Pharmacy & Therapeutics - October 2008 - (Page 605)

Medical Management of Parkinson’s Disease the motor and activities of daily living components of the UPDRS. The treating investigators also saw these highly significant differences between the treated and placebo groups. After the washout was completed, all active-treatment groups had returned to baseline. None of the three treatment groups’ UPDRS scores were ever worse than those of the placebo group, and there was no evidence of any hastening of the disease, at least after a two-week washout. The three treatments were neuroprotective because the results were better than those than in the placebo group. Adverse events included more headaches, slightly increased muscle tone, and dystonia in patients receiving 600 mg/day. Infection, nausea, and increased somnolence were reported in the higher-dose patients, although the incidence of somnolence did not reach statistical significance. More leg pain was reported in the untreated and low-dose groups. Dopaminergic adverse events included dyskinesias and a trend for wearingoff with 600 mg/day, compared with lower doses. However, freezing was more prevalent with the lower doses than with the higher doses. Neuroimaging results showed no differences at baseline on any of the striatal beta-CIT spectroscopy scores. At nine months, the decline in beta-CIT uptake was more pronounced in the levodopa groups than in the placebo group (–7.2%, –4%, –6%, and –1.4% with 600, 300, and 150 mg/day and placebo, respectively). This suggests contradictory results from that noted on beta-CIT spectroscopy and what was observed clinically. The evidence did not indicate that levodopa was harmful or that it hastened the progression of PD, but because of the uncertainty that levodopa’s long sustained benefit might derive from a more prolonged pharmacological or plasticity effect, it cannot be concluded that levodopa proved protective. Perhaps there might be a third type of benefit; there is a short-duration benefit and a long-duration benefit, but there might also be a more extended benefit. If so, the duration of any such benefit is unknown, and a much longer washout period than was attempted in ELLDOPA would need to be used to detect such an enduring change before neuroprotection could be confirmed. No claims can be made from the imaging study. Interpretation is fraught with uncertainty, because the study group was small and the duration was short. It is unclear whether levodopa had an effect on dopamine binding that might explain the decreased beta-CIT uptake. Additional study is needed. cause there is no compelling evidence favoring any single drug, treatment should be individualized. For the initial treatment of PD, the American Academy of Neurology recommends levodopa to improve motor disability or a dopamine agonist to lessen motor complications. After decades of clinical observation, levodopa has endured as the most effective primary medicinal agent. Entacapone (Comtan) and rasagiline (Agilect) may be able to reduce “off” time when PD has progressed and when medications are less reliable in relieving symptoms. Current guidelines for PD also include updates on the use of deep-brain stimulation (DBS), an emerging therapy. DBS of the subthalamic nucleus may improve motor function and reduce motor fluctuations, dyskinesia, and medication usage, although there is insufficient evidence to support DBS in other locations of the brain. More study of DBS is required. REFERENCES 1. Lang AE, Lozano AM. Parkinson’s disease. First of two parts. N Engl J Med 1998;339:1044–1053. 2. Gibb WR. Neuropathology of Parkinson’s disease–related syndromes. Neurol Clin 1992;10:361–376. 3. Fearnley J, Lees A. Pathology of Parkinson’s disease. In: Calne DB, ed. Neurodegenerative Diseases. Philadelphia, PA: WB Saunders; 1994:545–554. 4. Braak H, Braak E. Pathology of Alzheimer’s disease. In: Calne DB, ed. Neurodegenerative Diseases. Philadelphia, PA: WB Saunders, 1994; 585–614. 5. National Parkinson Foundation. About Parkinson disease: Who gets Parkinson’s disease? April 2008. Available at: www.parkinson. org/netcommunity/page.aspx?pid=225&srcid=201. 6. Albin RL. Parkinson’s disease: Background, diagnosis, and initial management. Clin Geriatr Med 2006;22:735–751. 7. Bower JH, Maraganore DM, McDonnell SK, et al. Incidence and distribution of parkinsonism in Olmsted County, Minnesota, 1976–1990. Neurology 1999:1214–1220. 8. LeWitt PA. Tobacco smoking, nicotine, and neuroprotection. In: Factor SA, Weiner WJ, eds. Parkinson’s Disease: Diagnosis and Clinical Management. New York: Demos; 2002:519–529. 9. Hardy J, Cookson MR, Singleton A. Genes and parkinsonism. Lancet Neurol 2003;2:221–228. 10. National Institute of Neurological Disorders and Stroke. Available at: www.ninds.nih.gov/disorders/parkinsons_disease/detail_ parkinsons_disease.htm. April 2008. Accessed May 3, 2008. 11. Ruane C. What is Parkinson’s disease? Available at: www.ezilon. com/information/printer_15984.shtml. February 2006. Accessed May 3, 2008. 12. Aminoff MJ. Pharmacologic management of parkinsonism and other movement disorders. In: Katzung BG, ed. Basic and Clinical Pharmacology, 10th ed. New York: McGraw-Hill Lange Medical; 2007:442–451. 13. Hauser R. Long-term care of Parkinson’s disease: Strategies for managing ‘wearing off’ symptom re-emergence and dyskinesias. Geriatrics 2006;61:14–20. 14. Alam ZI, Daniel SE, Lees AJ, et al. A generalized increase in protein carbonyls in the brain of Parkinson’s but not incidental Lewy body disease. J Neurochem 1997;69:1326–1329. 15. LeWitt PA. Parkinson’s disease: Etiologic considerations. In: Ahlskog JE, Adler CA. eds. Parkinson’s Disease and Movement Disorders: Diagnosis and Treatment Guidelines for the Practicing Physician. New York: Humana Press; 2000:91–100. 16. Leegwater-Kim J, Waters C. Parkinsonism. In: Rakel RE, Bope ET, eds. Conn’s Current Therapy. Philadelphia: WB Saunders, Elsevier; 2008:931–936. 17. Di Fonzo A, Tassorelli C, De Mari M, et al. Comprehensive analysis of the LRRK2 gene in sixty families with Parkinson’s disease. Eur J Hum Genet 2006;14:322–331. 18. Whaley NR, Uitti RJ, Dickson DW, et al. Clinical and pathologic CONCLUSION PD generally follows a progressive course. The benefits of levodopa often diminish with time, and serious adverse effects may complicate long-term levodopa treatment. Levodopa-sparing interventions (e.g., dopamine agonist monotherapy or rasagiline in early PD), may be able to delay motor complications, whereas the initiation of levodopa might be withheld until the patient needs additional symptomatic benefit or if side effects limit the use of other agents. The symptomatic treatment of mild PD is probably best avoided until a disability or symptoms begin to affect the patient’s lifestyle. Treatment of early PD with MAO-inhibitors, dopamine agonists, or levodopa/carbidopa improves quality of life. Be- Vol. 33 No. 10 • October 2008 • P&T® 605 http://www.parkinson.org/netcommunity/page.aspx?pid=225&srcid=201 http://www.parkinson.org/netcommunity/page.aspx?pid=225&srcid=201 http://www.ninds.nih.gov/disorders/parkinsons_disease/detail_parkinsons_disease.htm http://www.ninds.nih.gov/disorders/parkinsons_disease/detail_parkinsons_disease.htm http://www.ezilon.com/information/printer_15984.shtml http://www.ezilon.com/information/printer_15984.shtml

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Pharmacy & Therapeutics - October 2008 Contents Editorial Medication Errors Prescription: Washington New Drugs/Drug News/ New Medical Devices Drug Forecast Medical Management of Parkinson’s Disease Why Is Health Care Regulation So Complex? The Next President’s Prescription for Action on Drugs Trends in Managing Multiple Sclerosis Product Profiler: Sancuso®

Pharmacy & Therapeutics - October 2008

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