From: Freezing of gait in Parkinson’s disease: pathophysiology, risk factors and treatments
Study reference | Participants | Study design | Treatment | Main findings | FOG subtype |
---|---|---|---|---|---|
Levodopa | |||||
[3] | 19 PD with FOG | Prospective, open-label, uncontrolled | Patients were examined during “Off” and “On” states that approximately 1 h after they took their regular morning dose of levodopa. | Levodopa significantly decreased frequency and the number of FOG episodes (Video recorded). | Unknown, but levodopa induced FOG was excluded |
[59] | 20 PD with FOG | Prospective, open-label, uncontrolled | Similar with the above study but took 1.5 times the usual levodopa dose | FOG improved (customized FOG score and FOGQ). | Unknown |
Levodopa-carbidopa intestinal gel (LCIG) | |||||
[60] | 65 advanced PD | Observational, retrospective, a review of medical records | Mean duration of LCIG therapy was 3.7 years | FOG improved (FOG present only in 22% of patients at 1 year follow-up compared to 46% at baseline). | Unknown |
[61] | 91 advanced PD | Observational, retrospective, a review of medical records | Mean time of follow up of 18 ± 8.4 months | Gait disorders (freezing, festination, postural instability) improved in 61.4% of patients (three point scale). | Unknown |
[62] | 32 advanced PD with FOG | Observational, retrospective, a review of medical records | Mean duration of LCIG therapy was 2.59 ± 1.12 years | FOG that present in OFF condition and improved but did not disappear completely in ON condition can be further improved by LCIG (UPDRS freezing score). | 31 patients with responsive FOG and one with resistant-FOG |
[63] | 177 advanced PD, in which 122 patients with FOG | Observational, retrospective, multi-center, cross-sectional, uncontrolled | Mean duration of LCIG therapy was 34.7 months, 80.8% of patients ≥12 months | FOG improved in 76.2% of patients (subjective assessment by clinicians). | Unknown |
[64] | 28 PD | Prospective, open label, uncontrolled | 17/28 patients reached the 24-month follow-up | FOG improved (FOGQ) | Unknown |
[65] | 25 PD | Prospective, open label, uncontrolled | 20 patients continued on treatment to 6 months. | FOG improved (FOGQ) | Unknown |
[66] | 5 PD with FOG | Prospective, open label, uncontrolled | 24 h LCIG therapy, 6 months | 360° turn time reduced, FOG improved (FOGQ) and fall frequency reduced | Resistant |
[56] | 7 PD with FOG | Prospective, open label controlled, unrandomized | Evaluations were performed in “On” state (60–90 min after taking the morning oral levodopa or LCIG). | FOG improved on LCIG (FOGQ and UPDRS freezing score) | Resistant |
Dopamine agonist | |||||
[67] | 36 PD | Prospective, open label, uncontrolled | Pramipexole treatment for 3 months (started at 0.125 mg/day and increased to 1.5 mg/day) . | FOG improvement (FOGQ) | Unknown |
[68] | 111 PD, in which 54 patients with FOG | Prospective, open label controlled, unrandomized | Rotigotine transdermal patch (9-27 mg/day), pramipexole LA (1.5-4.5 mg/day), ropinirole CR (8-16 mg/day) for at least 6 months | FOG improvement in Rotigotine group (FOGQ) | 48 patients with “Off” FOG and 6 with “Off and On” FOG |
[69] | 10 PD with FOG | Prospective, open label, uncontrolled | Acute test of subcutaneous apomorphine bolus in the morning at “off” state, without other medication | No improvement (subjective assessment) | FOG occur in both “Off” and “On” state |
Monoamine oxidase B inhibitors | |||||
Selegiline | |||||
[70] | 14 PD with FOG | Prospective, open label, uncontrolled | Addition or increase in dose of selegiline, average dose: 4.0 mg/day for 3 months | FOG improved in 7/14 patients (FOGQ) | Unknown |
Rasagiline | |||||
[71] | 687 PD in which 278 patients with FOG | Prospective, double-blind, randomized, placebo-controlled | Oral rasagiline (1 mg once daily), entacapone (200 mg with every levodopa dose), or placebo for 18 weeks | FOG improved by Rasagiline (UPDRS-PIGD, UPDRS-freezing score) | Unknown |
[72] | 42 PD with FOG | Prospective, open label, uncontrolled, multicenter | 1 mg rasagiline daily as an add-on therapy for 3 months | FOG improved after 1, 2 and 3 months of therapy (FOGQ) | Unknown |
[73] | 18 PD with FOG | Prospective, open label, uncontrolled, | 1 mg rasagiline daily as an add-on therapy for 90 days | No overall improvement (Objective FOG counts and duration) | Resistant |
Methylphenidate (MPH) | |||||
[74] | 69 advanced PD with FOG who had received STN- stimulation | Double-blind, randomized, Placebo-controlled | MPH (1 mg/kg per day) or placebo capsules for 90 days | MPH reduces FOG in both “off” and “on” levodopa conditions (FOGQ and the number of freezing episodes while taking walking trajectory) | Resistant |
[75] | 17 STN-stimulated patients with advanced PD and gait disorders | Prospective, open label, uncontrolled | A daily dose of 1 mg/kg of MPH three times daily) for 3 months, including a 1-month titration phase | 3 months MPH improved FOG (number of FOG during Stand-Walk-Sit test) | Resistant |
[76] | 5 PD with FOG | Prospective, open label, uncontrolled | A single oral administration of 10 mg MPH. Reassessment 2 h later. | FOG improved (total walking time, total freezing time, number of freezing episodes and the non-freezing walking time during an “8” trajectory). | Responsive |
[77] | 17 PD with moderate gait impairment | Double-blind, randomized, placebo-controlled | MPH (maximum, up to 80 mg/day) or placebo for 12 weeks and crossed over after a 3-week washout. | No improvement (FOGQ) | Unknown |
Istradefylline | |||||
[78] | 14 PD patients with FOGQ 12.14 ± 5.82 | Prospective, open label, uncontrolled | 20 mg Istradefylline daily for 1 month | FOG improved (FOGQ) | Unknown |
[79] | 31 PD patients with FOG | Prospective, open label, uncontrolled, multicenter | 20 mg Istradefylline daily for 4 weeks, followed by 20 mg/day or an 40 mg/day for 8 weeks | FOG improved (FOGQ, NFOGQ, and MDS-UPDRS Part III (ON-state) gait-related items total score) | Unknown |
Antidepressants | |||||
[80] | 52 PD with mild to severe depressive | Prospective, open label, randomized, controlled, multicenter | Paroxetine 20 mg/day or 25 mg/day; escitalopram 10 mg/day; duloxetine 40 mg/day; 8 weeks’ maintenance period and 2 weeks’ incremental period | FOG (FOGQ) and depression improved | Unknown |
L-DOPS, droxidopa | |||||
[81] | 16 PD with FOG | Randomized, open label, controlled | L-DOPS and entacapone initially 100 mg per day, increase by 100 mg increments every 2 days up to 100 mg per each levodopa administration for 4 weeks | Co-administration of L-DOPS and entacapone improved FOG, yet entacapone or L-DOPS alone didn’t, and the improvement was found only in levodopa-resistant FOG (visual analogue scale, VAS) | 14 patients with “On and Off FOG”; 2 patients with “Off” FOG |
[82] | 13 advanced PD with FOG | Prospective, open label, uncontrolled | L-DOPS initially 100 mg/day with a weekly increase of 100 mg up to 600-900 mg/day maintenance | FOG improved in more than half of patients (walk 10 m and return, subjective assessment) | Unknown |
Amantadine | |||||
[83] | 11 PD with FOG | A retrospective chart review | Median 100 mg twice daily, and treatment duration was 20 months (range, 6-66 months). | Subjective self-reported improvement on FOG | Unknown |
[84] | 42 PD with FOG | Double-blind, randomized, placebo-controlled | 200 mg/500 mL normal saline twice a day for 5 days. | No improvement (FOGQ) | 50% patients with FOG at “On” state |
[85] | 15 patients with FOG including 6 PD | Prospective, open label, uncontrolled | 200 mg in 500 cm3 of saline solution given over a 3-h period, twice a day for 2 days | Improvement in PD patients (FOGQ) | Resistant |
[86] | 10 PD with FOG | Randomized double-blind placebo-controlled, crossover | Placebo (normal saline) or amantadine (400 mg/day) were injected four times for 2 days, 52-h washout, then switched. | No improvement (FOGQ, UPDRS, 4 × 10 m walking test) | Resistant |
Atomoxetine | |||||
[87] | 5 PD with FOG | Prospective, double-blind, randomized, placebo-controlled | 10 mg daily and 10 mg increments up to 40 mg per day over 3 weeks. | No improvement (7 M Step test, FOGQ, Clinician’s Global Index of Change (CGIC), Gait and Balance Scale) | Resistant |
[88] | 10 PD with FOG | Prospective, open label, uncontrolled | 40 mg daily for 2 weeks then increased to 40 mg twice daily for 4-week then reduced to 40 mg daily for 1 week | No improvement (FOGQ) | Resistant |
Acetylcholinesterase inhibitor | |||||
[89] | 41 PD with dementia | Open label, randomized, controlled | Galantamine 4 mg twice daily for the first 4 weeks, and then 8 mg twice daily to the end of the 24 week trial period. | FOG improved (UPDRS freezing subitem) | Unknown |
[90] | 130 PD | Randomized, double-blind, placebo-controlled | Rivastigmine was uptitrated from 3 mg per day to the target dose of 12 mg per day over 12 weeks | FOG did not improve (episodes of FOG in the past month; NFOGQ) | Unknown |
Botulinum toxin | |||||
[91] | 11 advanced PD with FOG | Randomized double blind placebo-controlled | BTX-A injection into each leg’s calf muscles, 150 IU per leg | No improvement (FOGQ, CGIC, UPDRS) | Off FOG |
[92] | 12 PD with FOG | Randomized double-blind placebo-controlled, crossover | BTX-A injection into calf muscles, 16.25 to 25 U /site, six injection sites per leg, 12-week washout, then switched | No improvement (FOGQ, diaries, TUG and “2-min walk test”) | Unknown |
[93] | 10 patients with FOG including 7 PD | Prospective, open label, uncontrolled | BTX-A injection into calf muscles, 3–6 sites per leg, 100-300 IU per session | FOG improved (CGIC) | 3 patients with “Off” FOG; 2 with “On” FOG; 2 with “On and Off” FOG |
[94] | 20 PD, 10 PD with FOG and 10 PD without FOG | Prospective, open label, uncontrolled | BTX-A injection into tensor fasciae latae muscle, 50 U per leg | FOG improved (FOGQ) | Resistant |
[95] | 14 PD with FOG | Double-blind, placebo-controlled, randomized | BTX-B injection into calf muscles of the predominantly affected leg in freezing, 5000 U | No improvement (UPDRS, VAS, and Modified Webster Step-Seconds test) | Resistant |