ADVANCES IN neurophysiology, pharmacology, surgical technology, and molecular biology have provided the basis for contemporary therapies (Table 1) for movement disorders. This article will focus on the treatment of 4 conditions commonly seen in a movement disorder practice: Parkinson disease (PD), dystonia, essential tremor, and tic disorders.
Symptomatic therapy for patients with early signs of PD is generally delayed until there is functional impairment.1 In the meantime, the issue of putative neuroprotection can be addressed with the patient. So far, there is no medication that has been unequivocally proven to halt or slow disease progression. Research on new potential neuroprotective agents is ongoing, and antiapoptotic agents, antioxidants, and drugs that interrupt the excitotoxic cascade are currently under study. Facilitating access to study centers for participation in clinical trials is an important intervention for interested subjects. The Parkinson Study Group is a consortium of neurologists with a particular interest in clinical trials (see their Web site, http://www.parkinson-study-group.org). Selegiline (a selective monamine oxidase–B inhibitor) has been used in early PD, and clinical studies indicated that it delays disability and the need to start stronger medication in previously untreated patients. Although selegiline prevents development of parkinsonian symptoms in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)–treated laboratory animals, it is still unclear if clinical benefit in humans relates primarily to a mild symptomatic effect or a neuroprotective mechanism.2 For mild symptom control of parkinsonism, older drugs like amantadine or anticholinergics are still used; however, once there is need for significant symptomatic therapy, treatment with levodopa or a dopamine agonist should be considered.3 Levodopa is the most effective drug for managing symptoms in PD, but its long-term use is associated with the development of dyskinesias and motor fluctuations that correlate with treatment duration.1 Dyskinesias are involuntary movements in response to levodopa's administration and can take the form of chorea, dystonia, myoclonus, ballismus, or akathisia. Motor fluctuations are changes between a medication-responsive "on"-state with good mobility and an "off"-state characterized by immobility and relative medication resistance. Whereas dopamine agonists are increasingly considered first-line treatment for patients younger than 70 years, levodopa remains the drug of choice for symptomatic treatment in several groups of patients: those who require rapid symptom improvement for medical, social, or employment reasons; those older than 70; and those with cognitive impairment.1 Levodopa is given in combination with a decarboxylase inhibitor, usually carbidopa. The drug should be given 1 hour before meals to avoid competition with dietary proteins. Nausea can be treated with additional carbidopa. Domperidone, a dopamine receptor antagonist, is another very effective way of treating nausea, but it is not readily available in the United States. A sustained-release formulation of levodopa (Sinemet CR; DuPont Pharmaceuticals, Wilmington, Del)) has equal efficacy as a standard formulation for patients with nonfluctuating PD and can be given less often.4 Dopamine agonists can provide comparable symptomatic efficacy as compared with levodopa in early disease stages. In addition, their use as monotherapy or with low doses of levodopa is not associated with the rate of dyskinesias and motor complications seen with levodopa alone.3 However, because these drugs are long acting, their efficacy may not be seen for several weeks and slow upward dosage titration to an optimal dose may take months. Side effects of dopamine agonists include nausea, vomiting, hallucinations, and psychosis. Postural hypotension is prevalent during the initiation phase of treatment. Side effects can be minimized by a careful, slow titration schedule. Recently, episodes of falling asleep while driving have been described in patients with PD who are taking dopamine agonists, an effect partially attributed to the dose-related sedating effect of dopaminergic drugs but also to the fatigue experienced by patients with PD and to associated sleep disorders. Patients receiving dopaminergic therapy should therefore be routinely assessed for excessive daytime sleepiness.
Goetz CG, Hinson VK. Therapies for Movement Disorders. Arch Neurol. 2002;59(5):699–702. doi:10.1001/archneur.59.5.699
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