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

Abstract

Since the discovery of levodopa (L-dopa) in 1967, the range of medications available to treat Parkinson's disease has increased significantly and guidance on the use, efficacy, and safety of these medications has evolved. To assess levels of adherence to national prescribing guidelines and awareness of changes in the efficacy and safety data published in the profiles of medications for the treatment of PD, we have reviewed studies on patterns and determinants of prescribing PD medications conducted in the last 50 years (since the discovery of L-dopa). A systematic literature review was conducted using EMBASE (1967 to March, 2018), Ovid MEDLINE(R) ALL (1967 to March 16, 2018), PsycINFO (1967 to the 2nd week of March, 2018), and PubMed to identify all studies measuring prescribing patterns of PD medication between 1967 and 2017. Study design, source of data, country, year of study, number of patients and/or prescriptions, unit of analysis, prescribing determinants, and percentage utilisation of PD medications were extracted where possible. 44 studies examining prescribing patterns and/or prescribing determinants across 17 countries were identified. Unsurprisingly, L-dopa was the most commonly prescribed medication in all studies, accounting for 46.50% to 100% of all prescriptions for PD. In several studies, the prescribing rate of ergot-derived dopamine agonists (DAs) decreased over time in concordance with guidance. In contrast, the prescribing rates of non-ergot DAs increased over the last ten years in most of the included studies. In examining prescribing factors, two major categories were exemplified, patients' factors and prescribers' factors, with patients' age being the most common factor that affected the prescription in most studies. In conclusion, L-dopa is now the most commonly prescribed medication for cases of PD but there is large variation in the prescribing rates of catechol-O-methyltransferase (COMT) inhibitors, monoamine oxidase B (MAO-B) inhibitors, amantadine, and anticholinergics between countries. New studies examining the effects of recent clinical trials and measuring the prescribing rates of newly approved medications are warranted.

Prescription Pattern of Monoamine Oxidase B Inhibitors Combined with Levodopa: A Retrospective Observational Analysis of Italian Healthcare Administrative Databases

“…Specifically, since PD has been ascertained to be age-dependent [ 3 ], the increasing treatment incidence with age was expected. Moreover, the selegiline cohort was the oldest, in line with literature [ 4 , 7 ]. The high prevalence of comorbidities was also foreseen, due to the older age of the cohorts and the high risk for multimorbidity in patients affected by PD [ 26 ], such as cardiovascular, musculoskeletal, and mental disorders, which in turn increases the need for support, morbidity, and mortality.…”

The Parkinson’s Real-World Impact Assessment (PRISM) Study: A European Survey of the Burden of Parkinson’s Disease in Patients and their Carers

“…In another study, conducted in the United Kingdom between 2004 and 2015, 21% of over 6000 people with PD treated with anti-PD medication were taking ropinirole monotherapy and a further 17% were taking pergolide monotherapy, over a median follow-up duration of 2.8 years [27]. The lower use of dopamine agonist monotherapy in PRISM may reflect changes in treatment recommendations and prescribing practice over time, since dopamine agonists and MAO-B inhibitors were preferred over levodopa as initial monotherapy options 25 years ago because of their perceived potential to delay the onset of dyskinesia and/or motor fluctuations, and a misplaced notion that they were neuroprotective [28].…”

Questions in the Chemical Enzymology of MAO

“…Safinamide has other effects beneficial against PD including blockage of voltage-dependent sodium channels and has low tyramine potentiation [164]. When reversible and irreversible inhibitors are compared, both have been found to be effective as adjuvant therapy to delay or reduce the need for Ldopa [165]. However, a meta-analysis comparing MAOI alone or with L-dopa showed that selegiline was the most effective drug and that both it and rasagiline were more effective than safinamide (selegiline > rasagiline > safinamide) [166].…”

“…This is partly due to the side effects that require dietary restrictions but probably more due to inexperience with these drugs [167,168]. Certainly for Parkinson's disease, prescribing habits vary from country to country [165].…”