Diagnostic and Treatment Guidelines in Parkinson's Disease 9780199333714, 9780199975914

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O A P N OX F O R D A M E R I C A N P O C K E T N O T E S

Diagnostic and Treatment Guidelines for Parkinson’s Disease

This material is not intended to be, and should not be considered, a substitute for medical or other professional advice. Treatment for the conditions described in this material is highly dependent on the individual circumstances. While this material is designed to offer accurate information with respect to the subject matter covered and to be current as of the time it was written, research and knowledge about medical and health issues are constantly evolving, and dose schedules for medications are being revised continually, with new side effects recognized and accounted for regularly. Readers must therefore always check the product information and clinical procedures with the most up-todate published product information and data sheets provided by the manufacturers and the most recent codes of conduct and safety regulation. Oxford University Press and the authors make no representations or warranties to readers, express or implied, as to the accuracy or completeness of this material, including without limitation that they make no representations or warranties as to the accuracy or efficacy of the drug dosages mentioned in the material. The authors and the publishers do not accept, and expressly disclaim, any responsibility for any liability, loss, or risk that may be claimed or incurred as a consequence of the use and/or application of any of the contents of this material. The Publisher is responsible for author selection and the Publisher and the Author(s) make all editorial decisions, including decisions regarding content. The Publisher and the Author(s) are not responsible for any product information added to this publication by companies purchasing copies of it for distribution to clinicians.

O A P N OX F O R D A M E R I C A N P O C K E T N O T E S

Diagnostic and Treatment Guidelines for Parkinson’s Disease Rajesh Pahwa, MD Professor of Neurology Director of the Parkinson’s Disease and Movement Disorder Center University of Kansas Medical Center Kansas City, Kansas

Kelly E. Lyons, PhD Research Professor of Neurology University of Kansas Medical Center Kansas City, Kansas

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Oxford University Press is a department of the University of Oxford. It furthers the University’s objective of excellence in research, scholarship, and education by publishing worldwide. Oxford New York Auckland Cape Town Dar es Salaam Hong Kong Karachi Kuala Lumpur Madrid Melbourne Mexico City Nairobi New Delhi Shanghai Taipei Toronto With offices in Argentina Austria Brazil Chile Czech Republic France Greece Guatemala Hungary Italy Japan Poland Portugal Singapore South Korea Switzerland Thailand Turkey Ukraine Vietnam Oxford is a registered trademark of Oxford University Press in the UK and certain other countries. Published in the United States of America by Oxford University Press 198 Madison Avenue, New York, NY 10016

© Oxford University Press 2013 All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, without the prior permission in writing of Oxford University Press, or as expressly permitted by law, by license, or under terms agreed with the appropriate reproduction rights organization. Inquiries concerning reproduction outside the scope of the above should be sent to the Rights Department, Oxford University Press, at the address above. You must not circulate this work in any other form and you must impose this same condition on any acquirer. Library of Congress Cataloging-in-Publication Data Pahwa, Rajesh. Diagnostic and treatment guidelines for Parkinson’s disease / Rajesh Pahwa, Kelly E. Lyons. p. ; cm. — (Oxford American pocket notes) Includes bibliographical references. ISBN 978-0-19-997592-1 (alk. paper) — ISBN 978-0-19-997591-4 (alk. paper) I. Lyons, Kelly E. II. Title. III. Series: Oxford American pocket notes. [DNLM: 1. Parkinson Disease—diagnosis—Handbooks. 2. Parkinson Disease—diagnosis—Practice Guideline. 3. Parkinson Disease—therapy— Handbooks. 4. Parkinson Disease—therapy—Practice Guideline. WL 39] 616.8’33—dc23 2012029561 9 8 7 6 5 4 3 2 1 Printed in China on acid-free paper

DIAGNOSTIC AND TREATMENT GUIDELINES FOR PARKINSON’S DISEASE

DISCLOSURES

Dr. Rajesh Pahwa has served as a consultant or received research support from Acadia, Adamas, Allon, Biotie, Ceregene, EMD Serono, GE Healthcare, Impax, Medtronic, National Parkinson Foundation, Novartis, Phytopharm, Schering, St. Jude Medical, Targacept, Teva Neuroscience and Xenoport. Dr. Lyons has served as a consultant for St. Jude Medical, Targacept and Teva Neuroscience.

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DIAGNOSTIC AND TREATMENT GUIDELINES FOR PARKINSON’S DISEASE

TABLE OF CONTENTS

Introduction 1 Epidemiology 3 Cost Issues 4 Guidelines 5 Evidence Levels 5 General Description 6 Diagnostic Issues 9 Differential Diagnosis 9 Diagnostic Criteria 9 Diagnostic Tools 11 Neuroprotection 13 Early Treatment 15 Treatment Guidelines 16 Treatment Options 18 Common Adverse Events 20 Advanced/Adjunctive Treatment 21 Treatment Guidelines 23 Treatment Options 26 Common Adverse Events 28

OAPN Nonmotor Symptoms 29 Neuropsychiatric Symptoms 30 Autonomic Symptoms 32 Sleep 33 Sleep Related Problems 34 Internet Resources 36 References 37

DIAGNOSTIC AND TREATMENT GUIDELINES FOR PARKINSON’S DISEASE

INTRODUCTION

Parkinson’s disease (PD) is a progressive neurodegenerative disease. It is estimated that PD affects over 1,000,000 people in the United States, with approximately 50,000 to 60,000 new cases diagnosed each year. The average age of PD onset is 60 years; although onset can be much later. On the other hand, up to 10% of patients are diagnosed with PD prior to the age of 40.1,2 The cardinal motor symptoms of PD are bradykinesia, rigidity, and resting tremor as well as postural instability in the later stages of the disease.3 PD patients may also experience a wide range of nonmotor symptoms including autonomic, neuropsychiatric, sensory, and sleep disturbances.4 The cause of PD is unknown and there is currently no cure. The primary neurochemical change is a loss of dopamine in the substantia nigra; although it is increasingly recognized that additional neurotransmitters and brain areas are involved.5,6 There are numerous challenges in the diagnosis and management of PD. Early symptoms may be subtle and may be attributed to aging, other health issues, or misdiagnosed as another movement disorder. Determining the appropriate treatment(s) can also be a challenge. It is important to consider the specific needs, presentation, and disability of each individual. Current treatment options include levodopa, dopamine agonists, monoamine oxidase type B (MAO-B) inhibitors, catechol-O-methyltransferase (COMT) inhibitors, amantadine, and anticholinergics as well as deep brain stimulation (DBS) surgery of the subthalamic nucleus (STN), globus pallidus interna (GPi), or ventral intermediate nucleus of the thalamus (Vim). The treatment goal is to reduce symptoms without causing side effects, and the ultimate goal is to stop or slow the progression of PD. 1

OAPN There have been several guidelines developed throughout the world to aid physicians in the diagnosis and treatment of PD. Although the majority of the guidelines are similar, there are also some differences. We will review the recommendations of six different guidelines for the diagnosis, potential neuroprotection, early treatment, advanced treatment, and treatment of nonmotor symptoms of PD.

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DIAGNOSTIC AND TREATMENT GUIDELINES FOR PARKINSON’S DISEASE

EPIDEMIOLOGY ■

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Cause of PD • Exposure to environmental toxins7 • Herbicide and pesticide exposure • Rural living, farming, well water consumption • Industrial chemical exposure • Genetic factors8 • Multiple genes and several additional loci identified • Genetics account for only about 10–15% of cases • Hypothesized that PD results from a combination of environmental and genetic factors Prevalence of PD (number of persons currently diagnosed) • Estimates range from 76 to 329 per 100,0001 • Prevalence rates increase with age • Approximately 60% of PD patients are male Incidence of PD (number of new cases each year) • Estimates range from 16 to 19 per 100,000 per year2 Primary risk factors • Age • Family history of PD • Male gender Lifetime risk of PD9 • 2.0% in men • 1.3% in women

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OAPN COST ISSUES ■

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Estimated US annual costs of PD as high as $25 billion • Healthcare costs • Medications and other treatments • Disability • Loss of productivity • Long-term care Age and gender matched PD versus non-PD control cost study10 • Costs similar for fi rst 5 years • Years 5–10 costs doubled for PD patients compared to non-PD controls • Increased hospital admissions • Longer hospital stays • Greater physician costs • Greater medication/treatment costs • Motor fluctuations are the strongest predictor of healthcare costs for PD patients.

DIAGNOSTIC AND TREATMENT GUIDELINES FOR PARKINSON’S DISEASE

GUIDELINES

The following guidelines were identified as providing recommendations for healthcare professionals on the diagnosis and/or treatment of PD. These guidelines have drawn conclusions and developed recommendations based on the available evidence in the literature and also good practice principles based on expert opinion, experience, and consensus. It should be noted that the guidelines are limited by the availability and quality of the literature and that newer guidelines reflect changes in the literature and practice principles, which may lead to discrepancies with aspects of the earlier guidelines. Evidence Levels All of the guidelines provide a review and rating of the literature. Although there are slight differences in how studies are rated, the following levels of evidence are a basis, which is relevant for all of the guidelines11,12: Level/Class I: High quality, well described, prospective, randomized, controlled trial (RCT). The trial should be powered appropriately and use appropriate statistical analyses, have a masked outcome assessment and include the appropriate population. The study should clearly describe the randomization process, primary outcome, inclusion/exclusion criteria, completers/dropouts, and baseline characteristics. Level/Class II: Prospective, high-quality, well described, case-control, or matched-group cohort study in the appropriate population with masked outcome assessment. Alternatively, an RTC that does not contain all of the items to qualify as a Level I study above. ■

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OAPN ■

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Level/Class III: All other controlled trials in the appropriate population, wherein outcome assessment is independent of patient treatment Level/Class IV: Evidence from uncontrolled studies, case series, case reports, or expert opinion

General Description American Academy of Neurology (AAN) • Diagnosis13 • Neuroprotective strategies14 • Initiation of treatment12 • Treatment of motor fluctuations and dyskinesia15 • Depression, psychosis and dementia16 • Non-motor symptoms17 The AAN guidelines are evidence-based with expert opinion and future directions noted where applicable. Recommendations are based on the following criteria: A – Effective, ineffective or harmful, requiring 2 consistent Class I studies B – Probably effective, ineffective or harmful, 1 Class I study or at least 2 consistent Class II studies C – Possibly effective, ineffective or harmful, 1 Class II study or 2 consistent Class III studies U – Data inadequate or conflicting (treatment unproven) Canadian Guidelines on Parkinson’s Disease18 • The Canadian guidelines are relevant to the Canadian Health C5are System and are evidence-based with expert consensus when evidence is not available. These guidelines are based on the fi ndings of the AAN, EFNS, and NICE guidelines, which are referenced as appropriate after each point in the Canadian guideline.

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DIAGNOSTIC AND TREATMENT GUIDELINES FOR PARKINSON’S DISEASE

European Federation of Neurological Societies (EFNS) • Early (uncomplicated) Parkinson’s disease11 • Late (complicated) Parkinson’s disease19 The EFNS guidelines are evidence-based. The recommendations are based on the following criteria: A – Effective, ineffective or harmful –a Class I study or 2 consistent Class II studies B – Probably effective, ineffective or harmful –a Class II study or overwhelming Class III evidence C – Possibly effective, ineffective, or harmful – at least 2 convincing class III studies GPP – Good practice point

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Movement Disorder Society (MDS) • Treatments for motor symptoms20 • Treatments for nonmotor symptoms21 The MDS guidelines are evidence-based. The recommendations are based on the following criteria: • Efficacious/non-efficacious –1 high quality (score >75%) RTC without confl icting Level I data • Likely efficacious/unlikely efficacious – Any level I study without confl icting level 1 data • Insufficient evidence – no trials meeting the requirements above National Institute for Health and Clinical Excellence (NICE) • Parkinson’s disease: Diagnosis and management in primary and secondary care22

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OAPN The NICE guidelines are published by the Royal College of Physicians of London and are clinical evidence-based guidelines for the National Health Service of England and Wales. Recommendations are based on the following criteria: A – High quality RCT with low risk of bias B – High quality case-control or cohort studies or extrapolation from RTCs C – Well-conducted, case-control or cohort studies or extrapolated from level B studies; D – Nonanalytic studies or expert opinion (GPP – good practice point) Scottish Intercollegiate Guidelines Network (SIGN) • Diagnosis and pharmacological management of Parkinson’s disease23 The SIGN guidelines are evidence-based. Recommendations are based on the following criteria:

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A – High quality RCT with low risk of bias B – High quality case-control or cohort studies or extrapolation from RTCs C – Well-conducted, case-control or cohort studies or extrapolated from level B studies D – Nonanalytic studies or expert opinion (GPP – good practice point)

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DIAGNOSTIC AND TREATMENT GUIDELINES FOR PARKINSON’S DISEASE

DIAGNOSTIC ISSUES

Differential Diagnosis According to the Canadian, NICE, and SIGN recommendations,18,22,23 PD should be considered in patients with tremor, rigidity, bradykinesia, and/or gait and balance issues. These guidelines also recommend that because the diagnosis of PD is clinical, patients suspected of having PD should be sent to a movement disorder specialist before being treated in order to obtain confi rmation of diagnosis, as other disorders can have similar symptoms, particularly early in the disease course. According to the AAN and Canadian guidelines,13,18 the most common symptoms used to rule out a diagnosis of PD include falls at disease presentation, poor levodopa response, symmetry at onset, rapid progression, lack of tremor, and dysautonomia. Diagnostic Criteria The United Kingdom Parkinson’s Disease Society Brain Bank clinical diagnostic criteria are the most commonly used criteria in the diagnosis of PD.24 These criteria are based on a three step process: (1) identify the primary symptoms of parkinsonism; (2) exclude the diagnosis of PD based on history, signs and symptoms uncharacteristic for idiopathic PD; and (3) identify at least three supporting criteria for the diagnosis of idiopathic PD: Step 1: Diagnosis of parkinsonism: • Bradykinesia (slow initiation of movement; progressive reduction in speed/amplitude with repetition) • And at least one of the following: • Muscular rigidity • 4–6 HZ rest tremor • Postural instability ■

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Step 2: Exclusion criteria for PD • History of repeated strokes with stepwise progression of parkinsonian features • History of repeated head injury • History of defi nite encephalitis • Oculogyric crisis • Neuroleptic treatment at onset of symptoms • More than one affected relative • Sustained remission • Strictly unilateral features after 3 years • Supranuclear gaze palsy • Cerebellar signs • Early, severe autonomic involvement • Early, severe dementia with disturbances of memory, language and praxis • Babinski sign • Presence of cerebral tumor or communicating hydrocephalus on CT scan • Negative response to large doses of levodopa (if malabsorption excluded) • MPTP exposure Step 3: Supportive criteria for PD (≥3 for defi nite PD diagnosis) • Unilateral onset • Rest tremor present • Progressive disorder • Persistent asymmetry affecting side of onset most • Excellent response (70–100%) to levodopa • Severe levodopa-induced chorea • Clinical course of 10 years or more

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DIAGNOSTIC AND TREATMENT GUIDELINES FOR PARKINSON’S DISEASE

Table 1 Differential Diagnosis for Parkinson’s Disease Differential Diagnosis

Symptoms Uncommon in PD

Brain tumor/trauma

Abnormal imaging fi ndings

Corticobasal degeneration (CBD)

Alien limb, apraxia, cortical sensory loss, dystonia, myoclonus

Dementia with Lewy bodies (DLB)

Early hallucinations; dementia within one year of parkinsonism

Drug-induced parkinsonism (DIP)

Recent exposure to neuroleptics or other offending agent; resolves with discontinuation; symmetric onset

Essential tremor (ET)

Bilateral action tremor; head or voice tremor; strong family history of tremor; tremor responds to alcohol; tremor primary symptom

Multiple system atrophy (MSA)

Early autonomic dysfunction; ataxia; cerebellar signs; early speech changes and falls; usually minimal to no response to levodopa: if there is response it is not sustained

Normal pressure hydrocephalus (NPH)

Subacute gait difficulty, dementia, and urinary incontinence; abnormal imaging fi ndings

Progressive supranuclear palsy (PSP)

Early postural instability and falls; gaze palsy, rapid progression, symmetric onset; minimal to no response to levodopa

Vascular parkinsonism

Sudden onset; stepwise progression; lower limbs more severely affected; abnormal imaging, minimal to no response to levodopa

Diagnostic Tools Currently there are no clinical tests or assessments that can defi nitely confi rm the diagnosis of PD. However, there are several diagnostic aids that have been proposed to differentiate PD from other forms of parkinsonism and tremor disorders. 11

AAN13

Canadian18

NICE22

SIGN23

Insufficient evidence

Not recommended (B)

Not recommended (A)

Insufficient evidence

Not recommended (B)

Not recommended (B)

PET MRI

Should be considered when PD diagnosis in doubt (B) Should be considered for PD vs. PSP or CBD but not PD vs. MSA (B) May not be useful to distinguish parkinsonism (C) Insufficient evidence Insufficient evidence

May not be useful to distinguish parkinsonism Insufficient evidence Insufficient evidence

CT

Not mentioned

Not mentioned

Recommended for specialists if ET cannot be differentiated from parkinsonism (A) Not recommended (B) May be considered for differential diagnosis of parkinsonian syndromes (D) but not for PD (B) Not mentioned

Recommended for PD vs. nondegenerative parkinsonism / tremor disorders (B) Not recommended (GPP) Recommended to identify lesions or cerebrovascular disease as well as brain atrophy for PD vs. other forms of parkinsonism (D) Recommended to identify lesions (D)

Levodopa/ apomorphine challenge Olfactory testing 123I-FP-CIT SPECT

Level of evidence/strength of recommendation is in parentheses after each comment; levels for each guideline are defi ned under the Guidelines section. Autonomic testing, brain sonography, electrooculography, GH stimulation with clonidine, urethral/anal EMG, and urodynamics were either not mentioned, found to have insufficient evidence or were not recommended by any of the guidelines as diagnostic tools for PD.

OAPN

Table 2 Recommendations for the use of various diagnostic tools for PD/parkinsonism

DIAGNOSTIC AND TREATMENT GUIDELINES FOR PARKINSON’S DISEASE

NEUROPROTECTION

Neuroprotection or disease modification refers to protecting neurons from degeneration and apoptosis (cell death) in an attempt to stop or slow disease progression. It is estimated that there is already a 60–80% loss of dopamine neurons at the time of PD diagnosis, highlighting the need for an earlier intervention to slow or reverse this damage.25 There are currently no approved neuroprotective treatments for PD and no treatments are defi nitively recommended by any of the current guidelines. Table 3 lists the recommendations for the treatments that have been examined for potential neuroprotection.

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AAN14

Canadian18

EFNS11

MDS20

NICE22

SIGN23

Co-enzyme Q10

Insufficient evidence

Should not be used

Use not supported

Not discussed

Should not be used (B)

Insufficient evidence

MAO-B inhibitors

Insufficient evidence

Should not be used

Selegiline – initial advantage not sustained Rasagiline – possibly efficacious (need longterm data)

Insufficient evidence

Should not be used (B)

Not discussed

Levodopa

No long-term evidence

No long-term evidence

Inconclusive

Insufficient evidence

Not discussed

Not discussed

Dopamine agonists

Insufficient evidence

Should not be used

No convincing evidence

Insufficient evidence

Should not be used (B)

Not discussed

Amantadine

Insufficient evidence

Insufficient evidence

Insufficient evidence

Insufficient evidence

Not discussed

Not discussed

Riluzole

Insufficient evidence

Not discussed

Use not supported

Not discussed

Not discussed

Not discussed

Tocopherol

Should not be considered (B)

Should not be used

Use not supported

Not discussed

Should not be used (A)

Not recommended (A)

Level of evidence/strength of recommendation is in parentheses after each comment; levels for each guideline are defined under the Guidelines section.

OAPN

Table 3 Guidelines for potential neuroprotection

DIAGNOSTIC AND TREATMENT GUIDELINES FOR PARKINSON’S DISEASE

EARLY TREATMENT

There are several early treatment options for PD, including MAO-B inhibitors, dopamine agonists, carbidopa/levodopa, amantadine, and anticholinergics. The guidelines are in agreement that there is not a defi nitive treatment plan for all patients, but rather, the individual’s lifestyle, employment, age, symptoms, side effects, fi nances, and other health issues will all impact the choice of the best initial treatment option.11,18,22 MAO-B inhibitors, dopamine agonists and carbidopa/levodopa are all considered fi rst line treatment options for early PD. Table 4 summarizes the recommendations for the treatment of early PD. Table 5 lists the currently available early treatment options for PD and Table 6 lists the common dopaminergic adverse effects associated with the early treatment options.

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Treatment

AAN (2002)12

Canadian (2012)18

EFNS (2011)11

MDS (2011)20

NICE (2006)22 SIGN (2010)23

MAO-B Inhibitors

Rasagiline - data unavailable Selegiline – mild efficacy (A)

May be used

Effective (A); more modest than levodopa and probably dopamine agonists; easy to administer; well tolerated, especially rasagiline (GPP)

Efficacious; Clinically useful

May be used (A)

May be considered (A)

Dopamine Agonists

Effective (A); less effective than levodopa, more frequent adverse events, and fewer motor complications

May be used; titrate to efficacious dose and if not tolerable change dopamine agonist or drug class; nonergot agonists preferred

Effective (A); Less effective than levodopa, more frequent adverse events; fewer motor complications

Efficacious; Clinically useful

May be used (A); titrate to efficacious dose and if not tolerable change dopamine agonist or drug class; nonergot agonists preferred (D-GPP)

May be considered (oral/transdermal) (A); ergot agonists should not be used as fi rst line therapy (B); warn patients about impulse control disorders and excessive sleepiness (A)

OAPN

Table 4 Early Treatment Guidelines

Efficacious; Clinically useful

May be used (A); keep dose as low as possible to maintain function and avoid motor complications (A)

May be considered (A); use lowest effective dose to minimize side effects; watch for dopamine dysregulation syndrome (GPP)

Anticholinergics

Mild effect mainly on tremor; No evidence of being better than levodopa (B)

May be used in young patients with severe tremor; not fi rst choice limited efficacy and neuropsychiatric side effects

Probably effective (B); Impact smaller than levodopa; poorly tolerated in elderly and mainly restricted to young patients (GPP)

Likely efficacious; Clinically useful

May be used in young patients with severe tremor; not fi rst choice: limited efficacy and neuropsychiatric side effects (B)

Should not be used as fi rst line treatment for PD (B)

Amantadine

Modest effect; Low adverse effect profi le (B)

May be used in early PD but is not a drug of fi rst choice

Probably effective (B); Impact smaller than levodopa

Likely efficacious; Possibly useful

May be used in early PD but is not a drug of fi rst choice (D-GPP)

Insufficient evidence

Level of evidence/strength of recommendation is in parentheses after each comment; levels for each guideline are defi ned under the Guidelines section.

DIAGNOSTIC AND

Most effective (A); Early use in elderly (GPP); Associated with development of motor complications (GPP)

TREATMENT GUIDELINES

May be used; keep dose as low as possible to maintain function and avoid motor complications

FOR PARKINSON’S DISEASE

Most effective (A); Risk of motor complications

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Levodopa

OAPN Table 5 Early Treatment Options Treatment

Available Dosages (mg)

Initial Dose and Titration

MAO-B Inhibitors (selectively block MAO-B to reduce dopamine metabolism) Rasagiline (Azilect)

0.5, 1

No titration, 1mg once daily

Selegiline (Eldepryl, generic)

5

5mg in morning and afternoon

Dopamine Agonists (stimulate post-synaptic dopamine receptors) Pramipexole (Mirapex, generic)

0.125, 0.25, 0.5, 1, 1.5

0.125mg tid & increase weekly to 0.25, 0.5, 0.75, 1, 1.25 and 1.5mg tid as needed; maximum 4.5 mg/d

Pramipexole extended release (Mirapex ER) Ropinirole (Requip, generic)

0.375, 0.75, 1.5, 3, 4.5 0.25, 0.5, 1, 2, 3, 4, 5

0.375 mg qd & increase in 5–7 days to 0.75mg and by 0.75mg every 5–7 days to a maximum of 4.5 mg/d 0.25mg tid & increase weekly to 0.5, 0.75, 1, 1.5, 2, 2.5, and 3mg tid; increase as need to maximum 24 mg/d

Ropinirole extended release (Requip XL, generic)

2, 4, 8

2mg qd for 1-2 wks & increase 2mg every 1–2 weeks to 8mg qd; increase as needed to maximum 24 mg/d;

Rotigotine patch (Neupro)

1, 2, 3, 4, 6

2mg/24hr & increase weekly as needed by 2mg/24hr to 6mg/24hr

Dopamine Precursor (converted to dopamine in the brain) Carbidopa/ levodopa (Sinemet, Parcopa, generic)

10/100, 25/100, 25/250

25/100 tid; can increase as necessary up to 2000 mg/d

DIAGNOSTIC AND TREATMENT GUIDELINES FOR PARKINSON’S DISEASE

Table 5 (Continued) Treatment

Available Dosages (mg)

Initial Dose and Titration

Antiglutamatergics (enhance dopamine release and/or reuptake inhibition; NMDA antagonist) Amantadine (Symmetrel)

100

100 mg/d & increase as needed to 300 mg/d

Anticholinergics (block acetylcholine) Used rarely and used with caution in patients over 60 Benztropine (Cogentin)

0.5, 1, 2

0.5mg bid & increase by 0.5–1 mg every 3–4 days as needed

Trihexyphenidyl (Artane)

2.5

1 mg qd or bid & increase by 0.5–1mg every 3–4 days as needed

Adverse Event

Selegilinea,b

Rasagilinec

Pramipexole

Pramipexole extended release

Ropini- Ropinirole Rotigo- Carbidopa/ role extended tine levodopad release

Anorexia/ weight loss Confusion Dizziness Hallucinations Nausea Orthostatic hypotension Peripheral edema Somnolence Vomiting

2%

>1%*

4%