Parkinson’s Disease Therapy – When to Start and What to Choose
Parkinson’s Disease Therapy – When to Start and What to Choose
Parkinson’s disease (PD) is a neurodegenerative disorder that, at least in the early stages, is predominantly characterised by a loss of nigrostriatal dopaminergic function, and the presence of bradykinesia is a sine qua non for diagnosis. As the disease progresses, additional non-motor symptoms sometimes emerge. The natural history of the disorder varies markedly from patient to patient, and attempts to delineate clinical subtypes have been made (tremor-dominant, axial and bulbar forms). Treatment decisions take into account individual disabilities and the patient’s age (biological and chronological), occupation and lifestyle.
Accurate diagnosis is an essential pre-requisite for providing advice on prognosis and planning of disease management. Several assessment tools are available for providing semi-quantitative measures of disease progression, including: the Unified Parkinson’s Disease Rating Scale (UPDRS), the current gold standard for motor assessment; the Mini Mental State Examination (cognitive); the Geriatric Depression Scale (GDS15); and the Parkinson’s Disease Questionnaire-39 (PDQ39) (quality of life [QoL]). Staging of PD using the Hoehn and Yahr (H&R) scale has also proved to be a useful and simple marker of disease progression.
The recognition of numerous non-motor symptoms in even the early stages of PD has prompted the Movement Disorders Society (MDS) to revise the UPDRS scale to include non-motor and QoL elements. Professor Christopher Goetz from Rush University Medical Center in Chicago is chairing the study group, and a publication appeared in the December 2008 issue of Movement Disorders.
Timing of Treatment
There are a number of guidelines regarding the optimal time-frame for onset of therapy and treatment choices for PD patients, but most of these are not supported by robust evidence-based literature. In the UK, the National Institute of Clinical Excellence (NICE) has developed recommendations for the management and pharmacotherapy of PD in primary and secondary care.1 The NICE guidelines recommend pharmacotherapy once motor symptoms begin to impair the patient’s functional ability. Useful practice parameters are also available from the Quality Standards Subcommittee of the American Academy of Neurology (AAN).2
Evidence-based reviews by the MDS also offer some guidance of when to initiate therapy, as do the European Federation of Neurological Societies (EFNS) guidelines, although the EFNS document is not widely used outside Europe. Other algorithms for the treatment and management of patients with PD have also been published, but these can be criticised on the grounds of pharmaceutical industry sponsorship.3,4 Ultimately, although some guidance for the initial treatment of PD is available, the question of when to start treatment and with what drug remains largely a decision for the treating physician.1,5
The optimal time-frame for onset of therapy has remained controversial since levodopa became routinely available in 1969. One view supports early treatment, exemplified by the substantial improvements observed in de novo patients treated with levodopa and reduced mortality.6–9 It has even been suggested that early treatment could offer some neuroprotection to active dopaminergic neurons and facilitate compensatory neuroplasticity.10
- National Institute for Health and Clinical Excellence. Parkinson’s Disease: Diagnosis and management in primary and secondary care. London: NICE 2006. Available at: www.nice.org.uk/nicemedia/pdf/cg035niceguideline.pdf (accessed November 2008).
- Miyasaki JM, Martin W, Suchowersky O, et al., 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;58:11–17.
- Bhatia K, Brooks DJ, Burn DJ, et al., Updated guidelines for the management of parkinson’s disease, Hosp Med, 2001;62: 456–70.
- Olanow CW, Watts RL, Koller WC, An algorithm (decision tree) for the management of parkinson’s disease (2001): Treatment guidelines, Neurology, 2001;56:S1–S88.
- Montgomery EB, Slowing parkinson’s disease progression: Recent dopamine agonist trials, Neurology, 2004;62:343, author reply 343–5.
- Markham CH, Diamond SG, Evidence to support early levodopa therapy in parkinson disease, Neurology, 1981;31:125–31.
- Markham CH, Diamond SG, Long-term follow-up of early dopa treatment in parkinson’s disease, Ann Neurol, 1986;19:365–72.
- Diamond SG, Markham CH, Hoehn MM, et al., Effect of age at onset on progression and mortality in parkinson’s disease, Neurology, 1989;39:1187–90.
- Hoehn MM, The natural history of parkinson’s disease in the pre-levodopa and post-levodopa eras, Neurol Clin, 1992;10: 331–9.
- Reichmann H, Initiation of parkinson’s disease treatment, J Neurol, 2008;255(Suppl. 5):57–9.
- Fahn S, Bressman SB, Should levodopa therapy for parkinsonism be started early or late? Evidence against early treatment, Can J Neurol Sci, 1984;11:200–205.
- Fahn S, Cohen G, The oxidant stress hypothesis in parkinson’s disease: Evidence supporting it, Ann Neurol, 1992;32:804–12.
- Grosset D, Taurah L, Burn DJ, et al., A multicentre longitudinal observational study of changes in self reported health status in people with parkinson’s disease left untreated at diagnosis, J Neurol Neurosurg Psychiatry, 2007;78:465–9.
- Lees A, Drugs for Parkinson’s disease, J Neurol Neurosurg Psychiatry, 2002;73(6):607–10.
- Oertel WH, Wolters E, Sampaio C, et al., Pergolide versus levodopa monotherapy in early parkinson’s disease patients: The pelmopet study, Mov Disord, 2006;21:343–53.
- Lees AJ, Katzenschlager R, Head J, Ben-Shlomo Y, Ten-year follow-up of three different initial treatments in de-novo pd: A randomized trial, Neurology, 2001;57:1687–94.
- Fahn S, Oakes D, Shoulson I, et al., Levodopa and the progression of parkinson’s disease, N Engl J Med, 2004;351: 2498–2508.
- 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;356:39–46.
- Van Camp G, Flamez A, Cosyns B, et al., Treatment of parkinson’s disease with pergolide and relation to restrictive valvular heart disease, Lancet, 2004;363:1179–83.
- Rezak M, Current pharmacotherapeutic treatment options in parkinson’s disease, Dis Mon, 2007;53:214–22.
- Moller JC, Oertel WH, Koster J, et al., Long-term efficacy and safety of pramipexole in advanced parkinson’s disease: Results from a european multicenter trial, Mov Disord, 2005;20:602–10.
- Palhagen S, Heinonen E, Hagglund J, et al., Selegiline slows the progression of the symptoms of parkinson disease, Neurology, 2006;66:1200–1206.
- Olanow CW, Attempts to obtain neuroprotection in parkinson’s disease, Neurology, 1997;49:S26–33.
- Olanow CW, Hauser R, Jankovic J, et al., A randomized, double-blind, placebo-controlled, delayed start study to assess rasagiline as a disease modifying therapy in parkinson’s disease (the adagio study): Rationale, design, and baseline characteristics, Mov Disord, 2008.
- . Parkinson Study Group, A controlled, randomized, delayedstart study of rasagiline in early parkinson disease, Arch Neurol, 2004;61:561–6.
- Fung VS, Herawati L, Wan Y, Quality of life in early parkinson’s disease treated with levodopa/carbidopa/entacapone, Mov Disord, 2008.
- Parkinson Study Group, A randomized controlled trial comparing pramipexole with levodopa in early parkinson’s disease: Design and methods of the CALM-PD study. Parkinson study group, Clin Neuropharmacol, 2000;23: 34–44.
- Katzenschlager R, Head J, Schrag A, et al., Fourteen-year final report of the randomized pdrg-uk trial comparing three initial treatments in pd, Neurology, 2008;71:474–80.
- Lees A, Alternatives to levodopa in the initial treatment of early parkinson’s disease, Drugs Aging, 2005;22:731–40.
