UPDRS part III, and MoCa at 12 and 18 months.	Phase III randomized, placebo-controlled, double-blind clinical trial	Non-significant differences in UPDRS III scores between the 2 study groups at 12 and 18 months. Significantly lower worsening in the MoCA scores in patients assigned to CoQ10 plus creatine.	I (>50%)
Yoritaka et al., 2015 [38]	Twenty-six patients with PD experiencing wearing off (group A) and 22 early PD patients without levodopa (with or without a dopamine agonist, group B). Treatment with 300 mg/day of ubiquinol-10 or placebo for 48 weeks (Group A, 14 ubiquinol-10, 12 placeboes) or 96 weeks (Group B, 14 ubiquinol-10, 8 placeboes).	Randomized, double-blind, placebo-controlled, parallel-group pilot trial	Significant improvement in UPDRS scores in patients treated with ubiquinol-10 compared with placebo in group A. Lack of significant changes in UPDRS scores in patients treated with ubiquinol-10 compared with placebo in group B.	I (>50%)

MoCA: Montreal Cognitive Assessment, PD: Parkinson’s disease, UPDRS: Unified Parkinson’s disease rating scale.