supplcp narcolepsy

8/8/2019 SupplCP Narcolepsy

http://slidepdf.com/reader/full/supplcp-narcolepsy 1/16

Dcbr 2007

Understanding,

diagnosing, and successfully

managing narcolepsy

FREE 1.5 CME CREDITS

Stay

Marc L. Gordon, MD

Paul P. Doghramji, MD, FAAFP

Joseph A. Lieberman III, MD, MPH

awake!

supplement to

Avaab a www.crrentpschiatr.c



S Dcbr 2007 n s Crrent Pschiatr

Credit hors: 1.5

Certifcation: CME

Release date: Decembe 2007

Expiration date: Decembe 2008

Target adience: Psciatists and pima cae clinicians

Overvie: Nacoleps is a conic, neuologic sleep disodeesulting om te dsegulation o sleep-ake ccles. Altougte exact etiolog o nacoleps is still unknon, clinical un-destanding o te undeling causes as ell as te teatmentoptions ave inceased in te last decade. Tis supplement illevie te epidemiolog, diagnosis, patopsiolog, pama-

colog, and teatment stategies o nacoleps, and is intendedto povide a cuent, evidence-based examination o nacoleps.

Learning Objectives:

Ate completing te CME activit, paticipants sould:• Descibe te clinical and diagnostic eatues o nacoleps• Evaluate te similaities and dieences beteen nacoleps

and ote sleep disodes elated to ote psciatic o medi-cal diagnoses

• Explain te neuobiological mecanisms tat cuentl ae be-lieved to bing about nacoleps and cataplex

• Dieentiate te pamacologic management o cataplex andexcessive datime sleepiness and explain nacoleps isteated smptomaticall

accreditatiOn and designatiOn:

Te Catam Institute is accedited b te Acceditation Coun-

cil o Continuing Medical Education (ACCME) to povide con-tinuing medical education o psicians. Te Catam Institutedesignates tis educational activit o a maximum o 1.5 AMAPRA Category 1 Credits™. Psicians sould claim cedit com-mensuate it te extent o tei paticipation in te activit.

discLOsure:

It is te polic o Te Catam Institute to ensue balance,independence, objectivit, and scientic igo in all o its edu-cational pogams. All acult, plannes, and manages o a-ect te content o medical education activities sponsoed bTe Catam Institute ae equied to disclose to te audiencean eal o appaent confict o inteest elated to te activit.Te activit acult is ute equied to disclose discussiono o-label uses in tei pesentations. Facult, plannes, andmanages not compling it te disclosue polic ill not bepemitted to paticipate in tis activit. Facult disclosue in-

omation is povided belo.

Marc L. Gordon, MD

Consulting fees: Miad Genetics, Inc, Teva Neuoscience Honoraria: EMD Seono/Pze, Miad Genetics, Inc, NovatisPamaceuticals Copoation, Oto-McNeil Neuologic, TevaNeuoscience

Pal P. Doghramji, MD, FAAFP

Advisory boards: Cepalon, Inc, sano-aventis U.S. LLC, TakedaPamaceuticals Not Ameica, Inc.

Honoraria: Cepalon, Inc, Pze Inc, sano-aventis U.S. LLC,Takeda Pamaceuticals Not Ameica, Inc.

Joseph A. Lieerman III, MD, MPH

Consulting fees: AstaZeneca Pamaceuticals LP, Pze Inc,Takeda Pamaceuticals Not Ameica, Inc.

Honoraria: sano-aventis U.S. LLC

Dan Dch, PhD

Scientic Diecto, Te Catam InstituteNo eal o appaent conficts o inteest to epot.

spOnsOrship and suppOrt:

Tis mateial as been submitted b Te Catam Institute.It as been edited and pee evieed b Current Psychiatry.

COPyrIGhT © 2007 DOwDEN hEALTh MEDIA

© Keith negling

Undstndn,

dnosn, nd succssfuy

mnn ncopsy

Tis activit is suppoted ban educational gant om

Tis activit issponsoed b



s Crrent Pschiatr n Dcbr 2007 S


S

leep is a psiologic state tat peoms an essential e-

stoative unction and acilitates leaning and memo

consolidation.1 wen sleep is disupted o moe tan a

sot time, nomal dail unctions decline. Mood, attention,and beavio deteioate. Sleepiness and disupted sleep can

esult om a lage numbe o patological disodes. Cu-

entl, 88 sleep disodes ae listed in te Intenational Clas-

sication o Sleep Disodes, as establised b te Ameican

Academ o Sleep Medicine, and sleep disodes advesel

aect moe tan an estimated 70 million Ameicans.2 Most

o tese disodes can be classied as causing insomnia and/

o pesomnia. Insomnia esults om disodes tat cause

dicult it alling asleep and staing asleep; examples ae

peaousal, cicadian dstmia, and omeostatic ds-

egulation.3,4

In contast, pesomnia ees to dicult instaing aake and is caacteized b ecuent episodes o

excessive datime sleepiness (EDS) o polonged nigttime

sleep.

hpesomnia can esult om seveal pima sleep diso-

des, including nacoleps, sleep apnea, estless legs sndome,

idiopatic pesomnia, and peiodic limb movement diso-

de.5 Te eects o some o tese sleep disodes and ote

conic illnesses on datime sleepiness ae measued using

te Epot Sleepiness Scale (ESS; Table 1).6,7 Nacoleps

as ound to cause some o te igest measues o excessive

sleepiness (FigUre 1).

Tis supplement uses a case-based appoac to descibete undeling patolog and smptoms o nacoleps. Die-

ential diagnosis o nacoleps and cuent teatment options

ill be discussed.

Ovvw of ncopsyNacoleps is a conic, neuologic sleep disode tat e-

sults om te dsegulation o sleep-ake ccles.8,9 Its 4 clas-

sic smptoms ae EDS, cataplex (a sudden dop in muscle

tone tat is tiggeed b emotional actos), sleep paalsis

(a genealized faccid paalsis tat appens sligtl beoe

Stay awake! Understanding, diagnosing,and successfully managing narcolepsy

Mc l. godon, MD

Chief of Neurology, The Zucker Hillside Hospital

Associate Professor of Clinical Neurology,Clinical Psychiatry, and Behavioral Sciences

Albert Einstein College of Medicine

New Hyde Park, NY

Pu P. Dohmj, MD, FaaFP

Assistant Medical Director, Health Services

Ursinus College

Collegeville, PA

Josph a. lmn iii, MD, MPH

Professor of Family MedicineJefferson Medical College

Philadelphia, PA



Stay awake! Understanding, diagnosing, and successfully managing narcolepsy


o at te time o alling asleep o on aakening),

and pnagogic allucinations (allucinations tatoccu ile alling asleep).8,10,11

EDS is te smptom tat is expeienced b almost

all patients it nacoleps.10 Cataplex is pesent in

about 70% o patients it nacoleps, eeas sleep

paalsis (30% to 50%) and pnagogic allucinations

(20% to 40%) ae expeienced less oten; all 4 smp-

toms ae pesent in an estimated 11% to 14% o pa-

tients it nacoleps.11

Altoug te oigins o nacoleps ae still not ell

knon, clinical undestanding o te neuologic ds-

unction tat undelies nacoleps as ell as teatment

options ave inceased makedl in te last decade.

Prevalence and ris actors

Accoding to te National Institute o Neuological

Disodes and Stoke, nacoleps is te tid most

equentl diagnosed pima sleep disode ound

in patients o seek teatment at sleep clinics, ate

obstuctive sleep apnea and estless legs sndome.8

Nacoleps appeas tougout te old in eve

acial and etnic goup, but pevalence ates va.8,12

repots in te United States estimate a pevalence o 1

pe 2000 population, eeas te pevalence in Japan

is consideabl ige (about 1 pe 600 population)

and in Isael it is muc loe (about 1 pe 500,000

population).8,9,11,12 Its incidence as been estimated to

be about 0.74 pe 100,000 peson-eas o nacolep-

s it cataplex, and 1.37 pe 100,000 peson-eas

o nacoleps it o itout cataplex.13 Altoug

nacoleps is about as common as multiple scleosis, it

is undediagnosed and undeteated8,12; te dela be-teen te emegence o te initial smptoms and diag-

nosis is usuall moe tan 10 eas.14

Te initiating event o nacoleps is not ell un-

destood, but inection, immune sstem dsunction,

tauma, omonal canges, o stess ma be pesent

beoe nacoleptic smptoms become maniest.8 Some

isk actos o nacoleps include eedit, obesit,

and gende. A genetic o amilial isk as been associ-

ated it nacoleps, and up to 10% o patients diag-

nosed it nacoleps it cataplex epot a close

elative it te same smptoms.12 hoeve, most

TAbLE 1

Epworth Sleepiness Scale

ess, ewr s sca.

t ess d dr v day .

A cr 10 r r cdrd y; a cr 18 r r vry y.

W r r J mW. Sleep. 1991;14:540-545.

Situation Chance of dozing (0-3)

s ad rad 0 1 2 3

Wac v 0 1 2 3

s acv a bc ac

— r xa, a ar r 0 1 2 3

A a ar a car r a r

w a brak 0 1 2 3

ly dw r ar 0 1 2 3

s ad ak 0 1 2 3

s qy ar c

(w y’v ad ac) 0 1 2 3

i a car, w d rac 0 1 2 3

0 = Would never doze

1 = Slight chance o dozing

2 = Moderate chance o dozing

3 = High chance o dozing

ESS total score ≥10

indicates excessive

daytime sleepiness

or sleep disorder

FIGuRE 1

Baseline ESS scoresin clinical studies

20

15

10

5

0

M e a n E S S s c o r e

Excessive

sleepiness

Narcolepsy

(N=271)a

Severe

untreated

OSA

(N=13)b

Parkinsondisease

(N=20)c

Seasonal

affective

disorder

(N=12)d

MDDwith

EDS/fatigue

(N=158)e

Depression,

untreated

(N=29)f

Depression,partial

response to

antidepressant

(N=118)g

Multiple

sclerosis

(N=72)h

Inclusion criteria in the majority o these studies

included an ESS score ≥10

aus mda narcy mcr sdy gr. Neurology. 2000;54:1166-1175.bJ mW. Sleep. 1991;14:540-545;c Adr Ch, a. Mov Disord. 2003;18:287-293;dld l. J Aect Disord. 2004;81:173-178;eFava m, a. J Clin Psychiatry . 2005;66:85-93;fna pt, a. J Clin Psychiatry. 2004;65:414-420;gDBaa C, a. J Clin Psychiatry . 2003;64:1057-1064;hRaa KW, a. J Neurol Neurosurg Psychiatry. 2002;72:179-183.

eDs, xcv day ; ess, ewr s sca; mDD, ajr

drv drdr; osA, brcv aa.

ma ba ess cr crc . pa w arcy adpark da (b rad) w eDs (ess cr ≥10). mDD ay a b

acad w eDs. i cr, v ay b w, b

a cr ay b r.





cases occu spoadicall, itout stong evidence o

ineitance.8 Being oveeigt o obese as also been

identied as a isk acto o nacoleps, but tis ma

be a consequence, ate tan a cause, o te disease.12

Tee appeas to be a sligtl ige isk o nacolepsin men tan in omen.12

Qalit o lie

Patients it nacoleps ave muc pooe ealt

and qualit o lie tan people itout nacoleps

(FigUre 2).10,15 Nacoleptic episodes can occu at an

time, causing sevee, detimental eects on dail unc-

tioning and ok. Patients ma all asleep involuntail

ile at ok o scool, duing social activities, o ile

diving o opeating azadous macine. Te naps

tpicall last om a e seconds to seveal minutes butcan continue o an ou o moe.8 Altoug no cue is

available, diagnosis and teatment o nacoleptic smp-

toms can minimize its deleteious eects.

Case study

An 18-year-old woman, 5 eet 6 inches tall and weighing 105

pounds, presents with a chie complaint o headaches. She is

a nonsmoker and does not drink alcohol. When she is asked

about how the headaches aect her day, she says that she

is tired all the time. This complaint is urther delineated to besleepiness (drowsiness, need to sleep) and not atigue (lack o

energy or stamina, desire to rest). She is asked about her sleep:

she has no trouble alling asleep at bedtime—or anytime or

that matter. In act, she oten alls asleep in class, especially

when it is boring. The patient goes to bed regularly at 8 PM and

always needs an alarm clock to wake her up at 6 AM. She oten

eels somewhat tired and unrereshed upon awakening, and

this worsens as the day goes on. She drinks caeinated sot

drinks to stay awake. She takes naps whenever she has the

opportunity and eels a bit better or a little while aterward. Be-

cause o the “tiredness” (sleepiness), the patient has not been

able to complete much o her homework and has allen behind

in her classes. She is regarded as a poor student. As an expla-

nation or this, the patient’s mother says that the patient is lazy

and does not eat properly; she also expresses concern that her

daughter might be depressed. The mother mentions that the pa-

tient’s brother has had similar tiredness problems. The patient

scores 19 on the ESS, indicating severe sleepiness (Table 1).

eDS: a symptom of mny dsodsEDS is a ve common complaint in pima cae and

is a smptom o man disodes. Some o te most

common ae listed in Table 2, and tese sould be con-

sideed en intevieing a patient. Sleep disodes

tat ma cause EDS all into 3 boad categoies: insu-

cient sleep (in ic sel-induced sleep depivation

is te most common cause); eatic o nonpsiologic

sleep pattens (cicadian tm disodes); and poo

qualit sleep, suc as sleep agmentation (mainl

obstuctive sleep apnea o peiodic limb movements

duing sleep). Less common causes o EDS ae idio-patic pesomnia and ecuent pesomnias, suc

as Kleine-Levin sndome and menstual-elated -

pesomnia.16,17 EDS also is common in patients it

some neuologic illnesses, suc as Pakinson disease,

aecting up to 50% o patients.18 Inteestingl, te

dopaminegic agents used to teat Pakinson disease

can ute incease EDS in tese patients; emoval

o eplacement o dopamine agonists can oe some

elie.18 Patients it a vaiet o ote neuologic

disodes, including ead tauma, encepalitis, and

Alzeime disease, also can pesent it EDS. Ote

FIGuRE 2

Negative eect o narcolepsyon quality-o-lie domains

ma ca

Fa ca

ma cr

Fa cr

*P = .0001**P = .04

gra a:=1072 , 1111 w

pa w arcy:=22 , 55 w

sF-36, mdca oc sdy sr-Fr 36 ha sa srvy.

nav c arcy qay-- da. ha-

rad qay wa ad by sF-36 qar r 77 nrwa

a w ad arcy w caaxy ad card w daa r

ra a. m ad w w arcy ad wr cr

a sF-36 da xc vay. m rdy acd wr bdy

a (, P = .0001; w, P = .0001), ca c (, P = .0001;

w, P = .0001), ad ra a (, P = .04; w, P = .0001).

W r r ervk s, a. Acta Neurol Scand. 2006;114:198-204.

90

80

70

60

50

40

30

20

10

0

Q u a l i t y o f l i f e ( % )

42.548.1

77.273.0

63.657.7

87.683.7

65.761.4

77.4 76.3

Bdy a sca c gra a

**

**

***





medical disodes associated it EDS include bo-

malgia, eumatoid diseases, congestive eat ailue,

cance, and potoidism.16

In most patients, EDS is te st smptom o naco-

leps to become appaent, usuall beteen te ages o 10 and 25 eas.8,19 hoeve, tee ma be age-elated

dieences in te appeaance o smptoms. One stud

ound tat cataplex appeaed st in 47% o patients

60 eas o olde, but maniested st in onl 21% o

ounge patients (P < .05).19

Undstndn th “td” ptnt

It is impotant to distinguis EDS om atigue. Bot

smptoms ae igl pevalent, ave ovelapping

pesentations, and can be easil conused b patients.

Te examine ma also become conused because

most patients use te tem “tiedness” o bot, so

clinicians must elicit additional inomation to acili-

tate a diagnosis. A patient it atigue ma be ex-

peiencing listlessness o letag—possibl due to

insomnia—ate tan a tendenc to all asleep.16 In contast, sleepiness is te popensit to all asleep

(dosiness), especiall in lo-stimulus situations.

wen EDS is due to nacoleps, a sot nap o 10 to

15 minutes ill educe “tiedness” and leave patients

eeling a bit eesed atead.9 hoeve, tis e-

ect does not last long.

Te Multiple Sleep Latenc Test (MSLT) can elp

to distinguis atigue om EDS.16 As te name implies,

te MSLT is a sleep test done in te sleep laboato

at multiple times duing te da, usuall consisting o

4 to 5 sessions lasting 20 minutes eac and ecoded

TAbLE 2

Dierential diagnoses or excessive daytime sleepiness

Disorder Distinguishing characteristics Diagnostic tools

Sleep-disordered breathing mdd a; a x; by; ry irvw w bd arr r dcr

d r, yr, r cardac a’ bavr (d r,

arrya a bra); yca

xaa; yray

Narcolepsy eDs r y arcc irvw w a ab caaxy;

rad rrra r mslt cr r rad

Rem

Sleep deprivation or Ard -wak cyc w jb, tr ry; rrra r

circadian misalignment acvy cd, j a, r wrk yray (d b ra)

Restless legs syndrome C v ; rr tr ry; yca

(Ekbom syndrome ) var a; b xaa; rvw w bd

vaca, ra, r arr r rr v

dccy aa, r abc abra

Substance use or abuse hry bac ddcy r tr ry ad dr cr

crr dr ab r ddc

Depression svr d drbac; dcv; tr ry; rrra r yca

ac rcca; ca a, xaa; rrra cr

w, bw ab, r caacy r arcy ( drdr d

xrc ar rd adra)

Kleine-Levin syndrome (rare) ma x (m/F ra, 3:1); adcc; tr ry

cv vra; aca; xa

yracvy

Idiopathic hypersomnia prd cra ; abc tr ry; b rrra

br aack; abc cr r mslt

cra a; w ar rd; ravack wak; vr ary awak

r

Inection hyra y; c Dagno of nfcton (eDs hould rolv

w ra dry da)

eDs, xcv day ; mslt, m s lacy t; Rem, rad y v.

W r r gr pm, sa mJ. Arch Fam Med. 1998;7:472-478.





seveal ous apat. Te patient is placed in a dak,

quiet oom and asked to t to all asleep. It is con-

sideed an abnomal esult en a patient alls asleep

itin 8 minutes.

Case study (continued)

Ater scoring the ESS, the clinician asks the patient whether

she experiences anything unny or unusual when she be-

comes emotional. The clinician urther clarifes by asking

i anything unusual happens when she laughs or becomes

excited or when she eels something pleasurable. The pa-

tient responds that she eels weak in her arms and legs prior

to sex. The clinician asks her to tell a joke that she thinks

is unny. When she starts to laugh, the clinician observes a

minor loss o muscle tone in the patient’s legs. The patientresponds positively when asked about sleep paralysis, stat-

ing that she has experienced it or years while going to sleep

and waking up. She denies hallucinations.

Ncopsy wth ctpxyTe 4 classic smptoms tat dene nacoleps—EDS,

cataplex, sleep paalsis, and pnagogic allucina-

tions—ae sometimes called te “nacoleptic tetad.”8,10,11

Cataplex occus in most cases o nacoleps but is not

common in ote sleep disodes; its pesence in combi-nation it EDS is denitive o nacoleps.12

Te sudden dop in muscle tone tat caacteizes

cataplex is tiggeed b emotional actos, usuall pos-

itive emotions suc as laugte o a pleasant supise,

o sometimes b ange, but almost neve b stess, ea,

o psical exetion.14 All stiated muscles except te

diapagm can be aected. Cataplex ma be patial

o genealized and is usuall bilateal. Cataplectic at-

tacks ae sometimes limited to te acial muscles o to

te ams o legs, esulting in dsatia, acial fickeing,

ja temo, ead o ja dooping, dopping o objects,

o unlocking o te knees.14 Toug ae, genealizedattacks can lead to collapse.8,9,17 Te patient is usuall

conscious and aae duing cataplectic attacks and

migt not see tem as patological.14 Iegula titc-

ing o te limbs o ace duing attacks o cataplex can

easil be mistaken o epileps.17 Cataplectic attacks

can last om a split second to seveal minutes; tei e-

quenc vaies om seveal episodes a da to less tan 1

episode a ea.14

Caeul, indiect questioning o te patient can be

used to eite elicit o conm te pesence o cata-

plex. Te goal is to make te patient laug and to

obseve o signs o cataplex en te do. Clinicians

also sould ask specicall about te incomplete o

limited oms o cataplex descibed above.14 ho-

eve, it sould be emembeed tat muscle eakness

in esponse to emotion is not uncommon (eg, “becameeak in te knees”), and te obsevation o suc mild

esponses sould be conmed it ote tests beoe

making a diagnosis o cataplex.


Ater observing potential signs o cataplexy, the clinician

discusses the possible diagnosis o narcolepsy with the pa-

tient. Long-term management o narcolepsy is discussed,

including, most valuably, inormation on sleep hygiene and

the need to take strategic naps. The patient is reerred orpolysomnography to rule out other causes o daytime sleepi-

ness. This is ollowed by an MSLT the next day to assess the

time to sleep onset and to veriy the presence o sleep onset

rapid eye movement periods (SOREMPs).

Based on a history and the physical exam, the patient’s

headaches are diagnosed as migraines. A triptan is prescribed,

to be taken immediately at the onset of migraine symptoms.

Sp chtctu nd ncopsy

Nacoleps esults om te dsegulation o sleep-ake ccles.8,9 Duing te sleep ccle, estoative

sleep is divided into 2 distinct states: apid ee-move-

ment (rEM; epesenting about 20-25% o sleep

time in adults) and non-rEM (NrEM) sleep.1 rEM

and NrEM sleep ma ave sepaate omeostatic

mecanisms.20

NrEM sleep is divided into 4 stages (S1, S2, S3,

and S4), based on caacteistic electoencepalogam

signals. Te slo equenc (<4 hz) S3/S4 cotical

aves, knon as slo-ave o delta sleep, povide an

indication o sleep dept.1 Nomal uman sleep alte-

nates beteen NrEM stages S1 to S4 and rEM sleepappoximatel eve 90 minutes; tis ccle is epeat-

ed 5 to 6 times a nigt (FigUre 3, top tace).1 Duing

te couse o nomal sleep, te 90-minute sleep ccle

canges om a pedominance o NrEM, slo-ave

sleep duing te st sleep ccle to a pedominance o

rEM sleep duing te nal sleep ccle (FigUre 3, top

tace).1 rEM sleep is te peiod duing ic most

deams occu. Muscle tone is geatl suppessed du-

ing rEM sleep (rEM sleep atonia). Cataplex in na-

coleps saes common neuopsiologic mecanisms

it rEM sleep atonia.14





MSLT, as te onl measue signicantl

associated it 2 o moe SOrEMPs. Te

autos concluded tat subpopulations it

excessive sleepiness (eg, sit okes, oung

adults, patients it apnea) ae likel to avea geate pevalence o SOrEMPs tan te

geneal population.23 Teeoe, esults om

te MSLT must be consideed in te context

o te patient’s medical isto.

Diagnostic citeia ave been publised

b te Ameican Academ o Sleep Medi-

cine to distinguis beteen nacoleps it

cataplex, nacoleps itout cataplex,

and nacoleps due to anote undeling

condition.12,24 A diagnosis o nacoleps in

te absence o cataplex sould be cau-tiousl evaluated because omal sleep stud-

ies ae not 100% sensitive o specic.12

Narcoleps and pschiatric disorders

Te smptoms o nacoleps ovelap it

smptoms o some psciatic illnesses and

can lead to a misdiagnosis o nacoleps

as depession o scizopenia. EDS as

been associated it a numbe o psciatic illnesses

(Table 2), and distinguising nacoleps as emained

poblematic.25

Beteen 10% and 20% o patients itmajo depessive disode (MDD) ave EDS; EDS as

been epoted in up to 36% o patients it atpical

MDD.26 Altoug tee ae ee epots o misdiagnosis

beteen nacoleps and bipola disease, bipola disode

ma also pesent it pscotic smptoms and pe-

somnia duing te depessive stage.25

hpnagogic allucinations in nacoleps ae simi-

la to te allucinations associated it rEM sleep

intusions tat occu duing peiods o akeulness

in some scizopenia patients, possibl esulting in

misdiagnosis.27 Te patient’s illness isto, along it

te clinical eatues and a caeul pscopatologic as-sessment, can elp to distinguis tese disodes.27 Te

natue o te epoted allucinations also can elp to

distinguis beteen nacoleps and scizopenia27:

most o te allucinations in patients it nacolep-

s ae sleep elated and dependent on bod postue,

eeas in patients it scizopenia, te ae not.27


The polysomnogram is unrevealing. During the MSLT, the

mean latency-to-sleep onset is less than 1 minute; SOREMPs

Sleep dsreglation in narcoleps

Patients it nacoleps ente rEM sleep moe apid-

l tan do people itout nacoleps (FigUre 3, loe

tace). Sometimes this tansition to rEM sleep can occuimmediately upon falling asleep (called SOrEMPs) with-

out eve enteing NrEM sleep,17 leading to the occuence

of hypnagogic hallucinations and sleep paalysis.9,10,21,22

In some cases o nacoleps, rEM sleep and atonia

ma become dissociated. Tis can esult in rEM sleep

beavio disode, in ic patients psicall enact

vivid deams due to te lack o paalsis.

Dsegulation esults in a distubed noctunal

sleep, and most nacoleptic patients expeience equent

aakenings unelated to rEM sleep (FigUre 3, loe

tace).8,9,17 Despite alling asleep duing te da, patients

it nacoleps do not spend a geate amount o timein sleep tan people itout nacoleps.8

use o sleep stdies in diagnosis

Fomal sleep studies, suc as te MSLT, can be used to

document sleepiness and SOrEMPs and to suppot a

diagnosis o nacoleps. hoeve, SOrEMPs do oc-

cu in people itout nacoleps. A ecent stud ound

tat 4% o a population-based sample expeienced 2

o moe SOrEMPs measued using nigttime polsom-

nogap and datime MSLT.23 O te vaiables assessed

in tis stud, objective sleepiness, as detemined b te

Lights Off Lights On AwakeStage 1Stage 2Delta

REM

MvmntApnea

Control subject

11p 12a 1a 2a 3a 4a 5a 6a 7a 8a

Lights OnLights Off AwakeStage 1Stage 2DeltaREM

MvmntApnea

Subject with narcolepsy

11p 12a 1a 2a 3a 4a 5a 6a 7a 8a

FIGuRE 3

Polysomnographic fndings

Rem, rad y v.

Car a yray r a cr bjc ( rac) ad a bjc w arcy

(b rac). i cr rac, bjc cyc r 4 w wav a (a 1,

a 2, ad Da a s3 ad s4) br r Rem ; Rem ccr r a 1

r ar bjc a a. i b rac, bjc w arcy r Rem a

a day a a. t bjc w arcy a d r

awak a a d cr bjc.





occur during the ourth and fth naps. The patient has dif-

culty staying awake between the naps. There are no instanc-

es o obstructive or central apnea and no hypopnea. The re-

sults confrm the presence o severe daytime sleepiness, and

the SOREMPs are highly suggestive o narcolepsy with cata-

plexy. A prescription is given or modafnil, 200 mg per day, to

be taken in the morning. The patient is asked to call weekly

or updates and the opportunity to endorse or fne tune man-

agement. A ollow-up visit is scheduled in 1 month.

Nuopthooy of ncopsyIdentication o te neuologic patas involved in

te sleep-ake ccle as advanced in te last decade.

Cuentl, it is potesized tat te contol o sleep

involves te inteactions o mutuall inibiting sleepand aousal centes in te bain.1,20,28 wakeulness is

pomoted b bainstem and potalamic neuons1,20;

neuons tat poduce acetlcoline, noepinepine,

dopamine, seotonin, istamine, and pocetin (also

called oexin) ma be involved.17,28 Counteacting tese

aousal netoks ae a goup o sleep-active cells in te

ventolateal peoptic nucleus (VLPO) o te potal-

amus.1,20 Tese cells ae active duing sleep and contain

te inibito neuotansmittes galanin and γ -amino-

butic acid (GABA). Te innevate ake-pomoting

bain egions and poduce sleep b coodinating te in-ibition o te majo ascending monoaminegic aousal

sstems.1,20,28 Nacoleps epesents a majo neuologic

malunction o tis contol sstem, and cental to te

patolog o nacoleps is impaiment o pocetin

neuotansmission.9,29

hpocetin peptides ae poduced b a cluste

o neuons in te posteio al o te lateal po-

talamus.20 Te pocetin neuons ae mainl active

duing akeulness and especiall duing moto activ-

it.9,14,20 Te ave ascending pojections to te cee-

bal cotex, as ell as descending pojections to all o

te monoaminegic and colinegic cell goups o teaousal sstems.9,14,20Tee ae also mutual pojections

beteen te VLPO neuons and te pocetin neu-

ons. Tus, te pocetin neuons appea to einoce

te aousal sstems, but pobabl do not diectl in-

ibit te sleep-active cells in te VLPO.20

Nacoleps as been associated it a loss o

pocetin activit in te bains o nacoleptic pa-

tients.9,14,20 Postmotem examination o bain tissue o

patients it nacoleps ound undetectable levels o

pe-pocetin rNA, loss o pocetin peptides, and

a selective loss o pocetin neuons.14,30-32 Te loss o

pocetin unction as not te esult o a genealized

neuonal dsunction in tese bain egions, because

melanin-concentating omone neuons tat ae no-

mall located itin te same egion as te pocetin

neuons ee intact.14 Patients it nacoleps it cataplex ave lo

concentations o pocetin in te ceebospinal fuid

(CSF); CSF pocetin 1 concentations loe tan

110 ng/L ave a ig positive pedictive value (94%)

o nacoleps it cataplex.14,29 In contols o in-

dividuals it ote sleep and neuologic disodes,

pocetin 1 concentations in te CSF ee almost

alas ound to be above 200 ng/L.29 In ae instances,

lo CSF pocetin concentations in te absence o

nacoleps ee indicative o Guillain-Baé sndome

o ead tauma.14 Togete, tese esults indicated tat pocetin

neuons and unction ae selectivel damaged in naco-

leptic patients, altoug peaps onl in patients it

associated cataplex.14 Te cause o tis neual loss is

not ell undestood, but it as been potesized to

esult om an autoimmune pocess.14 Te uman leu-

kocte antigen (hLA) DQB1*0602 is ound in 95%

o nacoleptic patients it cataplex and 41% o pa-

tients it nacoleps itout cataplex, but onl in

18% to 35% o te geneal population.17,33


At the ollow-up visit, the patient reports that although her

drowsiness has improved, it is still troublesome. The pre-

scription or modafnil is increased to 400 mg daily. She is

provided with more inormation about narcolepsy and rein-

orcing instructions on sleep hygiene. Another ollow-up visit

is scheduled, and the patient is given inormation about sup-

port groups.

Phmcooc mnmntof ncopsyAltoug te cental pocetin sstem plas a pom-

inent ole in nacoleps it cataplex, tee cuent-

l ae no teatments available to taget tis sstem.

Management o te disode elies on smptomatic

teapies; te paticula smptom tat needs te

most pamacologic empasis vaies om patient to

patient.14 Stimulants (mostl dopaminegic) ae given

to counte patients’ excessive sleepiness and sleep

attacks. rEM suppessants, pimail antidepessants,

ae used to taget cataplex and ote rEM-associated




S10 Dcbr 2007 n s Crrent Pschiatr

smptoms. hpnotics ae used to consolidate sleep.34

At tis time, sodium oxbate (γ -doxbutic acid

[GhB]) is te onl dug appoved b te US Food

and Dug Administation (FDA) o te teatment o

bot cataplex and EDS in patients o ave na-

coleps it cataplex.14 A list o cuentl available

nacoleps agents and tei pamacologic popeties

is pesented in Table 3.34

Altoug nacoleps itsel is not atal, uncontolled

EDS and cataplex can lead to accidents tat esult in

seious inju o deat.8 Patients it unteated naco-

leptic smptoms ae involved in automobile accidents

about 10 times moe equentl tan te geneal popu-

lation; accident ates ae nomal among ull managed

patients.8 Cuentl available medications do not al-

lo patients it nacoleps to maintain a consistent,

TAbLE 3

Currently available narcolepsy treatments and their pharmacologic properties

5-ht, r; DA, da; DAt, da rarr; ghB, γ -ydrxybyrc acd; mAo, a xda; ne, rr; VmAt, vcar a rarr.

W r r m e, n s. Sleep. 2005;28:754-763.

Compound Pharmacologic properties

Stimlants

Amphetamines icra a ra (DA>ne>>5-ht). prary c d rvr fx DA r

DAt. ib a ra r VmAt ad r c ccr a r d.

t D-r r cc r DA ra ad a br a cd. s

c caaxy (cay r l-r) cdary adrrc c ccr a r

d. Avaab a racc xr r r D-r; var -ra ra avaab.

Methamphetamines pr ar aa b r c w crad cra ra.

Methylphenidate Bck a (DA>ne>>5-ht) ak. n c rvr fx r VmAt. sr a-.

Avaab a racc xr r a r D-r ad var -ra ra.

Selegiline (L-deprenyl) mAo-B br w vv cvr l-aa ad l-aa.

Modafnil md ac dbad b rbaby vv rav cv DA rak b. Fwr

rra d c. lw-cy cd. Avaab a a racc xr. l ayaddcv a, b cac a aa r yda. t R-r

a a r a- ad dv.

Anticataplectic componds

Protriptyline trcycc adra. marc ak bckr (ne>5-ht>DA). Acrc c. A

adra av da c caaxy, b abr ca ra ca dc

vry vr rbd caaxy.

Imipramine trcycc adra. marc ak bckr (ne=5-ht>DA). Acrc c.

Dra a acv ab.

Desipramine trcycc adra. marc ak bckr (ne>>5-ht>DA). Acrc c.

Clomipramine trcycc adra. marc ak bckr (5-ht>ne>>DA). Acrc c.

Dycra (ne>>5-ht>DA) a acv ab. n ccy vv.

Venlaaxine Da r ad adrrc rak bckr (5-ht>ne). Vry cv b aa.

may av wr xa d c a r adra. s a; r a-;

xdd-ra ra rrrd.

Atomoxetine scc adrrc rak bckr (ne) ray dcad r a-dc yracvy

drdr. s a; r a-; rdc a.

Fluoxetine scc r ak bckr (5-ht>>ne=DA). Acv ab rfx a r

adrrc c. h rac d ar dd.

Other

Sodium oxybate (GHB) may ac va gABA(b) r cc ghB rcr. Rdc DA ra. nd 2 d r

w da c drbd cra ; rac c caaxy ad day

dayd.



s Crrent Pschiatr n Dcbr 2007 S11


nomal state o aletness, so pamacologic manage-

ment sould be supplemented it nonpamacologic

appoaces.8

Nonphmcooc ppochs

nd hvo stts

Patients sould be given ealistic expectations o teap

and must undestand tat even it teatment te ae

not going to be as ull alet as people itout nacolep-

s. Te sould avoid ove-te-counte and pesciption

dugs tat ma cause sleepiness. Pope sleep giene isimpotant. Patients sould avoid activities tat alte sleep

scedules, suc as sit ok. Ote simple measues

tat te patient can take to enance sleep qualit include

maintaining a egula sleep scedule, avoiding alcool

and caeine-containing beveages o seveal ous be-

oe bedtime, avoiding smoking, maintaining a comot-

able and adequatel amed bedoom envionment, and

engaging in elaxing activities beoe bedtime.8

Execising, except duing te 4 to 5 ous pio to

bedtime, can impove sleep qualit and elp patients

avoid gaining te excess eigt tat is associated it

nacoleptic patients.8 Sot naps oten can tempoailees patients it nacoleps and sould be encou-

aged.9 Fou 15-minute naps sceduled acoss te da

ma be moe benecial o nacoleps patients tan

a longe nap once a da. Patient suppot goups also

can be impotant in elping patients cope it tei

smptoms.8

Ttmnt of eDS

Stimulants suc as ampetamines and metlpenidate

ave taditionall been te pima teatment options

o EDS11; oeve, pamacologic options ave in-

ceased in ecent eas. Fou dugs ave been appoved

b te FDA o te teatment o EDS in nacoleps:

metlpenidate, dextoampetamine, modanil, and

sodium oxbate (Table 4).

Methlphenidate as been used to teat nacoleps

o moe tan 50 eas.35 It acts b blocking mono-

amine uptake and is available eite as a acemic mix-

tue o as a pue D-isome.34,36 Evidence o te ecac

o metlpenidate in teating EDS is based lagel on

clinical expeience because onl 3 case studies totaling

ee tan 200 patients ave been publised (evidencelevel V-C).36,37 Te appoved dose is 5 to 60 mg metl-

penidate pe da. hoeve, clinical epots indicate

tat te dose sould be titated to as muc as 200 mg

metlpenidate pe da to eac maximal ecac.35

Metlpenidate is a scedule II substance.

Amphetamines ae believed to impove sleepi-

ness toug pesnaptic stimulation o dopaminegic

tansmission.34 Te inibit te vesicula monoamine

tanspote, causing te empting o vesicula dopa-

mine stoes into te ctoplasm and a evese fux o

dopamine toug its euptake site.34,38,39 Tis esults

in a net incease in dopamine elease and an associ-ated eduction o pesnaptic dopamine stoes.34 Dex-

toampetamine is te dextoota steeoisome o

te ampetamine molecule; its popeties ae simila

to metlpenidate. Te dextoampetamine dosage

o nacoleps is 5 to 60 mg dail. Ampetamines ae

scedule II substances, and evidence o tei use comes

om 3 level II-B studies and 2 level V-C studies.36

Modafnil pomotes akeulness in bot no-

mal and pocetin-decit nacoleps in umans and

animal models (evidence level I-A).36 Tis suggests tat

te sites o action o tis compound ae donsteam

TAbLE 4

FDA-approved narcolepsy medications that treat EDS

ADhD, a-dc yracvy drdr; eDs, xcv day ; FDA, us Fd ad Dr Adra; osA, brcv aa;

sWsD, wrk drdr.

Physicians’ Desk Reerence. mva, nJ: mdca ecc Cay; 2005. W r r R ( r).

Drug Schedule FDA-approved indications FDA-approved dosages

Methlphenidate C-ii ADhD, arcy 5-60 /day

Dextroamphetamine C-ii narcy, ADhD 5-60 /day

w yracvy

Modafnil C-iV eDs acad w

arcy, osA, ad sWsD 200-400 /day

Sodim oxate C-iii eDs ad caaxy 4.5-9.0

a w arcy ta y d





o independent o te pocetin sstem.40 Modanil

as loe abuse potential and is likel to ave ee

cadiovascula side eects tan te olde stimulants.36

Te mecanism o action o modanil is still debated

but it ma involve dopamine euptake inibition.34 Itas ecentl been demonstated tat modanil activates

te ippocampus, ic eceives aeent innevation

om te sleep-ake cente o te potalamus.41,42

In addition to sleepiness, modanil as been ound to

impove subjective eelings o vigo and cognitive unc-

tioning and also to educe atigue.42,43 It is available as a

acemic mixtue, and te dosage ange is 200 to 400 mg

dail. Te FDA as ecentl appoved te r-isome o

modanil, amodanil, o teating excessive sleepiness.

Modanil is a scedule IV substance.

Te long-tem ecac and saet o modanil inpatients it EDS associated it nacoleps as ex-

amined in 2 open-label, 40-eek extension studies; 478

patients ee enolled and data om te 2 studies ee

combined.43 Te majoit o patients (appoximatel

75%) eceived 400 mg o modanil dail. Disease seve-

it impoved in moe tan 80% o patients tougout

te studies. Te mean (±SEM) ESS scoe impoved signi-

icantl om 16.5±0.2 at open-label baseline to 12.4±0.2

at eek 2, and emained at tat level toug eek 40

(P < .001). Qualit-o-lie scoes ee measued using te

Clinical Global Impession o Cange and te MedicalOutcomes Stud Sot-Fom 38 healt Status Suve

(SF-36). Scoes in 6 o te 8 SF-36 domains ee sig-

nicantl impoved compaed it open-label baseline

scoes (P < .001).43 Te most common teatment-elated

advese events ee eadace (13%), nevousness (8%),

and nausea (5%). Most advese events ee mild to mod-

eate in natue. Te autos concluded tat modanil is

eective o te long-tem teatment o EDS associated

it nacoleps and signicantl impoves peceptions

o geneal ealt.43 Ote studies ave also epoted tat

modanil is sae and eective o teating EDS associated

it nacoleps.44-46

Sodim oxate is te most ecent dug appoved

o teating nacoleps it cataplex (evidence level

I-A).34,48 It educes datime sleepiness and as an eect

on distubed nigttime sleep.34 Altoug te exact mec-

anism o action is unknon, it as been suggested tat

sodium oxbate ma act b stimulation o GABA(b) e-

ceptos, and possibl ote GhB-specic eceptos.34,48

It as stong eects on dopamine tansmission tat ma

be mediated toug GABA(b) eceptos on dopamine

cells.34 Sodium oxbate acutel educes neve cell ing,

but does so ile uncoupling o dopamine sntesis.34,48

Tis esults in inceased dopamine stoes.34 Tus, so-

dium oxbate appeas to educe dopamine elease at

nigt, ile causing a seconda dopamine incease

duing te da. Studies o te eects o sodium oxbate

o te teatment o nacoleps ave indicated tat itimpoves agmented nigttime sleep and EDS.47,49 Un-

like stimulants, it is taken at nigttime, al at bedtime

and al 2.5 to 4 ous late, o a total dose o 4.5 to 9 g

pe nigt.34,36

Te ecac o sodium oxbate o teatment o EDS

associated it nacoleps as assessed in an 8-eek,

multicente, double-blind, placebo-contolled tial.50

To unded tent-eigt adults it nacoleps it

cataplex ee enolled in 42 sleep clinics in te United

States, Canada, and Euope. Patients ee andoml

assigned to eceive 4.5 g, 6 g, o 9 g o sodium oxbatenigtl o placebo o 8 eeks. Doses o 6 g and 9 g

ee titated in eekl 1.5-g incements. Ate 8 eeks,

patients displaed dose-elated deceases in median ESS

scoes and in equenc o eekl inadvetent naps,

ic ee signicant at te 6-g and 9-g doses (o

eac, P < .001).50 Advese events it geate tan 5%

incidence included nausea, dizziness, and enuesis, ic

appeaed to be dose elated. Te autos concluded tat

sodium oxbate as ecacious in managing datime

sleepiness associated it nacoleps.50 Sodium oxbate

as also ound to educe EDS signicantl compaed itbaseline in long-tem studies up to 1 ea (FigUre 4).51

Distibution o sodium oxbate is tigtl contolled;

pesciption inomation is available at: .da.gov/

cde/dug/inopage/xem/xem_qa.tm#4. Sodium

oxbate is a scedule III substance.

Head-to-head stdies o EDS treatment. Limited

data ae available compaing te ecac o simi-

la doses o metlpenidate, dextoampetamine,

modanil, and sodium oxbate. A 1991 suve o te

liteatue on modanil, metlpenidate, and dex-

toampetamine ound tat onl te latte 2 dugs

inceased sleep latencies to 70% o moe o nomalvalues.52 hoeve, te doses o metlpenidate and

dextoampetamine ee at o above te ig ange

o ecommended doses, eeas modanil as in te

middle ange o pescibed doses; te total numbe o

patients examined in eac stud suveed anged om

5 o dextoampetamine to 21 o modanil.52

On te ote and, modanil and sodium oxbate

ave been compaed diectl in te same stud and

ee ound to ave simila ecacies in teating EDS

(Table 5).47 Te stud examined 270 adult patients it

nacoleps taking 200 to 600 mg o modanil dail o





te teatment o EDS. Patients eceived uncanged dos-

es o modanil duing a 2-eek baseline pase. Patients

ee andoml assigned to 1 o 4 teatment goups:

placebo, sodium oxbate plus placebo, modanil plus

placebo, o sodium oxbate plus modanil. Sodiumoxbate, 6 g, as administeed nigtl o 4 eeks and

ten inceased to 9 g nigtl o 4 additional eeks.

In te sodium oxbate goup, tee as no decease

in sleep latenc om te modanil teatment un-

in peiod, suggesting tat tis dug as as ecacious

in teating EDS as modanil. In contast, te sodium

oxbate/modanil goup demonstated an incease in

datime sleep latenc om 10.43 to 13.15 minutes

(P < .001), suggesting tat tis combination o dugs

poduced an additive eect. Te sodium oxbate goup

also demonstated a decease in median aveage ESSscoes, om 15.0 to 12.0, eeas te sodium oxbate/

modanil goup deceased om 15.0 to 11.0 (o bot,

P < .001; Table 5). Te autos concluded tat sodium

oxbate and modanil ae bot eective o teating

EDS in patients it nacoleps, poducing additive e-

ects en used togete.48

Ttmnt of ctpxy

Te onl dug appoved o te teatment o cataplex in

te United States and Euope is sodium oxbate.14 Tic-

clic antidepessants ave been used o decades to teatcataplex, and moe ecentl, te selective seotonin and

noepinepine euptake inibitos ave been pescibed

o tis use. hoeve, te eect o tese antidepessants

on cataplex as neve been examined in andomized

clinical tials.14 Monoamine oxidase inibitos also ma

be eective, but ae less commonl used. Te anticata-

plectic eects o te antidepessants occus muc moe

apidl tan tei antidepessant eects (less tan a

eek), but ebound cataplex can occu i tei use is

abuptl inteupted.14,53 Dugs tat teat cataplex also

educe pnagogic allucinations and sleep paalsis.14

Floxetine is a selective seotonin euptake inibitoit minimal antiistaminic and anticolinegic e-

ects tat is used to teat depession.36 Te teapeutic

doses needed to teat cataplex ae muc ige tan

tose needed to teat depession: 60 mg/d fuoxetine

o cataplex teatment vesus 20 to 40 mg/d fuox-

etine o depession.34 It can take time to ean a pa-

tient o te medication because o te long al-lie o

its active metabolite.

Venlaaxine is anote antidepessant used to teat

cataplex. It as less stimulant eect tan fuoxetine, as

ell as a sote al-lie. An extended-elease omu-

lation is available and it ma be peeed o cataplex

ove fuoxetine.34 Te usual dosage o venlaaxine is

beteen 75 and 375 mg/d.Tricclic antidepressants used to teat nacoleptic

cataplex include clomipamine, desipamine, imipa-

mine, and potiptline.14 Advese eects occu equent-

l, especiall anticolinegic eects.14 Ote potential

advese eects include otostatic potension, anoexia,

diaea, eigt gain, tiedness, and deceased libido.

Sodim oxate, administeed nigtl, esults in

signicant impovements in datime cataplex at-

tacks, as ell as sleepiness (evidence level I-A).50,51,54

Te exact mecanism o action o sodium oxbate in

cataplex emains unknon.

In a multicente, double-blind, placebo-contolledtial, 136 nacoleps patients it 3 to 249 (median,

21) cataplex attacks eekl ee studied.54 Subjects

ee andomized in double-blinded asion to eceive

3-, 6-, o 9-g doses o sodium oxbate o placebo taken

in equall divided doses upon etiing to bed and 2.5

to 4 ous late o 4 eeks. Compaed it placebo,

eekl cataplex attacks ee deceased b sodium

oxbate at te 6-g dose (P = .0529) and signicantl at

te 9-g dose (P = .0008). Tis eect as maintained o

moe tan 44 monts, and patients soed no evidence

o toleance.14,55 Unlike te antidepessants, tee as

FIGuRE 4

Improvement in EDS with sodiumoxybate over 1 year o treatment

20

18

16

14

12

10

8

6

M e d i a n E S S S c o r e

0 2 4 6 8 10 12m

narcy

Ra

nra Ra

**

****

ess, ewr s sca.

Dr db-bd ra, ess cr drd r a da ba va

18, 14 ad 12 w 6.0- ad 9.0- d d xyba, rcvy.

t x ra ba w adra d xyba 6.0 /.

ivar rad dr a 2-wk rva 1.5- cr r

dcr acv a cca c. A 12 , arxay 14%

a wr ak 3.0 , 9% a wr ak 4.5 , 36% wr ak 6.0

, 11% wr ak 7.5 , ad 30% wr ak 9.0 d xyba.

W r r us Xyr mcr sdy gr. Sleep. 2003;26:31-35.

Db-bd, acb-crd dy

o-ab x ra

n=118

*P < .001





no evidence o ebound cataplex upon abupt discon-

tinuation o teatment.55 Nausea, eadace, dizziness,

and enuesis ee te most commonl epoted advese

events. Te autos concluded tat sodium oxbate sig-

nicantl impoved cataplectic smptoms in patients

it nacoleps.54,55


At the next ollow-up, the patient complains that even

though she eels better than ever, she continues to have

trouble waking up in the morning and still eels signifcantly

drowsy during the day; she also continues to experience 1

or 2 episodes o cataplexy daily. She has become rustrated.

The clinician enrolls her in a sodium oxybate program and

continues her modafnil prescription o 400 mg daily.

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bca ba ad cca ca. Cell

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2006;10:247-254.

5. naa Cr s Drdr Rarc.

Problem Sleepiness in Your Patient. naa

i ha, nhlBi; 1997.

6. J mW. A w d r ar

day : ewr

ca. Sleep. 1991;14:540-545.

7. J mW. Day , r, ad

brcv aa. t ewr s-

sca. Chest. 1993;103:30-36.

8. naa i nrca Drdr

ad srk. Narcolepsy Fact Sheet. Avaab

a: ://www.d..v/drdr/arc-

y/da_arcy.. Accd oc-

br 12, 2007.

9. n s. Cca ad rbca ac

arcy. Sleep Med. 2007;8:373-399.

10. mr mm, hajdkvc R, era m, Kz JA.

narcy. J Clin Neurophysiol. 1990;7:93-

118.

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Reerences

SummyPamacologic management o patients it naco-

leps is usuall based on teating sepaate smptoms,

pimail cataplex and EDS. Teatment options o

cataplex include te antidepessants fuoxetine, ven-

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oxbate. Fo teating datime sleepiness, FDA-ap-

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ave simila, long-tem ecacies in teating EDS at

pescibed doses and ma ave additive eects en

used togete. n

TAbLE 5

ESS scores: Comparison o modafnil, sodium oxybate, and placebo

ess, ewr s sca.

mda ess cr, a brva carrd rward. V 3 wd 2 wk -bd da a rvy abd d (200-600 /d). V 4 wd 4 wk

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W r r Back J, h WC. Sleep. 2006;29:939-946.

Placebo Sodium oxybate Modainil Sodium oxybate/

(n=55) (n=50) (n=63) modainil (n=54)

Visit 3 16.0 (=54) 15.0 (=48) 14.0 (=61) 15.0 (=54)

Visit 4 17.0 (=53) 13.0 (=48) 15.0 (=62) 11.5 (=50)

Signifcance — P < .001 P = .071 P < .001

Visit 5 16.0 (=53) 12.0 (=49) 15.0 (=63) 11.0 (=53)

Signifcance — P < .001 P = .767 P < .001





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nAme DegRee(s)

stReet

CitY stAte Zip CoDe

DAYtime phone FAX

emAil

1.Symptomsofnarcolepsyusuallyfirstappearbetweentheagesof

a) Birth and 10 years c) 25 and 50 years

b) 10 and 25 years d) 50 and 70 years

2.Allofthefollowingareclassicsymptomsofnarcolepsy,except:a) Cataplexy c) Spending much more time asleep than

b) Excessive daytime people without narcolepsy do

sleepiness d) Sleep paralysis

3.Howisthesleeppatternofpatientswithnarcolepsydisturbed?

a) REM sleep is absent c) REM sleep is entered almost

b) NREM sleep is immediately upon falling asleep

unusually prolonged d) NREM sleep is absent

4.Hypnagogichallucinationsandsleepparalysisinnarcolepsy

maybemanifestationsof:

a) REM sleep c) Cataplexy

b) NREM sleep d) Too much sleep

5.Hallucinationsthataresleeprelatedandposturerelatedare

morecharacteristicofhallucinationsdescribedinwhichone

ofthefollowingdisorders?

a) Narcolepsy c) Bipolar disorder

b) Schizophrenia d) Parkinson disease

6.Whichneurotransmitterisfoundinabnormallylow

concentrationsinthecentralnervoussystemofpatients

withnarcolepsy?a) Acetylcholine c) Dopamine

b) Norepinephrine d) Hypocretin

7.Thelossofhypocretinfunctionistheresultofageneralized

neuronaldysfunctionincertainbrainregions.

a) True b) False

8.Antidepressantsareusedtotreatwhichsymptomofnarcolepsy?

a) EDS c) Sleep paralysis

b) Cataplexy d) Antidepressants are not used in the

treatment of narcolepsy

9.Comparedwithamphetamine,modafinil:

a) Does not have the cardiovascular side effects associated

with the older stimulants

b) Does not have the abuse potential associated with

the older stimulants

c) Does not cause nausea

d) Both a and b

10.Whichofthefollowinghasbeenapprovedfortreatingboth

cataplexyandEDSinnarcolepsy?

a) Sodium oxybate c) Fluoxetine

b) Modafinil d) Dextroamphetamine

STAy AwAkE! CME POSTTEST

PROGRAM EVALuATION Please complete the evaluation

1.Pleaseindicateyourlevelofagreementwiththefollowingstatements:

Strongly Strongly

Agree Disagree

Thenewsletteradequatelyaddressedthefollowingobjectives:

• Describe the clinical and diagnostic 5 4 3 2 1 features of narcolepsy

• Evaluate the similarities and differences 5 4 3 2 1 between narcolepsy and other sleep disordersrelated to other psychiatric or medical diagnoses

• Explain the neurobiological mechanisms that 5 4 3 2 1 currently are believed to bring aboutnarcolepsy and cataplexy

• Differentiate the pharmacologic management 5 4 3 2 1 of cataplexy and excessive daytime sleepinessand explain why narcolepsy is treatedsymptomatically

Strongly Strongly

Agree Disagree

Asaresultofreadingthisnewsletter,Iambetterableto:

• Describe the clinical and diagnostic 5 4 3 2 1 features of narcolepsy

• Evaluate the similarities and differences 5 4 3 2 1 between narcolepsy and other sleep disordersrelated to other psychiatric or medical diagnoses

• Explain the neurobiological mechanisms that 5 4 3 2 1 currently are believed to bring aboutnarcolepsy and cataplexy

• Differentiate the pharmacologic management 5 4 3 2 1 of cataplexy and excessive daytime sleepinessand explain why narcolepsy is treatedsymptomatically

2.Doyouplantomakeimprovementsinhowyoudiagnoseandtreatnarcolepsy(withorwithoutassociatedexcessivedaytimesleepiness)inyourpracticebasedonnewknowledgegainedfromthisactivity?(Checkoneanswer.)

n yes n I am consideing it n No (please explain)

3.Ifyes,whatnewstrategiesareyoulikelytotryfordiagnosingandtreatingnarcolepsy(withorwithoutassociatedexcessivedaytimesleepiness)inyourpracticethatyouhavenotusedbefore?(Checkallthatapply.)

n Different or new patient n Different or new nonmedicationinterview questions interventions

n Different or new diagnostic tests n Other

n Different or new medication choices

4.Doyouhaverecommendationsorsuggestionstoimprovefuturecontinuingeducationprograms?

or ax : 00--

To receive a statement o credit, please complete the posttestand evalation orm and mail to:

The Chatham Institute, Program T7J29MG-CPSY26 Main Street, Suite #350, Chatham, NJ 07928-2402

Please allow 6 to 8 weeks or processing.

Circle correct answer

Statements o credit will be awarded upon successul completion o assessment questions(70% or better) and completion o program evaluation. I a score o 70% or better is not achieved, no credit will be awarded and the participant will be notifed.

I AM REQuESTING 1.5 CME CREDITS _____

supplcp narcolepsy

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