Drugs for parkinsons disease

Some Drugs for Parkinson’s Disease Page 103 Treatment Guidelines Published by The Medical Letter, Inc.. Dopamine agonists, the next most effective class of drugs, can be used alone befor

Treatment Guidelines

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Drugs for Parkinson’s Disease p 101

Drugs for Parkinson’s Disease

Table

1 Some Drugs for Parkinson’s Disease Page 103

Treatment Guidelines

Published by The Medical Letter, Inc • 145 Huguenot Street, New Rochelle, NY 10801 • A Nonprofit Publication

Volume 11 (Issue 135) November 2013

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The motor symptoms of Parkinson’s disease (PD) are

caused primarily by progressive degeneration of

dopaminergic neurons in the substantia nigra The

non-motor 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

barri-er 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

fluctua-tions 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, levodopa-resistant 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 reduc-tion in dosage can cause a severe return of parkin-sonian 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

3 to 6 doses; some patients, such as those who

devel-op “wearing-off” phenomena, may require more fre-quent 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.1Although not FDA-approved, some clinicians have used “liq-uid” levodopa, crushed tablets dissolved in a carbon-ated 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-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

intro-duction 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

relative-ly intact cognition

For further information call: 800-211-2769

Related article(s) since publication

Drugs for Parkinson’s Disease

Treatment Guidelines from The Medical Letter • Vol 11 ( Issue 135) • November 2013

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

sustained-release 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,

halluci-nations, 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 FDA-approved 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 3 or 4 mg tid Many patients will need to continue gradually increasing the dose to a maximum

of 8 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 rec-ommended initial dose of extended-release ropinirole

(Requip XL, and generics) is 2 mg once daily for 1-2

weeks The dose can be increased at weekly intervals

by 2 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 2 mg/24 hours for early-stage disease and 4 mg/24 hours for advanced disease The dose can

be increased by 2 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, halluci-nations, 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 halluci-nations than levodopa.5Sudden 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

sleepi-ness 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, com-pulsive shopping, binge eating, hypersexuality, and compulsive repetitive behaviors can occur with use of dopamine agonists.6,7The behavioral problems

usual-ly improve or disappear when the dose is reduced or

the drug is discontinued

Peripheral dopaminergic side effects such as nausea

can be blocked by trimethobenzamide (Tigan, and

generics), or possibly ondansetron (Zofran, and

gener-ics) 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

pul-monary changes and retroperitoneal fibrosis can occur

Application site reactions and nail dyschromia have occurred with rotigotine.8

An Injectable Dopamine Agonist – Apomorphine

(Apokyn), a potent non-ergot dopamine agonist, is

FDA-approved for acute intermittent treatment of hypomobil-ity (“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 3 days before starting apomorphine and continued for the first 2 months or until tolerance develops Serotonin receptor antagonists such as ondansetron are contraindicated for use with

Drug Some Available Formulations Usual Daily Dosage 1 Cost 2

Carbidopa/Levodopa

immediate-release – generic 10/100 mg, 25/100 mg, 300-1500 mg levodopa, $38.00

orally disintegrating – generic 10/100 mg, 25/100 mg, 25/250 mg 300-1500 mg levodopa, 69.00

sustained-release – generic 25/100 mg, 50/200 mg tabs 400-1600 mg levodopa, 288.00

Dopamine Agonists

Oral

Bromocriptine – generic 2.5 mg tabs, 5 mg caps 15-45 mg divided 497.00

Pramipexole – generic 0.125, 0.25, 0.5, 0.75, 1, 0.5-1.5 mg tid 16.00

extended-release – Mirapex ER 0.375, 0.75, 1.5, 2.25, 3, 1.5-4.5 mg daily 371.00

3.75, 4.5 mg tabs

extended-release – generic 2, 4, 6, 8, 12 mg tabs 8-24 mg daily 195.00

Transdermal

Rotigotine – Neupro (UCB) 1, 2, 3, 4, 6, 8 mg/24 hr patch 3 4-8 mg/24 hr patch 4 450.00

Subcutaneous

Apomorphine – Apokyn (Ipsen) 30 mg/3 mL cartridges 2-6 mg SC 3-5x/day prn 5 995.00 6

COMT Inhibitors

MAO-B Inhibitors

Selegiline – generic 5 mg tabs, caps 5 mg bid with breakfast 103.00

orally disintegrating –

Zelapar (Valeant) 1.25 mg orally disintegrating tabs 1.25 to 2.5 mg in the morning 355.00

Other Drugs

50 mg/5 mL syrup

1 Dosage adjustment may be needed for renal or hepatic impairment.

2 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.

3 The 1 mg/24 hour formulation is not FDA-approved for Parkinson’s disease.

4 Usual dose is 4-6 mg/day for early-stage disease and 6-8 mg/day for advanced-stage disease.

5 Should be administered with an antiemetic such as trimethobenzamide.

6 Cost of one 3-mL cartridge.

7 Also available in a fixed-dose combination (Stalevo) with carbidopa/levodopa.

8 Entacapone should always be administered with each dose of carbidopa/levodopa (max 8 tabs/day).

9 Tolcapone does not need to be taken at the same time as carbidopa/levodopa Discontinue within 3 weeks if no clinical benefit.

10 Dose is 1 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.

Table 1 Some Drugs for Parkinson’s Disease

Drugs for Parkinson’s Disease

Treatment Guidelines from The Medical Letter • Vol 11 ( Issue 135) • November 2013

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

hypoten-sion, dyskinesias, confuhypoten-sion, hallucinations, and

psy-chosis 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-O-methyltransferase (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

hepa-totoxicity 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 8 times/day) It has a short

half-life and must be taken with each dose of

lev-odopa/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 3 weeks of starting therapy

Adverse Effects – Dyskinesias, nausea, diarrhea

(worse with tolcapone), and urine discoloration can

occur with both COMT inhibitors Serious

hepatotoxi-city has not been reported with entacapone Use of

tolcapone requires written informed consent and

hepatic monitoring every 2-4 weeks for the first 6

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

day-time 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 symp-toms is modest, but used as monotherapy in early dis-ease (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, mini-mizes first-pass metabolism, increasing

bioavailabili-ty and reducing serum concentrations of ampheta-mine 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 dis-ease (off-label) may help delay its progression In a double-blind, delayed-start trial of rasagiline, patients receiving 1 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 5

minutes before or after taking the drug After 6 weeks,

the dose can be increased to a maximum of 2.5 mg once per day The initial dosage of the conventional formulation is 5 mg once daily with breakfast, which can be increased to 5 mg with breakfast and with lunch The initial dosage of rasagiline is 1 mg once daily as monotherapy and 0.5 mg once daily as an adjunct to levodopa

Adverse Effects – Nausea and orthostatic

hypoten-sion can occur with use of MAO-B inhibitors Unlike MAO-A inhibitors used for treatment of depression, MAO-B inhibitors at recommended doses generally

do not cause hypertension after ingestion of tyramine-rich 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

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

resist-ant to dopaminergic treatment In some patients,

how-ever, 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

3 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

withdraw-al of amantadine may cause severe exacerbation of

parkinsonian symptoms or neuroleptic malignant

syn-drome 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,

uri-nary retention, and aggravation of narrow-angle

glau-coma Central nervous system adverse effects,

includ-ing impaired memory, confusion, and hallucinations,

may be particularly severe in elderly patients;

anti-cholinergics 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

levo-dopa, 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

pal-lidus from implanted electrodes has largely supplanted

ablative surgical procedures and is now the surgical

treatment of choice for PD.17A trial comparing

bilat-eral subthalamic to bilatbilat-eral pallidal DBS in 299

patients with advanced PD found that both procedures

resulted in similar improvements in motor function at

24 months.18In 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.19A 2-year randomized trial (EARLYSTIM) in 251 patients 18-60 years old with Parkinson’s disease >4 years and fluctuations or dyskinesias for <3 years compared bilateral subthalamic neurostimulation plus medical therapy to medical therapy alone; neurostimulation was significantly superior to medical therapy alone in improving quality of life (the primary endpoint) and motor function.16,20

After DBS, reductions in levodopa dosage may be maintained for several years In general, treated patients show marked improvement in off-medication motor function and improvement in dyskinesias when taking medication Some symptoms, such as speech disturbances, postural instability, freezing of gait, and cognitive problems, do not improve with the procedure and may continue to worsen

Adverse Effects – Adverse effects of DBS have

included intracranial hemorrhage, hemiparesis, infec-tion, confusion, attention/cognitive deficits, dysarthria, depression, and death Even with successful surgery, decreased verbal fluency and a variety of psychosocial problems have occurred Hardware problems, includ-ing lead migration, fracture, or malfunction, can also occur Cognitive decline is common after DBS in patients with pre-existing intellectual impairment and

in those >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 nortripty-line, 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 refrac-tory major depression and transiently improve the underlying parkinsonian symptoms

TREATMENT OF PSYCHOSIS — Clozapine

(Clozaril, and generics) is particularly useful in

con-trolling 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

antipsy-chotic drug often used for this indication It does not cause agranulocytosis and does not have anticholiner-gic effects Like clozapine, quetiapine can cause drowsiness

Treatment Guidelines from The Medical Letter • Vol 11 ( Issue 135) • November 2013

106

Drugs for Parkinson’s Disease

TREATMENT OF DEMENTIA — The oral

acetyl-cholinesterase 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

cogni-tive 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;24it

may be helpful for cognitive impairment and

poten-tially for an antiparkinson effect, but it may also

aggravate parkinsonian symptoms

1 Parcopa: a rapidly dissolving formulation of carbidopa/levodopa Med

Lett Drugs Ther 2005; 47:12.

2 R Schade et al Dopamine agonists and the risk of cardiac-valve

regur-gitation N Engl J Med 2007; 356:29.

3 R Zanettini et al Valvular heart disease and the use of dopamine

ago-nists for Parkinson’s disease N Engl J Med 2007; 356:39.

4 JG Nutt and GF Wooten Clinical practice Diagnosis and initial

man-agement of Parkinson’s disease N Engl J Med 2005; 353:1021.

5 KM Biglan et al Risk factors for somnolence, edema, and

hallucina-tions in early Parkinson disease Neurology 2007; 69:187.

6 D Weintraub et al Impulse control disorders in Parkinson disease: a

cross-sectional study of 3090 patients Arch Neurol 2010; 67:589.

7 V Voon et al Impulse control disorders in Parkinson disease: a

multi-center case-control study Ann Neurol 2011; 69:986.

8 HA Teive and RP Munhoz Rotigotine-induced nail dyschromia in a

patient with Parkinson’s disease Neurology 2011; 76:1605.

9 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-con-trolled 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

dis-ease: 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

ran-domised, 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

ther-apy for patients with advanced Parkinson disease: a randomized

con-trolled 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.

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Copyright 2013 ISSN 1541-2792

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, Pharm.D., Corinne Z Morrison, Pharm.D., Michael P Viscusi, Pharm.D.

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Carl W Bazil, M.D., Ph.D., Columbia University College of Physicians and Surgeons Vanessa K Dalton, M.D., M.P.H., University of Michigan Medical School Eric J Epstein, M.D., Albert Einstein College of Medicine

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1 Explain the current approach to the management of Parkinson's disease.

2 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.

3 Determine the most appropriate therapy given the clinical presentation of an individual patient.

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Treatment Guidelines from The Medical Letter • Vol 11 ( Issue 135) • November 2013

1 Which of the following is the most effective treatment for

sympto-matic relief of Parkinson’s disease?

a entacapone

b selegiline

c carbidopa/levodopa

d pramipexole

2 Which of the following dopamine agonists is available as a

trans-dermal formulation?

a rotigotine

b bromocriptine

c ropinirole

d pramipexole

3 Use of which of the following drugs has been associated with

cardiac-valve regurgitation?

a carbidopa/levodopa

b pramipexole

c ropinirole

d bromocriptine

4 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

5 Which of the following dopamine agonists should be taken with an

antiemetic?

a apomorphine

b pramipexole

c ropinirole

d rotigotine

6 Catechol-O-methyltransferase (COMT) inhibitors used in

combina-tion with levodopa can:

a increase dyskinesias

b decrease dyskinesias

c increase peak serum concentrations of levodopa

d increase levodopa dosage requirements

7 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

8 A 75-year-old man taking carbidopa/levodopa for Parkinson’s dis-ease 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

9 A 71-year-old woman taking carbidopa/levodopa and ropinirole for Parkinson’s disease complains that her medications are not con-trolling her tremor Which of the following drugs would you recom-mend 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

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Issue 135 Questions

ACPE UPN: 0379-0000-13-135-H01-P; Release: October 2013, Expire: October 2014