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

Dopamine agonists

12 evidence topics · 11 sources

Guideline recommendations for dopamine agonists as initial therapy

“Clinicians may prescribe dopamine agonists as the initial dopaminergic therapy to improve motor symptoms in select early PD in patients <60 years who are at higher risk for the development of dyskinesia.” (opens the source at this quote in a new tab)
“Clinicians should not prescribe dopamine agonists to patients with early-stage PD at higher risk of medication-related adverse effects, including individuals >70 years-of-age, patients with a history of ICDs, and patients with pre-existing cognitive impairment, excessive daytime sleepiness, or hallucinations.” (opens the source at this quote in a new tab)
“Clinicians should prescribe the lowest dose of dopamine agonist required to provide therapeutic benefit.” (opens the source at this quote in a new tab)

Comparative evidence among dopamine agonists and formulations

“This systematic review did not uncover strong evidence supporting the use of ropinirole vs pramipexole for the treatment of early PD.” (opens the source at this quote in a new tab)
“There are preliminary observational data that long-acting and transdermal formulations of dopamine agonists have lower rates of ICDs than short-acting formulations.” (opens the source at this quote in a new tab)
“Clinicians may opt to increase dosages gradually, stopping at the lowest dosage that is recognized to have clinical efficacy (6–9 mg/d of ropinirole, 1.5 mg/d of pramipexole, or 4 mg/24hrs of rotigotine).” (opens the source at this quote in a new tab)

Dopamine agonists compared with levodopa in early disease: impulse control disorders and other adverse effects

“DAs (vs levodopa) are associated with an increased risk of ICDs, EDS, sudden-onset sleep, nausea, and hallucinations in patients with early PD.” (opens the source at this quote in a new tab)
“Conclusion (moderate confidence): In early PD, DAs are probably more likely than levodopa to cause ICDs at 2 years (3 Class III studies, RD 23.2%, 95% confidence interval [CI] 14.3–32.1).” (opens the source at this quote in a new tab)
“Conclusion (low confidence): In early PD, DAs are possibly more likely than levodopa to cause ICDs at 5 years (2 Class III studies, RD 23.7%, 95% CI 1.1–46.3).” (opens the source at this quote in a new tab)
“The MCID in the risk of ICDs was determined by consensus to be 2%; RDs ≤1% were considered clinically unimportant.” (opens the source at this quote in a new tab)
“Although initial treatment with DAs is possibly more likely to cause hallucinations than treatment with levodopa, the difference between treatments for this outcome is small for the first 5 years of treatment.” (opens the source at this quote in a new tab)
“Although the trend suggests that AE-related discontinuation of treatment is higher with DAs than with levodopa at all time points, confidence in the evidence is low or very low due to study quality or poor precision of estimates.” (opens the source at this quote in a new tab)

Non-ergot dopamine agonists: evidence-based review implications for clinical practice by indication

Agent	Implication for clinical practice: symptomatic monotherapy	Implication for clinical practice: adjunct to levodopa in early or stable disease	Implication for clinical practice: motor fluctuations
Pramipexole immediate release	“Clinically useful”	“Clinically useful”	“Clinically useful”
Pramipexole extended release	“Clinically useful”	“Clinically useful”	“Clinically useful”
Ropinirole immediate release	“Clinically useful”	“Clinically useful”	“Clinically useful”
Ropinirole prolonged release	“Possibly useful”	Not reported	“Clinically useful”
Rotigotine	“Clinically useful”	“Clinically useful”	“Clinically useful”

“The relative efficacy of the different DAs appears to be similar.” (opens the source at this quote in a new tab)
“However, there is no evidence of clinical superiority in terms of tolerability or short- and long-term benefits of one DA over the other, including delaying or preventing motor fluctuations (as discussed previously).” (opens the source at this quote in a new tab)
“Deciding which DA to add is thus based on local availability and cost, and the decision whether to switch to a different DA later depends on individual tolerability/efficacy.” (opens the source at this quote in a new tab)
“All widely clinically available nonergot oral and transdermal dopamine agonists are “clinically useful” for reducing motor fluctuations.” (opens the source at this quote in a new tab)

Adjunctive dopamine agonists for motor fluctuations: guideline recommendation

“Offer a choice of dopamine agonists, MAO‑B inhibitors or catechol‑O‑methyl transferase (COMT) inhibitors as an adjunct to levodopa for people with Parkinson's disease who have developed dyskinesia or motor fluctuations despite optimal levodopa therapy, after discussing:” (opens the source at this quote in a new tab)
“Choose a non-ergot-derived dopamine agonist in most cases, because of the monitoring that is needed with ergot-derived dopamine agonists.” (opens the source at this quote in a new tab)

Efficacy conclusions for dopamine agonists in motor fluctuations

“Pramipexole immediate release and extended release are efficacious to treat motor fluctuations in PD patients on (attempted) optimal oral levodopa therapy.” (opens the source at this quote in a new tab)
“Ropinirole immediate release is efficacious to treat motor fluctuations in PD patients on oral levodopa therapy. Ropinirole prolonged release and ropinirole patch are likely efficacious to treat motor fluctuations in PD patients on oral levodopa therapy.” (opens the source at this quote in a new tab)
“They found a statistically significant and clinically meaningful reduction of OFF‐time by 0.9–1.8 h compared with placebo.” (opens the source at this quote in a new tab)

Adjunctive dopamine agonists: pooled off-time reduction

“DRAs produced a reduction in daily off-medication time with a WMD of −1.1 hours (95% CI −1.4 to −0.8) compared with placebo, whereas both COMT-Is and MAOB-Is were associated with a WMD of −0.8 hours (95% CI −1.0 to −0.6) and −0.9 hours (95% CI −1.2 to −0.6), respectively.” (opens the source at this quote in a new tab)
“Intraclass comparison showed that of the DRAs, pramipexole immediate-release (IR) provided the largest reduction in daily off-medication time with −2.2 hours (95% CI −2.7 to −1.6).” (opens the source at this quote in a new tab)
“The results of the current systematic review suggest that DRAs should be considered as the primary treatment choice for adjunctive oral therapy in PD with motor complications.” (opens the source at this quote in a new tab)

Adjunctive dopamine agonists: network meta-analysis ranking

“According to the SUCRA, ropinirole transdermal patch (SUCRA, 0.861) ranked the highest in change in daily off-time, followed by pramipexole (0.762), ropinirole ER (0.750), and safinamide (0.691) (Fig. 4, Supplementary Fig. 5A).” (opens the source at this quote in a new tab)
“These results suggest that DAs and MAOBIs are more effective than COMTIs and an A2ARA.” (opens the source at this quote in a new tab)

Efficacy and safety profile of non-ergot dopamine agonists

“Non-ergolinic DA agonists such as pramipexole, ropinirole, and rotigotine are efficacious in treating PD motor symptoms both as monotherapy as well as adjuncts to levodopa in patients with or without motor complications” (opens the source at this quote in a new tab)
“Their major limitations are related to an unfavourable safety profile regarding their potential to induce daytime somnolence and ICDs.” (opens the source at this quote in a new tab)

Receptor selectivity of currently available dopamine agonists

“Currently available oral and transdermal DAs (eg, pramipexole, ropinirole, rotigotine) preferentially target D2/D3 receptors, and are associated with an increased risk of adverse events (AEs) compared with oral levodopa alone, which is hypothesized to be partially attributed to widespread distribution of D2/D3 receptors in the brain and peripheral nervous system.” (opens the source at this quote in a new tab)

Dopamine agonist receptor targets, motor complication risk, and adverse effects

“Dopaminomimetics with direct activity to dopamine receptors (dopamine receptor agonist) mainly target the D2 receptor family and were first introduced into Parkinson disease therapy in the 1970s with the ergot alkaloid bromocriptine and have since become an important medical therapy for motor symptoms” (opens the source at this quote in a new tab)
“Overall, dopamine agonists are believed to induce less pulsatile striatal dopamine receptor stimulation than l-DOPA and this is taken as an explanation for the markedly reduced risk to induce motor complications when dopamine agonists are used as initial monotherapy in Parkinson disease” (opens the source at this quote in a new tab)
“Drawbacks include their reduced overall effect size as compared with l-DOPA and their potential to induce drowsiness and impulse dyscontrol — the latter being possibly associated with their preferential activity at D3 receptors that are located in the ventral striatum, which causes excessive stimulation of the brain reward systems” (opens the source at this quote in a new tab)

Prolonged-release dopamine agonists and early-morning OFF periods: observational study

“When comparing patterns of dopaminergic therapy, those taking PR dopamine agonists (ROP XL, PPX PR and RTG patch) had significantly less EMO periods compared with those taking levodopa therapy only.” (opens the source at this quote in a new tab)
“treated with RTG did not suffer from EMO (50.0%) compared with those receiving levodopa monotherapy (31.7% were free of EMO, p = 0.019; chi-squared test)” (opens the source at this quote in a new tab)
“Cohorts on monotherapy of the respective PR dopamine agonist showed an even higher rate of EMO free patients (RTG: 64.7%, ROP XL: 59.3% and PPX PR: 57.9%) than the ones on combination therapy stated above.” (opens the source at this quote in a new tab)
“Our study was not powered for, or aimed at, addressing the effect of dopaminergic medications on EMO specifically so that we can only make limited observations.” (opens the source at this quote in a new tab)
“Furthermore, we were unable to match the doses of the different DA's and as such direct comparison between the different DA's is not possible.” (opens the source at this quote in a new tab)