Dataset Information

Ophthalmologic Baseline Characteristics and 2-Year Ophthalmologic Safety Profile of Pramipexole IR Compared with Ropinirole IR in Patients with Early Parkinson's Disease.

ABSTRACT: Background. Parkinson's disease (PD) progressively affects dopaminergic neurotransmission and may affect retinal dopaminergic functions and structures. Objective. This 2-year randomized, open-label, parallel-group, flexible-dose study, NCT00144300, evaluated ophthalmologic safety profiles of immediate-release (IR) pramipexole and ropinirole in patients with early idiopathic PD with ?6 months' prior dopamine agonist exposure and without preexisting major eye disorders. Methods. Patients received labeled IR regimens of pramipexole (n = 121) or ropinirole (n = 125) for 2 years. Comprehensive ophthalmologic assessments (COA) included corrected acuity, Roth 28-color test, slit-lamp biomicroscopy, intraocular pressure, computerized visual field test, fundus photography, and electroretinography. Results. At baseline, we observed retinal pigmentary epithelium (RPE) hypopigmentation not previously reported in PD patients. The estimated relative risk of 2-year COA worsening with pramipexole versus ropinirole was 1.07 (95% CI: 0.71-1.60). Mean changes from baseline in Unified Parkinson's Disease Rating System parts II+III total scores (pramipexole: 1 year, -4.1 ± 8.9, and 2 years, -0.7 ± 10.1, and ropinirole: 1 year, -3.7 ± 8.2, and 2 years, -1.7 ± 10.5) and Hoehn-Yahr stage distribution showed therapeutic effects on PD symptoms. Safety profiles were consistent with labeling. Conclusions. The risk of retinal deterioration did not differ in early idiopathic PD patients receiving pramipexole versus ropinirole. RPE hypopigmentation at baseline was not previously reported in this population. This trial is registered with NCT00144300.

SUBMITTER: Seiple W

PROVIDER: S-EPMC5203898 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Ophthalmologic Baseline Characteristics and 2-Year Ophthalmologic Safety Profile of Pramipexole IR Compared with Ropinirole IR in Patients with Early Parkinson's Disease.

Seiple William W Jennings Danna D Rosen Richard B RB Borchert Leona L Canale Lee L Fagan Nora N Gordon Mark Forrest MF

Parkinson's disease 20161218

Background. Parkinson's disease (PD) progressively affects dopaminergic neurotransmission and may affect retinal dopaminergic functions and structures. Objective. This 2-year randomized, open-label, parallel-group, flexible-dose study, NCT00144300, evaluated ophthalmologic safety profiles of immediate-release (IR) pramipexole and ropinirole in patients with early idiopathic PD with ≤6 months' prior dopamine agonist exposure and without preexisting major eye disorders. Methods.</ ...[more]

PMID: 28078162

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Project description:Gambling Disorder (GD) has recently been reclassified from an impulse-control disorder to a behavioural addiction and, as in other addictive disorders, the dopaminergic reward system is involved. According to neuroimaging studies, alterations within the striatal dopaminergic signalling can occur in GD. However, the findings to date are controversial and there has been no agreement yet on how the reward system is affected on a molecular basis. Within the last 20 years, there has been growing evidence for a higher risk to develop GD in response to certain dopaminergic medication. Especially the dopamine agonists pramipexole and ropinirole, and the dopamine modulator aripiprazole seem to increase the likelihood for GD. The goal of this study was to examine the association between a prescription for either of the three pharmaceuticals and a GD diagnosis in a large cross-sectional study of the Swedish population. Compared to patients with any other dopaminergic drug prescription (38.7% with GD), the diagnosis was more common in patients with a dopamine agonist prescription (69.8% with GD), resulting in an odds ratio of 3.2. A similar association was found between aripiprazole prescriptions and GD diagnoses, which were analysed within the subgroup of all patients with schizophrenia or a schizotypal, delusional, or another non-mood psychotic disorder. An aripiprazole prescription increased the likelihood of GD (88.8%) in comparison to patients without an aripiprazole prescription (71.2%) with an odds ratio of 3.4. This study contributes to the increasingly reliable evidence for an association between several dopaminergic drugs and a higher risk for developing GD. Therefore, one future research goal should be a better understanding of the neurobiology in GD to be able to design more selective dopaminergic medication with less severe side effects. Additionally, this knowledge could enable the development of pharmacotherapy in GD and other addictive disorders.

Project description:The efficacy of dopamine agonists in treating major depressive disorder has been hypothesized to stem from effects on ventrostriatal dopamine and reward function. However, an important question is whether dopamine agonists are most beneficial for patients with reward-based deficits. This study evaluated whether measures of reward processing and ventrostriatal dopamine function predicted response to the dopamine agonist, pramipexole (ClinicalTrials.gov Identifier: NCT02033369). Individuals with major depressive disorder (n = 26) and healthy controls (n = 26) (mean ± SD age = 26.5 ± 5.9; 50% female) first underwent assessments of reward learning behaviour and ventrostriatal prediction error signalling (measured using functional MRI). 11C-(+)-PHNO PET before and after oral amphetamine was used to assess ventrostriatal dopamine release. The depressed group then received open-label pramipexole treatment for 6 weeks (0.5 mg/day titrated to a maximum daily dose of 2.5 mg). Symptoms were assessed weekly, and reward learning was reassessed post-treatment. At baseline, relative to controls, the depressed group showed lower reward learning (P = 0.02), a trend towards blunted reward-related prediction error signals (P = 0.07), and a trend towards increased amphetamine-induced dopamine release (P = 0.07). Despite symptom improvements following pramipexole (Cohen's d ranging from 0.51 to 2.16 across symptom subscales), reward learning did not change after treatment. At a group level, baseline reward learning (P = 0.001) and prediction error signalling (P = 0.004) were both associated with symptom improvement, albeit in a direction opposite to initial predictions: patients with stronger pretreatment reward learning and reward-related prediction error signalling improved most. Baseline D2/3 receptor availability (P = 0.02) and dopamine release (P = 0.05) also predicted improvements in clinical functioning, with lower D2/3 receptor availability and lower dopamine release predicting greater improvements. Although these findings await replication, they suggest that measures of reward-related mesolimbic dopamine function may hold promise for identifying depressed individuals likely to respond favourably to dopaminergic pharmacotherapy.

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Dataset Information

Ophthalmologic Baseline Characteristics and 2-Year Ophthalmologic Safety Profile of Pramipexole IR Compared with Ropinirole IR in Patients with Early Parkinson's Disease.

Publications

Ophthalmologic Baseline Characteristics and 2-Year Ophthalmologic Safety Profile of Pramipexole IR Compared with Ropinirole IR in Patients with Early Parkinson's Disease.

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