To evaluate the role of the practicing pharmacist in the identification and current treatment of the levodopa wearing-off phenomenon experienced by patients with Parkinson's disease (PD) who are receiving chronic levodopa therapy.
Data Sources:
Literature retrieval was accessed through MEDLINE (1967–June 2007) using the terms levodopa, wearing-off, and Parkinson's disease. In addition, reference citations from publications identified were reviewed.
Study Selection and Data Exthaction:
All articles that were identified from the data sources and written in English were evaluated.
Data Synthesis:
Levodopa is the most efficacious therapeutic agent in PD; however, the response of patients to levodopa changes over time. Eventually, the duration of response becomes shorter and more unpredictable, and complications emerge. One of the first complications observed with levodopa therapy is wearing-off, which can emerge within 1–3 years of initiation of levodopa treatment. Wearing-off is characterized by the predictable emergence of motor and nonmotor PD symptoms before the next scheduled dose of medication. Despite effective treatment options to tackle wearing-off, it remains underrecognized and under treated. With early identification and optimization of treatment, wearing-off can be managed effectively, resulting in improved quality of life for patients with PD.
Conclusions:
Owing to their training and accessibility, pharmacists play an increasingly important role in the management of patients with PD. Pharmacists are uniquely placed to identify wearing-off, offer timely advice, and facilitate the optimization of treatment regimens to improve patients’ quality of life and enhance long-term outcomes
AndersonS.The state of the world's pharmacy: a portrait of the pharmacy profession. J Interprof Care2002; 16: 391-404.
2.
de LauLM, BretelerMM. Epidemiology of Parkinson's disease. Lancet Neurol2006; 5: 525-35.
3.
ChaudhuriKR, HealyDG, SchapiraAHV. Non-motor symptoms of Parkinson's disease: diagnosis and management. Lancet Neurol2006; 5: 235-45.
4.
ObesoJA, OlanowCW, NuttJG. Levodopa motor complications in Parkinson's disease. Trends Neurosci2000; 23(10 suppl):S2-7.
5.
FearnleyJM, LeesAJ. Ageing and Parkinson's disease: substantia nigra regional selectivity. Brain1991; 114: 2283-301.
6.
SchapiraAHV. Etiology of Parkinson's disease. Neurology2006; 66(10 Suppl 4):S10-23.
7.
PahwaR, FactorSA, LyonsKE. Practice parameter: treatment of Parkinson disease with motor fluctuations and dyskinesia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology2006; 66: 983-95.
8.
MiyasakiJM, ShannonK, VoonV. Practice parameter: evaluation and treatment of depression, psychosis, and dementia in Parkinson disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology2006; 66: 996-1002.
9.
SuchowerskyO, GronsethG, PerlmutterJ, ReichS, ZesiewiczT, WeinerWJ. Practice parameter: neuroprotective strategies and alternative therapies for Parkinson disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology2006; 66: 976-82.
10.
MiyasakiJM, MartinW, SuchowerskyO, WeinerWJ, LangAE. 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. Neurology2002; 58: 11-7.
11.
RascolO, GoetzC, KollerW, PoeweW, SampaioC.Treatment interventions for Parkinson's disease: an evidence based assessment. Lancet2002; 359: 1589-98.
12.
OlanowCW, WattsRL, KollerWC. An algorithm (decision tree) for the management of Parkinson's disease (2001): treatment guidelines. Neurology2001; 56(11 suppl 5):S1-88.
13.
AgidY, OlanowCW, MizunoY.Levodopa: why the controversy (editorial)?Lancet2002; 360:575.
14.
JankovicJ.Levodopa strengths and weaknesses. Neurology2002; 58(4 suppl 1):S19-32.
ChapuisS, OuchchaneL, MetzO, GerbaudL, DurifF.Impact of the motor complications of Parkinson's disease on the quality of life. Mov Disord2005; 20: 224-30.
17.
StacyM, BowronA, GuttmanM. Identification of motor and non-motor wearing-off in Parkinson's disease: comparison of a patient questionnaire versus a clinician assessment. Mov Disord2005; 20: 726-33.
18.
StacyM, HauserR, OertelW. End-of-dose wearing off in Parkinson disease: a 9-question survey assessment. Clin Neuropharmacol2006; 29: 312-21.
19.
WitjasT, KaphanE, AzulayJP. Nonmotor fluctuations in Parkinson's disease: frequent and disabling. Neurology2002; 59: 408-13.
20.
DeweyRBJr.Management of motor complications in Parkinson's disease. Neurology2004; 62(6 suppl 4):S3-7.
21.
AhlskogJE, MuenterMD. Frequency of levodopa-related dyskinesias and motor fluctuations as estimated from the cumulative literature. Mov Disord2001; 16: 448-58.
22.
KollerWC, TseW.Unmet medical needs in Parkinson's disease. Neurology2004; 62(1 suppl 1):S1-8.
23.
Parkinson Study Group.Pramipexole vs levodopa as initial treatment for Parkinson disease: a randomized controlled trial. Parkinson Study Group. JAMA2000; 284:1931-8.
24.
RascolO, BrooksDJ, KorczynAD, De DeynPP, ClarkeCE, LangAE. A five-year study of the incidence of dyskinesia in patients with early Parkinson's disease who were treated with ropinirole or levodopa. 056 Study Group. N Engl J Med2000; 342: 1484-91.
25.
LiebermanA, VijayM.Wearing-off of greatest concern for PD patient (abstract P1284). Eur J Neurol2004; 11(suppl 2):S109.
26.
KollerW, VijayM.Physician beliefs and practices in levodopa therapy for PD: results of a US National Survey. Eur J Neurol2004; 11(suppl 2):S9-35.
27.
HillenME, SageJI. Nonmotor fluctuations in patients with Parkinson's disease. Neurology1996; 47: 1180-3.
28.
ChaudhuriKR, Martinez-MartinP, SchapiraAHV. International multicenter pilot study of the first comprehensive self-completed nonmotor symptoms questionnaire for Parkinson's disease: the NMSQuest study. Mov Disord2006; 21: 916-23.
29.
SchragA, QuinnN.Dyskinesias and motor fluctuations in Parkinson's disease. A community-based study. Brain2000; 123(pt 11):2297-305.
30.
FahnS.Does levodopa slow or hasten the rate of progression of Parkinson's disease?J Neurol2005; 252(suppl 4):iv37-42.
31.
KurlanR.“Levodopa phobia”: a new iatrogenic cause of disability in Parkinson disease. Neurology2005; 64: 923-4.
32.
Movement Disorder Society Taskforce.Management of Parkinson's disease: an evidence based review. Mov Disord2002; 17(suppl 4):S23-37.
33.
IvesNJ, StoweRL, MorrowJ.Monoamine oxidase type B inhibitors in early Parkinson's disease: meta-analysis of 17 randomised trials involving 3525 patients. BMJ2004; 329: 593-9.
34.
WatersCH, SethiKD, HauserRA, MolhoE, BertoniJM. Zydis selegiline reduces off time in Parkinson's disease patients with motor fluctuations: a 3-month, randomized, placebo-controlled study. Mov Disord2004; 19: 426-32.
35.
RascolO, BrooksDJ, MelamedE. Rasagiline as an adjunct to levodopa in patients with Parkinson's disease and motor fluctuations (LARGO, Lasting effect in Adjunct therapy with Rasagiline Given Once daily, study): a randomised, double-blind, parallel-group trial. Lancet2005; 365: 947-54.
36.
Parkinson Study Group.A randomized placebo-controlled trial of rasagiline in levodopa-treated patients with Parkinson disease and motor fluctuations: the PRESTO study. Arch Neurol2005; 62:241-8.
37.
SchragA.Entacapone in the treatment of Parkinson's disease. Lancet Neurol2005; 4: 366-70.
38.
Parkinson Study Group.Entacapone improves motor fluctuations in levodopa-treated Parkinson's disease patients. Ann Neurol1997; 42:747-55.
39.
RinneUK, LarsenJP, SidenA. Entacapone enhances the response to levodopa in parkinsonian patients with motor fluctuations. Neurology1998; 51: 1309-14.
40.
PoeweWH, DeuschlG, GordinA. Efficacy and safety of entacapone in Parkinson's disease patients with suboptimal levodopa response: a 6-month randomized placebo-controlled double-blind study in Germany and Austria (Celomen study). Acta Neurol Scand2002; 105: 245-55.
41.
SchapiraAH, ObesoJ.Timing of treatment initiation in Parkinson's disease: a need for reappraisal?Ann Neurol2006; 59: 559-62.
42.
NissinenH, KuoppamakiM, LeinonenM.Early initiation of entacapone leads to superior 5-year efficacy compared to delayed initiation in Parkinson's disease patients receiving traditional levodopa/DDCI therapy (abstract P962). Mov Disord2006; 21(suppl 15):S59.
43.
Stacy M, on behalf of the Wearing-Off Working Group.An abbreviated wearing-off patient questionnaire (WOPQ): sensitivity analysis. Parkinsonism Relat Disord2005; 11(suppl 2):S155.
44.
GrossetKA, ReidJL, GrossetDG. Medicine-taking behavior: implications of suboptimal compliance in Parkinson's disease. Mov Disord2005; 20: 1397-404.
45.
StocchiF.Managing the critical problems of advanced Parkinson's disease. Expert Rev Neurotherapeutics2002; 2: 835-47.
