Product information and disease description Place of product in therapy Approaches to treatment Current treatment options and standard of care

Device-aided therapies

14 evidence topics · 9 sources

Efficacy conclusions for infusion therapies

“Levodopa carbidopa intestinal gel is likely efficacious to treat motor fluctuations in PD patients on (attempted) optimal oral levodopa therapy.” (opens the source at this quote in a new tab)
“One placebo‐controlled study evaluated the use of levodopa carbidopa intestinal gel (~16 h/day) for reducing OFF‐time compared with levodopa carbidopa immediate release, showing a mean difference of −1.9 h (P < 0.01) between groups.” (opens the source at this quote in a new tab)
“One placebo‐controlled trial assessed whether the use of continuous subcutaneous foslevodopa foscarbidopa (24 h/day) reduces OFF‐time compared with levodopa carbidopa immediate release, showing a difference of −1.8 h (P = 0.002) between the two groups.” (opens the source at this quote in a new tab)
“A clinically meaningful difference between the two groups in the reduction of OFF‐time was observed, with a decrease of 1.9 h per day in favor of apomorphine (p = 0.0025).” (opens the source at this quote in a new tab)

Levodopa-carbidopa enteral suspension: off time, on time without troublesome dyskinesia, and device-related adverse events

“Treatment with levodopa-carbidopa enteral suspension reduces off times (−1.19 hours per day [95% CI, −2.25 to −0.12]) and increases time when symptoms are well-controlled without troublesome dyskinesias (0.55 hours per day [95% CI, 0.20-0.90]).” (opens the source at this quote in a new tab)
“Adverse events relating to the percutaneous endoscopic transgastric jejunostomy are common and include complications of device insertion, abdominal pain, tube dislocation, and knotting.” (opens the source at this quote in a new tab)

Subcutaneous foslevodopa/foscarbidopa: approval and tolerability

“Both trials had high discontinuation rates ranging from 35.1% in the 12-week RCT to 44.8% in the 12-month open-label study” (opens the source at this quote in a new tab)
“pLD/pCD has received marketing authorization of the EMA in 2022 and FDA-approval in 2024 for the treatment of motor fluctuations associated with advanced PD.” (opens the source at this quote in a new tab)
“Due to an extensive first-pass effect apomorphine lacks adequate enteral bioavailability and subcutaneous on-demand injections or continuous infusions have been in clinical routine use in Europe for more than 30 years” (opens the source at this quote in a new tab)
“but continuous subcutaneous apomorphine infusions were only recently granted FDA approval in 2025” (opens the source at this quote in a new tab)

Deep brain stimulation: efficacy conclusions

“High‐quality evidence indicates that subthalamic nucleus (STN) deep brain stimulation (DBS) is efficacious to improve motor impairment in patients with PD who experience motor fluctuations on oral levodopa therapy.” (opens the source at this quote in a new tab)
“Seven studies reported improvement in motor impairment, as measured by the UPDRS‐III in the off‐medication state, with an average improvement of 18.6 points in the STN DBS group.” (opens the source at this quote in a new tab)
“Bilateral internal globus pallidus (GPi) DBS is likely efficacious to treat motor fluctuations in PD patients on (attempted) optimal oral levodopa therapy.” (opens the source at this quote in a new tab)

Deep brain stimulation compared with best medical therapy in advanced disease

“Patients who received deep brain stimulation gained a mean of 4.6 h/d of on time without troubling dyskinesia compared with 0 h/d for patients who received best medical therapy (between group mean difference, 4.5 h/d [95% CI, 3.7-5.4 h/d]; P < .001).” (opens the source at this quote in a new tab)
“At least 1 serious adverse event occurred in 49 deep brain stimulation patients and 15 best medical therapy patients (P < .001), including 39 adverse events related to the surgical procedure and 1 death secondary to cerebral hemorrhage.” (opens the source at this quote in a new tab)

Deep brain stimulation in early motor complications

“In this 2-year trial, we randomly assigned 251 patients with Parkinson's disease and early motor complications (mean age, 52 years; mean duration of disease, 7.5 years) to undergo neurostimulation plus medical therapy or medical therapy alone.” (opens the source at this quote in a new tab)
“For the primary outcome of quality of life, the mean score for the neurostimulation group improved by 7.8 points, and that for the medical-therapy group worsened by 0.2 points (between-group difference in mean change from baseline to 2 years, 8.0 points; P = 0.002).” (opens the source at this quote in a new tab)
“Time with good mobility and no troublesome dyskinesia, as recorded by the patients in daily diaries, increased by 20% in the neurostimulation group, with a between-group difference of 1.9 hours (P = 0.01)” (opens the source at this quote in a new tab)
“Time with bad mobility was significantly shortened in the neurostimulation group, with a between-group difference of 1.8 hours (P = 0.006)” (opens the source at this quote in a new tab)
“The levodopa-equivalent daily dose was reduced by 39% in the neurostimulation group but was increased by 21% in the medical-therapy group” (opens the source at this quote in a new tab)
“Serious adverse events related to surgical implantation or the neurostimulation device occurred in 17.7% of patients.” (opens the source at this quote in a new tab)

Deep brain stimulation in early motor complications: serious adverse events

Serious adverse event	Neurostimulation (N = 124), participants with event (%)	Medical therapy (N = 127), participants with event (%)
Any serious adverse event	“68 (54.8)”	“56 (44.1)”
Death, all by suicide	“2 (1.6)”	“1 (0.8)”
Event related to medication or stimulation	“24 (19.4)”	“38 (29.9)”
Worsening of mobility	“5 (4.0)”	“11 (8.7)”
Motor fluctuations	“0”	“7 (5.5)”
Psychosis or hallucinations	“0”	“6 (4.7)”
Impulse control disorder	“1 (0.8)”	“5 (3.9)”
Depression	“6 (4.8)”	“1 (0.8)”
Suicide attempt	“2 (1.6)”	“2 (1.6)”
Event related to surgery or device	“22 (17.7)”	Not applicable
Impaired wound healing	“4 (3.2)”	Not applicable
Intracerebral abscess or edema	“2 (1.6)”	Not applicable
Dislocation of device	“4 (3.2)”	Not applicable
Reoperation necessary	“2 (1.6)”	Not applicable

“Two patients in the neurostimulation group and 1 in the medical-therapy group committed suicide; these were the only deaths.” (opens the source at this quote in a new tab)
“Suicidal ideation and suicide attempts were of similar frequency in the two groups, but depression was more frequent in the neurostimulation group. Serious adverse events related to motor problems, impulse control disorders, and psychotic manifestations were more common in the medical-therapy group.” (opens the source at this quote in a new tab)
“Of 26 serious adverse events related to surgery or the implanted device, including a brain abscess and a case of unspecific edema, all but 1 resolved completely; the exception was a case of impaired wound healing, which resulted in mild scarring.” (opens the source at this quote in a new tab)

Deep brain stimulation in early motor complications: trial population and funding

“Patients with Parkinson’s disease were eligible for the study if they met the following inclusion criteria: an age of 18 to 60 years; disease duration of 4 years or more; a disease severity rating below stage 3 in the on-medication condition, according to the Hoehn and Yahr scale, with scores ranging from 0 to 5 and higher scores indicating more severe disease” (opens the source at this quote in a new tab)
“The mean duration of Parkinson’s disease was 7.5 years, and patients were included in the study a mean of 1.7 years after the onset of levodopa-induced motor complications of any severity.” (opens the source at this quote in a new tab)
“This patient population with relatively mild parkinsonian motor signs differed from the populations in previous controlled studies of neurostimulation: the mean duration of disease in the patients in our study was only 7.5 years, as compared with 11.1 to 13.8 years” (opens the source at this quote in a new tab)
“Medtronic provided additional funding for the study but had no role in the study design, data accrual, data analysis, or manuscript preparation.” (opens the source at this quote in a new tab)
“Neurostimulation may be a therapeutic option for patients at an earlier stage than current recommendations suggest.” (opens the source at this quote in a new tab)

Focused ultrasound pallidotomy

“In the active-treatment group, 45 patients (69%) had a response, as compared with 7 (32%) in the control group (difference, 37 percentage points; 95% confidence interval, 15 to 60; P = 0.003).” (opens the source at this quote in a new tab)
“Pallidotomy-related adverse events in the active-treatment group included dysarthria, gait disturbance, loss of taste, visual disturbance, and facial weakness.” (opens the source at this quote in a new tab)
“At 6 months, among 50 patients who initially underwent FUSA of the globus pallidus internus and had available data, 38 (76%) had a response; 53 of 65 patients in the active-treatment group were available for the 12-month follow-up, and 37 of 53 (70%) had a response at 12 months” (opens the source at this quote in a new tab)
“Of the 45 patients in the active-treatment group who had a response at 3 months, 6 were lost to follow-up and 9 no longer had a response at 12 months” (opens the source at this quote in a new tab)
“Gait disturbance and loss of taste were mild, and they resolved; however, moderate dysarthria in one patient persisted for 1 year. Visual disturbance and mild facial weakness were observed in one patient each at 3 months and were resolved by 1 year.” (opens the source at this quote in a new tab)
“Fifteen adverse events in the active-treatment group (10 patients) and 1 adverse event in the control group fulfilled FDA criteria for a serious adverse event during the 12-month follow-up.” (opens the source at this quote in a new tab)
“The nonfatal pulmonary embolism, which occurred within 1 week after treatment, was the only serious adverse event categorized by the data and safety monitoring board as procedure-related.” (opens the source at this quote in a new tab)

Focused ultrasound pallidotomy: procedural and trial limitations

“The procedure has recently been approved by the FDA for unilateral treatment only, whereas most patients with Parkinson’s disease have bilateral motor signs and symptoms.” (opens the source at this quote in a new tab)
“Unlike deep-brain stimulation, there is no opportunity to treat progressive worsening of motor symptoms.” (opens the source at this quote in a new tab)
“Limitations of the trial include missing primary-outcome data for approximately 7% of the patients and unsatisfactory blinding of the trial-group assignments.” (opens the source at this quote in a new tab)
“A total of 62 of 65 patients (95%) in the active-treatment group believed that they had received the active treatment, and 14 of 24 patients (58%) in the control group believed that they had received the active treatment.” (opens the source at this quote in a new tab)

Focused ultrasound subthalamotomy

“Among 40 enrolled patients, 27 were assigned to focused ultrasound subthalamotomy (active treatment) and 13 to the sham procedure (control).” (opens the source at this quote in a new tab)
“Focused ultrasound subthalamotomy in one hemisphere improved motor features of Parkinson's disease in selected patients with asymmetric signs. Adverse events included speech and gait disturbances, weakness on the treated side, and dyskinesia.” (opens the source at this quote in a new tab)
“the between-group difference was 8.1 points (95% CI, 6.0 to 10.3; P<0.001)” (opens the source at this quote in a new tab)
“The change from baseline to 12 months in the MDS-UPDRS III score for the more affected side among 25 patients with available data in the active-treatment group was 11.6 points (95% CI, 9.9 to 13.3).” (opens the source at this quote in a new tab)
“Among the 27 patients in the active-treatment group, new-onset dyskinesia on the treated side occurred in 12 patients, persisted in 3 at the 4-month primary safety evaluation, and persisted in 2 at 12 months.” (opens the source at this quote in a new tab)
“Speech disturbance developed in 15 patients (56%) in the active-treatment group and persisted in 3 patients at 4 months and in 1 patient at 12 months.” (opens the source at this quote in a new tab)
“Strength in both patients had recovered at 12 months, but hand clumsiness and asymmetric stride persisted in both.” (opens the source at this quote in a new tab)
“In 6 patients in the active-treatment group, some of these deficits were present at 12 months.” (opens the source at this quote in a new tab)
“No complications of the active procedure were detected by MRI, except for perilesional edema, which resolved by 4 months in all the patients in this group” (opens the source at this quote in a new tab)
“There were no intracerebral hemorrhages.” (opens the source at this quote in a new tab)

Device-aided therapies: evidence-based review conclusions and setting of care

“Subcutaneous apomorphine continuous infusion is widely used in clinical practice in patients with motor complications, but to date a double-blind RCT has been published in abstract form only.” (opens the source at this quote in a new tab)
“Percutaneous infusion of levodopa (levodopa-carbidopa intestinal gel) is clinically useful for certain patients with severe motor fluctuations, although it requires appropriate clinical support, restricting use to specialized centers.” (opens the source at this quote in a new tab)
“DBS targeting the STN or GPi remains clinically useful for carefully selected PD patients and is again restricted to specialized centers.” (opens the source at this quote in a new tab)
“There are no RCTs directly comparing device-aided therapies, but expert consensus opinions discussing the pros and cons of each approach have been published.” (opens the source at this quote in a new tab)

Focused ultrasound subthalamotomy: selected population and trial limitations

“Patients chose to participate in this trial of ultrasound subthalamotomy because they declined to undergo deep-brain stimulation (11 patients); had minor motor signs on the less affected side, no meaningful levodopa-related motor complications that would make the patient a candidate for deep-brain stimulation, or both (26 patients); or were poor candidates for intracranial surgery owing to advanced age or coexisting conditions (3 patients).” (opens the source at this quote in a new tab)
“Subthalamotomy was performed in one hemisphere, and the natural evolution of Parkinson’s disease eventually leads to motor impairment on both sides of the body in most patients.” (opens the source at this quote in a new tab)
“The small sample size and the enrollment of almost all the patients at one of the two trial sites (36 patients at one site and 4 at the other) limits the generalizability of the results because the trial approximates a single-center trial. Patients and assessors correctly guessed the trial-group assignments, which eliminates the intended effect of blinding.” (opens the source at this quote in a new tab)

Guideline position on device-aided therapy

“Offer people with advanced Parkinson's disease best medical therapy, which may include intermittent apomorphine injection and/or continuous subcutaneous apomorphine infusion.” (opens the source at this quote in a new tab)
“Do not offer deep brain stimulation to people with Parkinson's disease whose symptoms are adequately controlled by best medical therapy.” (opens the source at this quote in a new tab)
“Consider deep brain stimulation for people with advanced Parkinson's disease whose symptoms are not adequately controlled by best medical therapy.” (opens the source at this quote in a new tab)