Treatment Guidelines from The Medical Letter® Published by The Medical Letter, Inc • 145 Huguenot Street, New Rochelle, NY 10801 • A Nonprofit Publication IN THIS ISSUE (starts on next page) Drugs for Parkinson’s Disease p 101 Important Copyright Message The Medical Letter® publications are protected by US and international copyright laws Forwarding, copying or any distribution of this material is prohibited Sharing a password with a non-subscriber or otherwise making the contents of this site available to third parties is strictly prohibited By accessing and reading the attached content I agree to comply with US and international copyright laws and these terms and conditions of The Medical Letter, Inc For further information click: Subscriptions, Site Licenses, Reprints or call customer service at: 800-211-2769 FORWARDING OR COPYING IS A VIOLATION OF US AND INTERNATIONAL COPYRIGHT LAWS The Medical Letter publications are protected by US and international copyright laws Forwarding, copying or any other distribution of this material is strictly prohibited For further information call: 800-211-2769 Treatment Guidelines from The Medical Letter® Published by The Medical Letter, Inc • 145 Huguenot Street, New Rochelle, NY 10801 • A Nonprofit Publication Volume 11 (Issue 135) November 2013 www.medicalletter.org Table Some Drugs for Parkinson’s Disease Page 103 Drugs for Parkinson’s Disease Related article(s) since publication Levodopa combined with carbidopa is still the most effective treatment for symptoms of Parkinson’s disease Dopamine agonists, the next most effective class of drugs, can be used alone before the introduction of levodopa or as an adjunct to levodopa Addition of a peripherally-acting COMT inhibitor or an MAO-B inhibitor to levodopa can reduce motor fluctuations in patients with advanced disease Amantadine may have mild symptomatic benefit and can decrease levodopa-induced dyskinesias Anticholinergics are rarely used because of their adverse effects, but can be a useful addition to levodopa for control of tremor and drooling Subcutaneous apomorphine should be available for rescue use in patients with “off” episodes Deep brain stimulation is an option for patients with levodopa-induced motor complications and relatively intact cognition The motor symptoms of Parkinson’s disease (PD) are caused primarily by progressive degeneration of dopaminergic neurons in the substantia nigra The nonmotor symptoms of the disease are thought to be caused by degeneration of other neurotransmitter systems LEVODOPA — Dopamine itself cannot be used to treat PD because it does not cross the blood-brain barrier Levodopa, the immediate precursor of dopamine, is decarboxylated to dopamine in both the brain and peripheral tissues The combination of levodopa with carbidopa, a peripheral decarboxylase inhibitor, is the most effective treatment available for symptomatic relief of PD Limitations – For the first 2-5 years of treatment, levodopa produces a sustained response, but as the disease progresses, the duration of benefit from each dose becomes shorter (the “wearing-off” effect), and some patients develop sudden, unpredictable fluctuations between mobility and immobility (the “on-off” effect) After about 5-8 years, the majority of patients have motor fluctuations and dyskinesias (chorea, dystonia) As the disease progresses, levodoparesistant motor problems including difficulties with balance, gait, speech, and swallowing, and non-motor symptoms such as autonomic, cognitive, sleep, and psychiatric difficulties become more prominent Sudden discontinuation of levodopa or abrupt reduction in dosage can cause a severe return of parkinsonian symptoms Dosage – The half-life of levodopa when given with carbidopa is only 60-90 minutes The daily dosage range is usually 300-1500 mg of levodopa divided into to doses; some patients, such as those who develop “wearing-off” phenomena, may require more frequent or higher doses Foods high in protein may decrease the effectiveness of levodopa by competing with the drug for absorption from the intestine and transport across the blood-brain barrier Relatively complete inhibition of peripheral dopa decarboxylase requires 75-100 mg/day of carbidopa; some patients require doses of up to 200 mg/day Carbidopa (Lodosyn) is available alone as 25-mg tablets and can be added to carbidopa/levodopa Carbidopa/levodopa is available as immediate- and sustained-release tablets (Sinemet, Sinemet CR, and generics) and as orally disintegrating tablets (Parcopa) that can be taken without liquid.1 Although not FDA-approved, some clinicians have used “liquid” levodopa, crushed tablets dissolved in a carbonated beverage for rapid absorption, as rescue treatment for “off” episodes Sustained-release formulations may be beneficial for patients who have “wearing-off” phenomena, but they can be erratically absorbed and have a slower and less predictable onset of action than immediate-release for- Federal copyright law prohibits unauthorized reproduction by any means and imposes severe fines 101 Drugs for Parkinson’s Disease mulations Many patients must take a half or a whole immediate-release (IR) carbidopa/levodopa tablet concomitantly with sustained-release preparations, particularly with the first dose of the day Only about 70% of levodopa is absorbed from the sustainedrelease formulation; therefore, the dosage should be about 30% higher than that of the IR formulation to achieve a comparable effect Adverse Effects – In vitro, levodopa can be a potent neurotoxin and damage dopaminergic cells, but there is no convincing clinical evidence suggesting a toxic effect of the drug in patients with PD Peripheral adverse effects of levodopa, including anorexia, nausea, vomiting, and orthostatic hypotension, may be prominent during initiation of therapy With chronic therapy, somnolence, vivid dreams, hallucinations, delusions, confusion, and agitation can occur, especially in older patients with dementia Impulsive and hypersexual behavior have also been associated with levodopa therapy Strategy – Some expert clinicians prefer to start therapy with low doses of levodopa or a drug other than levodopa because of concerns about inducing early dyskinesias and wearing-off complications This strategy is used particularly in younger patients, who must live with PD for a longer period of time DOPAMINE AGONISTS — Dopamine agonists are less effective than levodopa in treating the motor symptoms of PD, but they may be less likely to cause dyskinesias or motor fluctuations Used as adjuncts to levodopa in advanced disease, they can reduce motor fluctuations and permit a reduction in levodopa dosage Two oral non-ergot dopamine agonists, pramipexole (Mirapex, and generics) and ropinirole (Requip, and generics), are widely used for treatment of both early (as monotherapy) and advanced disease (in combination with levodopa) Rotigotine (Neupro), another non-ergot dopamine agonist, is available in a transdermal formulation The ergot-derivative dopamine agonist bromocriptine (Parlodel, and generics) is still marketed for treatment of PD in the US; it has been reported to increase the risk of cardiac valve regurgitation.2,3 Effectiveness – All of these drugs are effective as monotherapy in early, mild disease, but most patients taking dopamine agonists require addition of levodopa within a few years of starting treatment.4 They are also effective when used as add-on treatment in patients with levodopa-induced motor fluctuations Dosage – Pramipexole should be started at 0.125 mg tid and gradually increased to 0.5 mg tid over >3 102 weeks Further increases should be slower The FDAapproved maximum daily dosage is 4.5 mg, but some studies have found no additional efficacy and an increase in adverse effects at doses higher than 1-1.5 mg/day Ropinirole should be started at 0.25 tid and slowly titrated upward by 0.25 mg or 0.5 mg per dose each week to or mg tid Many patients will need to continue gradually increasing the dose to a maximum of mg tid Both pramipexole and ropinirole are also available as controlled-release formulations that can be taken once daily Extended-release pramipexole (Mirapex ER) is usually started at a dose of 0.375 mg daily The dose is slowly titrated upward with weekly (or even slower) increases to 0.75 mg per day and then in increments of 0.75 mg up to a maximum of 4.5 mg per day The recommended initial dose of extended-release ropinirole (Requip XL, and generics) is mg once daily for 1-2 weeks The dose can be increased at weekly intervals by mg/day increments to a maximum daily dose of 24 mg The rotigotine transdermal patch is applied to intact hairless skin and changed every 24 hours; the usual starting dose is mg/24 hours for early-stage disease and mg/24 hours for advanced disease The dose can be increased by mg/24 hours weekly to a target dose of 4-6 mg/24 hours for early-stage and 6-8 mg/24 hours for advanced-stage PD As the dosage of the dopamine agonist increases, levodopa dosage may have to be reduced Adverse Effects – Dopamine agonists can cause nausea, somnolence, lower-extremity edema, hallucinations, and postural hypotension, which may limit their use In a controlled trial of pramipexole vs levodopa for initial therapy, pramipexole caused a higher incidence of somnolence, edema, and hallucinations than levodopa.5 Sudden somnolence can occur with dopamine agonists alone or in combination with levodopa Rather than sacrifice motor performance by reducing the dose or eliminating the dopamine agonist, some expert clinicians treat excessive daytime sleepiness with modafinil (Provigil, and generics) 200 mg once/day after breakfast (not FDA-approved for this indication) Dopamine agonists, used alone or in low doses, can cause confusion and psychosis, particularly in elderly patients They should generally not be used in patients with dementia Pathologic gambling, compulsive shopping, binge eating, hypersexuality, and compulsive repetitive behaviors can occur with use of dopamine agonists.6,7 The behavioral problems usual- Treatment Guidelines from The Medical Letter • Vol 11 ( Issue 135) • November 2013 Drugs for Parkinson’s Disease Table Some Drugs for Parkinson’s Disease Drug Carbidopa/Levodopa immediate-release – generic Sinemet (Merck) orally disintegrating – generic Parcopa (Schwarz) sustained-release – generic Sinemet CR (Merck) Dopamine Agonists Oral Bromocriptine – generic Parlodel (Novartis) Pramipexole – generic Mirapex (Boehringer-Ingelheim) extended-release – Mirapex ER Ropinirole – generic Requip (GSK) extended-release – generic Requip XL Transdermal Rotigotine – Neupro (UCB) Subcutaneous Apomorphine – Apokyn (Ipsen) COMT Inhibitors Entacapone7 – generic Comtan (Novartis) Tolcapone – Tasmar (Valeant) MAO-B Inhibitors Rasagiline – generic Azilect (Teva) Selegiline – generic Eldepryl (Somerset) orally disintegrating – Zelapar (Valeant) Other Drugs Amantadine – generic Carbidopa – Lodosyn (Aton) Some Available Formulations Usual Daily Dosage1 Cost2 10/100 mg, 25/100 mg, 25/250 mg tabs 10/100 mg, 25/100 mg, 25/250 mg orally disintegrating tabs 25/100 mg, 50/200 mg tabs 300-1500 mg levodopa, divided 300-1500 mg levodopa, divided 400-1600 mg levodopa, divided $38.00 80.00 69.00 244.00 288.00 519.00 2.5 mg tabs, mg caps 15-45 mg divided bid or tid 0.5-1.5 mg tid 497.00 806.00 16.00 402.00 371.00 0.125, 0.25, 0.5, 0.75, 1, 1.5 mg tabs 0.375, 0.75, 1.5, 2.25, 3, 3.75, 4.5 mg tabs 0.25, 0.5, 1, 2, 3, 4, mg tabs 2, 4, 6, 8, 12 mg tabs 1.5-4.5 mg daily 3-8 mg tid 8-24 mg daily 47.00 292.00 195.00 228.00 1, 2, 3, 4, 6, mg/24 hr patch3 4-8 mg/24 hr patch4 450.00 30 mg/3 mL cartridges 2-6 mg SC 3-5x/day prn5 995.006 200 mg tabs 200 mg tid or qid8 100 mg tabs 100 mg tid9 0.5, mg tabs 0.5-1 mg daily10 mg tabs, caps mg caps mg bid with breakfast and lunch 536.0011 435.00 103.00 200.00 1.25 mg orally disintegrating tabs 1.25 to 2.5 mg in the morning 355.00 100 mg caps; 100 mg tabs; 50 mg/5 mL syrup 25 mg tabs 100 mg bid 25 mg tid or 285.00 379.00 1450.00 96.00 qid12 400.00 Dosage adjustment may be needed for renal or hepatic impairment Approximate wholesale acquisition cost (WAC) of 30 days’ treatment with the lowest recommended dosage Source: $ource® Monthly (Selected from FDB MedKnowledge™) October 5, 2013 Reprinted with permission by FDB, Inc All rights reserved ©2013 www.fdbhealth.com/policies/drug-pricing-policy Actual retail prices may be higher The mg/24 hour formulation is not FDA-approved for Parkinson’s disease Usual dose is 4-6 mg/day for early-stage disease and 6-8 mg/day for advanced-stage disease Should be administered with an antiemetic such as trimethobenzamide Cost of one 3-mL cartridge Also available in a fixed-dose combination (Stalevo) with carbidopa/levodopa Entacapone should always be administered with each dose of carbidopa/levodopa (max tabs/day) Tolcapone does not need to be taken at the same time as carbidopa/levodopa Discontinue within weeks if no clinical benefit 10 Dose is mg as monotherapy and 0.5-1 mg when given with carbidopa/levodopa 11 Cost according to a local CVS pharmacy 12 Dosage for individual titration of levodopa and carbidopa Dosage for patients who need additional carbidopa is 25 mg once/day; additional doses may be needed ly improve or disappear when the dose is reduced or the drug is discontinued Application site reactions and nail dyschromia have occurred with rotigotine.8 Peripheral dopaminergic side effects such as nausea can be blocked by trimethobenzamide (Tigan, and generics), or possibly ondansetron (Zofran, and generics) Ergot-type effects, such as erythromelalgia, edema, pain, and digital spasms in the extremities, occur rarely with bromocriptine Pleural effusions causing sudden onset of shortness of breath and/or cough, which have occurred rarely with bromocriptine, are reversible if the drug is stopped, but fibrotic pulmonary changes and retroperitoneal fibrosis can occur An Injectable Dopamine Agonist – Apomorphine (Apokyn), a potent non-ergot dopamine agonist, is FDAapproved for acute intermittent treatment of hypomobility (“off” episodes) in patients with advanced PD.9 Administered subcutaneously, it can cause emesis and must be taken with an antiemetic Trimethobenzamide (300 mg tid) should be started days before starting apomorphine and continued for the first months or until tolerance develops Serotonin receptor antagonists such as ondansetron are contraindicated for use with Treatment Guidelines from The Medical Letter • Vol 11 ( Issue 135) • November 2013 103 Drugs for Parkinson’s Disease apomorphine because the combination can cause severe hypotension with loss of consciousness Injection-site reactions can occur, generally in the form of subcutaneous nodules Like oral dopamine agonists, apomorphine can cause nausea, orthostatic hypotension, dyskinesias, confusion, hallucinations, and psychosis Yawning and drowsiness are common Hypersexuality and increased erections can occur and have been associated with abuse of the drug COMT INHIBITORS — Levodopa is metabolized in the periphery by dopa decarboxylase and catechol-Omethyltransferase (COMT) Used in combination with levodopa, drugs that inhibit peripheral or intestinal activity of COMT prolong the half-life of levodopa (without affecting peak serum concentrations) and decrease parkinsonian disability The combination can, however, increase dyskinesias; a reduction in levodopa dosage may be required for control Entacapone (Comtan, and generics) acts peripherally and has been effective in improving “off” time, motor scores, and levodopa requirements in patients with motor fluctuations It is available both alone and as a carbidopa/levodopa/entacapone combination (Stalevo, and generics) Tolcapone (Tasmar), a more potent COMT inhibitor, has been associated with fatal hepatotoxicity and was taken off the market in Canada, but is available in the US for use in patients who have not responded to entacapone.10,11 Dosage – The usual dosage of entacapone is 200 mg tid or qid (maximum of times/day) It has a short half-life and must be taken with each dose of levodopa/carbidopa The initial dosage of tolcapone is 100 mg tid, which can be increased to a maximum of 200 mg tid, and does not need to be taken at the same time as levodopa Tolcapone should be stopped if there is no benefit within weeks of starting therapy Adverse Effects – Dyskinesias, nausea, diarrhea (worse with tolcapone), and urine discoloration can occur with both COMT inhibitors Serious hepatotoxicity has not been reported with entacapone Use of tolcapone requires written informed consent and hepatic monitoring every 2-4 weeks for the first months and periodically thereafter Since these drugs are used in combination with levodopa, the levodopa dose may have to be reduced in patients who develop dyskinesias, nausea, or hallucinations Increased daytime sleepiness and sleep attacks have been reported with both entacapone and tolcapone MAO-B INHIBITORS — Selegiline (Eldepryl, and others), an irreversible inhibitor of monoamine oxi- 104 dase type B (MAO-B), inhibits catabolism of dopamine in the brain Selegiline’s effect on symptoms is modest, but used as monotherapy in early disease (not an FDA-approved indication), it can delay initiation of levodopa treatment Used in addition to levodopa in advanced disease, it can permit use of lower doses of levodopa Selegiline is available as a conventional tablet or capsule and in a lower-dose orally-disintegrating tablet formulation (Zelapar) Use of the orally-disintegrating tablet formulation, which is absorbed through the oral mucosa, minimizes first-pass metabolism, increasing bioavailability and reducing serum concentrations of amphetamine metabolites Rasagiline (Azilect, and generics), the second irreversible MAO-B inhibitor approved for treatment of PD, also appears to be modestly effective when taken alone for early disease or in addition to carbidopa/levodopa for advanced disease.12,13 Rasagiline administered early in the course of the disease (off-label) may help delay its progression In a double-blind, delayed-start trial of rasagiline, patients receiving mg daily of the drug had significantly less disability after 72 weeks than those who received placebo, but those receiving 2-mg doses did not.14 In advanced disease, improvement in “off” time is similar to that with entacapone.15 Dosage – The initial dosage of Zelapar is 1.25 mg in the morning Patients should not eat or drink for minutes before or after taking the drug After weeks, the dose can be increased to a maximum of 2.5 mg once per day The initial dosage of the conventional formulation is mg once daily with breakfast, which can be increased to mg with breakfast and with lunch The initial dosage of rasagiline is mg once daily as monotherapy and 0.5 mg once daily as an adjunct to levodopa Adverse Effects – Nausea and orthostatic hypotension can occur with use of MAO-B inhibitors Unlike MAO-A inhibitors used for treatment of depression, MAO-B inhibitors at recommended doses generally not cause hypertension after ingestion of tyraminerich foods or with concomitant levodopa therapy Nevertheless, some manufacturers recommend dietary restrictions Combined use of MAO-B inhibitors and tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), or meperidine (Demerol, and generics) has rarely resulted in severe toxicity Their package inserts also advise against concurrent use of dextromethorphan, propoxyphene, tramadol, and methadone MAO-B inhibitors can increase levodopa adverse effects, particularly dyskinesias and psychosis in elderly patients Treatment Guidelines from The Medical Letter • Vol 11 ( Issue 135) • November 2013 Drugs for Parkinson’s Disease AMANTADINE — Amantadine, an antiviral drug, acts as an antagonist at N-methyl-D-aspartate (NMDA) receptors Its precise mechanism of action in PD is unknown It has been used alone to treat early PD or as an adjunct in later stages, usually in patients with levodopa-induced dyskinesias Amantadine may be effective in controlling tremor, which is often resistant to dopaminergic treatment In some patients, however, the symptomatic benefit of amantadine can last only a few weeks Amantadine is started at a dose of 100 mg once daily, which can be increased to 100 mg times daily Nausea, dizziness, insomnia, confusion, hallucinations, peripheral edema, and livedo reticularis can occur High serum concentrations of amantadine can cause severe psychosis, particularly in the elderly Amantadine and anticholinergics may have additive adverse effects on mental function Sudden withdrawal of amantadine may cause severe exacerbation of parkinsonian symptoms or neuroleptic malignant syndrome and acute delirium ANTICHOLINERGICS — Anticholinergics, which include trihexyphenidyl and benztropine (Cogentin, and generics), can be useful in some patients with PD, especially for treatment of tremor and drooling Adverse effects include dry mouth, constipation, urinary retention, and aggravation of narrow-angle glaucoma Central nervous system adverse effects, including impaired memory, confusion, and hallucinations, may be particularly severe in elderly patients; anticholinergics are generally contraindicated in this age group Abrupt discontinuation of any of these drugs can cause severe exacerbation of symptoms SURGICAL TREATMENT — Surgical ablation or deep brain stimulation (DBS) has generally been recommended for patients with advanced PD and intolerable dyskinesias or motor fluctuations on levodopa, although recently DBS has also been tried in some patients with early motor complications.16 Appropriate candidates for surgery are those whose cognition is relatively intact, who are not depressed, and who have no medical contraindications Deep Brain Stimulation – High-frequency electrical stimulation of the subthalamic nucleus or globus pallidus from implanted electrodes has largely supplanted ablative surgical procedures and is now the surgical treatment of choice for PD.17 A trial comparing bilateral subthalamic to bilateral pallidal DBS in 299 patients with advanced PD found that both procedures resulted in similar improvements in motor function at 24 months.18 In a randomized trial in 255 patients with advanced PD and motor complications, subjects who underwent bilateral DBS of the subthalamic nucleus or globus pallidus had improved motor function, com- pared to subjects treated with medical therapy.19 A 2year randomized trial (EARLYSTIM) in 251 patients 18-60 years old with Parkinson’s disease >4 years and fluctuations or dyskinesias for 70 years old TREATMENT OF DEPRESSION — Depression commonly accompanies PD and must be treated if the patient is to benefit adequately from antiparkinson drugs Tricyclic antidepressants, especially nortriptyline, may be more effective than SSRIs, but they can cause cognitive impairment and increase the risk of falls.21 Antidepressants may also help the sleep abnormalities commonly associated with PD Electroconvulsive therapy (ECT) may alleviate refractory major depression and transiently improve the underlying parkinsonian symptoms TREATMENT OF PSYCHOSIS — Clozapine (Clozaril, and generics) is particularly useful in controlling psychosis associated with levodopa or dopamine agonists Drowsiness is a common adverse effect Clozapine has caused agranulocytosis in 0.6% of patients; blood counts should be obtained weekly for the first six months, and biweekly thereafter Quetiapine (Seroquel, and generics) is another antipsychotic drug often used for this indication It does not cause agranulocytosis and does not have anticholinergic effects Like clozapine, quetiapine can cause drowsiness Treatment Guidelines from The Medical Letter • Vol 11 ( Issue 135) • November 2013 105 Drugs for Parkinson’s Disease TREATMENT OF DEMENTIA — The oral acetylcholinesterase inhibitors donepezil (Aricept, and generics), rivastigmine (Exelon, and generics), and galantamine (Razadyne, and generics) used to treat Alzheimer’s disease may be useful in treating cognitive and behaviorial symptoms in PD patients, but may worsen tremor in some.22 Of these, only rivastigmine is FDA-approved for treatment of dementia in PD.23Memantine (Namenda), an NMDA-receptor antagonist, is another drug used to treat dementia;24 it may be helpful for cognitive impairment and potentially for an antiparkinson effect, but it may also aggravate parkinsonian symptoms Parcopa: a rapidly dissolving formulation of carbidopa/levodopa Med Lett Drugs Ther 2005; 47:12 R Schade et al Dopamine agonists and the risk of cardiac-valve regurgitation N Engl J Med 2007; 356:29 R Zanettini et al Valvular heart disease and the use of dopamine agonists for Parkinson’s disease N Engl J Med 2007; 356:39 JG Nutt and GF Wooten Clinical practice Diagnosis and initial management of Parkinson’s disease N Engl J Med 2005; 353:1021 KM Biglan et al Risk factors for somnolence, edema, and hallucinations in early Parkinson disease Neurology 2007; 69:187 D Weintraub et al Impulse control disorders in Parkinson disease: a cross-sectional study of 3090 patients Arch Neurol 2010; 67:589 V Voon et al Impulse control disorders in Parkinson disease: a multicenter case-control study Ann Neurol 2011; 69:986 HA Teive and RP Munhoz Rotigotine-induced nail dyschromia in a patient with Parkinson’s disease Neurology 2011; 76:1605 Apomorphine (Apokyn) for advanced Parkinson’s disease Med Lett Drugs Ther 2005; 47:7 10 SZ Marsala et al A systematic review of catechol-O-methyltransferase inhibitors: efficacy and safety in clinical practice Clin Neuropharmacol 2012; 35:185 11 Entacapone to Tolcapone Switch Study Investigators Entacapone to tolcapone switch: Multicenter double-blind, randomized, active-controlled trial in advanced Parkinson’s disease Mov Disord 2007; 22:14 12 Rasagiline (Azilect) for Parkinson’s disease Med Lett Drugs Ther 2006; 48:97 13 LW Elmer Rasagiline adjunct therapy in patients with Parkinson’s disease: post hoc analyses of the PRESTO and LARGO trials Parkinsonism Relat Disord July 9, 2013 (epub) 14 CW Olanow et al ADAGIO Study Investigators: A double-blind, delayed-start trial of rasagiline in Parkinson’s disease N Engl J Med 2009; 361:1268 15 O Rascol et al Rasagiline as an adjunct to levodopa in patients with Parkinson’s disease and motor fluctuations (LARGO, Lasting effect in Adjunct therapy with Rasagiline Given Once daily, study): a randomised, double-blind, parallel-group trial Lancet 2005; 365:947 16 Deep brain stimulation for Parkinson’s disease Med Lett Drugs Ther 2013; 55:81 17 MS Okun Deep-brain stimulation for Parkinson’s disease N Engl J Med 2012; 367:1529 18 KA Follett et al Pallidal versus subthalamic deep-brain stimulation for Parkinson’s disease N Engl J Med 2010; 362:2077 19 FM Weaver et al Bilateral deep brain stimulation vs best medical therapy for patients with advanced Parkinson disease: a randomized controlled trial JAMA 2009; 301:63 20 WM Schuepach et al Neurostimulation for Parkinson’s disease with early motor complications N Engl J Med 2013; 368:610 21 M Menza et al A controlled trial of antidepressants in patients with Parkinson disease and depression Neurology 2009; 72:886 22 M Emre et al Rivastigmine for dementia associated with Parkinson’s disease N Engl J Med 2004; 351:2509 23 Drugs for cognitive loss and dementia Treat Guidel Med Lett 2013; 11:95 24 Memantine for Alzheimer’s disease Med Lett Drugs Ther 2003; 45:73 106 Coming Soon in Treatment Guidelines: Drugs for Migraine – December 2013 Drugs for HIV Infection – January 2014 Follow us on Twitter @MedicalLetter Treatment Guidelines ® from The Medical Letter EDITOR IN CHIEF: Mark Abramowicz, M.D EXECUTIVE EDITOR: Gianna Zuccotti, M.D., M.P.H., F.A.C.P., Harvard Medical School EDITOR: Jean-Marie Pflomm, Pharm.D ASSISTANT EDITORS, DRUG INFORMATION: Susan M Daron, 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program content includes current information and unbiased reviews of FDA-approved and off-label uses of drugs, their mechanisms of action, clinical trials, dosage and administration, adverse effects and drug interactions The Medical Letter delivers educational content in the form of self-study material The expected outcome of the CME Program is to increase the participant’s ability to know, or apply knowledge into practice after assimilating, information presented in materials contained in Treatment Guidelines The Medical Letter will strive to continually improve the CME program through periodic assessment of the program and activities The Medical Letter aims to be a leader in supporting the professional development of healthcare professionals through Core Competencies by providing continuing medical education that is unbiased and free of industry influence The Medical Letter is supported solely by subscription fees and accepts no advertising, grants or donations GOAL: Through this program, The Medical Letter expects to provide the healthcare community with unbiased, reliable and timely educational content that they will use to make independent and informed therapeutic choices in their practice LEARNING OBJECTIVES: The objective of this activity is to meet the need of healthcare professionals for unbiased, reliable and timely information on treatment of major diseases The Medical Letter expects to provide the healthcare community with educational content that they will use to make independent and informed therapeutic choices in their practice Participants will be able to select and prescribe, or confirm the appropriateness of the prescribed usage of the drugs and other therapeutic modalities discussed in Treatment Guidelines with specific attention to clinical evidence of effectiveness, adverse effects and patient management Upon completion of this program, the participant will be able to: Explain the current approach to the management of Parkinson's disease Discuss the pharmacologic options available for treatment of Parkinson's disease and compare them based on their efficacy, dosage and administration, potential adverse effects, and drug interactions Determine the most appropriate therapy given the clinical presentation of an individual patient Privacy and Confidentiality: The Medical Letter guarantees our firm commitment to your privacy We not sell any of your information Secure server software (SSL) is used for commerce transactions through VeriSign, Inc No credit card information is stored IT Requirements: Windows 98/NT/2000/XP/Vista/7/8, Pentium+ processor, Mac OS X+ w/ compatible processor; Microsoft IE 6.0+, Mozilla Firefox 2.0+ or any other compatible Web browser Dial-up/high-speed connection Have any questions? Call us at 800-211-2769 or 914-235-0500 or e-mail us at: custserv@medicalletter.org Questions start on next page Treatment Guidelines from The Medical Letter • Vol 11 ( Issue 135) • November 2013 DO NOT FAX OR MAIL THIS EXAM To take CME exams and earn credit, go to: medicalletter.org/CMEstatus Issue 135 Questions Which of the following is the most effective treatment for symptomatic relief of Parkinson’s disease? a entacapone b selegiline c carbidopa/levodopa d pramipexole Monamine oxidase type B (MAO-B) inhibitors: a increase catabolism of dopamine in the brain b can delay initiation of levodopa therapy c cause hypertension after ingestion of tyramine-rich foods d prevent dyskinesias in patients taking levodopa Which of the following dopamine agonists is available as a transdermal formulation? a rotigotine b bromocriptine c ropinirole d pramipexole A 75-year-old man taking carbidopa/levodopa for Parkinson’s disease complains of drooling Which of the following drugs would be a reasonable choice for treatment of drooling for this patient? a selegiline b apomorphine c benztropine d tolcapone Use of which of the following drugs has been associated with cardiac-valve regurgitation? a carbidopa/levodopa b pramipexole c ropinirole d bromocriptine A 72-year-old woman with Parkinson’s disease has been taking pramipexole for several months Her daughter noticed that she is exhibiting some compulsive behaviors recently and is concerned that her disease is getting worse Which of the following would you tell her? a compulsive behaviors are a common adverse effect of dopamine agonists such as pramipexole b behavioral problems usually improve when the dose of pramipexole is reduced c behavioral problems usually improve when pramipexole is stopped d all of the above Which of the following dopamine agonists should be taken with an antiemetic? a apomorphine b pramipexole c ropinirole d rotigotine Catechol-O-methyltransferase (COMT) inhibitors used in combination with levodopa can: a increase dyskinesias b decrease dyskinesias c increase peak serum concentrations of levodopa d increase levodopa dosage requirements A 71-year-old woman taking carbidopa/levodopa and ropinirole for Parkinson’s disease complains that her medications are not controlling her tremor Which of the following drugs would you recommend for this patient? a selegiline b amantadine c entacapone d tolcapone 10 Anticholinergics can cause: a dry mouth b constipation c urinary retention d all of the above 11 Surgical ablation or deep brain stimulation has generally been reserved for patients on carbidopa/levodopa with: a intolerable dyskinesias b motor flucuations c advanced Parkinson’s disease d all of the above 12 Which of the following acetylcholinesterase inhibitors is approved for the treatment of dementia in Parkinson’s disease? a donepezil b rivastigmine c memantine d galantamine ACPE UPN: 0379-0000-13-135-H01-P; Release: October 2013, Expire: October 2014 Treatment Guidelines from The Medical Letter • Vol 11 ( Issue 135) • November 2013 ... Table Some Drugs for Parkinson’s Disease Page 103 Drugs for Parkinson’s Disease Related article(s) since publication Levodopa combined with carbidopa is still the most effective treatment for symptoms... may be higher The mg/24 hour formulation is not FDA-approved for Parkinson’s disease Usual dose is 4-6 mg/day for early-stage disease and 6-8 mg/day for advanced-stage disease Should be administered... Guidelines from The Medical Letter • Vol 11 ( Issue 135) • November 2013 Drugs for Parkinson’s Disease Table Some Drugs for Parkinson’s Disease Drug Carbidopa/Levodopa immediate-release – generic Sinemet