Unrecognized and Untreated: Preventing and Treating Depression in Patients With

Epilepsy
November 01, 2004 | Depression, Somatoform Disorder, Comorbidity In Psychiatry, Maor
Depressive Disorder, !ddiction, !"coho" !b#se
$y !ntoaneta $a"abanov, MD and !ndres M% &anner, MD
M#"tip"e epidemio"o'ica" st#dies have sho(n that depression is the most fre)#ent comorbid
psychiatric disorder in patients (ith epi"epsy *&anner and $a"abanov, 2002+% Preva"ence rates
ran'e from 20, to --, in patents (ith rec#rrent sei.#res and /, to 0, in patients (ith
(e""1contro""ed sei.#res *2a#ser and &#r"and, 134-5 &o'eor'os et a"%, 13025 Mende. et a"%,
130/5 M#n'as, 13025 6obertson et a"%, 1304+% In addition, s#icide is one of the most common
ca#ses of death in patients (ith epi"epsy *$arrac"o#'h, 13045 6obertson et a"%, 1304+5 it (as
fo#nd to be a"most 10 times more fre)#ent in these patients than in the 'enera" pop#"ation
*6obertson et a"%, 1304+% In a st#dy carried o#t in a 'ro#p of patients (ith refractory epi"epsy
admitted to a video1e"ectroencepha"o'ram monitorin' #nit, $oy"an and co""ea'#es *2004+
fo#nd -0, of the patients (ere depressed, 13, had s#icida" ideation, and on"y 14, (ere
bein' treated (ith antidepressant medications% Despite the hi'h preva"ence of depression and
s#icide ris7, depression often 'oes #nreco'ni.ed and #ntreated in these patients% 6easons for
this inc"#de8
9reatin' physicians pay attention on"y to sei.#re contro" and fai" to in)#ire abo#t the
presence of psychiatric symptoms5
Patients are hesitant to report mood chan'es, and (hen they do, they tend to minimi.e
them o#t of fear of bein' tho#'ht of as cra.y5
Physicians and patients often consider symptoms of depression to be a norma" adaptation
process to epi"epsy and its associated prob"ems5 and
! fear amon' c"inicians that antidepressant dr#'s can e:acerbate the #nder"yin' sei.#re
disorder prevents many patients from receivin' treatment even (hen the need for
antidepressant treatment is reco'ni.ed%
9he 'oa" of this artic"e is to hi'h"i'ht the importance of reco'ni.in', preventin' and treatin'
depression in patients (ith epi"epsy%
Associated Risk Factors
Seizure-related factors% Many investi'ators have tried to find an association bet(een
depression and epi"epsy (ith respect to a'e of onset and sei.#re type, fre)#ency, and d#ration
*Indaco et a"%, 13325 &o'eor'os et a"%, 1302+% Depression has been identified more fre)#ent"y
in patients (ith sei.#res invo"vin' "imbic str#ct#res *predominant"y tempora" and fronta"
"obes+ and "ess often in patients (ith 'enera"i.ed sei.#re disorders% ;atera"ity of sei.#re foc#s
a"so has been considered as a possib"e ris7 factor, (ith sei.#re disorders of "eft hemispheric
ori'in bein' more "i7e"y to be associated (ith depression *Mende. et a"%, 130/+% 9his
association has been )#estioned by severa" investi'ators, ho(ever% 9here is evidence that
sei.#res ori'inatin' in or propa'atin' to the fronta" "obes increase ris7 of depression% <or
instance, patients (ith "eft tempora" foc#s and depression have been fo#nd to disp"ay bi"atera"
inferior fronta" hypometabo"ism on both positron emission tomo'raphy *P=9+ and sin'"e
proton emission comp#ted tomo'raphy *SP=C9+ st#dies *$romfie"d et a"%, 1332+% In fact,
decreased fronta" metabo"ism on P=9 and SP=C9 has been fo#nd in primary depression
*M#sse"man et a"%, 1330+%
Do depression and epi"epsy share common patho'enic mechanisms> 9(enty1si: cent#ries
a'o, 2ippocrates (as the first to s#''est a bidirectiona" re"ationship bet(een epi"epsy and
depression (hen he (rote *;e(is, 13?4+8
Me"ancho"ics ordinari"y become epi"eptics, and epi"eptics me"ancho"ics8 (hat
determines the preference is the direction the ma"ady ta7es5 if it bears #pon the body,
epi"epsy, if #pon the inte""i'ence, me"ancho"y%
9his observation has been s#pported by pop#"ation1based, contro""ed st#dies p#b"ished in the
past 10 years% <ors'ren and Nystrom *1330+ cond#cted a pop#"ation1based, case1contro""ed
st#dy of patients (ith ne("y dia'nosed epi"epsy in S(eden% 9hey discovered that patients
(ith epi"epsy (ere si: times more "i7e"y than contro"s to have e:perienced a history of
depression prior to the onset of the sei.#re disorder% In a separate st#dy, 2esdorffer et a"%
*2000+ cond#cted a pop#"ation1based, case1contro""ed investi'ation of the preva"ence of ne(1
onset epi"epsy amon' ad#"ts a'es -- and o"der and sho(ed that compared to contro"s,
patients (ere ?%4 times more "i7e"y to have had a history of depression prior to the onset of
their sei.#re disorder% 9hese researchers contro""ed for the impact of medica" therapies for
depression on sei.#re occ#rrence%
9hese data do not s#''est that depression ca#ses epi"epsy or vice versa, b#t they do s#''est
that the t(o disorders may share common patho'enic mechanisms% Indeed, epi"epsy and
depression may share common patho'enic mechanisms mediated by abnorma" serotoner'ic,
noradrener'ic, 1aminob#tyric acid *@!$!+1er'ic and dopaminer'ic secretion in the
centra" nervo#s system *Aobe et a"%, 13335 6ona"d and D#man, 13335 Schi"d7ra#t, 134?,
13/-+% In primary depression, decreased activity of these ne#rotransmitters has been
identified as one of the pivota" patho'enic mechanisms and the basis for antidepressant
pharmaco"o'ic treatment *@ar"o( et a"%, 13335 Maes and Me"t.er, 133-5 6iche"son, 1331+% In
anima" mode"s of epi"epsy #sin' the 'enetica""y epi"epsy1prone rat, decreased activities of
serotonin and norepinephrine have been sho(n to faci"itate the 7ind"in' process *Aobe et a"%,
1333, 133-5 ;ehmann, 13/45 Me"dr#m et a"%, 1302+, e:acerbate the sei.#re severity and
intensify sei.#re predisposition% Bther common patho'enic mechanisms for primary
depression and epi"epsy inc"#de dist#rbance of mesia" tempora" str#ct#res, partic#"ar"y
amy'da"a and hippocampa" formation, (hich have been fo#nd to be atrophic in both
disorders *Mathern et a"%, 13345 She"ine, 200?+%
Psychosocial factors% Patients (ith epi"epsy are s#bected to discrimination and "ac7 of
acceptance% Si'nificant ris7 factors for the deve"opment of depression inc"#de the sti'ma of
havin' epi"epsy5 the "ac7 of socia" s#pport5 the need to ma7e si'nificant ad#stments in
"ifesty"e, s#ch as 'ivin' #p drivin' privi"e'es or havin' to chan'e obs5 and the "imited
ed#cationa" and emp"oyment opport#nities% 9he individ#a"Cs sense of "ac7 of contro" over
their "ife may res#"t in overa"" fear of sei.#res and a'oraphobic behavior that may not
corre"ate (ith the act#a" severity of sei.#re activity% In addition, se:#a" dysf#nction has been
a very preva"ent prob"em amon' patients (ith epi"epsy, (ith rates ran'in' from 14, to //,
*Morre"", 1331+% !"tho#'h bio"o'ic and medication factors are "ar'e"y ca#sative, they c"ear"y
faci"itate the deve"opment of decreased se"f1esteem and depression%
Iatrogenic factors% !ntiepi"eptic dr#'s can ca#se psychiatric symptoms, especia""y
depression% Phenobarbita" *;#mina"+, fe"bamate *<e"bato"+, primidone *Myso"ine+, tia'abine
*@abitri"+, vi'abatrin *Sabri"+, topiramate *9opama:+ and "evetiracetam *&eppra+ are 7no(n
to ca#se depressive episodes *$arabas and Matthe(s, 13005 $rent et a"%, 13045 Co""aborative
@ro#p for =pidemio"o'y of =pi"epsy, 130/5 <errari et a"%, 130?5 McConne"" and D#ncan,
13305 6in' and 6eyno"ds, 13305 Smith and Co""ins, 1304+% In addition, co'nitive side effects
associated (ith some of these dr#'s *e%'%, topiramate+ are c"ose"y associated (ith previo#s or
c#rrent history of depression *&anner et a"%, 2000a+% Carbama.epine *9e'reto"+ and va"proic
acid *Depa7ene+ are anti1epi"eptic dr#'s (ith mood1stabi"i.in' effects, b#t can occasiona""y
ca#se depressive symptoms as (e"" *Smith and Co""ins, 1304+%
Depression and other psychiatric comp"ications have been seen after epi"epsy s#r'ery and
especia""y fo""o(in' an anterior tempora" "obectomy for the treatment of pharmacoresistant
tempora" "obe epi"epsy *Savard et a"%, 1330+% It is act#a""y not #n#s#a" to see mood "abi"ity
(ithin the initia" si: (ee7s after the s#r'ery% Most of the time these symptoms s#bside, b#t in
#p to ?0, of the patients, overt symptoms of depression become evident (ithin the first si:
months% Patients (ith prior history of depression are at 'reater ris7% 9he deve"opment of this
depression is independent of the posts#r'ica" sei.#re contro"%
Depression in patients (ith epi"epsy can be the e:pression of a re"ative"y rare phenomenon
7no(n as forced normalization% It consists of the deve"opment of psychiatric symptoms
fo""o(in' the cessation of sei.#res in patients (hose sei.#res had fai"ed to be contro""ed for a
"on' time% Dorsenin' of intericta" depression in patients (hen sei.#re contro" is achieved
may a"so be an e:pression of this phenomenon *6obertson, 1330+%
1 See more at8 http8EE(((%psychiatrictimes%comEartic"esE#nreco'ni.ed1and1#ntreated1
preventin'1and1treatin'1depression1patients1epi"epsyFsthash%0<)6B!.I%dp#f
http8EE(((%psychiatrictimes%comEartic"esE#nreco'ni.ed1and1#ntreated1preventin'1and1
treatin'1depression1patients1epi"epsy
$eberapa st#di epidemio"o'i te"ah men#n#77an bah(a depresi ada"ah yan' pa"in' serin'
teradi pada 'an''#an 7ei(aan dan mer#pa7an 7omorbid pada pasien den'an epi"epsi%
9in'7at preva"ensi ber7isar dari 20, menadi --, pada pasien den'an 7ean' ber#"an' dan
/, sampai 0, pada pasien den'an 7ean' yan' ter7enda"i den'an bai7% Se"ain it#, b#n#h diri
mer#pa7an sa"ah sat# penyebab pa"in' #m#m 7ematian pada pasien den'an epi"epsi%
Ditem#7an hampir 10 7a"i "ebih serin' pada pasien ini dibandin'7an pada pop#"asi #m#m%
Da"am seb#ah pene"itian yan' di"a7#7an pada se7e"ompo7 pasien den'an epi"epsi refra7ter
men'a7# #nit monitorin' video1e"ectroencepha"o'ram, $oy"an dan re7an *2004+ menem#7an
-0, dari pasien men'a"ami depresi, 13, memi"i7i ide b#n#h diri, dan hanya 14, sedan'
dira(at den'an obat antidepresan%
<a7tor 7ean'%
$anya7 pene"iti te"ah mencoba #nt#7 menem#7an h#b#n'an antara depresi dan epi"epsi
seh#b#n'an den'an #sia onset dan enis 7ean', fre7#ensi, dan d#rasi% Depresi te"ah
diidentifi7asi "ebih serin' pada pasien den'an 7ean' yan' me"ibat7an *ter#tama "ob#s
tempora" dan fronta"+ str#7t#r "imbi7 dan 7#ran' serin' pada pasien den'an 'an''#an 7ean'
#m#m% ;atera"itas fo7#s 7ean' #'a te"ah dian''ap seba'ai fa7tor risi7o yan' m#n'7in,
den'an 'an''#an 7ean' yan' berasa" dari be"ahan ota7 7iri menadi "ebih m#n'7in ter7ait
den'an depresi% !da b#7ti bah(a 7ean' yan' berasa" ata# menyebar7an 7e "ob#s fronta"
menin'7at7an risi7o depresi% Misa"nya, pasien den'an fo7#s tempora" 7iri dan depresi te"ah
ditem#7an #nt#7 menampi"7an hypometabo"ism fronta" bi"atera" yan' rendah pada 7ed#a
positron emission tomo'raphy *P=9+ dan emisi proton t#n''a" comp#ted tomo'raphy
*SP=C9+% $ah7an, pen#r#nan metabo"isme fronta" pada P=9 dan SP=C9 te"ah ditem#7an
da"am depresi primer%
D#a p#"#h enam abad yan' "a"#, 2ippocrates ada"ah oran' pertama yan' men#n#77an
h#b#n'an d#a arah antara epi"epsi dan depresi 7eti7a dia men#"is oran' yan' memp#nyai
7epribadian me"an7o"is biasanya menadi penderita epi"epsi% Pen'amatan ini te"ah did#7#n'
o"eh berbasis pop#"asi, st#di ter7ontro" yan' diterbit7an da"am 10 tah#n tera7hir% <ors'ren
dan Nystrom *1330+ me"a7#7an st#di 7as#s1ter7ontro" berbasis pop#"asi pasien yan' bar#
didia'nosis epi"epsi di S(edia% Mere7a menem#7an bah(a pasien den'an epi"epsi yan' enam
7a"i "ebih m#n'7in men'a"ami depresi dibandin'7an 7ontro"% =pi"epsi dan depresi dapat
dapat teradi pada berba'ai me7anisme pato'en #m#m yan' dimediasi o"eh serotoner'i7
norma", noradrener'i7, asam1aminob#tyric *@!$!+ se7resi1er'i7 dan dopaminer'i7 da"am
sistem saraf p#sat% Da"am depresi primer, pen#r#nan a7tivitas ne#rotransmiter ini te"ah
diidentifi7asi seba'ai sa"ah sat# me7anisme pato'en pentin' dan dasar #nt#7 pen'obatan
farma7o"o'i antidepresan% Me7anisme pato'eni7 #m#m "ainnya #nt#7 depresi primer dan
epi"epsi me"ip#ti 'an''#an str#7t#r mesia" tempora", 7h#s#snya ami'da"a dan pembent#7an
hippocamp#s, yan' te"ah ditem#7an menadi atrofi di 7ed#a 'an''#an%
<a7tor psi7ososia"%
Pasien den'an epi"epsi yan' men'a"ami dis7riminasi dan 7#ran'nya penerimaan% <a7tor
risi7o yan' si'nifi7an #nt#7 pen'emban'an depresi termas#7 sti'ma memi"i7i epi"epsi5
7#ran'nya d#7#n'an sosia"5 7eb#t#han #nt#7 memb#at penyes#aian yan' si'nifi7an da"am
'aya hid#p, seperti memberi7an ha7 istime(a men'em#di ata# har#s men''anti pe7eraan5
dan 7esempatan pendidi7an dan 7era yan' terbatas% 6asa individ# dari 7#ran'nya 7ontro"
atas hid#p mere7a dapat menyebab7an 7eta7#tan terhadap 7ean' dan peri"a7# a'oraphobic
yan' m#n'7in tida7 ber7ore"asi den'an 7eparahan a7tivitas 7ean'% Se"ain it#, disf#n'si
se7s#a" te"ah menadi masa"ah yan' san'at #m#m di antara pasien den'an epi"epsi, den'an
tarif ber7isar antara 14, sampai //,% Mes7ip#n seba'ian besar penyebab ada"ah fa7tor1
fa7tor bio"o'is dan obat1obatan, e"as menyebab7an pen#r#nan har'a diri dan depresi
*$a"abanov, 2004+%
<a7tor iatro'eni7%
Bbat antiepi"epsi dapat menyebab7an 'ea"a 7ei(aan, 7h#s#snya depresi%
<enobarbita" *;#mina"+, fe"bamate *<e"bato"+, primidone *Myso"ine+, tia'abine *@abitri"+,
vi'abatrin *Sabri"+, topiramate *9opama:+ dan "evetiracetam *&eppra+ di7etah#i
menyebab7an episode depresi% Carbama.epine *9e'reto"+ dan va"proat asam *Depa7ene+
ada"ah obat anti1epi"epsi den'an efe7 menstabi"7an s#asana hati, tapi 7adan'17adan' dapat
menyebab7an 'ea"a depresi #'a *$a"abanov, 2004+%
Depresi dan 7omp"i7asi 7ei(aan "ainnya te"ah ter"ihat sete"ah operasi epi"epsi dan
ter#tama meny#s#" "obe7tomi tempora" anterior #nt#7 pen'obatan pharmacoresistant epi"epsi
"ob#s tempora"% 2a" ini sebenarnya tida7 biasa #nt#7 me"ihat s#asana hati "abi"itas da"am
a(a" enam min''# sete"ah operasi% Seba'ian besar (a7t# 'ea"a ini mereda, tetapi pada ?0,
pasien, 'ea"a yan' e"as dari depresi menadi e"as da"am enam b#"an pertama% Pasien den'an
ri(ayat depresi memi"i7i risi7o "ebih besar% Per7emban'an depresi ini tida7 ter'ant#n' pada
7ontro" 7ean' pascaoperasi% Depresi pada pasien den'an epi"epsi dapat menadi e7spresi dari
fenomena yan' re"atif "an'7a yan' di7ena" seba'ai norma"isasi pa7sa% Ini terdiri dari
pen'emban'an 'ea"a 7ei(aan sete"ah bera7hirnya 7ean' pada pasien yan' 7ean'nya 'a'a"
di7ontro" #nt#7 (a7t# yan' "ama% Memb#r#7nya depresi interi7ta" pada pasien 7eti7a 7ontro"
7ean' dicapai #'a dapat menadi e7spresi fenomena ini *$a"abanov, 2004+%