Redefining Treatment Success in Patients With Parkinson’s Disease
Case Study
A 53-year-old male patient visits the neurologist because he is experiencing a recent onset of a unilateral, intermittent tremor in his right arm that occurs primarily with stress. Neurologic evaluation reveals mild right arm rigidity in addition to the rest tremor on the right side. However, the patient shows no signs of associated disability. No additional neurologic signs or symptoms are present, and the patient does not report any neuropsychiatric symptoms other than mild anxiety. The neurologist concludes that the patient is experiencing early signs of Parkinson’s disease.
COMMENT
The traditional approach to treatment of early-stage Parkinson’s disease (PD) is to delay treatment until symptoms substantially impair the patient’s ability to function.1 However, an early diagnosis provides the opportunity to administer disease-modifying therapy (once identified) and monitor the rate of disease progression from an early stage. Levodopa remains the most effective treatment for the motor symptoms of PD, and all patients with PD will most likely require therapy with levodopa during the course of their disease.2,3 Because levodopa therapy is associated with the development of dyskinesia and motor fluctuations, as well as nausea and vomiting in some cases, younger patients with early-stage PD should ordinarily be offered levodopa-sparing strategies to minimize the risk of these complications. Some physicians prefer to administer a second-generation dopamine receptor agonist (eg, pramipexole, ropinirole, rotigotine) as initial therapy for PD and add levodopa as adjunct therapy as the disease progresses. However, treatment with these dopamine agonists is associated with adverse events, including nausea, vomiting, postural hypotension, somnolence, hallucinations, and impulse-control disorders.2-4 Treatment with monoamine oxidase-B (MAO-B) inhibitors has been employed by some neurologists as a potential disease-modifying strategy, though definitive proof is lacking.3 There is insufficient clinical evidence supporting the efficacy of selegiline as monotherapy (ie, in the absence of levodopa therapy) in patients with early-stage PD. Moreover, selegiline is metabolized to amphetamine and methamphetamine, which can cause sleep-wake disturbances and hallucinations.5 Rasagiline, a second-generation MAO-B inhibitor, is distinguished from selegiline by its lack of amphetamine metabolites and broader clinical evidence base for efficacy as monotherapy in early-stage PD. Guidelines put forth by the American Academy of Neurology and the Movement Disorder Society conclude that rasagiline may provide symptomatic benefit as initial monotherapy in early PD and may be considered as initial therapy before administration of dopaminergic agonists.5,7 Thus, rasagiline should be regarded as a potential first-line treatment strategy in patients with early-stage PD without disability.
REFERENCES
1. Schapira AHV, Obeso J. Timing of treatment initiation in Parkinson's disease: a need for reappraisal? Ann Neurol. 2006;59(3):559-562. 2. Olanow CW, Watts RL, Koller WC. An algorithm (decision tree) for the management of Parkinson's disease (2001): treatment guidelines. Neurology. 2001;56(11 suppl 5):S1-S88. 3. Weintraub D, Comella CL, Horn S. Parkinson's disease—part 2: treatment of motor symptoms. Am J Manag Care. 2008;14(2 suppl):S49-S58. 4. Jankovic J. An update on the treatment of Parkinson's disease. Mt Sinai J Med. 2006;73(4):682-689. 5. MAO-B inhibitors for the treatment of Parkinson's disease. Mov Disord. 2002;17 (suppl 4):S38-S44. 6. Lecht S, Haroutiunian S, Hoffman A, Lazarovici P. Rasagiline—a novel MAO B inhibitor in Parkinson's disease therapy. Ther Clin Risk Manag. 2007;3(3):467-474. 7. Miyasaki JM, Martin W, Suchowersky O, Weiner WJ, Lang AE. Practice parameter: initiation of treatment for Parkinson's disease: an evidence-based review: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2002;58(1):11-17.
