Management of Parkinson's Disease
Management of Parkinson's Disease
Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease, and is responsible for significant morbidity and costs. Current treatments target the replacement of dopamine loss through the administration of dopaminergic agents such as levodopa (converted to dopamine in the brain) and dopamine agonists. Several medications have been tested for neuroprotection, but results so far are inconclusive. Symptomatic therapies allow good motor control for many years, until cognitive impairment and balance problems develop.
Risk–Benefit Assessment of Current Dopaminergic Medications
Levodopa is the gold standard for treatment of Parkinson’s disease, but its oral administration is associated with a high risk of motor fluctuations and dyskinaesia. This is due primarily to the pulsatility of oral administration in combination with the progressive loss of dopamine nerve terminals.
Dopamine agonists have been widely used in recent years because their long-term utilisation reduces the risk of motor fluctuations and dyskinaesia. They are divided into two classes:
- ergot (pergolide, cabergoline); and
- non-ergot (pramipexole, ropinirole and rotigotine).
The use of ergot dopamine agonists has recently decreased significantly as their intake is associated with pleuro-pulmonary or reperitoneal fibrotic reactions, as well as heart valvulopathy.1 The latter in particular is viewed with concern because severe regurgitation may require heart valve replacement, which increases the disability of patients. The mechanism of heart valvulopathy is mediated by the 5-HT2B agonistic activity of pergolide and cabergoline on serotonergic receptors expressed on cardiac valvular fibroblasts.
In addition to performing a population study, we recently reviewed the available literature and found that the frequency of moderate to severe regurgitation in patients receiving cabergoline and pergolide is markedly increased compared with patients treated with non-ergot agonists and non-Parkinson controls (see Table 1 and Figure 1).2 This evidence led to the withdrawal of pergolide marketing authorisation in the US, while in Europe the prescription of both pergolide and cabergoline is restricted.
Another issue concerns the risk of psychiatric adverse events such as addictive behaviour, pathological gambling and hypersexuality. We recently assessed the frequency of these disturbances using specific scales in a cohort of PD patients and non-PD controls. Overall, 28% of the PD patients and 20% of the healthy controls reported at least one abnormal behaviour.3 PD patients had higher scores than controls for impulsivity, compulsivity and depression; however, there was no correlation between impulsivity, compulsivity and depression scores in PD. Male gender and higher impulsivity score, but not dose and kind of dopaminergic medications, were associated with increased probability of impulse control disorders in PD. We concluded that individual susceptibility factors such as impulsivity and depression underline abnormal behaviours in PD patients treated with stable dopaminergic therapy.
PD = Parkinson’s disease. Source: Antonini and Poewe, Lancet Neurol, 2007
- Zanettini R, Antonini A, Gatto G, et al., Valvular heart disease and the use of dopamine agonists for Parkinson s disease, N Engl J Med, 2007;356(1):39 46.
- Antonini A, Poewe W, Fibrotic heart-valve reactions to dopamine-agonist treatment in Parkinson s disease, Lancet Neurol, 2007;6(9):826 9.
- Isaias IU, Siri C, De Gaspari D, et al., The relationship between impulsivity and impulse control disorders, Mov Disord, 2007, in press.
- De Gaspari D, Siri C, Landi A, et al., Clinical and neuropsychological follow up at 12 months in patients with complicated Parkinson s disease treated with subcutaneous apomorphine infusion or deep brain stimulation of the subthalamic nucleus, J Neurol Neurosurg Psychiatry, 2006;77(4):450 53.
- Antonini A, Continuous dopaminergic stimulation-From theory to clinical practice, Parkinsonism Relat Disord, 2007;13(Suppl.):S24 8.
- Antonini A, Ioannis UI, Canesi M, et al., Duodenal levodopa infusion for advanced Parkinson s disease: 12-month treatment outcome, Mov Disord, 2007;15;22(8):1145 9.
- Antonini A, Mancini F, Canesi M, et al., Duodenal levodopa infusion improves quality of life in advanced Parkinson s disease, Neurodegenerative Disease, 2007, in press.
