wazir dissertation ii final

7/26/2019 Wazir Dissertation II Final

1/80

1

Abstract

Introduction: Depression is well known common co-morbid psychiatric condition

associated with primary epilepsy. This study showed that frequency of depression was

62% in primary epilepsy patient presenting to the eurology out-patient clinic of a

tertiary care hospital. !emale gender" high sei#ures frequency" polytherapy with $Ds

and long duration of primary epilepsy were found to be the factors leading to frequent

occurrence of depression in primary epilepsy patients

Objective:To determine the frequency of depression in patients with primary epilepsy

presenting to the eurology outpatient clinic of $ga &han 'ni(ersity )ospital &arachi.

Study Design:*ross-sectional study.

Study Setting: eurology outpatient department at $ga &han 'ni(ersity )ospital"

&arachi.

Duration of study: +2.11.2++, to 2.+.2+1+

Patients and Methods:$ total of one hundred cases of primary epilepsy patients were

enrolled in the study" after informed consent. They were asked to complete the /eck

depression in(entory while waiting in the neurology outpatient clinic. 0atients score more

than , were diagnosed as depression. esults were analy#ed on 0 (ersion 13.

Results: 4ut of hundred patients 56 56%7 and 55%7 were male and females

respecti(ely. The mean age of the patients was 82.1915.+8. The frequency of depression

was found to be 62 %7 in primary epilepsy patient.

Conclusions:The frequency of depression was found to be (ery high.

Key ords:0rimary pilepsy" Depression" :cteral depression" 0osticteral Depression.


2/80

2

Introduction

:t is of paramount importance that in 8+-+ % of patients epilepsy and depression are

found together. This frequency of depression in epileptics is of such an importance that it

cannot be o(erlooked or underestimated. /oth these disorders are (ery common in the

world and the two are linked together to such a significant le(el that the treating

physicians must be able to identify this coe;istence and treat both these disorders to a(oid

sufferings" mortality and morbidity. This approach of treatment will also reduce the

complications of these two ma


3/80

8

depressi(e illness associated with epilepsy the early inter(ention and starting treatment of

both these disorders will definitely minimi#e the patients" sufferings and will positi(ely

contribute to impro(e their quality of life.


4/80

5

Rationale of Study

ationale of the study is as follows>-

1. To determine the burden of this important co-morbidity depression7 in our

epileptic population.

2. To gi(e insight to general practitioners about this common association that is

(ery commonly under diagnosed and not treated appropriately.

8. This study will help to plan strategies to impro(e our knowledge in this regard

among communities of general practitioners" psychiatrists and neurologists.

5. This study will enable them to identify and treat depression in epileptic

patients on time" which will further impro(e control of sei#ures and quality of

life of patients with epilepsy.


5/80

Revie! of "iterature

pilepsy is one of the most common neurologic problems worldwide. The pre(alence of

epilepsy in the general population has been estimated to be -1+ per 1+++ people 17.

4(erall pre(alence of epilepsy in 0akistan is estimated to be ,.,, per 1+++ population

and highest pre(alence is seen in people younger than 8+ years of age 27.

The concept of common man regarding the etiology of epilepsy is (ery contro(ersial in

0akistan. $ recent study re(ealed that of those inter(iewed" 2% belie(ed that epilepsy

was caused by e(il spirits" black magic and en(y by others and certain other things 87.

imilar data from Turkey showed that 3+% of people thought that epilepsy resulted from

supernatural causes 57. De(eloping countries bear more than ,+% of the total burden of

disease caused by epilepsy worldwide as estimated by Disability $d


6/80

6

,-117. Depression is also common among people with epilepsy who e;perience many

sei#ures. esearchers plan to follow up with studies designed to see whether the co-

ccurrence of depression and epilepsy is e;plained by shared genetic susceptibility and

with studies that e;amine possible common underlying neurotransmitter abnormalities.

The association between epilepsy and depression has been known since ancient times.

)ippocrates was the first to suggest a bidirectional relationship between epilepsy and

depression when he said that melancholics ordinarily became epileptics and epileptics"

melancholics.127

#$ile$sy and Suicide:

The risk of suicide in epilepsy in the presence of depression is fi(efold higher in

women and twofold higher in men than in the general population.187 Therefore

recogni#ing depression in people with epilepsy is not only important to initiate

appropriate treatment but also to identify patients at risk for suicide. ilsson and

colleagues reported a , fold increase in the risk of suicide in the conte;t of a mental

illness in a large cohort of adults with epilepsy C,+617. 157 &anner et al suggested that

epilepsy and depression may share common pathogenic transmitter mechanisms

in(ol(ing decreased serotonergic" noradrenergic" dopaminergic" and $/$ergic acti(ity.

127 $ chronic illness is in itself depressing and burdensome. $ number of factors

contribute to depression in epileptic patients> the patientEs sense of ha(ing no control o(er

sei#ures" the ad(erse effects of medication" the illness itself" loss of independence" need

for life-long medication" fear that the stigma attached to epilepsy will interfere with social

relationships" and an;iety about finances and medical insurance. $ number of


7/80

3

antiepileptic drugs ha(e been implicated in the etiology of depression" especially

barbiturates.17*aplan et al. demonstrated that" among 131 children and adolescents with

epilepsy" 88% had an affecti(e or an;iety disorder" and 2+% had suicidal ideation.

)owe(er" among these children and adolescents" only 88% were recei(ing some form of

mental health ser(ice.167:ncreased suicide rates ha(e also been reported after temporal

lobe surgery e(en if the outcome was successful. $lthough some studies ha(e pointed to a

decrease in psychiatric morbidity in those who undergo surgical treatment for epilepsy. 137

$ questionnaire study from *anada found that lifetime pre(alence of suicidal ideation in

people with epilepsy 2%7 was higher than in people without epilepsy 18%7

17

. :n a

recent re(iew of epilepsy and suicide" it was stated that Fpredicting death caused by

suicide is a nearly impossible taskE. 1,7 :t is also suggested" howe(er" that when epilepsy is

diagnosed" a psychiatric and psychosocial assessment should be made to determine the

risk of suicide. :f the risk is thought to be increased" then inter(entions might include

appropriate treatment" referral to psychiatrist or e(en hospitali#ation. 1,7Depression in

patients with epilepsy has been reported peri- and inter-ictally. )owe(er" in patients with

frequent sei#ures" differentiation may be difficult.


8/80

DSM I% Criteria &or Major De$ressive Disorder

This disorder is characteri#ed by the presence of the ma

G Depressed mood most of the day" nearly e(ery day" as indicated by either sub


9/80

,

'able(): Classification of #$ile$sy

The :?$ re(ised criteria for the classification of epilepsies and epileptic

syndromes the :*7 was published in 1,,. :t maintains the basic dichotomy of

partial and generali#ed sei#ures. The term localization-relatedis used instead of partial or

focal to recogni#e that some types of sei#ures ha(e a shifting sei#ure focus.

1. ?ocali#ation-related focal" local" partial7 epilepsies and syndromes

1.1. :diopathic with age-related onset7

/enign childhood epilepsy with centrotemporal spikes

*hildhood epilepsy with occipital paro;ysms

0rimary reading epilepsy

1.2. ymptomatic

*hronic progressi(e epilepsia partialis continua of

childhood &o


10/80

1+

2. enerali#ed epilepsies and syndromes

2.1. :diopathic with age-related onset7

/enign neonatal familial con(ulsions

/enign neonatal con(ulsions

/enign myoclonic epilepsy in infancy

*hildhood absence epilepsy pyknolepsy7

=u(enile absence epilepsy

=u(enile myoclonic epilepsy impulsi(e petit mal7

pilepsy with grand mal sei#ures generali#ed tonic-clonic

sei#ures7 on awakening

4ther generali#ed idiopathic epilepsies not defined abo(e

pilepsies with sei#ures precipitated by specific modes of

acti(ation

2.2. *ryptogenic or symptomatic

o Best syndrome infantile spasms" /lit#-ick-

alaam &rampfe7

o ?enno;-astaut syndrome

o pilepsy with myoclonic-astatic sei#ures

o pilepsy with myoclonic absences

2.8. ymptomatic

2.8.1. onspecific cause

o arly myoclonic encephalopathy

o arly infantile epileptic encephalopathy with

suppression-burst


11/80

11

o 4ther symptomatic generali#ed epilepsies not

defined abo(e

2.8.2. pecific syndromes

o pileptic sei#ures complicating disease states

8. pilepsies and syndromes undetermined whether focal or generali#ed

8.1. Bith both generali#ed and focal sei#ures

o eonatal sei#ures

o e(ere myoclonic epilepsy in infancy

o pilepsy with continuous spike-wa(e acti(ity

during slow-wa(e sleep

o $cquired epileptic aphasia ?andau-&leffner

syndrome7

o 4ther undetermined epilepsies not defined abo(e

8.2. Bithout unequi(ocal generali#ed or focal features

5. pecial syndromes

5.1. ituation-related sei#ures

o !ebrile con(ulsions

o :solated sei#ures or isolated status epilepticus

o ei#ures occurring only with acute metabolic or to;ic e(ent

(Modified from the Commission on Classification and Terminology of the International

League Against Epilepsy.)


12/80

12

Pre Ictal De$ression

0rodromal depressi(e moods or irritability can occur hours to days before a sei#ure" and

are often relie(ed by the con(ulsion.2+7This was eloquently described by the 1,th century

psychiatrist rule Fphysicians and attendants do hope for a seizure in these often ery

difficult patients! "hich comes li#e a salation for eery$ody% the patient is much more

$eara$le for "ee#s thereafter. 0eople with epilepsy and with depression 217 and

psychosis" compared with those without psychiatric comorbidity" ha(e more e;tensi(e

functional imaging changes in cerebral regions such as the frontal lobes. Depressi(e

disorders which occur peri-ictally are usually short lasting and self-limiting. ecognition

and treatment of co-morbid depression and an;iety thus form an important consideration

in impro(ing quality of life in epilepsy ,7.4ne study e(aluated 15 adult patients with

epilepsy of whom 12 had partial sei#ure227. $ third of the patients with partial sei#ures

reported premonitory symptoms usually before secondarily generali#ed sei#ures

compared with the patients with primary generali#ed epilepsy 07. )alf of the

symptoms were emotional in nature and consisted of feelings of apprehension" dysphoria"

fear" elation" and anger. The symptoms continued for hours to days with wa;ing and

waning course.

Ictal De$ression

Depression can occur as part of the ictus itself. The common symptoms are guilt"

hopelessness" worthlessness" and suicidal ideation. ood descriptions are also found of

ictal sadness 287 and other psychic phenomena of a clearly epileptic nature" such as"

impulsions and suicidal tendencies. Aarini et al. 257present two cases of noncon(ulsi(e


13/80

18

status epilepticus" one with confused psychiatric manifestations and one with depressi(e

mood" where it also pro(ed (ery difficult to make the differential diagnosis between

epilepsy and a psychiatric disorder. :ctal depression appears to be more common in

patients with T?" in whom rates of o(er 1+% ha(e been reported.27aitat#is et al.37

conclude that 1+H2+% of people with temporal lobe epilepsy suffer from a psychiatric

disorder" with mood disorders" particularly depression" being the most common. o

association with laterality of sei#ure focus has been found. Borkers ha(e found ictal

depression to be of prolonged duration" often persisting into the postictal period" which

may represent that underlying depression was the most common ictal emotion.

@amamoto et al.267 described three cases of women with a depressi(e syndrome

comprising a decrease in energy and dri(e" loss of interest" loss of appetite" insomnia and

general fatigue" accompanied by hypochondriacal pains in the tongue and throat. hortly

afterwards" the three showed a temporal lobe epilepsy in the form of partial sei#ures.

Aende# and Doss reported a patient with a history of ictal depression who committed

suicide during a cluster of comple; partial sei#ures" *0s7. *omple; formed

hallucinations might accompany the depressi(e feelings. 0aciello et al. 237mention partial

sei#ures as a possible etiological factor of depression in epilepsy" especially in men with

left-sided epileptic foci. :nterestingly" se(eral workers ha(e found ictal depression to be

of prolonged duration" often persisting into the postictal period" which may represent

underlying subclinical sei#ure acti(ity.

'reat*ent of Pre(ictal and Ictal De$ression

0rodromal depression and ictal dysphoric state do not require treatment as suchI

impro(ement in sei#ure frequency should reduce the occurrence of these forms of


14/80

15

depression. /ut $nti-epileptic drugs may cause significant psychiatric side effects.

&anner27 studied 1++ patients who were treated for depression in epilepsy. :n almost a

third of these patients" the depression was considered iatrogenic" pro(oked by $Ds.

?e(etiracetam therapy was associated with depression in 2.% indi(idualsI this was dose

dependent and was also related to a past history of febrile sei#ures and status epilepticus.

2,7o(el treatments such as (agal ner(e stimulation ha(e recently been shown to ha(e a

positi(e effect on both epilepsy and co-morbid depression.8+7 ome patients may regard

these depressi(e pre and peri-ictal feelings as an Jearly warning systemJ. These early

warning symptoms actually alert patients and help them to seek early help and mo(e to

the place of safety. Aedication such as fast-acting ben#odia#epines"beha(ioural methods

such as progressi(e muscular rela;ation" biofeedback" and yogamay abort or pre(ent the

de(elopment of the attack.

Postictal De$ression

0ost-ictal depression is not uncommon although its pre(alence has ne(er been estimated.

:t can last from Khours to daysL and has features typical of a depressi(e syndrome.

/lumer has postulated that postictal depression is a consequence of the inhibitory

mechanisms in(ol(ed in the termination of sei#ures. 0sychiatric diseases and a sei#ure

frequency of less than one sei#ure per month were significantly associated with postictal

depressions.7


15/80

1

Inter(ictal De$ression

#$ide*iology

:nter-ictal depression between sei#ures is said to be (ery common than preictal

depression" but the e;act pre(alence is not known. :n literature" it is estimated as 2+%H

3+% depending on the patient group in(estigated.817

Depression is more common andMor more se(ere in patients with epilepsy than in patients

with other neurological and chronic medical conditions.There are many arguments for a

biological etiology of depression in epilepsy. The pre(alence of depression is greater in

patients with epilepsy as compared to other clinical groups with similar le(els of

disability.$nd among epileptics"patients with T? ha(e a higherincidence of depression

than do patients with either generali#ed epilepsy or e;tratemporal foci. These data

highlight the role of limbic structures in regulating affecti(e tone and emotional

e;perience. /rain magnetic resonance imaging A:7 studies re(ealstructural changes in

left mesial temporal and frontal regions 82-857. $lthough se(eral studies are in agreement

that an;iety and depression are more frequent in people with epilepsy than in the general

population" there is wide di(ergence with respect to the determining factors. 8-837 Nuiske

et al. 87ha(e shown that T? can be one factor of (ulnerability to the de(elopment of

mood disorders in focal epilepsy. :n a study" illiam and &anner8,7pro(ided additional

e(idence on the relationship between se(erity of depression and temporal lobe

dysfunction. They carried out proton magnetic resonance spectroscopy 1)A7 of the

temporal lobes in 88 patients with refractory T? with a mean age of 8 years and a

mean age of sei#ure onset of 1 years. e(erity of 1)A correlated significantly with

depression. The actual risk of antidepressant drugs causing worsening of sei#ures in


16/80

16

patients with epilepsy is small and should not deter the start of therapy. :n a study at the

ush pilepsy *enter" sertraline was found to definitely worsen sei#ures in only 1 out of

1++ patients. afnsson et al5+7 reported the results of a population-based incidence cohort

study from :celand" in which suicide had the highest standardi#ed mortality ratio A7

of . of all causes of death in persons with epilepsy. The rate of depression appears to be

lowest in community studies" increasing in patients attending hospital outpatient centers"

and is highest in patients with medically intractable epilepsy being e(aluated for epilepsy

surgery. Depression affects the quality of life of patients with epilepsy" e(en more than

sei#ures.

," 517

winkels and colleaguesE study showed that neither laterali#ation nor locali#ation predicts

risk of depression or an;iety in patients with partial epilepsy. $ prospecti(e" multicenter"

epilepsy surgery study of 86+ patients found no differences in the rates of depression or

an;iety based on the side or lobe of sei#ure focus at baseline or the side or lobe of

surgery.527

#tiology

Oarious causati(e factors ha(e been proposed for the de(elopment of depression in

people with epilepsy Table-17. The etiology is most likely to be multifactorial" with

se(eral different factors playing a part in each indi(idual patient.

+ender

!ew studies ha(e addressed this (ariable. :n the study of $ltshuler et al.587the highest

/eck Depression :n(entory scores were those of male patients with temporal lobe

epilepsy. $ssociation between epilepsy and psychiatric pathology is well recogni#ed in

those with a learning disability" who also tend to ha(e more se(ere epilepsy.55" 57


17/80

13

e(ertheless" not all authors could confirm the predominance of men among those who

attempt suicide and those who complete suicide" and &ohler et al.567con(ersely reported

a pre(alence of women. These contradictions on the gender distribution of depressi(e

epileptic patients may be e;plained by the lack of a representati(e sample. :n a recent

study" &alinin et al.187showed that the ratio between males and females with respect to

attempted suicide in each group was nearly 1>2. ei#ure control has consistently been

found to be a predictor of depression. 4ne study found that the pre(alence of depression

was high in those with acti(e epilepsy 13%7 compared with those in sei#ure remission

5%7.

537

$lthough the results of the (arious studies are not congruent" the ma


18/80

1

pre(alence of depression in A in this study was 2%. 4ne study on stroke patients

found a clear relation between pro;imity of the lesion to the left frontal pole and

depression" especially in the first few months after stroke. 5,7)owe(er" some studies ha(e

not found a structural brain lesion to be associated with depression in patients with

epilepsy.

+enetic vs. environ*ental factors

$ family history of depression has been reported in some studies. /eing female and

ha(ing a family history of mood disorders are common depression predisposing factors.

+" 17

spie et al.

27

found that increasing sei#ure frequency predicted psychiatric cases.

4thers" howe(er" ha(e found no association depression in epilepsy and family history.87

4nly one study has compared the incidence of psychiatric disorders in first-degree

relati(es and probands of patients with acquired epilepsy probands and relati(es of

patients with genetic epilepsy"


19/80

1,

'able(/: &actors contributing to de$ression in e$ile$tic $atients

!ollowing factors are considered important in both initiating and perpetuating depression

in epileptic patients" which are subsequently discussed in detail.

1.eurologic conditions like head in


20/80

2+

Intelligence 0uotient

tudies ha(e shown that uncontrolled epilepsy could affect normal brain de(elopment

and cause long-term cogniti(e impairment. 4ne study showed that intellectual

dysfunction defined as :N P3,7 was present in 3% of children with temporal lobe

epilepsy. $ge at onset of epilepsy is the best predictor of intellectual dysfunction. $nother

study showed that children with epilepsy did show a significantly less gain in !ull cale

:N o(er 1 year follow up when compared with normal children and suggested that there is

a process of mental deterioration shortly after the onset of epilepsy 7. $nother study

showed that there is long-term reduction in the white matter of the brain in those children

who ha(e chronic temporal lobe epilepsy. The reduction of white matter in the brain is

associated with long-term neuropsychological impairment.67

$lthough o(erall intellectual ability in children with epilepsy is comparable to the normal

childhood population they are at greater risk for learning problems and academic under

achie(ement. (en in those with normal intelligence" reports of deficits in specific areas

related to thinking and learning abilities are common" particularly in the areas of attention

and concentration" memory" organi#ational skills and academic achie(ement 3" 7.

ecent studies suggest that as many as one third of children with epilepsy are at risk of

ha(ing an autism spectrum disorder and that this risk is highest in those children who

ha(e sei#ure onset at a younger age. ,7:n children with autism" appro;imately one third

ha(e epilepsy" with the highest risk for those patients with se(ere mental retardation.6+" 617

#ndocrine1*etabolic factors

The impact of epilepsy itself and" in particular" antiepileptic drug $D7 treatment on

changes in hormones and metabolism has attracted rising attention in recent years. 62-67$s


21/80

21

a general consensus" different hormone or metabolic systems" usually balanced and

regulated (ia feedback mechanisms" are potentially in(ol(ed and deranged. nhanced

turno(er of norepinephrine has been reported in chemically induced sei#ures" and a wide

range of changes in tryptophan and -hydro;y indoleacetic acid -):$$7 ha(e been

documented during both electrically and chemically induced sei#ures. orepinephrine"

tryptophan" and -):$$ ha(e all been implicated in theories regarding the de(elopment

of depression. ndocrine changes" such as increases in prolactin and (asopressin" are seen

after spontaneous generali#ed sei#ures and after both unmodified and modified *T"

suggesting that they are not a consequence of the peripheral e(ents of a generali#ed

sei#ure but arise from the electrical sei#ure acti(ity. :n contrast" increases in plasma

growth hormone" adrenocorticotropic hormone $*T)7" and cortisol are less after

modified *T compared with unmodified *T. $fter generali#ed sei#ures" marked

acti(ation of the autonomic ner(ous system has been reported" with increases in

epinephrine and norepinephrine. $fter prolonged sei#ures" blood glucose increases" which

may promote insulin release" resulting in secondary hypoglycemia.

The abo(e changes are a reflection of enhanced neuronal and sympathetic acti(ity.

*oncomitant beha(ioral changes are belie(ed to result from enhanced e;citation and

synchronicity in some e;citatory systems and from enhanced inhibition affecting other

pathways or structures.

Age(at(onset and duration of e$ile$sy

$lthough some studies ha(e found an association between age-at-onset and duration of

epilepsy and depression. $ negati(e social attitude toward disability has been reported to


22/80

22

affect the ad


23/80

28

"aterali2ation of sei2ure focus

!lor-)enrywas the first who showed the more frequent occurrence of depressi(e disorder

in the right focus" while psychoses with schi#ophrenic symptoms in the left-sided focus in

temporal lobe epilepsy. Bhile according to chmit#" the opposite rule is true" and

depression in epilepsy has occurred more frequently in patients with left temporal foci.

e(eral ha(e found that laterali#ation was not a significant etiologic factor. 87 De(insky

and DEsposito indicated that with left-sided focus an;iety is de(eloping more frequently

simultaneously with depression" while in right-focus epilepsy isolated depression appears

more frequently. Oictoroff et al. suggested that in indi(iduals with left-sided foci" there is

a progressi(e (ulnerability to depressi(e KdecompensationL. 327 The Klaterality

hypothesisL has" howe(er been challenged by Nuiske"who noted a similar preponderance

of depressi(e symptoms in both right and left-sided pathologies. Depression in left-sided

epilepsy has been hypothesi#ed to be a consequence of sei#ure acti(ity. This has been

confirmed by euber et al.who found that following left-sided lobectomy" only patients

who became sei#ure-free impro(ed with respect to mood. 0atients with left-sided

epilepsies who did not become sei#ure-free and patients with right-sided T? howe(er"

did not impro(e.

:n summary" although there are studies associating depression with either left- or right-

sided foci" the ma


24/80

25

r*/!7" ha(e also been reported.357 0erico et al.reported that se(erity of depressi(e mood

and r*/! was in(ersely correlated in the left amygdala" lentiform nucleus" and

parahippocampal gyrus" and positi(ely correlated with right postero-lateral parietal

corte;. chmit# et al. howe(er" noted that patients with left-sided epilepsy and higher

scores on the /D: were found to ha(e more contralateral temporal and bilateral frontal

hypoperfusion measured with 0*T. The authors obser(ed that the hypoperfusion may

represent the widespread perfusion changes in(ol(ing the limbic frontal regions seen in

people with T?" which may be related to functional differentiation" interictal inhibition

of o(er acti(ity" or postictal depletion of substrates.

The inconsistencies in findings may in part be e;plained by the difficulty in reliably

laterali#ing the sei#ure focus using scalp electrodes. )owe(er" efforts ha(e been

made using automated means to detect and locali#e spikes recorded by depth andM or

subdural electrodes" )ufnagel at al. 37 obtained good correlations with regions of sei#ure

origin.

'he role of forced nor*ali2ation

obertson suggested that a decrease in the sei#ure frequency and thus forced

normali#ation can be brought about by> 17 a spontaneous reduction in sei#ures"

27 $ntiepileptic drugs" 87 temporal lobectomy. &rishnamoorthy suggests that the

phenomenon of forced normali#ation could be a unique kind of channelopathy. Aende#

et al367found that patients with epilepsy and depression had significantly fewer

generali#ed sei#ures than those without depression. These authors postulated that non-

reacti(e depression may worsen when $D therapy pre(ents generali#ation from an

epileptic focus. 4thers" howe(er" ha(e documented association with an increase in


25/80

2

sei#ure frequency337. ecent quality of life studies ha(e found" frequent sei#ures to be

associated with increased an;iety" depression" and stigma.867

Iatrogenic de$ression

Antie$ile$tic *edications

$nti-epileptic medications may cause significant psychiatric side effects. &anner

studied 1++ patients who were treated for depression in epilepsy. :n almost a third of

these patients" the depression was considered iatrogenic" pro(oked by $Ds. The $Ds"

which ha(e been commonly reported as depressogenic" are (igabatrin 1+%7" tiagabine

%7" topiramate 1%7 and phenobarbitone. ?e(etiracetam therapy was associated with

depression in 2.% indi(idualsI this was dosedependent and was also related to a past

history of febrile sei#ures and status epilepticus2,7.

*ertain $Ds ha(e been found to be psychotropic" are associated with beha(ioral changes

and depression. 0henobarbital 0/7 has been associated with depression in adults. /aren

found a higher pre(alence of both depression and suicidal ideation in adolescents and

children taking 0/ compared with carbama#epine */Q7. Dodrill 37 re(iewed ,+ studies in

which the beha(ioral effects of phenytoin 0)T7" barbiturates" */Q" or (alproic acid

O0$7 were assessed in patients with epilepsy and normal (olunteers. /arbiturates were

most clearly associated with negati(e beha(ioral changes" including depression. :n more

than half the studies" positi(e beha(ioral changes were associated with */Q decreased

an;iety and depression7 and O0$ impro(ed mood and increased happiness. 0henytoin

produced positi(e and negati(e effects in similar numbers of reports. Dalby reported a

psychotropic effect in appro;imately half the patients treated with */Q" which has also

been shown to be associated with less depression than primidone0A7 and 0)T.3,7*/Q


26/80

26

is also efficacious as an antidepressant in patients without epilepsy and is prophylactic in

the control of manic-depressi(e illness" as is O0$.

!ewer studies ha(e been performed with the newer anticon(ulsants. Oigabatrin O/7 is

an irre(ersible inhibitor of gamma-aminobutyric acid $/$7-transaminase and thus

increases le(els of the inhibitory neurotransmitter $/$. This drug appears to be

particularly associated with depression" de(eloping in up to 1+% of patients. The

depression typically occurs within a few weeks after the drug is introduced or after dose

increments. $ past history of psychiatric disturbance has been found to be a ma


27/80

23

of depression because" like O/" it increases the cerebral le(el of $/$. :ntra(enous

$/$ can produce dysphoria and an;iety in both normal (olunteers and patients with

bipolar affecti(e disorder. arly reports ha(e documented asthenia" ner(ousness and

depression to be ad(erse e(ents" although a monotherapy study reported ad(erse mood

changes only with rapidly titrated high-doses of T/ 7. :t is therefore too soon to make

recommendations about T/" but at present caution is ad(ised in prescribing it for

patients with a history of psychiatric disorder.

Metabolic effects of Anti(#$ile$tic Drugs

'ry$to$han

0ratt et al. reported that 0henobarbital 0/7 and phenytoin 0)T7 reduced plasma free

tryptophan" whereas */Q increased the le(els compared with normal (olunteers and

untreated patients with epilepsy. 0lasma free tryptophan influences serotonin turno(er.

Therefore" the authors postulated that this may be the mechanism that produces the

psychotropic effect of */Q and the depressant effects of 0/ and 0)T. $ randomi#ed

double-blind" triple crosso(er study in comple; partial epilepsy patients found no

cogniti(e differences between carbama#epine and phenytoin" but phenobarbital produced

greater cogniti(e deficits than the other two $Ds.67The magnitude of cogniti(e side

effects for (alproate treatment is likewise comparable to those seen in carbama#epine and

phenytoin therapies.37

&olate deficiency

$D therapy causes a decrease in serum" red blood cell" and *! folate le(els in 11-1%

of patients with epilepsy compared with normal controls. 7 Aost studies assessing O0$

ha(e found little effect unless the patient was also taking en#yme inducers" and the single


28/80

2

study assessing ?T has found no reduction in folate ,7. !olate deficiency has been

associated with psychiatric morbidity predominantly depression in patients both with and

without epilepsy ,+7. Oitamin /l2 deficiency has also been documented in patients with

epilepsy" especially those with psychiatric disturbance. :t is belie(ed to be secondary to

the antifolate action of the $Ds and may be e;acerbated by the administration of oral

folic acid supplements. !olates appear to ha(e a ma


29/80

2,

mechanism. Therefore" the postoperati(e lessening of e;citatory acti(ity and relati(e

predominance of inhibition may predispose to the emergence of dysphoric" affecti(e" and

psychotic disorders. :n adults with epilepsy" e(ents are controlled by e;ternal factors

more than by personal influence" causing an;iety and depression. :n addition" the

occurrence of sei#ures as well as the psychosocial problems triggered by epilepsy can

lead to the de(elopment of an e;ternal locus of control. 0atients only e;periencing simple

partial sei#ure 07 postoperati(ely also continue to e;perience depression ,57"perhaps

because the continued premonitory symptoms may act as a reminder of their sei#ures and

cause alarm that the aura may herald a generali#ed sei#ure.

Aany in(estigators ha(e found the side of temporal lobe surgery to be predicti(e of

postoperati(e depression. )owe(er" the (arious studies ha(e produced contradictory

findings. !enwick assessed ,6 patients after temporal lobectomy. $ quarter had

postoperati(e depressi(e symptoms" of which 32% had undergone a right-sided and 2%

a left-sided operation. 4ther authors ha(e also reported more mood changes after right-

sided surgery ,7.

Depression has been reported occurring de no(o after temporal lobectomy ,8" ,67 and

amygdalohippocampectomy ,7. 0ostoperati(e depression tends to be more common in

the first 2 months after surgery ,87and is often transient. ing et al.,37obser(ed that at 6

weeks after surgery 23% had de(eloped de no(o symptoms of an;iety and 28% of

depression" and 5% of patients had increased emotional lability. $t 8 months after

surgery" emotional lability and an;iety symptoms had diminished but depression tended

to persist.

Aany studies ha(e shown deterioration in the psychiatric and social status of patients


30/80

8+

after temporal lobectomy" especially if there is only partial impro(ement in their sei#ures

,7. Despite this" little research has e;amined this surprising and important aspect of

epilepsy surgery. (en postoperati(e freedom from sei#ures can be associated with

depression and beha(ioral problems ," ,,7.

:n the series reported by /ladin ,,7"6% of patients found ad these are as followsI

1. ;cellent sei#ure control.

2. o or mild preoperati(e psychopathology.

8. ood family support.

5. ood preoperati(e relationships at work and with friends.

. $ge at surgery P8+ years.

6. ood schooling and higher preoperati(e :N.


31/80

81

Psychosocial factors

pilepsy is associated with repeated but unpredictable episodes of loss of consciousness

or alteration in beha(ior" often resulting in embarrassment and loss of dignity. This may

predispose to depression" and this has been de(eloped into the concept of locus of

control. 0reoperati(e depression has been correlated with an e;ternal locus of control" a

perception of e(ents not being attributable to the patientRs own efforts but rather to the

effects of fate. Aore recently" the concept of attri$utional style has been (iewed as a

marker of learned helplessness. $ pessimistic attributional style is characteri#ed by the

attribution of causality for positi(e e(ents to Je;ternal" unstable and specific causesJ and

negati(e or ad(erse e(ents to Jinternal" stable and global causes"J an e;ample of which is

epilepsy. 0atients with epilepsy and a pessimistic attributional style may therefore

attribute global difficulties" such as


32/80

82

also reported. The authors stressed that employment did not merely pro(ide an income

but also pro(ided a daily occupation" which in turn would enhance self-esteem.

mployment rehabilitation needs to focus on pro(iding skills to cope with fear of

sei#ures and


33/80

88

this" in turn" may result in the later de(elopment of nonepileptic sei#ures.

0arental e;pectations of their child with epilepsy" along with family and social re


34/80

85

percei(ed as stigmati#ing" the indi(idual should ha(e limited the disclosure of the

attribute to few others and the indi(idual should percei(e that" if that attribute were more

widely known" significant redefinition of self-accompanied by (arious restrictions and

regulation of conduct" would follow. The stigmati#ing nature of epilepsy has caused the

psychosocial problems to outweigh the clinical problems of sei#ure control. pilepsy has

long been associated with disreputability" satanic possession" e(il and (iolence. Ayths"

misconceptions" pre


35/80

8

including lack of confidence" depression" and an;iety. $ study assessed fear of sei#ures in

,6 patients with (arious degrees of sei#ure control. They found that concern about

emotional functioning" followed by concerns about a(oiding sei#ure-inducing stimuli"

were the most frequently endorsed items. They also found that these concerns were

related to beha(ioral and emotional ad


36/80

86

differentiated between a depressi(e reaction or reactie depression and a depressi(e

illness or endogenous depression. Depressi(e feelings usually respond to circumstance

and tend to be understandable as a reaction to an e(ent. /etts describes a Jgrief reactionJ

that may affect the patient and family when the diagnosis of epilepsy is gi(en. !irst" there

may be a period of denial followed bystruggle during which guilt and anger may be

e;perienced and then depressie feelings as they come to terms with the diagnosis. This

depressi(e reaction should be regarded as normal. 0atients and their family should be

encouraged to work through it until acceptance and resignation occur. Depressi(e

illnesses can be diagnosed using the International Classification of /isease criteria

:*Dl+7. Depressed mood" reduced energy" and loss of interest and en reduced concentration and attention reduced self-esteem" self-confidence"

ideas of guilt and unworthiness" pessimistic (iews of the future" ideas or acts of self-harm

or suicide" disturbed sleep" and diminished appetite. 4ne can also diagnose depression

according to DA-:O criteria227" which also ha(e strict stipulations. The low mood tends

to be per(asi(e and long lasting. *lassically" patients wake early feeling unrefreshed"

with low mood that may impro(e as the day progresses diurnal mood (ariation7. Despite

these guidelines" diagnosis can be difficult and it has been stressed that drug into;ication

especially with 0)T" can resemble depression.

Pheno*enology of Interictal De$ression


37/80

83

Aende# et al. compared 2+ hospitali#ed depressed patients with epilepsy with 2+ patients

suffering from depression alone. They found that more than half of the depressed patients

presented with an agitated" psychotic depression with impulsi(e suicidal beha(ior. /oth

groups had a similar number of prior suicide attempts and shared the following

characteristics of depression> anhedonia" tearfulness" psychomotor retardation" reduced

energy and libido" along with appetite and sleep disturbances. 0atients with epilepsy and

depression had significantly fewer JneuroticJ traits such as an;iety" guilt" rumination"

hopelessness" low self-esteem" and somati#ation. )owe(er" these patients had

significantly more JpsychoticJ symptoms such as paranoia" delusions" and persecutory

auditory hallucinations. /etween episodes of ma


38/80

8

month. They further in(estigated these symptoms in 3 patients with epilepsy undergoing

neurodiagnostic monitoring and found 55% to ha(e an interictal dysphoric disorder. The

syndrome comprised eight symptoms" of which most patients e;perienced fi(e>

depressi(e moods intense to the point of suicidal despair" accompanied by anergia" pain"

insomnia" an;iety" phobic state" intermittent paro;ysmal irritability to the point of

e;plosi(e anger or rage" and euphoric moods consisting of a Jsudden" endogenous sense

of blissful euphoria in the absence of elated hyperacti(ityJ. /lumer stressed that patients

with a large number of the abo(e symptoms may be at increased risk for sudden

une;pected suicide attempts and the de(elopment of an interictal psychosis. )e noted that

all the symptoms" not merely the depressi(e ones" tend to respond rapidly to low-dose

antidepressants.


39/80

8,

'reat*ent of Interictal De$ression

Psychological treat*ent

0sychotherapeutic approach addressing the emotional and cogniti(e state of the patients

by trained therapists should be offered to all newly diagnosed patients and their families.

This would pro(ide an opportunity to educate the patients and their families about

epilepsy" to determine their emotional reactions to the condition" and to correct false

beliefs. Qiegler suggested the approach of optimistic fatalism! e;plaining that they ha(e

epilepsy" which may or may not get better" and suggesting that they focus on Jhow to

make the best of it.J

Depressi(e reactions should be treated with supporti(e therapy" counseling 87" and

rehabilitation 1+57. /etts has stressed that these reactions should not be treated medically

unless prolonged" and therefore it is ad(ocated that rehabilitation following epilepsy

surgery" to enable the patients to li(e without the help of an illness that had been both a

Jweapon and a shieldL because such episodes may become protracted if treated with

antidepressants or tranquili#ers. Aore se(ere actions may require speciali#ed

psychotherapy" such as" cogniti(e-beha(ioral therapy. $n inter(ention aimed to alter

attributional style toward optimism has been de(eloped for patients with epilepsy which

may ameliorate depression 1+7. 0sychotherapy can also be used to impro(e coping skills"

and this has been shown to impro(e mild depressi(e illness and an;iety and to reduce

sei#ure frequency.1+7 0atient support groups introduce patients to fellow Rsufferers who

can pro(ide emotional support and help o(ercome feelings of hopelessness" re


40/80

5+

Adjust*ent of antie$ile$tic drugs 3A#Ds4

The sei#ure and epilepsy syndrome should be ree(aluated and treated with the most

appropriate $D" preferably as monotherapy. Oalproate" */Q" and ?T should be

considered as first-line $Ds and" whene(er possible" barbiturates" 0)T" and O/

should be a(oided. )owe(er" priority should be gi(en to attaining optimal control

because remission of sei#ures has been found to be accompanied by an impro(ement in

psychosocial function.

Antide$ressant treat*ent

+eneral consideration

$ppro;imately 6+-3+% of acute ma


41/80

51

with respect to efficacy as compared with the T*$s 1+6" 1+37" although there is some

e(idence that (enlafa;ine may ha(e a more rapid onset of action. 1+7

Cognitive and neurological Side effects of antide$ressants.

Me*ory

0atients with epilepsy often complain of memory disturbance. Depression has also been

shown to ad(ersely affect memory and other cogniti(e functions. The older T*$s"

especially amitriptyline" along with mianserin and tra#odone" ha(e been found to produce

cogniti(e impairment and therefore should be a(oided. The :s 1+17and mirta#apine 8,7

ha(e not been shown to impair memory processes

Se5ual function

e;ual dysfunction" both impaired desire and performance" has been reported in both

men and women with epilepsy ,37. Diminished se;ual satisfaction is often reported in

outpatients suffering from depression. The reported incidence of se;ual dysfunction

associated with antidepressant treatment (aries widely among studies and can affect

libido" arousal" and orgasm. /alon found se;ual dysfunction in 58.8% and painful orgasm

in 1% of male patients treated with antidepressants. They did not find that dysfunction

was linked to any particular antidepressant. T*$s" mianserin" A$4 inhibitors"

(enlafa;ine" :s and rebo;etine data on fileI 0harmacia and 'p


42/80

52

study7 and the :s. e;ual dysfunction has been reported in -3% with fluo;etine"

mainly anorgasmia" although retrograde e


43/80

58

this" its use in patients with epilepsy is not recommended that may predispose to the

precipitation of drug-induced sei#ures and that these may be either patient- or drug-

related. The patient-related predisposing factors ha(e been documented in o(er half the

patients who e;perienced sei#ures when taking the T*$s and buproprion 327. $nother

report has suggested that patients at risk for de(eloping sei#ures during psychotropic drug

treatment can be identified by ha(ing enhanced amplitude of the early cortical

somatosensory e(oked potentials 0s7 after median ner(e stimulation.

#lectro convulsive thera$y

*T is not contraindicated in patients with epilepsy and may be life-sa(ing in those with

se(ere or psychotic depression not responding to antidepressants. :t has e(en been found

to be safe after temporal lobectomy. There ha(e been reports of spontaneous sei#ure in

patients after *T 8,7.tudies ha(e also shown that the sei#ure threshold tends to rise by

an a(erage of +% range 2-2++%7 during the course of treatment" therefore some

workers consider *T to be an effecti(e anticon(ulsant. The efficacy of *T may be

reduced if $Ds decrease the intensity of the induced sei#ures.


44/80

55


45/80

5

ORI+I-A" S'6D7


46/80

56

Objective:

To determine the frequency of depression in patients with primary epilepsy presenting to

the eurology outpatient clinic of $ga &han 'ni(ersity )ospital &arachi.

O$erational Definition:

Pri*ary e$ile$sy>Two or more unpro(oked sei#ures paro;ysmal brief spells lasting

less than minutes" (arying in presentation from subtle staring to generali#ed shaking

and falling down7 at least 25 hours apart with no immediate identifiable causeI without

focal neurological deficitI normal laboratory tests metabolic profile and *! analysis7

and normal neuroimaging *T with no hypodense or hyperdense lesionsM A: with no T1

and T2 hypointense or hyperintense lesions and no gadolinium enhancement7" were

diagnosed as primary idiopathic7 epilepsy.

De$ression:Depression was diagnosed according to /eck Depression :n(entory. $ total

score S, was taken as depression.


47/80

53

Material and Methods

Setting:eurology outpatient department at $ga &han 'ni(ersity )ospital" &arachi.

Study Design:*ross-sectional study.

Duration of Study: +2.11.2++, to 2.+.2+1+

Sa*$le Si2e: $ total of one hundred cases of primary epilepsy patients were enrolled in

the study" after informed consent.

Sa*$le 'echni0ue: on-probability purposi(e sampling.

Sa*$le selection

Inclusion:

1. 0atients of primary epilepsy abo(e 1 years of age with duration of epilepsy

greater than 1 year.

2. ither gender.

#5clusion:

1. Diagnosed cases of depression and on antidepressants prior to de(elopment of

epilepsy.

2. 0atients in whom the diagnosis of primary epilepsy was in doubt.

8. 0atients of 0arkinson disease" multiple sclerosis" dementia" stroke" mental

retardation" $l#heimer disease" *ancer" )uman immunodeficiency (irus infection"

diabetes mellitus" chronic hepatitis on :nterferon therapy" hypothyroidism"

*ushing syndrome.


48/80

5

Data collection:0atients meeting inclusion and e;clusion criteria were enrolled from

outpatient department of neurology" after informed consent. 0atients were assured of

confidentiality. They were gi(en Nuestionnaire with /eck depression in(entory while

waiting in the neurology outpatient clinic. They were requested to read each item

carefully prior to encircling the numbers +" 1" 2 or 87.

The assigned questionnaire was collected with the demographic data of age and gender

besides duration and types of the sei#ures" anti-epileptic drugs and the frequency of

sei#ures. Nuestionnaire was taken back after 2 minutes. The numbers encircled were

summed up after the patientEs completion of questionnaire. 0atients who scored more

than , were diagnosed as depression. The identified depressed patients were offered

treatment.

Data analysis: $ll the analysis was conducted on tatistical 0ackage for ocial ciences

07 (ersion 13. Aean 9 standard de(iations were calculated for continuous (ariables

e"gI age" duration of epilepsy7. !requencies and percentages were calculated for gender"

type of sei#ures" type of $D therapy" number of attacks of sei#ures per year and

depression in the epileptic patients. tratification was done with regard to gander" type of

sei#ures and type of $D therapy.


49/80

5,

Results

The data of the study is analy#ed by using 0 software getting frequency tables of

(arious (ariables of the study. To see the effect of (arious (ariables on depression in

primary epilepsy patients cross tabulation were obtained through the software.

Total number of known primary epilepsy patients enrolled in this study were 1++ out of

which 5656%7 and 55%7 were male and female respecti(ely" as shown in table-8. The

mean age of the patients was 82.1915.+8" as shown with table-5. The frequency of

depression was found to be 62 %7 in primary epilepsy patient" as shown in table-6. The

types of sei#ures in our primary epilepsy patients were generali#ed sei#ures and partial

sei#ures i.eI either comple; partial sei#ures or secondarily generali#ed partial sei#ures7 in

6262%7 and 88%7 respecti(ely" as shown in table-3.!or the treatment of their primary

epilepsy" 5353%7 and 88%7 of patients were recei(ing $Ds as monotherapy and

polytherapy respecti(ely" as shown in table-. umbers of attacks of sei#ures per year

were +-1+" 11-2+ and 21-2 in ++%7" 2222%7 and 22%7 patients respecti(ely" as

shown in table-,. The mean duration of epilepsy of the patients was 12.,9+,.+6" as

shown in table-.

ender-wise frequency of depression in primary epileptic patients was found to be 2

5+.8%7 and 83,.3%7 in male and female respecti(ely" as shown in table-1+. !requency

of depression in primary epilepsy patients with respect to the type of sei#ures" was found

to be 25 8.3%7 and 8 61.8%7 in those with partial sei#ures and generali#ed sei#ures

respecti(ely" as shown in table-11. !requency distribution of depression with respect to

$D therapy in patient" was found to be 121,.5%7 and ++.6%7 in those on


50/80

+

monotherapy and polytherapy respecti(ely" as shown in table-12.!requency distribution

of depression in epilepsy patient with respect to numbers of sei#ure attacks per year in

this study was found to be 18 21.+%7" 21 88.,%7 and 2 5.+%7 in those with +-1+" 11-

2+ and 21-2 attacks of sei#ures per year respecti(ely" as shown in table-18.


51/80

1

'able(8: Male1&e*ale Distribution of #$ile$tics

n 9 )

+ender &re0uency

Male 5656%7

&e*ale 55%7

'otal 1++1++%7

-u*ber 3;4


52/80

2

'able(


53/80

8

'able(=: Duration of e$ile$sy

Mean 12.90years

Std. deviation 09.06


54/80

5

'able(>: De$ression in #$ile$sy

n9)

Depression FrequencyYES 62 (62%)NO 38 (38%)

Total 100(100%)

-u*ber 3;4


55/80

'able(?: 'y$e of e$ile$tic sei2ures

n 9 )

Type of seizures Frequencyartial seizures 38(38%)!eneralized

seizures

62(62%)

Total 100(100%)

-u*ber3;4


56/80

6

'able(@: 'y$e of A#D thera$y

n 9 )

"ED T#erapy Frequency

Monot#erapy 47(47%)

olyt#erapy 53(53%)

Total 100(100%)

-u*ber 3;4


57/80

3

'able(: -o. of sei2ure attacBs1year

n 9)

No. of attac$%year Frequency

&'(& 50(50%)

((')& 22(22%)

)(')* 28(28%)

Total 100(100%)

-u*ber 3;4


58/80

'able(): +ender !ise fre0uency of de$ression in e$ile$sy

n9)

+ender De$ression ve De$ression (ve

Male 2 5+.8%7 21.8%7

&e*ale 83,.3%7 1355.3%7

'otal 621++%7 81++%7

-u*ber 3;4


59/80

,

'able()): 'y$e of sei2ure !ise fre0uency of de$ression in $ri*ary e$ile$sy

n 9 )

'y$e of sei2ures De$ression ve De$ression (ve

Partial sei2ures 25 8.3%7 15 86.%7

+enerali2ed sei2ures 8 61.8%7 25 68.2%7

'otal 62 1++%7 8 1++%7

-u*ber 3;4


60/80

6+

'able()/: A#D thera$y !ise fre0uency of de$ression in e$ile$sy

n 9 )

A#D thera$y De$ression ve De$ression (ve

Monothera$y 12 1,.5%7 8 ,2.1%7

Polythera$y + +.6%7 8 3.,%7

'otal 62 1++%7 8 1++%7

-u*ber 3);4


61/80

61

'able()8: -o. of sei2ures attacB $er year !ise fre0uency of de$ression in e$ile$sy

n 9 )

-o. of attacB $er year De$ression ve De$ression (ve() attacBs $er year 18 21.+%7 83 ,3.5%7

))(/ attacBs $er year 21 88.,%7 1 2.6%7

/)(/= attacBs $er year 2 5.+%7 + +.+%7

'otal 62 1++%7 8 1++%7

-u*ber 3;4


62/80

62

DISC6SSIO-

This cross-sectional study showed that rate of depression is our primary epilepsy patient

was high i.eI 62%7 comparable to the high rate of depression in the epileptic patients in

one :ranian study i.eI 6%7.This study further documents that depression is a frequent

accompaniment of primary epilepsy. o all primary epilepsy patients should be screened

for depression and treated in time to a(oid the complications associated with depression

like suicide" the risk of which is estimated to be 1+ times higher than that in the general

population.

This study showed that frequency of depression with respect gender in epileptic patients

was 5+.8% and ,.3% in male and female respecti(ely. The higher frequency of

depression in female gender in our study is comparable to that found in other studies"

where the pre(alence of depression has been reported to be from 2-66 % in females.

This higher frequency of depression in female epileptic can be e;plained on the basis of

decreased support" lack of guidance" lack of autonomy" decreased decision-making

power" socioeconomic status" financial difficulties and low educational le(els.

4ur study showed that epileptic patients with high sei#ure frequency and on high number

of antiepileptic drugs i.eI polytherapy7 were ha(ing depression more frequently as

compared to those epileptics patient who had less frequent sei#ures and were on a low

number of antiepileptic drugs i.eI monotherapy7. amilar effects of these (ariables high

sei#ure frequency and polytherapy7 on the frequency of depression in epilepsy has been

shown in (arious studies.


63/80

68

:n one hospital based cross-sectional study" similar to our study" conducted in in three

uni(ersity hospitals of reece" 2+1 patients with epilepsy were enrolled. 4ut of 2+1

patient 1.2% males with mean age 88.2 9 1+.+ years and mean disease duration of 18.,

9 ,. years almost similar to mean age and mean disease duration of the patient of our

study. Depression was assessed in the interictal state with the /eck Depression :n(entory

e;actly in same way as in our study. The results of this study are comparable to our study.

This reek study found that high sei#ure frequency and high number of antiepileptic

drugs i.eI polytherapy7 were positi(ely associated with depression in epilepsy whereas

less frequent sei#ures and a low number of antiepileptic drugs i.eI monotherapy7 were

negati(ely associated with epilepsy.

4ur study showed that the frequency of depression was 8.3% and 61.8%" in those with

partial sei#ures and generali#ed sei#ures types" respecti(ely. These results contrast other

studies 2+" 8" 317where there is frequent occurrence of depression in patient with partial

sei#ures. This difference could be because of the confounding factors" like gender" age"

duration of disease" frequency of attack of sei#ures and types of $Ds being recei(ed by

the patients.

Depressi(e disorders are the most common type of psychiatric co-morbidity in patients

with epilepsy. $lthough no one questions that epilepsy is a risk for depression" recent

studies ha(e also re(ealed that a history of depression is associated with a 5- to 6-fold

greater risk of de(eloping epilepsy.

Depression in people with epilepsy often remains undiagnosed and under treated 67.The

pre(alence of depression in epilepsy has been estimated to range between 2+% and +%


64/80

65

of patients7.Bhether preceding the onset of epilepsy or becoming apparent during the

course of epilepsy" depression is a chronic illness that negati(ely affects the quality of life

of people with epilepsy.," 1+74n the other hand" achie(ement of the sei#ure-free state

significantly impro(es quality of life ,-117.ot only are patients with epilepsy more likely

to e;perience a depressi(e disorder but a history of depressi(e disorder preceding the

onset of the sei#ure disorder is more likely to be identified in patients with epilepsy than

in a control group.1+,7These data suggest either a possible Jbi-directionalJ relationship

between these two disorders or the presence of common pathogenic mechanisms that

facilitate the occurrence of one in the presence of the other.

/lumer argues that intractable temporal lobe epilepsy is often accompanied by a

psychiatric syndrome" which he calls Jinterictaldysphoric disorderJ. :nterictaldysphoric

disorder is surprisingly responsi(e to antidepressant medications" although it is seldom

diagnosed or treated.11+7

:n a meta-analysis on ele(en studies in(estigating factors associated with depression in

0akistan" gender" socioeconomic status" lack of support" financial difficulties and low

educational le(els were found to ha(e statistically significant positi(e associations with

depression. 11174ther factors identified by some studies include age" lack of autonomy

and unemployment.

$ssociation of depression with epilepsy is well documented and again the quality of life

of epileptic patient is primarily determined by the emotional state of patient rather than

the primary illness.

$lthough there is general agreement that pre(alence rates of psychiatric co-morbidity are

higher among epilepsy patients" the relationship between sei#ure type and sei#ure focus


65/80

6

remains uncertain.

pilepsy is one of the most common and serious brain disorder worldwide affecting

indi(iduals of all ages" races" and social class. either social nor geographical boundaries

are e;empted. De(eloping countries bear more than ,+% of the total burden of disease

caused by epilepsy worldwide as estimated by Disability $d


66/80

66

&eeping this in mind" screening high-risk patients and" if necessary" the in(ol(ement of a

consulting psychiatrist can pro(e to be critical in impro(ing patient outcome.

The negati(e cognition in epileptic patients with depression and the stigma attached to it

needs psychological inter(ention apart from drug therapy. o it is important to identify

and treat depression in our epileptic patients on time" which will further impro(e control

of sei#ures and quality of life of patients with epilepsy.


67/80

63

Conclusions

This study concludes that the frequency of depression is found to be (ery high in our

primary epileptic patients (isiting a tertiary care hospital. o" recommendations in the

light of this study are as follow>

1. &eeping in (iew the high pre(alence of clinical depression in epileptic patients"

e(ery patient with epilepsy must be looked for depressi(e disorder.

2. Treated promptly to a(oid the complications associated with depression like

suicide.

8. tigmati#ation of epilepsy per se which could be a reacti(e element for emotional

upset may be considered and attention should be gi(en to effecti(e

destigmati#ation dri(e.


68/80

6

R#R#-C#S

1. /ell " ander =B. The epidemiology of epilepsy> the si#e of the problem.

ei#ure. 2++1 =unI1+57>8+6-15I qui# 1-6.

2. &hatri :$" :annaccone T" :lyas A" $bdullah A" aleem . pidemiology of

epilepsy in 0akistan> re(iew of literature. = 0ak Aed $ssoc. 2++8

DecI8127>,5-3.

8. hafiq A TA" Tariq $" aleem $" Qafar A" &huwa82-8.

5. $#i# )" u(ener $" $khtar B" )asan &Q. *omparati(e epidemiology of

epilepsy in 0akistan and Turkey> population-based studies using identical

protocols. pilepsia. 1,,3 =unI867>316-22.

. &anner $A. Depression in epilepsy> a frequently neglected multifaceted disorder.

pilepsy /eha(. 2++8 DecI5 uppl 5>11-,.

6. =ones =" )ermann /0" /arry ==" illiam !" &anner $A" Aeador &=. *linical

assessment of $;is : psychiatric morbidity in chronic epilepsy> a multicenter

in(estigation. = europsychiatry *lin eurosci. 2++ pringI1327>132-,.

3. aitat#is $" Trimble A" ander =B. The psychiatric comorbidity of epilepsy.

$cta eurol cand. 2++5 4ctI11+57>2+3-2+.

. &anner $A 0. Depression in epilepsy> a common but often unrecogni#ed

comorbid malady. pilepsy /eha(. 2+++I117>83H1.

,. =ohnson &" =ones =" eidenberg A" )ermann /0. The relati(e impact of

an;iety" depression" and clinical sei#ure features on health-related quality of life

in epilepsy. pilepsia. 2++5 AayI57>55-+.


69/80

6,

1+. ?oring DB" Aeador &=" ?ee 0. Determinants of quality of life in epilepsy.

pilepsy /eha(. 2++5 DecI67>,36-+.

11. /oylan ? !?" ?abo(it# D?. Depression but not sei#ure frequency predicts

quality of life in treatment-resistant epilepsy. eurology. 2++5I62>2H61.

12. &anner $A. Depression in epilepsy> a neurobiologic perspecti(e. pilepsy *urr.

2++ =an-!ebI17>21-3.

18. &alinin OO" 0olyanskiy D$. ender differences in risk factors of suicidal

beha(ior in epilepsy. pilepsy /eha(. 2++ AayI687>525-,.

15. ilsson ?" $hlbom $" !arahmand /@" $sberg A" Tomson T. isk factors for

suicide in epilepsy> a case control study. pilepsia. 2++2 =unI5867>655-1.

1. 0lioplys . Depression in children and adolescents with epilepsy. pilepsy /eha(.

2++8 4ctI5 uppl 8>8,-5.

16. *aplan " iddarth 0" urbani " )anson " ankar " hields BD. Depression

and an;iety disorders in pediatric epilepsy. pilepsia. 2++ AayI567>32+-8+.

13. Bachi A" Tomikawa A" !ukuda A" &ameyama " &asahara &" asagawa A" et

al. europsychological changes after surgical treatment for temporal lobe

epilepsy. pilepsia. 2++1I52 uppl 6>5-.

1. Telle#-Qenteno =!" 0atten /" =ette " Billiams =" Biebe . 0sychiatric

comorbidity in epilepsy> a population-based analysis. pilepsia. 2++3

DecI5127>2886-55.

1,. Oerrotti $" *icconetti $" corrano /" De /erardis D" *otellessa *" *hiarelli !" et

al. pilepsy and suicide> pathogenesis" risk factors" and pre(ention.

europsychiatr Dis Treat. 2++ $prI527>86-3+.


70/80

3+

2+. ?ambert AO" obertson AA. Depression in epilepsy> etiology" phenomenology"

and treatment. pilepsia. 1,,,I5+ uppl 1+>21-53.

21. al#berg A" Taher T" Da(ie A" *arne " )icks =" *ook A" et al. Depression in

temporal lobe epilepsy surgery patients> an !D-0T study. pilepsia. 2++6

DecI53127>212-8+.

22. )ughes = D" !eldmann " /romfield . . 0remonitory symptoms in epilepsy. .

ei#ure. 1,,8 2>2+1-8.

28. /artolomei !" Trebuchon $" a(aret A" egis =" Bendling !" *hau(el 0. $cute

alteration of emotional beha(iour in epileptic sei#ures is related to transient

desynchrony in emotion-regulation networks. *lin europhysiol. 2++

4ctI1161+7>2538-,.

25. Aarini *" 0armeggiani ?" Aasi " DR$rcangelo " uerrini . oncon(ulsi(e

status epilepticus precipitated by carbama#epine presenting as dissociati(e and

affecti(e disorders in adolescents. = *hild eurol. 2++ $ugI2+7>6,8-6.

2. De(insky + !" antos =" Oahle O" *arter =" /rown &" )ecimo(ic ). Depression

in epilepsy> ignoring clinical e;pression of neuronal network dysfunction .

pilepsia. 2++5I5uppl 2>2-88.

26. @amamoto " Aiyamoto T" Aorita " @asuda A. Depressi(e disorders preceding

temporal lobe epilepsy. pilepsy es. 2++2 $prI5,27>18-6.

23. 0aciello " Aa##a A" Aa##a . UDepression in epilepsy> symptom or syndromeV.

*lin Ter. 2++2 o(-DecI1867>8,3-5+2.

2. &anner $A &$" !rey A. The use of sertraline in patients with epilepsy> :s it safe

pilepsy /eha(. 2+++I1>1++-.


71/80

31

2,. Aula A" Trimble A" @uen $" ?iu " ander =B. 0sychiatric ad(erse e(ents

during le(etiracetam therapy. eurology. 2++8 ep ,I617>3+5-6.

8+. )arden *?" 0ul(er A*" a(din ?D" ikolo( /" )alper =0" ?abar D. $ 0ilot

tudy of Aood in pilepsy 0atients Treated with Oagus er(e timulation.

pilepsy /eha(. 2+++ $prI127>,8-,.

81. A. 0sychiatric disorders in epilepsy> clinical aspects. pilepsy /eha(.

2++2I8>8,H5.

82. /rody $?" /arsom AB" /ota " a;ena . 0refrontal-subcortical and limbic

circuit mediation of ma1+2-12.

88. Aer(aala " !ohr =" &ononen A" Oalkonen-&orhonen A" Oainio 0" 0artanen &" et

al. Nuantitati(e A: of the hippocampus and amygdala in se(ere depression.

0sychol Aed. 2+++ =anI8+17>113-2.

85. /remner =D" arayan A" $nderson " taib ?)" Ailler )?" *harney D.

)ippocampal (olume reduction in ma11-.

8. )ecimo(ic )" oldstein =D" heline @:" illiam !. Aechanisms of depression

in epilepsy from a clinical perspecti(e. pilepsy /eha(. 2++8 4ctI5 uppl 8>2-

8+.

86. /aker $" =acoby $" *hadwick DB. The associations of psychopathology in

epilepsy> a community study. pilepsy es. 1,,6 epI217>2,-8,.


72/80

32

83. )ermann /0" eidenberg A" /ell /. 0sychiatric comorbidity in chronic epilepsy>

identification" consequences" and treatment of ma81-51.

8. Nuiske $" )elmstaedter *" ?u; " lger *. Depression in patients with temporal

lobe epilepsy is related to mesial temporal sclerosis. pilepsy es. 2+++

$prI8,27>121-.

8,. illiam !" &anner $A. Treatment of depressi(e disorders in epilepsy patients.

pilepsy /eha(. 2++2 4ctI87>2-,.

5+. afnsson O" 4lafsson " )auser B$" udmundsson . *ause-specific mortality

in adults with unpro(oked sei#ures. $ population-based incidence cohort study.

euroepidemiology. 2++1 4ctI2+57>282-6.

51. #aflarski =0" #aflarski A. ei#ure disorders" depression" and health-related

quality of life. pilepsy /eha(. 2++5 !ebI17>+-3.

52. De(insky 4" /arr B/" Oickrey /" /erg $T" /a#il *B" 0acia O" et al. *hanges

in depression and an;iety after resecti(e surgery for epilepsy. eurology. 2++

Dec 18I6117>1355-,.

58. $ltshuler ??" De(insky 4" 0ost A" Theodore B. Depression" an;iety" and

temporal lobe epilepsy. ?aterality of focus and symptoms. $rch eurol. 1,,+

AarI5387>25-.

55. Acrother *B" /haumik " Thorp *!" )auck $" /ranford D" Batson =A.

pilepsy in adults with intellectual disabilities> pre(alence" associations and

ser(ice implications. ei#ure. 2++6 epI167>836-6.


73/80

38

5. Aatsuura A" $dachi " Auramatsu " &ato A" 4numa T" 4kubo @" et al.

:ntellectual disability and psychotic disorders of adult epilepsy. pilepsia.

2++I56 uppl 1>11-5.

56. &ohler *" orstrand =$" /altuch " 4R*onnor A=" ur " !rench =$" et al.

Depression in temporal lobe epilepsy before epilepsy surgery. pilepsia. 1,,,

AarI5+87>886-5+.

53. Aensah $" /ea(is =A" Thapar $&" &err A. The presence and clinical

implications of depression in a community population of adults with epilepsy.

pilepsy /eha(. 2++6 !ebI17>218-,.

5. 0atten /" /eck *$" Billiams =O" /arbui *" Aet# ?A. Aa a population-based perspecti(e. eurology. 2++8 Dec

,I61117>125-3.

5,. arushima &" &osier =T" obinson . $ reappraisal of poststroke depression"

intra- and inter-hemispheric lesion location using meta-analysis. =

europsychiatry *lin eurosci. 2++8 !allI157>522-8+.

+. )arden *?. The co-morbidity of depression and epilepsy> epidemiology" etiology"

and treatment. eurology. 2++2 ep 25I,6 uppl 57>5-.

1. /eghi " oncolato A" Oisona . Depression and altered quality of life in women

with epilepsy of childbearing age. pilepsia. 2++5 =anI517>65-3+.

2. spie *$" Batkins =" *urtice ?" spie $" Duncan " yan =$" et al.

0sychopathology in people with epilepsy and intellectual disabilityI an

in(estigation of potential e;planatory (ariables. = eurol eurosurg 0sychiatry.

2++8 o(I35117>15-,2.


74/80

35

8. :ndaco $" *arrieri 0/" appi *" entile " triano . :nterictal depression in

epilepsy. pilepsy es. 1,,2 =unI1217>5-+.

5. Aurray " $bou-&halil /" riner ?. (idence for familial association of

psychiatric disorders and epilepsy. /iol 0sychiatry. 1,,5 ep 1I8667>52-,.

. eyens ?" $ldenkamp $0" Aeinardi )A. 0rospecti(e follow-up of intellectual

de(elopment in children with a recent onset of epilepsy. pilepsy es. 1,,,

$prI852-87>-,+.

6. )ermann /" eidenberg A" /ell /" utecki 0" heth " uggles &" et al. The

neurode(elopmental impact of childhood-onset temporal lobe epilepsy on brain

structure and function. pilepsia. 2++2 epI58,7>1+62-31.

3. mith A?" lliott :A" ?ach ?. *ogniti(e skills in children with intractable

epilepsy> comparison of surgical and nonsurgical candidates. pilepsia. 2++2

=unI5867>681-3.

. Billiams =. ?earning and beha(ior in children with epilepsy. pilepsy /eha(.

2++8 $prI527>1+3-11.

,. *larke D!" oberts B" Daraksan A" Dupuis $" Ac*abe =" Bood )" et al. The

pre(alence of autistic spectrum disorder in children sur(eyed in a tertiary care

epilepsy clinic. pilepsia. 2++ DecI56127>1,3+-3.

6+. Tuchman " apin :. pilepsy in autism. ?ancet eurol. 2++2 4ctI167>82-.

61. abis ?" 0omeroy =" $ndriola A. $utism and epilepsy> cause" consequence"

comorbidity" or coincidence pilepsy /eha(. 2++ DecI357>62-6.


75/80

3

62. /auer =" /lumenthal " euber A" toffel-Bagner /. pilepsy syndrome" focus

location" and treatment choice affect testicular function in men with epilepsy.

eurology. 2++5 =an 23I6227>258-6.

68. )er#og $" !owler &A. ensiti(ity and specificity of the association between

catamenial sei#ure patterns and o(ulation. eurology. 2++ !eb I3+67>56-3.

65. ?uef " $braham :" Trinka " $lge $" Bindisch =" Da;enbichler " et al.

)yperandrogenism" postprandial hyperinsulinism and the risk of 0*4 in a cross

sectional study of women with epilepsy treated with (alproate. pilepsy es.

2++2 =anI51-27>,1-1+2.

6. heth D" /inkley " )ermann /0. 0rogressi(e bone deficit in epilepsy.

eurology. 2++ =an 1I3+87>13+-6.

66. Billiams =" teel *" harp /" Deloseyes " 0hillips T" /ates " et al. 0arental

an;iety and quality of life in children with epilepsy. pilepsy /eha(. 2++8

4ctI57>58-6.

63. 4gu# $" &urul " Dirik . elationship of epilepsy-related factors to an;iety and

depression scores in epileptic children. = *hild eurol. 2++2 =anI1317>83-5+.

6. )elmstaedter *" onntag-Dillender A" )oppe *" lger *. Depressed mood and

memory impairment in temporal lobe epilepsy as a function of focus laterali#ation

and locali#ation. pilepsy /eha(. 2++5 4ctI7>6,6-3+1.

6,. /erko(ic !" =ackson D. The hippocampal sclerosis whodunit> enter the genes.

$nn eurol. 2+++ AayI537>3-.


76/80

36

3+. ing )$" $cton 0D" cull D" *osta D*" acino(ik " Trimble A. 0atterns of

brain acti(ity in patients with epilepsy and depression. ei#ure. 1,,,

4ctI37>8,+-3.

31. Aanchanda " chaefer /" Ac?achlan " /lume BT. :nterictal psychiatric

morbidity and focus of epilepsy in treatment-refractory patients admitted to an

epilepsy unit. $m = 0sychiatry. 1,,2 $ugI15,7>1+,6-.

32. Oictoroff =:" /enson !" rafton T" ngel =" =r." Aa##iotta =*. Depression in

comple; partial sei#ures. lectroencephalography and cerebral metabolic

correlates. $rch eurol. 1,,5 !ebI127>1-68.

38. ?angdon " *oltheart A. ecognition of metaphor and irony in young adults> the

impact of schi#otypal personality traits. 0sychiatry es. 2++5 =an 8+I1217>,-2+.

35. Dre(ets B*. !unctional anatomical abnormalities in limbic and prefrontal

cortical structures in ma518-81.

3. )ufnagel $" Dumpelmann A" Qentner =" chi555-3.

33. oth D?" oode &T" Billiams O?" !aught . 0hysical e;ercise" stressful life

e;perience" and depression in adults with epilepsy. pilepsia. 1,,5 o(-

DecI867>125-.


77/80

33

3. Dodrill */. /eha(ioral effects of antiepileptic drugs. $d( eurol. 1,,1I>218-

25.

3,. De(insky 4. 0sychiatric comorbidity in patients with epilepsy> implications for

diagnosis and treatment. pilepsy /eha(. 2++8 DecI5 uppl 5>2-1+.

+. eunanen A" Dam A" @uen $B. $ randomised open multicentre comparati(e

trial of lamotrigine and carbama#epine as monotherapy in patients with newly

diagnosed or recurrent epilepsy. pilepsy es. 1,,6 AarI2827>15,-.

1. porn =" achs . The anticon(ulsant lamotrigine in treatment-resistant manic-

depressi(e illness. = *lin 0sychopharmacol. 1,,3 =unI1387>1-,.

2. hor(on " tefan ). 4(er(iew of the safety of newer antiepileptic drugs.

pilepsia. 1,,3I8 uppl 1>5-1.

8. yback " /rodsky ?" Aunasifi !. abapentin in bipolar disorder. =

europsychiatry *lin eurosci. 1,,3 pringI,27>8+1.

5. chaffer */" chaffer ?*. abapentin in the treatment of bipolar disorder. $m =

0sychiatry. 1,,3 !ebI1527>2,1-2.

. Dodrill */" $rnett =?" hu O" 0i;ton *" ?en# T" ommer(ille &B. ffects of

tiagabine monotherapy on abilities" ad


78/80

3

. !roscher B" Aaier O" ?aage A" Bolfersdorf A" traub " othmeier =" et al.

!olate deficiency" anticon(ulsant drugs" and psychiatric morbidity. *lin

europharmacol. 1,, $prI127>16-2.

,. ander =B" 0atsalos 0. $n assessment of serum and red blood cell folate

concentrations in patients with epilepsy on lamotrigine therapy. pilepsy es.

1,,2 4ctI1817>,-,2.

,+. odfrey 0" Toone /&" *arney AB" !lynn T" /ottiglieri T" ?aundy A" et al.

nhancement of reco(ery from psychiatric illness by methylfolate. ?ancet. 1,,+

$ug 1I8863127>8,2-.

,1. *rellin " /ottiglieri T" eynolds ). !olates and psychiatric disorders. *linical

potential. Drugs. 1,,8 AayI57>628-86.

,2. &ellett AB" mith D!" /aker $" *hadwick DB. Nuality of life after epilepsy

surgery. = eurol eurosurg 0sychiatry. 1,,3 =ulI6817>2-.

,8. /lumer D" Bakhlu " Da(ies &" )ermann /. 0sychiatric outcome of temporal

lobectomy for epilepsy> incidence and treatment of psychiatric complications.

pilepsia. 1,, AayI8,7>53-6.

,5. Deb " )unter D. 0sychopathology of people with mental handicap and epilepsy.

::> 0sychiatric illness. /r = 0sychiatry. 1,,1 DecI1,>26-8+" 88-5.

,. aylor $" og(i-)ansen /" &essing ?" &ruse-?arsen *. 0sychiatric morbidity

after surgery for epilepsy> short-term follow up of patients undergoing

amygdalohippocampectomy. = eurol eurosurg 0sychiatry. 1,,5

o(I3117>183-1.


79/80

3,

,6. &rahn ?" ummans T$" 0eterson *" *ascino D" harbrough !B.

lectrocon(ulsi(e Therapy for Depression $fter Temporal ?obectomy for

pilepsy. *on(uls Ther. 1,,8I,87>213-,.

,3. ing )$" Aoriarty =" Trimble A. $ prospecti(e study of the early postsurgical

psychiatric associations of epilepsy surgery. = eurol eurosurg 0sychiatry. 1,,

AayI657>6+1-5.

,. te(ens =. 0sychiatric consequences of temporal lobectomy for intractable

sei#ures> a 2+-8+-year follow-up of 15 cases. 0sychol Aed. 1,,+ $ugI2+87>2,-

5.

,,. /ladin 0!. 0sychosocial difficulties and outcome after temporal lobectomy.

pilepsia. 1,,2 ep-4ctI887>,-,+3.

1++. *ramer =$" /lum D" !anning &" eed A. The impact of comorbid depression on

health resource utili#ation in a community sample of people with epilepsy.

pilepsy /eha(. 2++5 =unI87>883-52.

1+1. Aartin " Oogtle ?" illiam !" !aught . )ealth-related quality of life in senior

adults with epilepsy> what we know from randomi#ed clinical trials and

suggestions for future research. pilepsy /eha(. 2++8 DecI567>626-85.

1+2. Aende# A!" Doss *. :ctal and psychiatric aspects of suicide in epileptic

patients. :nt = 0sychiatry Aed. 1,,2I2287>281-3.

1+8. !iordelli " /eghi " /ogliun " *respi O. pilepsy and psychiatric disturbance.

$ cross-sectional study. /r = 0sychiatry. 1,,8 4ctI168>556-+.

1+5. ?eppik :. Tiagabine> the safety landscape. pilepsia. 1,,I86 uppl 6>1+-8.


80/80

+

1+. illham $. efractory epilepsy> an e(aluation of psychological methods in

outpatient management. pilepsia. 1,,+ =ul-$ugI8157>523-82.

1+6. De(insky 4" &elley &" @acubian A" ato " &ufta *O" Theodore B)" et al.

0ostictal beha(ior. $ clinical and subdural electroencephalographic study. $rch

eurol. 1,,5 AarI187>25-,.

1+3. )ay !" ?inkowski 0. U$ntidepressants> T*$ (ersus : (ersus other new

agentsV. e( Aed /ru;. 2++5 epI257>$81-2+.

1+. oldstein ?). ffecti(eness of psychological inter(entions for people with poorly

controlled epilepsy. = eurol eurosurg 0sychiatry. 1,,3 $ugI6827>183-52.

1+,. &anner $A. Depression in epilepsy> pre(alence" clinical semiology" pathogenic

mechanisms" and treatment. /iol 0sychiatry. 2++8 $ug 1I587>8-,.

11+. /lumer D. 0sychiatric aspects of intractable epilepsy. $d( ;p Aed /iol.

2++2I5,3>188-53.

111. Aumford D/" Ainhas !$" $khtar :" $khter " Aubbashar A). tress and

psychiatric disorder in urban awalpindi. *ommunity sur(ey. /r = 0sychiatry.

2+++ DecI133>3-62.

wazir dissertation ii final

Documents