supplcp narcolepsy
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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
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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
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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
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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.
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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
**
**
***
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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.
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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.
Case study (continued)
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
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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
Case study (continued)
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.
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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
Case study (continued)
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
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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.
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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
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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
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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
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Stay awake! Understanding, diagnosing, and successfully managing narcolepsy
S1 Dcbr 2007 n s Crrent Pschiatr
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
Case study (continued)
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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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-
laaxine, imipamine, and potiptline, and sodium
oxbate. Fo teating datime sleepiness, FDA-ap-
poved medications include metlpenidate, dexto-
ampetamine, modanil, and sodium oxbate. Sodium
oxbate is te onl dug appoved o teating botcataplex and EDS. Modanil and sodium oxbate
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
acb r d xyba, 6 y, ad/r da a rvy abd d. V 5 wd 4 wk acb r d xyba, 9 y, ad/r da
a rvy abd d (200-600 /d). scac wa a card w acb.
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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s Crrent Pschiatr n Dcbr 2007 S1
Avaab a www.crrentpschiatr.c
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nAme DegRee(s)
stReet
CitY stAte Zip CoDe
DAYtime phone FAX
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 _____
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