Therapeutic interventions and adjustments in the management of Parkinson disease: role of combined carbidopa/levodopa/entacapone (Stalevo®)
Paolo Solla, Antonino Cannas, Francesco Marrosu, Maria Giovanna MarrosuMovement Disorders Center, Institute of Neurology, University of Cagliari, Cagliari, ItalyAbstract: Parkinson disease (PD) is a neurodegenerative disorder characterized by 3 cardinal motor symptoms: resting tremor, rigidity, and...
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Dove Medical Press
2010
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oai:doaj.org-article:6d9b1dd11bcb4d0fb05ee3eb7f9f9cb52021-12-02T06:33:23ZTherapeutic interventions and adjustments in the management of Parkinson disease: role of combined carbidopa/levodopa/entacapone (Stalevo®)1176-63281178-2021https://doaj.org/article/6d9b1dd11bcb4d0fb05ee3eb7f9f9cb52010-08-01T00:00:00Zhttp://www.dovepress.com/therapeutic-interventions-and-adjustments-in-the-management-of-parkins-a4973https://doaj.org/toc/1176-6328https://doaj.org/toc/1178-2021Paolo Solla, Antonino Cannas, Francesco Marrosu, Maria Giovanna MarrosuMovement Disorders Center, Institute of Neurology, University of Cagliari, Cagliari, ItalyAbstract: Parkinson disease (PD) is a neurodegenerative disorder characterized by 3 cardinal motor symptoms: resting tremor, rigidity, and bradykinesia. Since its introduction 40 years ago, levodopa has represented the gold standard for dopaminergic stimulation therapy in patients with PD. Levodopa is routinely combined with a dopa-decarboxylase inhibitor (DDCI) to prevent the conversion of levodopa into dopamine in peripheral circulation. However, up to 80% of patients treated with continuous levodopa manifest the onset of disabling motor complications capable of producing an adverse effect on quality of life as the disease progresses. In recent years, a new, safe, and efficacious armamentarium of treatment options has been provided by the marketing of the catechol-O-methyltransferase (COMT) inhibitor, entacapone, a peripheral blocker of dopa to 3-0-methyldopa metabolism, which increments levodopa brain availability. When administered with levodopa, entacapone conjugates the rapid onset of levodopa-induced effects with a protracted efficiency, thus providing additional benefits to classic levodopa treatment by increasing “on” time in fluctuating PD patients, and theoretically providing a more continuous and physiological-like stimulation of dopamine receptors implying a reduced risk of motor complications. In this context, the use of a single administration of combined ­carbidopa/levodopa/entacapone (Stalevo®) in the treatment of PD affords clinical improvements similar to those obtained by 2 separate tablets (ie, levodopa/DDCI and entacapone), although the former produces a more positive effect on quality of life than the latter. Additionally, the STalevo Reduction In Dyskinesia Evaluation (STRIDE-PD) study was designed with the aim of demonstrating that the combination of levodopa, carbidopa, and entacapone, used as initial levodopa therapy, significantly delays the onset of dyskinesias compared with the conventional levodopa/carbidopa formulation. Unfortunately, STRIDE-PD failed to prove the benefit of continuous dopaminergic stimulation with triple therapy in a ­clinical setting. Recently, the effect of combined COMT inhibitor with levodopa administration in ­reducing homocysteine synthesis has been described. To this regard, clear evidence has been presented indicating homocysteine as a risk factor for vascular diseases, cognitive impairment, and dementia. Several studies have discussed the potential of entacapone as adjunct to levodopa/DDCI in reducing plasma homocysteine levels with contrasting results.Keywords: Parkinson disease, carbidopa/levodopa/entacapone Paolo SollaAntonino CannasFrancesco Marrosuet alDove Medical PressarticleNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol 2010, Iss Issue 1, Pp 483-490 (2010) |
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Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 |
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Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Paolo Solla Antonino Cannas Francesco Marrosu et al Therapeutic interventions and adjustments in the management of Parkinson disease: role of combined carbidopa/levodopa/entacapone (Stalevo®) |
| description |
Paolo Solla, Antonino Cannas, Francesco Marrosu, Maria Giovanna MarrosuMovement Disorders Center, Institute of Neurology, University of Cagliari, Cagliari, ItalyAbstract: Parkinson disease (PD) is a neurodegenerative disorder characterized by 3 cardinal motor symptoms: resting tremor, rigidity, and bradykinesia. Since its introduction 40 years ago, levodopa has represented the gold standard for dopaminergic stimulation therapy in patients with PD. Levodopa is routinely combined with a dopa-decarboxylase inhibitor (DDCI) to prevent the conversion of levodopa into dopamine in peripheral circulation. However, up to 80% of patients treated with continuous levodopa manifest the onset of disabling motor complications capable of producing an adverse effect on quality of life as the disease progresses. In recent years, a new, safe, and efficacious armamentarium of treatment options has been provided by the marketing of the catechol-O-methyltransferase (COMT) inhibitor, entacapone, a peripheral blocker of dopa to 3-0-methyldopa metabolism, which increments levodopa brain availability. When administered with levodopa, entacapone conjugates the rapid onset of levodopa-induced effects with a protracted efficiency, thus providing additional benefits to classic levodopa treatment by increasing “on” time in fluctuating PD patients, and theoretically providing a more continuous and physiological-like stimulation of dopamine receptors implying a reduced risk of motor complications. In this context, the use of a single administration of combined ­carbidopa/levodopa/entacapone (Stalevo®) in the treatment of PD affords clinical improvements similar to those obtained by 2 separate tablets (ie, levodopa/DDCI and entacapone), although the former produces a more positive effect on quality of life than the latter. Additionally, the STalevo Reduction In Dyskinesia Evaluation (STRIDE-PD) study was designed with the aim of demonstrating that the combination of levodopa, carbidopa, and entacapone, used as initial levodopa therapy, significantly delays the onset of dyskinesias compared with the conventional levodopa/carbidopa formulation. Unfortunately, STRIDE-PD failed to prove the benefit of continuous dopaminergic stimulation with triple therapy in a ­clinical setting. Recently, the effect of combined COMT inhibitor with levodopa administration in ­reducing homocysteine synthesis has been described. To this regard, clear evidence has been presented indicating homocysteine as a risk factor for vascular diseases, cognitive impairment, and dementia. Several studies have discussed the potential of entacapone as adjunct to levodopa/DDCI in reducing plasma homocysteine levels with contrasting results.Keywords: Parkinson disease, carbidopa/levodopa/entacapone |
| format |
article |
| author |
Paolo Solla Antonino Cannas Francesco Marrosu et al |
| author_facet |
Paolo Solla Antonino Cannas Francesco Marrosu et al |
| author_sort |
Paolo Solla |
| title |
Therapeutic interventions and adjustments in the management of Parkinson disease: role of combined carbidopa/levodopa/entacapone (Stalevo®) |
| title_short |
Therapeutic interventions and adjustments in the management of Parkinson disease: role of combined carbidopa/levodopa/entacapone (Stalevo®) |
| title_full |
Therapeutic interventions and adjustments in the management of Parkinson disease: role of combined carbidopa/levodopa/entacapone (Stalevo®) |
| title_fullStr |
Therapeutic interventions and adjustments in the management of Parkinson disease: role of combined carbidopa/levodopa/entacapone (Stalevo®) |
| title_full_unstemmed |
Therapeutic interventions and adjustments in the management of Parkinson disease: role of combined carbidopa/levodopa/entacapone (Stalevo®) |
| title_sort |
therapeutic interventions and adjustments in the management of parkinson disease: role of combined carbidopa/levodopa/entacapone (stalevo®) |
| publisher |
Dove Medical Press |
| publishDate |
2010 |
| url |
https://doaj.org/article/6d9b1dd11bcb4d0fb05ee3eb7f9f9cb5 |
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