Parkinson's Disease: Advances in Treatment and the Syntheses of Various Classes of Pharmaceutical Drug Substances.

An overview of Parkinson's disease (PD) prevalence, diagnosis, and currently available treatment options is provided. A comprehensive list of different classes of marketed pharmaceutical drug products and the syntheses of various drug substances are summarized based on published literature.

Performance of Force-Field- and Machine Learning-Based Scoring Functions in Ranking MAO-B Protein-Inhibitor Complexes in Relevance to Developing Parkinson's Therapeutics.

Monoamine oxidase B (MAOB) is expressed in the mitochondrial membrane and has a key role in degrading various neurologically active amines such as benzylamine, phenethylamine and dopamine with the help of Flavin adenine dinucleotide (FAD) cofactor. The Parkinson's disease associated symptoms can be treated using inhibitors of MAO-B as the dopamine degradation can be reduced. Currently, many inhibitors are available having micromolar to nanomolar binding affinities. However, still there is demand for compounds with superior binding affinity and binding specificity with favorable pharmacokinetic properties for treating Parkinson's disease and computational screening methods can be majorly recruited for this. However, the accuracy of currently available force-field methods for ranking the inhibitors or lead drug-like compounds should be improved and novel methods for screening compounds need to be developed. We studied the performance of various force-field-based methods and data driven approaches in ranking about 3753 compounds having activity against the MAO-B target. The binding affinities computed using autodock and autodock-vina are shown to be non-reliable. The force-field-based MM-GBSA also under-performs. However, certain machine learning approaches, in particular KNN, are found to be superior, and we propose KNN as the most reliable approach for ranking the complexes to reasonable accuracy. Furthermore, all the employed machine learning approaches are also computationally less demanding.

[Prescribing patterns of antiparkinson drugs in a group of Colombian patients, 2015].

INTRODUCTION: Parkinson's disease, whose prevalence in Colombia is 4.7 per 1,000 inhabitants, is a public health problem and a therapeutic challenge for health professionals. OBJECTIVE: To determine the prescribing patterns of antiparkinson drugs and the variables associated with its use in a population from Colombia. MATERIALS AND METHODS: We conducted a descriptive cross-sectional study. We selected patients who had been given antiparkinson drugs uninterruptedly between January 1st and March 31st, 2015 from a systematized database of approximately 3.5 million people affiliated to the Colombian health system. We included sociodemographic, pharmacologic and comedication variables. For the multivariate analysis, we used the IBM SPSS™-22 software. RESULTS: A total of 2,898 patients was included; the mean age was 65.1years, and 50.7% were men; 69.4% (n=2010) of people received monotherapy and 30.6% combination therapy with two to five antiparkinson drugs. The most frequently prescribed drugs were: levodopa 45.5% (n=1,318 patients), biperiden 23.1% (670), amantadine 18.3% (531) and pramipexole 16.3% (471). The most commonly used association was levodopa/carbidopa + entacapone (n=311; 10.7%). Multivariate analysis showed that being male (OR=1.56; 95%CI: 1.321-1.837), over 60 years (OR=1.41; 95%CI 1.112-1.782) and receiving treatment in the city of Barranquilla (OR=2.23; 95%CI 1.675-2.975) were statistically associated with a greater risk of using combination therapy; 68.2% (n=1,977) patients were given concomitant treatment with other drugs. CONCLUSIONS: Prescribing habits of drugs with high therapeutic value predominated, mainly in antiparkinson drugs monotherapy. Most were employed in the usual recommended doses. It is necessary to explore the clinical effectiveness of the medications studied and differentiate between disease and parkinsonian syndromes subtypes.

Classics in chemical neuroscience: levodopa.

Levodopa was the first and most successful breakthrough in the treatment of Parkinson's disease (PD). It is estimated that PD affects approximately 1 million people in the United States alone. Although PD was discovered in 1817, prior to levodopa's discovery there was not an effective treatment for managing its symptoms. In 1961, Hornykiewicz pioneered the use of levodopa to enhance dopamine levels in the striatum, significantly improving symptoms in many patients. With the addition of carbidopa in 1974, the frequency of gastrointestinal adverse drug reactions (ADRs) was significantly reduced, leading to the modern treatment of PD. Although levodopa treatment is more than 50 years old, it remains the "gold standard" for PD treatment. This Review describes in detail the synthesis, metabolism, pharmacology, ADRs, and importance of levodopa therapy to neuroscience in the past and present.

[Dopaminergic treatment in Parkinson's disease: what has each therapeutic family got to offer?]. / Tratamiento dopaminérgico en la enfermedad de Parkinson: ¿qué puede ofrecer cada familia terapéutica?

Different families of dopaminergic agents have allowed to increase the availability of dopamine within the central nervous system by different mechanisms of action. Each drug family has specific efficacious properties, as well as a different profile of adverse events. The knowledge in detail of these specificities is mandatory to avoid severe systemic or neuropsychiatric complications. Despite these limitations, the development of new drugs within the past 20 years has prolonged survival in Parkinson's disease, increasing the time with preserved daily day functionality compared with the levodopa era, when this drug was the only dopaminergic drug available. The correct combination of dopaminergic drugs with different mechanisms of action allows the management of Parkinson's disease motor symptoms within safety dose ranges, and up to day, this appears as the best algorithm to maintain functionality for longer periods of time.

TITLE: Tratamiento dopaminergico en la enfermedad de Parkinson: que puede ofrecer cada familia terapeutica?Diferentes familias de farmacos dopaminergicos han permitido aumentar el suministro de dopamina en el estriado por diferentes mecanismos. Cada familia de farmacos posee un grado de eficacia determinado, asi como un perfil de efectos secundarios especifico que debe conocerse en detalle para evitar complicaciones sistemicas y neuropsiquiatricas graves. A pesar de estas limitaciones, la disponibilidad de multiples farmacos ha permitido aumentar la supervivencia media en la enfermedad de Parkinson, con un periodo de funcionalidad en el dia a dia significativamente mas largo al que se conseguia cuando la levodopa era practicamente el unico farmaco disponible. La correcta adicion de farmacos dopaminergicos con diferentes mecanismos de accion permite tratar la enfermedad de Parkinson sin tener que llegar a dosis excesivamente altas de ninguno de ellos, lo que parece, en el momento actual, el mejor algoritmo para el control de los sintomas motores durante un periodo lo mas duradero posible.

Problem based review: a patient with Parkinson's disease.

Parkinson's disease (PD) is a chronic, progressive neurodegenerative disease characterized by bradykinesia, tremor and/ or rigidity, often with gait disturbance and postural instability. In addition to these typical features, patients with PD may experience further problems related to the disease itself or to the medications used to treat it. These comorbid problems include neuropsychiatric conditions (including psychosis, hallucinations, excessive daytime sleepiness, anxiety, depression, fatigue and dementia) as well as problems associated with autonomic nervous system function such as bowel and bladder function. PD can also present in emergency situations with a 'neuroleptic malignant like picture' and acute psychosis. It is not uncommon to see motor fluctuations due to drug interactions and 'withdrawal' symptoms following dose reduction of dopamine agonists. In patients with PD, disturbances of mental state constitute some of the most difficult treatment challenges of advanced disease, often limiting effective treatment of motor symptoms and leading to increased disability and poor quality of life. While some of these symptoms may be alleviated by antiparkinsonian medication, especially if they are 'off-period' related, treatment-related phenomena are usually exacerbated by increasing the number or dosage of antiparkinsonian drugs. Elimination of exacerbating factors and simplification of drug regimens are the first and most important steps in improvement of such symptoms.

Emerging therapies for Parkinson's disease.

PURPOSE OF REVIEW: The experimental therapeutics of Parkinson's disease are reviewed, highlighting the current pipeline of emerging therapeutic approaches. RECENT FINDINGS: This review includes novel approaches to dopaminergic drug delivery such as intraintestinal infusions or new extended-release formulations of levodopa and also intrapulmonary delivery of apomorphine as well as novel dopaminergic agents like the monoamine oxidase-B inhibitor safinamide or novel catechol-O-methyl transferase inhibitors. An even greater number of ongoing clinical trials assess the efficacy and safety of nondopaminergic approaches to enhance motor control or reduce motor complications like fluctuations and dyskinesias. These include adenosine A2A antagonists, α-adrenergic and serotonergic agonists as well as drugs acting on the glutamatergic system. Gene-based or cell-based intrastriatal delivery of therapeutic principles that enhance striatal dopaminergic transmission directly or via the stimulation of trophic activity has also reached phase II clinical development with encouraging results in some studies. Finally, a wide spectrum of agents with a potential for slowing disease progression is currently tested. SUMMARY: A variety of medical and nonmedical interventions in different phases of clinical development provide an interesting and promising portfolio of emerging therapies for Parkinson's disease.

Transepithelial transport of biperiden hydrochloride in Caco-2 cell monolayers.

The aim of this research has been to determine the biperiden hydrochloride permeability in Caco-2 model, in order to classify it based on the Biopharmaceutics Classification System (BCS). The World Health Organization (WHO) as well as many other authors have provisionally assigned the drug as BCS class I (high solubility-high permeability) or III (high solubility-low permeability), based on different methods. We determined biperiden BCS class by comparing its permeability to 5 pre-defined compounds: atenolol and ranitidine hydrochloride (low permeability group) and metoprolol tartrate, sodium naproxen and theophylline (high permeability group). Since biperiden permeability was higher than those obtained for high permeability drugs, we classified it as a BCS class I compound. On the other hand, as no differences were obtained for permeability values when apical to basolateral and basolateral to apical fluxes were studied, this drug cannot act as a substrate of efflux transporters. As a consequence of our results, we suggest that the widely used antiparkinsonian drug, biperiden, should be candidate for a waiver of in vivo bioequivalence studies.

The evidence for disease modification in Parkinson's disease.

Disease modification or slowing the progression of any neurodegenerative disorder represents a dire unmet need. There have been trials for several decades specifically designed to help evaluate whether a specific therapy might be able to slow the progression of Parkinson's disease (PD) or be disease modifying. Trials evaluating the use of coenzyme Q10, pramipexole, and levodopa suggest that these medications offer symptomatic benefit uniquely, while other studies reveal that rasagiline and selegiline may be disease modifying. This review will discuss in detail the design and results of clinical trials for varied medical therapies that were specifically undertaken to discern whether a particular treatment might be disease modifying in the treatment of PD.

Diagnosis and initiation of treatment in Parkinson's disease.

Parkinson's disease (PD) is the most common cause of parkinsonism, yet the diagnosis and management can be a challenge. The United Kingdom Parkinson's Disease Society Brain Bank Clinical Diagnostic Criteria and dopamine transporter/single-photon emission computed tomography (DaT-SPECT) are diagnostic aids that can improve diagnostic accuracy. Even though PD is a progressive disease, for years, physicians and patients have delayed treatment until functional disability occurs. However, studies of monoamine oxidase-type B (MAO-B) inhibitors, dopamine agonists, and levodopa, all of which can be used as initial therapy, have demonstrated that PD patients receiving treatment do better than those who do not receive treatment, and some studies have shown that those receiving treatment earlier do better long term. Therefore, the management strategy for PD has moved toward earlier initiation of treatment. Although treatment for each patient should be individualized and based on their specific symptoms, severity, and lifestyle, in general MAO-B inhibitors may be used initially to treat mild symptoms, adding a dopamine agonist in younger patients or levodopa in older patients, as symptoms become more severe.

The Movement Disorder Society Evidence-Based Medicine Review Update: Treatments for the motor symptoms of Parkinson's disease.

The objective was to update previous evidence-based medicine reviews of treatments for motor symptoms of Parkinson's disease published between 2002 and 2005. Level I (randomized, controlled trial) reports of pharmacological, surgical, and nonpharmacological interventions for the motor symptoms of Parkinson's disease between January 2004 (2001 for nonpharmacological) and December 2010 were reviewed. Criteria for inclusion, clinical indications, ranking, efficacy conclusions, safety, and implications for clinical practice followed the original program outline and adhered to evidence-based medicine methodology. Sixty-eight new studies qualified for review. Piribedil, pramipexole, pramipexole extended release, ropinirole, rotigotine, cabergoline, and pergolide were all efficacious as symptomatic monotherapy; ropinirole prolonged release was likely efficacious. All were efficacious as a symptomatic adjunct except pramipexole extended release, for which there is insufficient evidence. For prevention/delay of motor fluctuations, pramipexole and cabergoline were efficacious, and for prevention/delay of dyskinesia, pramipexole, ropinirole, ropinirole prolonged release, and cabergoline were all efficacious, whereas pergolide was likely efficacious. Duodenal infusion of levodopa was likely efficacious in the treatment of motor complications, but the practice implication is investigational. Entacapone was nonefficacious as a symptomatic adjunct to levodopa in nonfluctuating patients and nonefficacious in the prevention/delay of motor complications. Rasagiline conclusions were revised to efficacious as a symptomatic adjunct, and as treatment for motor fluctuations. Clozapine was efficacious in dyskinesia, but because of safety issues, the practice implication is possibly useful. Bilateral subthalamic nucleus deep brain stimulation, bilateral globus pallidus stimulation, and unilateral pallidotomy were updated to efficacious for motor complications. Physical therapy was revised to likely efficacious as symptomatic adjunct therapy. This evidence-based medicine review updates the field and highlights gaps for research.

Current strategies in the treatment of Parkinson's disease and a personalized approach to management.

Parkinson's disease is a progressive, neurodegenerative disorder affecting millions of people worldwide. Given the aging population, the prevalence of the disease is expected to increase substantially. The mainstay of treatment has been dopamine replacement therapy with carbidopa, levodopa, dopamine agonists, monoamine oxidase type B inhibitors, catechol-O-methyltransferase inhibitors and amantadine. Nonmotor features, such as cognitive impairment, mood disorders, autonomic dysfunction, gastrointestinal and genitourinary dysfunction, have a substantial impact on Parkinson's disease patients and their quality of life. This review will provide an overview on medications currently available for management of both motor and nonmotor symptoms of Parkinson's disease. Focus will be placed on recent and evolving studies evaluating symptomatic and neuroprotective effects of medications, and how such studies may impact the future management of Parkinson's disease.

Levodopa/carbidopa/entacapone in Parkinson's disease.

Levodopa is the most efficacious agent for the treatment of motor features of Parkinson's disease but its chronic use is associated with the development of motor complications. Mounting evidence indicates the short half-life of levodopa and resultant pulsatile stimulation of striatal dopamine receptors leads to wearing off, motor fluctuations and dyskinesias. Longer acting dopaminergic agents, such as dopamine agonists, are less likely to cause motor fluctuations and dyskinesias but are not as efficacious for control of motor symptoms. Therefore, there is interest in exploring ways to deliver levodopa in a more continuous fashion, in an effort to maintain benefit through the day and reduce the development of motor fluctuations and dyskinesias. A dopa decarboxylase inhibitor (DDCI), such as carbidopa or benserazide, is administered with levodopa to attenuate its peripheral conversion to dopamine, reduce nausea and increase central bioavailability. When levodopa is administered with a DDCI, its main route of peripheral metabolism is via catechol-O-methyl transferase (COMT). A COMT inhibitor can be added to the combination of levodopa and a DDCI to further extend the levodopa peripheral half-life and increase central bioavailability. Stalevo is a combination tablet comprised of levodopa, carbidopa, and the COMT inhibitor entacapone. It is available in fixed-dose combinations of levodopa/carbidopa/entacapone, 50/12.5/200, 75/18.75/200, 100/25/200, 125/31.25/200, 150/37.5/200 and 200/50/200 mg. Stalevo is currently approved for use in Parkinson's disease patients with end-of-dose wearing off.

Drugs used to treat Parkinson's disease, present status and future directions.

Parkinson's disease (PD) is the second most common neurodegenerative disorder, after Alzheimer's disease. In PD, motor symptoms result from the degeneration and loss of pigmented dopaminergic neurons of the substantia nigra pars compacta of the basal ganglia. Other neuronal fields and neurotransmitter systems are also involved, including non-adrenergic, serotonergic and cholinergic neurons. Since the early 1960s the treatment of PD has been based on the pharmacologic replacement of dopamine accomplished with the precursor of dopamine, 3, 4-dihydroxy-L-phenylalanine (L-dopa). The addition of carbidopa, an inhibitor of the decarboxylase represented a tremendous improvement in therapy and is still a mainstay of the treatment of PD. Dopamine agonists may also be used, as well as inhibitors of monoamine oxidase-B or catechol-O-methyltransferase. Other medications include anticholinergics and amantadine. These therapies are only symptomatic and none halt or lessen dopaminergic neuron degeneration and the progression of the disease. This has prompted the search for novel and alternative pharmacological targets and neuroprotective therapies. In this context, there are data to suggest a benefit from glial cell line-derived neurotrophic factor, neuroimmumophilin ligands, minocycline, Coenzyme Q10, creatine, reduced glutathione, adenosine A2A receptor antagonists as well as glutamate release inhibitors. Restorative techniques to compensate for cell loss include tissue transplantation and gene transfer therapy. Due to the paucity of data regarding non-pharmacological approaches such as diet therapy or antioxidant therapy, these await more studies. There are also few studies on medicinal plants. Other areas of increasing importance would thus include the investigation of active constituents of plants and phytomedicines with a view to the discovery of new compounds. Finally, stem cell therapy may offer the promise of restoring functionality.

Impact of newer pharmacological treatments on quality of life in patients with Parkinson's disease.

Parkinson's disease is a common progressive neurodegenerative condition with multiple motor and nonmotor features contributing to impairment of health-related quality of life (HR-QOL). Pharmacological treatments have been directed primarily at dopamine replacement with levodopa and agents to improve its bioavailability, including DOPA decarboxylase inhibitors, catechol-O-methyltransferase (COMT) inhibitors and monoamine oxidase B (MAO-B) inhibitors, as well as synthetic dopamine agonists. These treatments to restore motor function are often very successful in early Parkinson's disease, with objective improvement and concomitant improvement in subjective HR-QOL scores. However, as the disease progresses, motor complications and nonmotor symptoms predominate and are often refractory to therapeutic interventions. Antiparkinsonian medications have been shown to improve motor severity and motor complications of advancing disease, and there is increasing evidence that this can be translated into subjective improvement of HR-QOL from a patient's point of view. However, the degree of improvement is less marked on HR-QOL scores than on motor scores, and some studies do not show improvement of HR-QOL in parallel to motor improvements. A number of explanations are possible, including limitations of the scales used, trial designs and lack of clinical improvement from the patients' point of view. This review concentrates on clinical trials with an index of HR-QOL as an outcome measure, with particular emphasis on well designed, randomized, double-blind, placebo-controlled or active comparator-controlled methodology. Drugs that have been more recently added to the armamentarium of Parkinson's disease, including the oral (pramipexole, ropinirole and piribedil) and transdermal (rotigotine) non-ergotamine-derived dopamine agonists, the novel MAO-B inhibitor rasagiline and the COMT inhibitors tolcapone and entacapone, were included. The effect of each of these agents on overall HR-QOL and depression, a factor that has been shown to significantly contribute to HR-QOL in several multivariate analyses, is discussed.Overall, the literature search revealed 14 double-blind, placebo- or active comparator-controlled trials with an index of HR-QOL as an outcome measure. Entacapone resulted in HR-QOL improvement in nonfluctuating patients (one study) but not clearly in those with motor fluctuations (two studies). Tolcapone was only tested in patients with motor fluctuations and resulted in significant improvement in two of four studies using HR-QOL as an outcome measure. Rasagiline improved HR-QOL as monotherapy in early Parkinson's disease (one study), but not clearly in more advanced disease (one study). Rotigotine improved HR-QOL in both early Parkinson's disease (one study) and more advanced disease with motor fluctuations (one study). The impact of ropinirole and pramipexole on HR-QOL as monotherapy in early Parkinson's disease versus placebo has not been assessed, but both agents have resulted in improved HR-QOL in patients with motor fluctuations (ropinirole one study, pramipexole one study). The evidence for antidepressant efficacy of antiparkinsonian medications is limited.

Antiparkinsonian therapy modifications in PD patients after STN DBS: a retrospective observational analysis.

OBJECTIVE: This study reports a retrospective analysis of 67 consecutive parkinsonian patients to assess changes in antiparkinsonian medications after Deep Brain Stimulation (DBS) of the Subthalamic Nucleus (STN). METHODS: All antiparkinsonian drugs, including levodopa, dopamine agonists, associated drugs such as COMT and MAO inhibitors, amantadine and anticholinergics, were evaluated pre- and post-operatively at 1 and 3 years follow-up. RESULTS: The levodopa mean daily dose was reduced approximately 60% after 1 year and remained stable after 3 years. Apomorphine, bromocriptine, tolcapone, entacapone and selegiline were withdrawn after STN DBS. Three years post-operatively, 9 patients (13.4%) no longer required levodopa and 6 patients (8.9%) completely stopped all dopaminergic medications. More patients were on monotherapy of either levodopa or dopamine agonist and fewer patients required a combined treatment of dopamine agonist and levodopa, compared to the pre-surgical condition. CONCLUSIONS: STN DBS treated PD patients experience a significant long-term reduction and simplification of the pharmacological treatment.

Medical management of levodopa-associated motor complications in patients with Parkinson's disease.

Parkinson's disease is a neurodegenerative disorder that affects approximately 1% of people over the age of 60 years. Levodopa is standard, and often initial, therapy for patients with this condition; however, with continued treatment and as the disease progresses, up to 80% of patients experience 'wearing-off' symptoms, dyskinesias and other motor complications. These levodopa-associated problems may become disabling and profoundly affect quality of life. Medications commonly used to manage these symptoms include monoamine oxidase type B (MAO-B) inhibitors, catechol-O-methyltransferase (COMT) inhibitors, the NMDA receptor antagonist amantadine and dopamine receptor agonists. Agents that block MAO-B, such as rasagiline and selegiline, are used as both initial and adjunctive therapy in patients with Parkinson's disease. These medications increase concentrations of dopamine in the brain by blocking its reuptake from the synaptic cleft, a mechanism that can slow motor decline, increase 'on' time and improve symptoms of Parkinson's disease. Adverse events with these agents can include confusion, hallucination and orthostatic hypotension. MAO-B inhibition may elicit drug-drug interactions if administered with TCAs, SSRIs or SNRIs. Conventional oral selegiline is associated with potentially harmful plasma concentrations of three major amphetamine metabolites, although metabolite concentrations are significantly lower with a new orally disintegrating tablet (ODT) selegiline formulation. Selegiline ODT is also absorbed more efficiently and shows less pharmacokinetic variability than conventional oral selegiline.COMT mediates peripheral catabolism of levodopa. Therefore, agents that block COMT, such as tolcapone and entacapone, increase the elimination half-life of levodopa. Given adjunctively with levodopa, COMT inhibitors can decrease 'off' time and increase 'on' time, as well as lower the daily levodopa dose. Although more potent than entacapone, tolcapone requires monitoring for hepatotoxicity. Amantadine is a noncompetitive NMDA receptor antagonist shown to lower dyskinesia scores and improve motor complications in patients with Parkinson's disease when given adjunctively with levodopa. Dopamine agonists, also used as initial and adjunctive therapy in Parkinson's disease, improve motor response and decrease 'off' time purportedly through direct stimulation of dopamine receptors. Current dopamine agonists include bromocriptine, pergolide, cabergoline, lisuride, apomorphine, pramipexole, ropinirole and rotigotine. Although effective, this class of medications can be associated with cardiovascular and psychiatric adverse effects that can limit their utility. All medications used to manage levodopa-associated motor complications in patients with Parkinson's disease have had differing degrees of success. Although head-to-head comparisons of drugs within classes are rare, some differences have emerged related to effects on motor fluctuations, dyskinesias and on/off times, as well as to adverse effects. When choosing a drug to treat levodopa-induced complications, it is important to consider the risks and benefits of the different classes and of the specific agents within each class, given the different efficacy and safety profiles of each.

Treatment of Parkinson's disease: a survey of patients and neurologists.

BACKGROUND: The treatment of Parkinson's disease (PD) is complex and highly individual. The choice between available treatment options depends on clinical characteristics such as the patient's age, disease severity and presence of comorbidities, lifestyle characteristics and preferences, costs of different medications and awareness and perception of available treatment options, and education of the treating physician. The impact of PD treatment regimens on patients' health-related quality of life (QOL) is also an important healthcare feature. The objective of the present study was to assess treatment options, treatment satisfaction and opinions about treatment improvements in patients with PD and neurologists treating the disease. METHODS: Two surveys using face-to-face interviews and an additional phone survey were carried out in the US and five European countries (France, Germany, Italy, Spain and the UK). Patients with early and advanced stages of PD were included. To participate in the neurologist survey, neurologists were required to personally treat ten or more PD patients per month, including both early and advanced stage patients. Interviews consisted of a mix of closed and open-ended questions; some of these questions involved show cards. RESULTS: Of the 500 patients who were surveyed, 49% had early and 51% had advanced PD. Early-stage PD patients, both in the US and Europe, take a mean of 3.2 tablets daily of PD-medication. In contrast, the mean daily tablet load of PD medication is much higher for advanced-stage patients (9.9 and 8.4 tablets in the US and Europe, respectively). Tablet load was perceived as a major problem; the majority of patients wished to see improvements regarding daily medication intake and expressed interest in other delivery systems such as patches. Overall, patients rated their treatment with a score of 6.6 points (6.7 for early-stage and 6.6 for advanced-stage patients) [scale of 1-10; 10 being highest]. Physicians (n = 592) were satisfied with a number of current PD medications and assumed they improve the QOL of the patients. They regarded efficacy and safety as the most important features for the improvement of PD medication. CONCLUSION: Further research is needed into PD treatment options not only for symptom alleviation but for better delivery systems that could improve compliance and QOL for patients with PD. Treatment guidelines need to incorporate QOL aspects and general communication between the health professional and the patient.