Review Article

Patterns and Determinants of Prescribing for Parkinson’s Disease: A Systematic Literature Review

Table 1

Studies that examined prescribing patterns of PD medications.

StudyCountryType of study and source of dataPD case ascertainmentYearSettingNumber of patients and/or prescriptionsUnit of analysisPrescribing determinantsComments/main findingsQuality score (out of 10)

Ezat et al. [41]NorwayRetrospective study from three hospitals in NorwayPD diagnosis confirmed by clinical experts2009–2013
No comparison
Inpatient setting262 patientsNumber of patients treated per 100,000 inhabitantsGeographical locationOut of all PD medication, the study examined prescribing of L-dopa intestinal gel alone.
There is a significant variation of L-dopa intestinal gel prescribing in Norwegian counties (Rosalind county has the highest rate of prescribing).
3

Tripathi et al. [42]IndiaRetrospective chart review from a neurology clinic in IndiaPD diagnosis confirmed by clinical experts2014
No comparison
Community100 patientsPercentage of patients prescribed each drug/drug class/drug combinationsN/AL-dopa monotherapy is the most commonly prescribed regimen.
L-dopa + anticholinergic is the second most common regimen followed by L-dopa + DA.
4

Surathi et al. [43]IndiaCross-sectional prescription review studyPD diagnosis confirmed by clinical experts2011–2014
No comparison
Community800 patientsPercentage of patients prescribed each drug/drug class/drug combinationsN/AL-dopa monotherapy is the most commonly prescribed regimen.
Anticholinergic is the second most common regimen.
4

Jost et al. [44]GermanyCross-sectional surveys with patients and physicians.PD diagnosis confirmed by clinical experts2017Community4485 patients, and 271 physiciansPercentage of patients prescribed each drug/drug class/drug combinationsN/AThe most commonly prescribed medication is L-dopa (90.27%) followed by DAs (40.66%).4
Dahodwala et al. [45]USARetrospective cohort from a random sample of annual 5% Medicare Parts A and B claimReimbursement data using ICD-9 code.
There were efforts to exclude atypical parkinsonism by excluding patients with history of atypical parkinsonism
2007–2010
No comparison
Inpatient and community settings9482 to 9626 patientsPercentage of patients prescribed each drug/drug class/drug combinationsAge, gender, race, income, comorbidities, and neurology clinic visits.Most PD patients receive PD medications.
African Americans and patients not seen by neurologists are undertreated.
9

Liu et al. [46]TaiwanRetrospective cohort from Taiwan National Health Insurance DatabaseReimbursement data using ICD-9 code.
There were efforts to exclude atypical parkinsonism by excluding patients with history of atypical parkinsonism
2004/2011Community19,302 patients in 2004 and 41,606 patients in 2011Percentage of prescriptions. (one prescription may include more than one prescribed medication)AgeGeneral increase in L-dopa monotherapy prescribing.
More than doubling of DA prescribing for younger patients.
Most of the DA prescriptions are non-ergot derivatives after 2008.
8

Keränen and Virta [47]FinlandRetrospective cohort from a drug insurance reimbursement registerReimbursement data using ICD-10 code.
The reimbursement data were not validated against patient charts.
2005/2012Community1436 patients in 2005 and 1607 patients in 2012Percentage of patients prescribed each drug/drug classAgeL-dopa is the most prescribed medication in patients aged >75 y.
DAs and MOA-B inhibitors are the most prescribed medications in patients aged <60 y.
Prescribing changes are in accordance with changes in guidelines.
4
Hand et al. [48]EnglandRetrospective study used The Northumbria Healthcare NHS Foundation Trust PD servicePD clinic data.
Atypical parkinsonism included, such as multiple system atrophy (MSA) and progressive supranuclear palsy (PSP).
2015Community and care home settings377 patientsPercentage of patients prescribed each drug/drug class/drug combinations and L-dopa equivalent daily dose (LEDD)Care settingsAge and disease stage were higher in those living in care homes. LEDD was lower in those living in care homes.
Older age, LEDD, and severe disease stage were significantly associated with care home placement. Use of DAs, MAO-B inhibitors, and COMT inhibitors was higher in patients living in their homes.
6

Degli Esposti et al. [50]ItalyThis retrospective study used databases of three Italian Local Health AuthoritiesData linkage study.
There were efforts to exclude atypical parkinsonism by linking prescription data to hospital data.
2009–2011
No comparison
Inpatient and community settings1607 patients on selegiline or rasagilinePercentage of patients prescribed each drug/drug class/drug combinationsAge and gender63.3% of patients were on selegiline while 36.2% were on rasagiline.
DAs and L-dopa were more prescribed in rasagiline group.
5

Crispo et al. [51]USARetrospective cohort from the Cerner Health Facts databaseHospital diagnosis ICD-9 code.
There were efforts to exclude atypical parkinsonism by excluding patients ages less than 40 years
2001/2011Inpatient16,785 patientsPercentage of patients prescribed each drug/drug classAge and genderL-dopa was the most prescribed medication from 2001 to 2011.
Decline in DA use over 2007–2011.
Stable rate of DA use in patients aged ≥80 y over 2001–2011.
7
Pitcher et al. [53]New ZealandRetrospective cohort from national prescription database in New ZealandDrug sales database.
No efforts to exclude atypical parkinsonism.
1995/2011Community and rest (care) homes. No comparison.N/ADefined daily doses (DDD) per 1000 inhabitants per dayN/AGeneral increase in L-dopa prescribing over 1995–2011.
Slight decrease in DA prescribing over the same interval.
Slight increase in COMT inhibitor and amantadine prescribing.
An increase in pergolide prescriptions even after 2007.
3

Nakaoka et al. [54]JapanRetrospective cohort from medical claim database in JMDC, Tokyo, JapanReimbursement data using ICD-10 code.
There were efforts to exclude atypical parkinsonism by excluding patients aged <30 years
2005/2010Inpatient and community settings714 patientsPercentage of patients prescribed each drug/drug classAge.L-dopa is the most prescribed medication over 2005–2010.
Of newly diagnosed patients, 30% are prescribed anticholinergics.
Non-ergot DA prescribing increases after 2007 in accordance with label revision of ergot DAs.
8

Junjaiah et al. [55]IndiaProspective study that included interviews with PD patientsPD diagnosis confirmed by clinical experts2011–2013
No comparison
Community100 patientsPercentage of patients prescribed each drug/drug class/drug combinationsDisease duration48% of PD patients received L-dopa alone.
52% of PD patients received combination therapies.
5
Guo et al. [56]TaiwanRetrospective study used the National Health Insurance Research Database of TaiwanReimbursement data using ICD-9 code.
There were efforts to exclude atypical parkinsonism by excluding patients who used drugs inducing parkinsonism
2000–2005/2006–2010Inpatient and community settings1645 patientsPercentage of patients prescribed each drug/drug class/drug combinationsAge, gender, prescriber type, and interval between PD diagnosis and starting medicationThe study examined the initial therapy for newly PD diagnosed patients.
L-dopa monotherapy is the most commonly prescribed regimen.
DAs were prescribed mainly by neurologists.
7

Gaida et al. [57]South AfricaRetrospective cohort from national community pharmacy group in South AfricaDrug sales database.
There were efforts to exclude atypical parkinsonism by excluding patients aged <50 years
2010
No comparison
Community5,168 patients and 25,523 prescriptions.Percentage of prescriptionsAge and gender.The most commonly prescribed medications are L-dopa + COMT inhibitors.
The second most commonly prescribed medications are non-ergot DAs.
Patients aged 50–59 y are prescribed DAs more than L-dopa while >70 y group are prescribed more L-dopa.
5

Skogar et al. [84]Sweden and NorwayUsing questionnaires with PD patients and drug registry dataNo efforts to exclude atypical parkinsonism.2010–2013
No comparison
Community1553 patients in Sweden and 1244 patients in NorwayPercentage of patients prescribed each drug/drug class/drug combinationsNAL-dopa products were the most commonly used PD medications in both countries.
Selegiline was significantly used more in Norway than in Sweden.
4
Morrish [58]EnglandRetrospective study that used online statistics at the National Health Service (NHS) Information CentreDrug sales data.
No efforts to exclude atypical parkinsonism
1999/2010All drug sales in both inpatients and community settingsN/ATotal net ingredient cost for PD medication in pound (£)N/AThe total net ingredient cost of PD medication was increased from £37 million in 1998 to £130 million in 2010.
DAs accounted for the largest portion of overall spending growth.
A static spending was seen in L-dopa products.
There was a decrease in ergot-DAs spending especially after 2004.
3

Hattor et al. [59]USA/JapanUsing questionnaires with PD patients followed by interviews with PD patients.No efforts to exclude atypical parkinsonism.2003 in USA and 2008 in JapanCommunity300/3548 patientsPercentage of patients prescribed each drug/drug class/drug combinationsDrug side effects.Patients who had already experienced dyskinesia were less concerned about L-dopa dyskinesia.
The most commonly prescribed medication was L-dopa in both countries followed by DAs.
2

Schroder et al. [60]GermanyA cross-sectional survey of neurologistsPD diagnosis confirmed by clinical experts2004
No comparison
Inpatient and community settings60 neurologists complete the medical charts of 320 patients.Percentage of patients prescribed each drug/drug class/drug combinationsAge and disease severity53% of patients aged <70 years were used DAs without L-dopa.
In patients aged >70 years, 50–52% were used L-dopa without dopamine agonists.
5

Ooba et al. [61]JapanRetrospective study used the National Japanese database vendorReimbursement data using ICD-10 code.
There were efforts to exclude atypical parkinsonism by excluding patients aged <40 years
2005/2008Inpatient and community settings547 patientsPercentage of patients prescribed each drug/drug class/drug combinationsAge, gender, and pergolide withdrawal from the USA market in 2007Percentage of patients prescribed cabergoline or pergolide did not decrease; rather, it tended to increase after 2007.5
Hollingworth et al. [62]AustraliaRetrospective study using prescription data from Medicare Australia and Drug Utilisation Sub-Committee (DUSC) databasesReimbursement data.
No efforts to exclude atypical parkinsonism
1995/2009Community5,078,242 prescriptionsDefined daily doses (DDD) per 1000 inhabitants per dayAge, gender, and type of prescriberDecline in anticholinergics and DAs over 14 years.
General increase in L-dopa use over 14 years.
An increase in pramipexole prescribing after 2008.
4

Fayard et al. [63]FranceA population-based study that included interviews with PD patientsPD diagnosis confirmed by clinical experts≤2000–>2000Community308 patientsPercentage of patients prescribed each drug/drug class/drug combinationsAge and type of prescriber.Agreement with the French recommendations increased after 2000 compared to before 2000. For patients aged <60 years, 35% increase in DAs prescribing after 2000. For patients aged >70 years, about 1% increase in L-dopa prescribing after 2000.8

Wei et al. [64]USARetrospective study used the Medicare Current Beneficiary Survey and Medicare claimsReimbursement data using ICD-9 code.
The reimbursement data were not validated against patients’ charts.
2000–2003
No comparison
Inpatient, community, and nursing home settings571 patientsPercentage of person-years prescribed each drug/drug class/drug combinationsAge, sex, race, education, marital status, annual income, care setting, and comorbidity scores.Half of the patients did not use any PD medication in the period of the study.
L-dopa was the most PD medication prescribed as a monotherapy or as a combination therapy.
Age, prescription drug coverage, residing in an institution, education, dementia, and depression had an effect on PD medication use.
5
Rosa et al. [65]EuropeRetrospective study that used “intercontinental marketing services” health and examined antiparkinsonian sales in 26 European countriesDrug sales data.
No efforts to exclude atypical parkinsonism
2003/2007CommunityA value of 663 million antiparkinsonian consumption in 2003 and 717 million in 2007Defined daily doses (DDD) per 1000 inhabitants per dayN/ALevodopa and DAs accounted for half of the drug use in most countries.
Between 2003 and 2007, the hugest increase in sales occurred with L-dopa and MAO-B inhibitors.
Heterogeneity was seen in the use of PD medications in Europe.
5

Trifiro et al. [66]ItalyRetrospective study used the Arianna database (GPs database)GPs and prescription data.
GP data were not validated against patients’ charts.
2003/2005Community1479 patientsPercentage of patients prescribed each drug/drug class/drug combinationsAgeStable prevalence of PD medication use during the years of the study.
L-dopa was the most PD medication prescribed as a monotherapy or as a combination therapy.
Non-ergot DAs use was increased in 2005, especially in elderly people.
6

Osinaga et al. [67]SpainRetrospective study used the ECOM database of the Spanish Ministry of HealthDrug sales data.
No efforts to exclude atypical parkinsonism
1992/2004CommunityN/ADefined daily doses (DDD) per 1000 inhabitants per dayN/AL-dopa was the most prescribed PD medication.
Consumption of PD medications has increased during the years of the study.
4
Swarztrauber et al. [68]USARetrospective study used the Pacific Northwest Veterans Health Administration (VHA) Data WarehouseAdministrative data using ICD-9 code.
The data were validated against patient charts by a neurologist.
1998–2004
No comparison
Community530 patientsPercentage of patients prescribed each drug/drug class/drug combinationsAge and type of prescriber29% of the initial antiparkinsonian therapy was initiated by neurologists.
20% of patients younger than 65 years received DAs.
Initial antiparkinsonian therapy is strongly influenced by the prescriber’s specialty. Additionally, it is mostly initiated by primary care physicians (without PD expertise).
7

Huse et al. [69]USARetrospective study used MedStat’s MarketScan Research DatabasesDrug registry data using ICD-9 code.
No efforts to exclude atypical parkinsonism
1999–2001
No comparison
Community4846 patientsPercentage of patients prescribed each drug/drug class/drug combinationsAge, gender, comorbidity (Charlson index), and type of insurance.L-dopa was the most prescribed PD medication as a monotherapy or as a combination therapy regardless of age or type of insurance.
DAs are the second most prescribed PD medication, but it only accounted for about 15% of patients younger than 65 years.
6
Tan et al. [70]SingaporeRetrospective study used patients’ charts at a tertiary referral centre. Then factors that influence neurologists’ decisions were examined by surveying a sample of neurologists.PD diagnosis confirmed by clinical expertsN/ACommunity306 patients.
11 neurologists participated in the survey.
Percentage of patients prescribed each drug/drug class/drug combinationsAge, disease severity, intolerance of side effects, drug side effects, drug availability, clinical experience with the drug, drug cost, patient preference, and drug company sponsorship92.3% of patients were on L-dopa.
Most of the patients who were on L-dopa were older and had a higher stage of PD severity scale (Hoen and Yahr).
26.8% of patients were on DAs.
From surveying the neurologists, the most important factors influencing their prescribing behaviors were severity of symptoms, intolerance of side effects, and efficacy. The real prescribing behaviours showed a significant positive association of medication usage with cost subsidy by the hospital. There was no mention in the manuscript when this study was conducted, although it was published in 2005.
8

Grandas and Kulisevsky [71]SpainA population-based study that included surveying 241 physiciansPD diagnosis confirmed by clinical experts1999Community1803 patients and 241 physiciansPercentage of patients prescribed each drug/drug class/drug combinationsType of prescriberL-dopa was the most prescribed PD medication (90.4%) regardless of type of prescriber. DAs were the second common PD medication prescribed (44%).
Movement disorder specialists tended to prescribe DAs and COMT inhibitors more than other prescribers followed by neurologists.
General physicians used to prescribe anticholinergics more than other prescribers.
6

Askmark et al. [72]SwedenRetrospective study that used the prescription sales of 906 community pharmacies and 89 hospital pharmacies.Drug sales data.
PD diagnosis confirmed by clinical experts.
1995/2001Inpatient and community settingsN/ADefined daily doses (DDD) per 1000 inhabitants per dayAge and number of neurologists in a particular countyBetween 1995 and 2001, L-dopa prescriptions sales increased.
After 1997, there has been an increase in sales of DAs (cabergoline, pramipexole, and ropinirole).
There was no correlation between the sales of all PD medications and the densities of neurologists or population ages in any particulate county in the study.
5
Leoni et al. [73]ItalyCross-sectional surveys with patients.PD diagnosis confirmed by clinical experts.1997–1998 No comparisonCommunity130 patientsPercentage of patients prescribed each drug/drug class/drug combinationsAge, disease severity, and duration of the diseaseL-dopa was the most prescribed PD medication (98.5%) followed by DAs (43.7%). Use of PD medications increased with duration and severity of the disease. Increased age is associated with increased use of PD medications.7

Lapane et al. [83]USARetrospective study that used (systematic assessment of geriatric drug use via epidemiology) database in 5 states in USA.Clinical database.
Atypical parkinsonism, included such as multiple system atrophy (MSA), and progressive supranuclear palsy (PSP).
1992–1996
No comparison
Nursing homes24,402 patientsPercentage of patients prescribed each drug/drug class/drug combinationsGender, race, age and cognitive function44% of all PD patients in nursing homes received one of the PD medications. DAs were the most common PD medications prescribed (75%) followed by L-dopa (52.27%), MAO-B inhibitor (20.45%), and anticholinergics (18.18).
Female, African Americans, and older age patients were less likely to receive PD medication in nursing homes.
7
Fukunaga et al. [74]JapanCross-sectional surveys with patients.PD diagnosis confirmed by clinical experts.1994–1996
No comparison
Inpatient and community settings104 patientsPercentage of patients prescribed each drug/drug class/drug combinationsDuration of the diseaseL-dopa was the most prescribed PD medication (78.84%) followed by DAs (76.92%).
Combination therapies (2-3 PD medications) were common in patients with duration of disease less than 5 years.
The combination therapy of 4 PD medications was common in patients with duration of disease of 7–9 years.
4

Menniti-Ippolito et al. [75]ItalyRetrospective study that used prescriptions of drugs included in the National Drug FormularyAtypical parkinsonism, including such as multiple system atrophy (MSA), and progressive supranuclear palsy (PSP).1986–1991
No comparison
Community6572 patientsPercentage of patients prescribed each drug/drug class/drug combinationsN/AL-dopa was the most PD medication prescribed (86.2%) followed by selegiline (24.6%).
The main aim of this study was to estimate the prevalence of PD by using the number of patients who used PD medications.
6