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Parkinson’s Disease Treatment Guidelines

New Medications For Off Time

Parkinson’s Disease Treatment Guide Books – Dr. Eric Ahlskog

A number of new medications approved recently are designed to reduce OFF time. These medications fall into two major categories:

  • Medications that lengthen the effect of a carbidopa/levodopa dose
  • Medications that are used as needed if medication effects wear off

Well give specific examples below. In general, new medications that extend the length of a carbidopa/levodopa dose are used if OFF time is somewhat predictable and occurs prior to next dose. New medications that are used as needed are most beneficial when OFF time is not predictable.

New medications that lengthen the effect of a dose of carbidopa/levodopa

  • Istradefylline is an adenosine A2A receptor antagonist which was approved in the US in 2019 as an add-on therapy to levodopa for treatment of OFF time in PD. Unlike many of the other medications, it has a novel mechanism of action and is the first medication in its class to be approved for PD. It acts on the adenosine receptor, which modulates the dopaminergic system, but is not directly dopaminergic. The drug was developed in Japan and underwent clinical trials both in Japan and in the US.
  • Opicapone is a catechol-O-methyltransferase inhibitor that is taken once a day. It was approved in the US in 2020 as an add-on therapy to levodopa for motor fluctuations.

New formulations of levodopa designed to be used as needed if medication effects wear off

Other medications used as needed if medication effects wear off

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Adherence To Treatment Guideline Recommendations For Parkinsons Disease In Japan: A Longitudinal Analysis Of A Nationwide Medical Claims Database Between 2008 And 2016

  • Roles Conceptualization, Formal analysis, Investigation, Methodology, Writing review & editing

    Affiliation Department of Neurology, The Jikei University Katsushika Medical Center, Katsushika-ku, Tokyo, Japan

  • Roles Conceptualization, Formal analysis, Investigation, Methodology, Writing review & editing

    Affiliation Japan Medical Affairs, Takeda Pharmaceutical Company Limited, Chuo-ku, Tokyo, Japan

  • Roles Conceptualization, Formal analysis, Investigation, Methodology, Writing review & editing

    Affiliation Japan Medical Affairs, Takeda Pharmaceutical Company Limited, Chuo-ku, Tokyo, Japan

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Treating Motor Symptoms In Early Parkinson Disease: Aan Releases New Guidelines

The American Academy of Neurology released updated guidelines on the initiation of dopaminergic therapy for the treatment of motor symptoms in patients with early Parkinson disease . A summary of these guidelines was published in Neurology.

During early PD, patients can experience tremor, rigidity, bradykinesia, and gait and balance impairment. The treatment strategy for these symptoms is to enhance the dopaminergic tone by using dopamine agonists , monoamine oxidase type B inhibitors, and/or levodopa. There are no current disease-modifying pharmacologic treatment options, and these therapies solely aim at symptom management.

In 2002, the AAN released guidelines about treatment of early PD. Since that time, many new therapeutic options have become available, leading the AAN to release 6 updated recommendations. The neurology group reviewed peer-reviewed studies up until June 2020 that focused on patients with early PD and they also assessed the medications prescribed using the Unified Parkinsons Disease Rating Scale part III, which measures motor symptoms.

Like levodopa, DAs come in multiple formulations such as short-acting or long-acting and they are also available in various delivery methods, including oral and as transdermal injection. There was little evidence to support the use of a specific

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Study Screening And Selection Criteria

Parkinsons Disease Treatment Algorithm

Types of Participants

We included studies of participants with PD in the early stages .

Types of Interventions

We included studies of DAs, levodopa, monoamine oxidase type B inhibitors, and catechol-O-methyltransferase inhibitors to treat motor symptoms of PD in the early stages of the disease.

Comparison Group

We included studies using active comparators only.

Types of Studies

For clinical questions 1 through 6, we included only randomized controlled trials. For clinical questions 7 and 8, we included randomized controlled trials, population-based epidemiologic studies, and prospective cohort studies.

Types of Outcome Measures

The preferred outcome measure was the Unified Parkinson’s Disease Rating Scale part III, which measures motor symptoms. To determine the change in motor symptoms, the authors calculated the raw mean difference between scores on the UPDRS part III at baseline and at follow-up. To determine the change in dyskinesia, hallucinations, adverse event related discontinuation, and impulse control disorders , the risk differences were calculated.

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Treating Parkinsons With Complementary Medicine

Complementary medicine incorporates many different practices that can be used alongside conventional medicine to try to ease PD symptoms. There is typically not as much rigorous data to support the use of complementary medicine techniques, as compared to conventional medicine, but many patients find them helpful. These include yoga and massage.

Data Synthesis And Confidence In Evidence Statements For Risk Of Icds

  • 7. In people with early PD, what is the risk of ICDs with medications used for the treatment of motor symptoms and does the risk differ between drug formulations?

The MCID in the risk of ICDs was determined by consensus to be 2% RDs 1% were considered clinically unimportant.

Confidence in Evidence Statements

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Deep Brain Stimulation For The Treatment Of Pd Patients

Current surgical indications for PD include reducing motor fluctuations, off time, dyskinesias, tremor, and improvement of levodopa-responsive symptoms. Deep brain stimulation is probably the most critical advance in treatment of PD since the introduction of levodopa. The beneficial effects of DBS on motor symptoms and quality of life in advanced PD have been shown in randomized, controlled studies6666. Deuschl G, Schade-Brittinger C, Krack P, Volkmann J, Schäfer H, Bötzel K, et al. A randomized trial of deep-brain stimulation for Parkinsons disease. N Engl J Med. 2006 Aug 31 355:896-908. ,6767. Williams A, Gill S, Varma T, Jenkinson C, Quinn N, Mitchell R, et al. Deep brain stimulation plus best medical therapy versus best medical therapy alone for advanced Parkinsons disease : a randomised, open-label trial. Lancet Neurol. 2010 Jun 1 9:P581-91. .

Assembling Your Care Team

What are the current recommendations for the treatment of early Parkinson’s Disease.

Assembling a team that will provide you with physical and emotional support and adapt to your needs over time is one of the best ways to remain healthy. Parkinsons disease is complex and requires an interdisciplinary approach to care. The care team may include, but is not limited to:

  • Movement disorder specialist
  • Rehabilitation specialists including physical, occupational, and speech therapists
  • Nurse

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American Academy Of Neurology

In 2010, the AAN released guidelines on the treatment of nonmotor symptoms of Parkinson disease. Recommendations included the following :

  • Sildenafil citrate may be considered to treat erectile dysfunction

  • Polyethylene glycol may be considered to treat constipation

  • Modafinil should be considered for patients who subjectively experience excessive daytime somnolence

  • For insomnia, evidence is insufficient to support or refute the use of levodopa to improve objective sleep parameters that are not affected by motor symptoms evidence is also insufficient to support or refute the use of melatonin for poor sleep quality

  • Levodopa/carbidopa should be considered to treat periodic limb movements of sleep in Parkinson disease, but there are insufficient data to support or refute the use of nonergot dopamine agonists to treat this condition or that of restless-legs syndrome

  • Methylphenidate may be considered for fatigue

  • Evidence is insufficient to support or refute specific treatments of orthostatic hypotension, urinary incontinence, anxiety, and RMD

  • Hauser RA, Grosset DG. FP-CIT SPECT Brain Imaging in Patients with Suspected Parkinsonian Syndromes. J Neuroimaging. 2011 Mar 16. .

  • Wirdefeldt K, Adami HO, Cole P, Trichopoulos D, Mandel J. Epidemiology and etiology of Parkinson’s disease: a review of the evidence. Eur J Epidemiol. 2011 Jun. 26 Suppl 1:S1-58. .

  • Bekris LM, Mata IF, Zabetian CP. The genetics of Parkinson disease. J Geriatr Psychiatry Neurol. 2010 Dec. 23:228-42. . .

  • Managing Your Symptoms With Medication

    Almost all patients with Parkinsons disease eventually need to take medication to help with their motor symptoms. Several classes of medications are available and can be viewed here. Carbidopa/Levodopa remains the most effective symptomatic therapy and is available in many strengths and formulations. It also may be used in combination with other classes of medications including Dopamine Agonists, COMT Inhibitors, MAO Inhibitors, and Anticholinergic agents. Treatment is highly individualized and adjusted over time based on symptoms and side effects.

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    The Surgical Option: Deep Brain Stimulation

    Some patients with Parkinsons disease may benefit from deep brain stimulation , a surgical therapy that has been FDA approved for over a decade. DBS involves implanting an electrode into a targeted area of the brain, usually the subthalamic nucleus or the globus pallidus interna . The implants can be done on one side or both sides of the brain as needed. The electrodes are stimulated through a connection to a pacemaker-like device located under the skin in the chest. Patients that are considered good candidates for this procedure are those with a robust response to Levodopa, no significant cognitive or psychiatric problems, and no significant problems with balance. The procedure can help patients with medication-resistant tremors. It can also help patients who have significant motor fluctuations in which medication response varies during the day and dyskinesias or extra movements may occur as a side effect of medication.

    Therapeutic And Formalized Pattern Exercises

    Parkinsons disease: summary of updated NICE guidance

    The SPARX study enrolled 128 de novo patients and compared high- and moderate-intensity treadmill exercises with a wait-list control group. After six month of 3 days per week exercise, the results showed that the high-intensity group, who exercised at 80 to 85% maximum heart rate, had less change in motor symptoms compared with the usual care group9898. Schenkman M, Moore CG, Kohrt WM, Hall DA, Delitto A, Comella CL, et al. Effect of high-intensity treadmill exercise on motor symptoms in patients with de novo Parkinson disease: a phase 2 randomized clinical trial. JAMA Neurol. 2018 Feb 1 75:219-26. . The Park-in-shape trial , a home-based study, recruited 130 PD patients in Hoehn & Yahr stage 2 who were randomized either to exercise on a stationary cycle or stretching at least three times per week. After the 6-month program, the MDS-UPDRS motor score change was smaller in the aerobic group, resulting in a between-group adjusted mean difference of 4.2 points favoring the cycling group9999. Van der Kolk NM, de Vries NM, Kessels RPC, Joosten H, Zwinderman AH, Post B, et al. Effectiveness of home-based and remotely supervised aerobic exercise in Parkinsons disease: a double-blind, randomised controlled trial. Lancet Neurol. 2019 Nov 1 18:P998-1008. .

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    Diagnosis Of Parkinsons Disease

    The diagnosis of PD is clinical and requires bradykinesia, defined as slowness of movement and decrement in amplitude or speed, usually assessed using finger tapping, foot tapping or pronationsupination hand movements. In addition, rest tremor or rigidity is required to confirm a parkinsonian syndrome. Tremor was absent at presentation in 30% in one series of pathologically proven PD. Patients with suspected PD should be referred quickly and untreated to a specialist in movement disorders for evaluation. Key points for discussion at diagnosis include the need to inform vehicle licensing agencies and insurers, signposting to written or web-based information on newly diagnosed PD, and provision of contact details for the local PD nurse specialist .

    Current International Parkinson and Movement Disorder Society diagnostic criteria for Parkinsons disease adapted from Postuma RB, Berg D, Stern M et al. MDS clinical diagnostic criteria for Parkinsons disease. Mov Disord 2015 30:1591601. At least two supportive criteria and no red flags required for a diagnosis of clinically established Parkinsons disease. Conditions in italics should be considered if the corresponding exclusion criteria or red flags are present.

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    Motor Fluctuations And Dyskinesia

    For the treatment of motor features of tremor, bradykinesia, and rigidity associated with Parkinsons disease, dopaminergic therapies are initially effective however, motor fluctuations eventually complicate therapy and can cause significant disability and impair quality of life. Sustained-release carbidopa/levodopa and bromocriptine have not been found to reduce off time.

    Risk factors for motor complications include disease severity, younger age at onset of Parkinsons disease, high levodopa dosage, and longer disease duration. The motor fluctuations usually are addressed with levodopa adjustments as well as adjunctive medications or surgery as discussed below.

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    Iii Prognosis Neuroprotection And Treatment


    The rate of progression of PD is dependent on a number of factors such as age, presence of comorbidities and primary symptom of presentation.


    Pharmacists should expect a more rapid rate of motor progression in newly diagnosed PD if, at onset, the person is/does the following:

    • Is male or older.
    • Presents with rigidity/hypokinesia as an initial symptom. Such persons may also develop cognitive decline and dementia earlier.
    • Presents with associated comorbidities such as stroke, auditory deficits, visual impairments and/or postural instability/gait difficulty.

    Pharmacists can expect a slower rate of progression in newly diagnosed PD in persons

    • who present with tremors as the primary symptom. Such persons may also experience benefit from levodopa for a longer period of time.


    Neuroprotection in PD has been defined as an intervention with the potential to slow, stop or reverse the progression of PD.8 Although none of the medications used in the treatment of PD has been conclusively shown to have this effect, clinical trials with other agents are ongoing.


    Pharmacists should do the following:

    • Not recommend vitamin E, coenzyme Q10, dopamine agonists or monoamine oxidase inhibitors for neuroprotection in PD, except in the context of clinical trials.
    • Understand that there is no long-term evidence to recommend levodopa for neuroprotection.


    Aan Releases Recommendations On Treatment Of Parkinsons Disease

    Parkinson’s Disease – Prescribing Guidelines by Dr Najah Alenezi ,15,4,2015

    Am Fam Physician. 2007 Mar 15 75:922-924.

    Guideline source: American Academy of Neurology

    Literature search described? Yes

    Evidence rating system used? Yes

    Available at:

    Parkinsons disease is the second most common neurodegenerative disease and is characterized by bradykinesia tremor at rest rigidity and abnormalities of balance, posture, and gait. Its etiology remains unknown in most patients. Recommendations from the Quality Standards Subcommittee of the American Academy of Neurology discuss the following aspects of this condition in a collection of articles in the April 2006 issue of Neurology: diagnosis and prognosis neuroprotective strategies and alternative therapies treatment and evaluation and treatment of depression, psychosis, and dementia in patients with Parkinsons disease.

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    American Academy Of Neurology Issues Guidelines For Treating Motor Symptoms

    The guidance updates the recommendations on dopaminergic medications that were published in 2002 on the initiation treatment for Parkinson disease.

    The American Academy of Neurology has issued guidelines for treating movement symptoms, known as motor symptoms, for individuals with early Parkinson disease.

    The guidelines update the recommendations on dopaminergic medications that were published in 2002 on the initiation treatment for Parkinson disease.

    We carefully reviewed the available research on the effectiveness and possible risks of medications to treat motor symptoms in people with early Parkinson disease and found that levodopa is usually the best first treatment for these symptoms, Tamara Pringsheim, MD, MSc, of the University of Calgary and a fellow of the AAN, said in a statement.

    The new guidelines recommend that health care providers should counsel individuals with early Parkinson disease on the benefits and risks of 3 initial therapy options: dopamine agonists, which mimic the effects of dopamine levodopa, a drug that is converted into dopamine in the brain and monoamine oxidase B inhibitors, which prevent MAO-B enzymes from breaking down dopamine.

    The guidelines also state that treatment with levodopa provides superior benefits at reducing motor symptoms than the other options.

    The guidelines recommend that health care providers prescribe the lowest effective dose to minimize the risk of dyskinesia and optimize benefits.

    Tapering And Discontinuing Das

    Recommendation 5 Rationale

    Adverse effects associated with DAs can lead to substantial impairments in psychosocial functioning, interpersonal relationships, and quality of life for the patient and caregivers. The consequences of medication-related adverse effects may be mitigated through adjustments to prescribed medications, including DAs, or through additional behavioral or pharmacologic interventions, if appropriate.

    Patients may experience undesirable side effects when attempting to decrease dopaminergic medications, especially DAs, including dopamine agonist withdrawal syndrome or low mood and apathy. These side effects can make it difficult to taper or discontinue DAs. Staged reduction in dosing may reduce the severity of withdrawal symptoms and improve compliance with medication recommendations.

    Recommendation 5 Statements

    • 5a. Clinicians should recommend tapering or discontinuation of DAs if patients experience disabling medication-related adverse effects, including ICDs, EDS, sudden-onset sleep, cognitive impairment, or hallucinations .

    • 5b. When DAs must be discontinued due to adverse effects, clinicians should monitor patients for symptoms of DAWS and, when possible, gradually decrease the dosage to minimize symptoms .

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    Drug And Medication Therapies

    The purpose of treating Parkinsons is to reduce the effect of symptoms on your daily life. Without treatment, you will eventually find that the symptoms make it hard to perform daily activities. Symptoms, such as shaking and stiffness, may cause discomfort the risk of injury from falls may increase, and swallowing may become more difficult. People are encouraged to maintain open and ongoing discussions with their Parkinsons healthcare team when exploring treatment options.

    Medication will help you function, but may cause side effects. It is important to find the right balance between the medications benefits and side effects. Everyone with Parkinsons is unique and will experience different symptoms, which means the treatment you receive will be geared to your specific needs. Drugs for Parkinsons work on the brains complex chemistry and may need to be taken several times a day. Use them as prescribed and do not alter your doses without consulting your doctor. Current treatment neither cures Parkinsons nor stops it from advancing.


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