Effects of Ropinirole on Nonmotor Symptoms of Parkinson Disease

Rektorová, Irena; Baláž, Marek; Svátová, Jindra; Zárubová, Kateřina; Honig, Igor; Dostál, Václav; Sedláčková, Silvie; Nestrašil, Igor; Mastík, Jiří; Bareš, Martin; Velı́šková, Jana; Dušek, Ladislav

doi:10.1097/wnf.0b013e31815d25ce

Cited by 70 publications

(41 citation statements)

References 29 publications

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“…Given the predominance of dopamine D3 receptors in the mesolimbic dopaminergic system, there is a clear rational in targeting these receptors using dopamine agonist to improve hypodopaminergic manifestations (Sokoloff et al, 2006). This hypothesis is further supported by non-controlled studies showing an improvement in parkinsonian apathy following the reintroduction of dopaminergic agonists such as ropinirole (Czernecki et al, 2008;Rektorova et al, 2008). Other authors have also shown that pramipexole alleviates depression in Parkinson's disease or patients without Parkinson's disease (Leentjens et al, 2009;Barone et al, 2010).…”

Section: Introductionsupporting

confidence: 51%

Parkinsonian apathy responds to dopaminergic stimulation of D2/D3 receptors with piribedil

Thobois

Lhommée

Klinger

et al. 2013

Brain

225

186

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Apathy is one of the most common symptoms encountered in Parkinson's disease, and is defined as a lack of motivation accompanied by reduced goal-directed cognition, behaviour and emotional involvement. In a previous study we have described a delayed withdrawal syndrome after successful motor improvement related to subthalamic stimulation allowing for a major decrease in dopaminergic treatment. This withdrawal syndrome correlated with a diffuse mesolimbic dopaminergic denervation. To confirm our hypothesis of parkinsonian apathy being related to mesolimbic dopaminergic denervation, we performed a randomized controlled study using piribedil, a relatively selective D2/D3 dopamine agonist to treat parkinsonian apathy, using the model of postoperative apathy. A 12-week prospective, placebo-controlled, randomized, double-blinded trial was conducted in 37 patients with Parkinson's disease presenting with apathy (Starkstein Apathy Scale score 4 14) following subthalamic nucleus stimulation. Patients received either piribedil up to 300 mg per day (n = 19) or placebo (n = 18) for 12 weeks. The primary end point was the improvement of apathy under treatment, as assessed by the reduction of the Starkstein Apathy Scale score in both treatment groups. Secondary end points included alleviation in depression (Beck Depression Inventory), anxiety (Beck Anxiety Inventory), improvement of quality of life (PDQ39) and anhedonia (Snaith-Hamilton Pleasure Scale). Exploratory endpoints consisted in changes of the Robert Inventory score and Hamilton depression scales. An intention to treat analysis of covariance analysis was performed to compare treatment effects (P 5 0.05). The number of premature study dropouts was seven in the placebo and five in the piribedil groups, mostly related to intolerance to hypodopaminergic symptoms. At follow-up evaluation, the apathy score was reduced by 34.6% on piribedil versus 3.2% on placebo (P = 0.015). With piribedil, modifications in the Beck depression and anxiety scores were À19.8% and À 22.8%, respectively versus + 1.4% and À 8.3% with placebo, without reaching significance level. Piribedil led to a trend towards improvement in quality of life ( À 16.2% versus + 6.7% on placebo; P = 0.08) and anhedonia (À 49% versus À 5.6% on the placebo; P = 0.08). Apathy, assessed by the Robert Inventory score, improved by 46.6% on piribedil and worsened by 2.3% on placebo (P = 0.005). Depression, measured by the Hamilton score, improved in the piribedil group (P = 0.05). No significant side effects were observed. The present study provides a class II evidence of the efficacy of the dopamine agonist piribedil in the treatment of apathy in Parkinson's disease.

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Section: Introductionsupporting

confidence: 51%

Parkinsonian apathy responds to dopaminergic stimulation of D2/D3 receptors with piribedil

Thobois

Lhommée

Klinger

et al. 2013

Brain

225

186

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“…[116] However, no other convincing, undisputable clinical data are available. [159,160] Conversely, dysautonomic parkinsonian symptoms, like orthostatic hypotension, are often aggravated by DAs (as by any dopaminergic medication), probably through dopaminergic sympatholytic mechanisms.…”

Section: Symptomatic Control Of Non-motor Problemsmentioning

confidence: 98%

Dopamine Receptor Agonists for the Treatment of Early or Advanced Parkinsonʼs Disease

2010

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Dopamine receptor agonists are indicated for the symptomatic treatment of early, moderate or advanced Parkinson's disease as well as for the reduction of levodopa-related motor complications. Ergolinic dopamine agonists, such as bromocriptine or pergolide, were initially developed and marketed, and then non-ergolinic dopamine agonists, such as pramipexole and ropinirole, were introduced, reducing the risk of drug-induced fibrotic reactions. Once-daily, controlled-release oral and transdermal formulations have been developed aiming at providing more stable 24-hour plasma drug concentrations and more convenient administration. A disease-modifying effect of dopamine agonists has not been demonstrated clinically. As with any other drug, dopamine agonists can also cause adverse drug reactions, which can be related or unrelated to dopaminergic hyperactivation. Dopaminergic reactions include nausea, hallucinations, confusion and orthostatic hypotension, among others, which were readily identified in pre-marketing clinical trials. During post-marketing surveillance, important adverse reactions were identified, such as daytime somnolence, impulse-control disorders and heart valve fibrosis. Other issues, including the efficacy of dopamine agonists for the treatment of non-motor symptoms, remain under evaluation.

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“…Ropinirole, another D 2 /D 3 agonist, acts on D 3 preferentially and showed effects on NMSs in PD patients with motor fluctuations and/or dyskinesias [29]. In addition, Pahwa et al reported in a double-blind placebo-controlled study, that Ropinirole improved NMSs in PD patients [30].…”

Section: Depressionmentioning

confidence: 99%

Neurobiology of Depression and Anxiety in Parkinson's Disease

Kano

Ikeda

Cridebring

et al. 2011

Parkinson's Disease

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Depression and anxiety are common in Parkinson's disease (PD) and have important consequences on quality of life. These have long been recognized as frequent accompanying syndromes of PD, and several reports suggest that these are the causative process or risk factors that are present many years before the appearance of motor symptoms. The neurochemical changes in PD involving dopamine, norepinephrine, and serotonin might be related to the pathophysiology of depression and anxiety, but this is still not clear. Several studies showed that anxiety in PD patients occurs earlier than depression, during premotor phase, suggesting that there may be a link between the mechanisms that cause anxiety and PD. Whereas a recent study reported that PD patients with depression and anxiety were associated with different demographic and clinical features.

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Effects of Ropinirole on Nonmotor Symptoms of Parkinson Disease

Abstract: In addition to controlling motor symptoms, ropinirole improved both anxiety and depressive symptoms in PD patients with motor fluctuations and/or dyskinesias. Changes in mood and anxiety correlated with changes in sleep scores.

Cited by 70 publications

References 29 publications

Parkinsonian apathy responds to dopaminergic stimulation of D2/D3 receptors with piribedil

Parkinsonian apathy responds to dopaminergic stimulation of D2/D3 receptors with piribedil

Dopamine Receptor Agonists for the Treatment of Early or Advanced Parkinsonʼs Disease

Neurobiology of Depression and Anxiety in Parkinson's Disease

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