Current Pharmacotherapeutic Treatment Options in Parkinson’s Disease (original) (raw)
Related papers
Pharmacotherapy for Parkinson's disease
Pharmacotherapy, 2007
The available pharmacotherapies for Parkinson's disease address symptomatology because no agent has been demonstrated to provide definite neuroprotection against the disease. Choice of pharmacotherapy must include consideration of short-term benefits as well as long-term consequences. Patients with mild Parkinson's disease often function adequately without symptomatic treatment. However, recent data suggest that initiation of treatment with a well-tolerated agent (e.g., the monoamine oxidase [MAO]-B inhibitor rasagiline) in the absence of functional impairment is associated with improved long-term outcomes. Consideration should also be given to many patient-specific factors, including patient expectations, level of disability, employment status, functional as well as chronologic age, expected efficacy and tolerability of drugs, and response to previous Parkinson's disease therapies. Increasingly, initial monotherapy begins with a nondopaminergic agent or, if the patient is considered functionally young, a dopamine agonist. Since Parkinson's disease is a progressive disorder, adjustments to pharmacotherapy must be expected over time. When greater symptomatic relief is desired, or in the more frail elderly patient, levodopa therapy should be considered. If motor fluctuations develop, addition of a catechol-O-methyltransferase inhibitor or MAO-B inhibitor should be considered. For management of levodopa-induced dyskinesias, addition of amantadine is an option. Surgery may be considered when patients need additional symptomatic control or are experiencing severe motor complications despite pharmacologically optimized therapy.
Amantadine extended release for levodopa-induced dyskinesia in Parkinson's disease (EASED Study)
Movement Disorders, 2015
extended-release capsule formulation of amantadine HCl administered once daily at bedtime. This study investigated the safety, efficacy, and tolerability of ADS-5102 in Parkinson's disease (PD) patients with levodopa-induced dyskinesia. This was a randomized, double-blind, placebocontrolled, parallel-group study of 83 PD patients with troublesome dyskinesia assigned to placebo or one of three doses of ADS-5102 (260 mg, 340 mg, 420 mg) administered daily at bedtime for 8 weeks. The primary efficacy analysis compared change from baseline to week 8 in Unified Dyskinesia Rating Scale (UDysRS) total score for 340 mg ADS-5102 versus placebo. Secondary outcome measures included change in UDysRS for 260 mg, 420 mg, Fatigue Severity Scale (FSS), Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), patient diary, Clinician's Global Impression of Change, and Parkinson's Disease Questionnaire (PDQ-39). ADS-5102 340 mg significantly reduced dyskinesia versus placebo (27% reduction in UDysRS, P 5 0.005). In addition , ADS-5102 significantly increased ON time without troublesome dyskinesia, as assessed by PD patient diaries, at 260 mg (P 5 0.004), 340 mg (P 5 0.008) and 420 mg (P 5 0.018). Adverse events (AEs) were reported for 82%, 80%, 95%, and 90% of patients in the placebo, 260-mg, 340-mg, and 420-mg groups, respectively. Constipation, hallucinations, dizziness, and dry mouth were the most frequent AEs. Study withdrawal rates were 9%, 15%, 14%, and 40% for the placebo, 260-mg, 340-mg, and 420-mg groups, respectively. All study withdrawals in the active treatment groups were attributable to AEs. ADS-5102 was generally well tolerated and resulted in significant and dose-dependent improvements in dyskinesia in PD patients. V
Amantadine infusion in treatment of motor fluctuations and dyskinesias in Parkinson's disease
Journal of Neural Transmission, 2000
Efficiency and safety of amantadine sulfate (AMS) infusions were investigated in late stage complications of Parkinson's disease (PD). In an open-label study, 21 PD patients suffering from motor fluctuations and/or dyskinesias were administered AMS infusions (PK-Merz®, 400 mg per day) during seven days. Oral AMS treatment followed. Significant improvement of UPDRS motor scores was observed between day 0 and day 7, remaining improved until day 21. Based on patients' diary notes, both severity and occurrence of hypokinetic "off" state significantly decreased (from 6.6 to 3.1 hours, p Ͻ 0.001, average "off" time per day) as well as dopaminergic-induced dyskinesias (from 2.5 to 1.3 hours, p Ͻ 0.05, average duration of dyskinesias per day). AMS infusions followed by oral administration appeared as a safe method for improvement of both motor fluctuations and dyskinesias in advanced PD. In advantage to simple oral therapy, AMS infusions allowed fast introduction of a profound and durable treatment effect.
Diagnosis and Pharmacological Management of Parkinson's Disease: A Review
https://www.ijhsr.org/IJHSR\_Vol.12\_Issue.2\_Feb2022/IJHSR-Abstract.015.html, 2022
Parkinson's disease is a common and progressive neurological illness affecting persons aged 55 to 65. Parkinson's disease (PD) is the second most common neurological disorder. It has the potential to result in considerable impairment and a low quality of life. However, symptomatic medications may assist patients in living more comfortably. Apart from distal resting tremor and stiffness, the condition manifests itself via bradykinesia and an asymmetric start. Progressive motor and non-motor symptoms have a detrimental effect on an individual's overall quality of life. Non-motor symptoms are increasingly gaining recognition. It might be difficult to treat both motor and non-motor complaints. As a result, primary care physicians should be capable of diagnosing and treating Parkinson's disease. The article examines various healthcare practitioners' diagnosis accuracy and their use of multiple diagnostic procedures to differentiate Parkinson's disease from other comparable illnesses. There is no cure for Parkinson's disease, although there are treatments. On the other hand, it examines non-motor symptoms of Parkinson's disease. Drug-induced dyskinesia is a side effect of levodopa, the primary Parkinson's disease medication. Treatment with a dopamine agonist initially alleviates motor problems. Alternative medications (monoamine oxidase type B inhibitors (MAOBIs), amantadine, anticholinergics, b-blockers, or dopamine agonists) may be provided first to avoid levodopa-related motor difficulties. Modifying the levodopa dosage or adding MAOBIs or dopamine agonists may assist in regulating motor fluctuations. Primary care doctors will benefit from this article's focus on early diagnosis and pharmaceutical treatment of Parkinson's disease's characteristic motor symptoms. Parkinson's disease-related motor symptoms may be treated with levodopa and dopamine agonists, according to several trials. No evidence exists to back up alternative treatments for motor or nonmotor symptoms. A subspecialist's opinion is often sought.
Monoamine oxidase type B inhibitors in the treatment of Parkinson's disease
Progress in medicinal chemistry, 1984
's disease (PD) is a progressive neurodegenerative disorder. It has been classically described as a movement disorder involving the striato-nigral pathway characterized by resting tremor, bradykinesia, rigidity, and postural instability. It is now considered a multisystem disorder that includes motor and non-motor symptoms. 1 The early form of the disease can have predominantly non-motor symptoms, which are non-specific and can be overlooked for years until the cardinal motor symptoms emerge. The non-motor symptoms can be sensory, cognitive/psychiatric, or autonomic. The non-motor features by themselves can be a considerable cause of disability for many patients. Options for Initiation of Treatment in Parkinson's Disease There are several US Food and Drug Administration (FDA)-approved options for monotherapy in PD. Treatment of early disease can be initiated with amantadine, anticholinergic agents, monoamine oxidase type B (MAO-B) inhibitors, dopamine agonists or carbidopa-levodopa (CD/LD). Levodopa initially provides stable relief for the symptoms of PD; however, 50-90% of patients develop motor complications (such as motor fluctuations and dyskinesias) after five to 10 years of CD/LD therapy. 2,3 Delaying the initiation of levodopa may be appropriate to defer these problems. Dopamine agonists are useful in initial monotherapy for controlling motor symptoms with less risk of developing motor complications. Studies suggest that the mechanism by which agonists delay complications is by permitting a delay in the starting of levodopa rather than by any direct disease-modifying effect. 4 Dopamine agonists are associated with a number of side effects such as hallucinations, impulse-control disorders, excessive daytime sleepiness, vomiting, and orthostatic hypotension. 5,6 Amantadine has been shown to be somewhat helpful with rigidity and akinesia initially, 7 but these effects are not longlasting and livedo reticularis, edema, confusion, and hallucinations are common side effects. Anticholinergics can be used in younger patients with predominant tremor, 8 but their use is limited by peripheral cholinergic side effects, confusion, memory impairment, and possible withdrawal effects. Monoamine Oxidase Type B Inhibition and Parkinson's Disease Dopaminergic neurons decline steadily in PD, with motor symptoms emerging when about 50% of nigral neurons have degenerated. 9 At
Neurodegenerative disease management, 2018
Levodopa is the most efficacious treatment for Parkinson's disease (PD). Long-term treatment with levodopa is limited due to dyskinesia. Dyskinesia in PD can be socially and functionally disabling. Extended-release amantadine (amantadine ER) is the first approved medication for the treatment of dyskinesia. When it is given at bedtime, it reaches plasma concentration approximately twice the level achieved by amantadine immediate release. Amantadine ER reduces the severity and duration of dyskinesia during the day, reduces OFF time and increases ON time without troublesome dyskinesia. The most common side effects are hallucination, dizziness, orthostatic hypotension and pedal edema. This review discusses the safety and efficacy of amantadine ER in dyskinesia in PD patients.
Journal of movement disorders, 2018
We examined whether amantadine can prevent the development of dyskinesia. Patients with drug-naïve Parkinson's disease (PD), younger than 70 years of age and in the early stage of PD (Hoehn and Yahr scale < 3), were recruited from April 2011 to December 2014. The exclusion criteria included the previous use of antiparkinsonian medication, the presence of dyskinesia, significant psychological disorders, and previous history of a hypersensitivity reaction. Patients were consecutively assigned to one of 3 treatment groups in an open label fashion: Group A-1, amantadine first and then levodopa when needed; Group A-2, amantadine first, dopamine agonist when needed, and then levodopa; and Group B, dopamine agonist first and then levodopa when needed. The primary endpoint was the development of dyskinesia, which was analyzed by the Kaplan-Meier survival rate. A total of 80 patients were enrolled: Group A-1 ( = 27), Group A-2 ( = 27), and Group B ( = 26). Twenty-four patients were ex...
Journal of Neural Transmission, 2002
It has been reported that non-Caucasian populations often suffer from an atypical type of Parkinson's disease (PD) characterized by poor levodopa response, early cognitive impairment and autonomic dysfunction. We tested the effect of a well known antiparkinsonian compound, amantadine, in 23 Afro-American patients with PD in a time-limited (six months), open-label, clinical and electrophysiological (simultaneously recorded primary and cognitive visual evoked potentials) trial. Patients were given amantadine either as monotherapy (first group) or added to levodopa treatment (second group). Amantadine produced a significant (p Ͻ 0.05) shortening of the latency of the event related potential (P300) obtained in a visual discrimination paradigm, while the timing of primary visual evoked potentials was little or not at all affected. Amantadine also showed significant beneficial effects (p Ͻ 0.01) on the motor score of both groups as assessed by the Rated Parkinson's Disease Neurological Exam, including items related to autonomic dysfunction. These findings suggest that amantadine alone and as adjuvant to levodopa can significantly improve both the speed of visual cognitive processing and the clinical score in non caucasian patients with PD. For these populations amantadine can be thus considered a helpful therapeutical option.
Levodopa in the treatment of Parkinson's disease: an old drug still going strong
2010
After more than 40 years of clinical use, levodopa (LD) remains the gold standard of symptomatic efficacy in the drug treatment of Parkinson's disease (PD). Compared with other available dopaminergic therapies, dopamine replacement with LD is associated with the greatest improvement in motor function. Long-term treatment with LD is, however, often complicated by the development of various types of motor response oscillations over the day, as well as drug-induced dyskinesias. Motor fluctuations can be improved by the addition of drugs such as entacapone or monoamine oxidase inhibitors, which extend the half-life of levodopa or dopamine, respectively. However, dyskinesia control still represents a major challenge. As a result, many neurologists have become cautious when prescribing therapy with LD. This review summarizes the available evidence regarding the use of LD to treat PD and will also address the issue of LD delivery as a critical factor for the drug's propensity to induce motor complications.
Movement disorders : official journal of the Movement Disorder Society, 2017
The treatment of levodopa-induced dyskinesia in Parkinson's disease (PD) is an unmet need with no approved drug therapy. The purpose of this study was to investigate the efficacy and safety of 274 mg ADS-5102 (amantadine) extended-release capsules (equivalent to 340-mg amantadine HCl) for levodopa-induced dyskinesia in a randomized controlled trial. PD patients with ≥1 hour of troublesome dyskinesia and at least mild functional impact were randomized to placebo or ADS-5102 once daily at bedtime for 13 weeks. The primary efficacy analysis was based on change from baseline to week 12 on the Unified Dyskinesia Rating Scale total score in the modified intent-to-treat population. OFF time was a key secondary measure. At week 12, least-squares mean change in the Unified Dyskinesia Rating Scale was -20.7 (standard error 2.2) for ADS-5102 (n = 37) and -6.3 (standard error 2.1) for placebo (n = 38; treatment difference -14.4, 95% confidence interval -20.4 to -8.3, P < .0001), indicati...