Overview

The International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE) define epilepsy as a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures and by the biologic, cognitive, psychological, and social consequences of this condition This association !ay reflect the anato!ical and neurobiological source of both epileptic seizures and the behavioral !anifestations Antiepileptic drugs (AE"s) can play a role in the genesis of psychiatric sy!pto!s# on the other hand, so!e psychotropic !edications can lo$er the seizure threshold and provo%e epileptic seizures Indeed, there is a general agree!ent that the incidence of neurobehavioral disorders is higher in patients $ith epilepsy than in the general population, although so!e authors argue that this apparent overrepresentation is due to sa!pling errors or inadequate control groups &any, but not all, authors also accept the proposition that the lin% bet$een neurobehavioral disorders and te!poral lobe or co!ple' partial epilepsy is particularly strong (o to Epilepsy and )eizures for an overvie$ of this topic Additionally, go to *sychogenic +onepileptic )eizures for co!plete infor!ation on this topic

Factors in the relationship between epilepsy and behavioral disorders

&echanis!s for a relationship bet$een epilepsy and behavioral disorders include the follo$ing,

-o!!on neuropathology (enetic predisposition "evelop!ental disturbance Ictal neurophysiologic effects Inhibition or hypo!etabolis! surrounding the epileptic focus )econdary epileptogenesis Alteration of receptor sensitivity )econdary endocrinologic alterations *ri!ary, independent psychiatric illness -onsequence of !edical or surgical treat!ent -onsequence of psychosocial burden of epilepsy

&ultiple interacting biologic and psychosocial factors deter!ine the ris% for the develop!ent of either schizophrenifor! psychoses or !a.or depression in patients $ith epilepsy, and behavioral disorders in epilepsy have !ultiple ris% factors and !ultifactorial etiologies /01

Role of the neurologist in the psychiatric management of patients with epilepsy

As neurologists, $e tend to focus on seizure control, and psychiatric co!orbidities are often underesti!ated 2ecognizing psychiatric !anifestations is an area that needs i!prove!ent 3nce sy!pto!s are identified, the follo$ing questions arise/41 ,

Are the sy!pto!s related to the occurrence of seizures (preictal, ictal, postictal)5 Are the sy!pto!s related to AE"s5 Is the onset of sy!pto!s associated $ith the re!ission of seizures in patients $ho had previously failed to respond to AE"s5

Because of the pheno!enology of epilepsy, the close association bet$een epilepsy and psychiatry has a long history The traditional approach to epilepsy care has been to focus on the seizures and their treat!ent -oncentrating only on the treat!ent of the seizures, $hich occupy only a s!all proportion of the patient6s life, does not see! to address !any of the issues that have an adverse i!pact on the quality of life of the patient $ith epilepsy )ac%ellares and Berent stated that co!prehensive care of the epileptic patient requires 7attention to the psychological and social consequences of epilepsy as $ell as to the control of seizures 7/81 Although undoubtedly i!portant in the care of the patient $ith epilepsy, advances in neurologic diagnosis and treat!ent tended to obscure the behavioral !anifestations of epilepsy until (ibbs dre$ attention to the high incidence of behavioral disorders in patients $ith te!poral lobe epilepsy /91

Frequency of psychiatric disorders in patients with epilepsy

It is esti!ated that 4:;8:< of patients $ith epilepsy have psychiatric disturbances /=1 3f patients $ith intractable co!ple' partial seizures, >:< !ay have 0 or !ore diagnoses consistent $ith the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R)# =?< of these patients have a history of depressive episodes, 84< have agoraphobia $ithout panic or other an'iety disorder, and 08< have psychoses /@1 The ris% of psychosis in patients $ith epilepsy !ay be @;04 ti!es that of the general population, $ith a prevalence of about >;?<# in patients $ith treat!ent;refractory te!poral lobe epilepsy, the prevalence has been reported to range fro! :;0@< />1 "ifferences in the rates !ay result fro! differences in the populations studied, ti!e periods investigated, and diagnostic criteria

The !ost co!!on psychiatric conditions in epilepsy are depression, an'iety, and psychoses /?, A, 0:, 00, 04, 081 ()ee the Table belo$ ) Table *revalence 2ates of *sychiatric "isorders in *atients Bith Epilepsy and the (eneral *opulation (4::> data)/?1 (3pen Table in a ne$ $indo$) Psychiatric Disorder &a.or depressive disorder An'iety disorder &oodCan'iety disorder )uicidal Ideation 3thers Controls Patients With Epilepsy 0: >< 0> 9< 00 4< 44 ?< 0A @< 89 4< 08 8< 4= :< 4: >< 8= =<

The psychiatric sy!pto!s characteristic of the neurobehavioral syndro!e of epilepsy (ie, &orel syndro!e) tend to be distinguished in the follo$ing $ays,

Atypical for the psychiatric disorder Episodic *leo!orphic

Psychotic Disorders
*sychotic disorders are severe !ental disorders that cause abnor!al thin%ing and perception *sychotic individuals lose relation $ith reality )y!pto!s generally described as either positive, such as hallucinations, delusions, and disorganized behaviors, or negative, such as di!inished range of e!otion, reduced speech, and inability to initiate and sustain goal;directed activities Duilleu!ier and Eallon found that 4;A< of patients $ith epilepsy have psychotic disorders /091 *erez and Tri!ble reported that about half of epileptic patients $ith psychosis could be diagnosed $ith schizophrenia /0=1 The etiology and pathogenesis of psychosis in epilepsy are poorly understood# ho$ever, neuroanato!ical changes have been observed in patients $ith psychosis and include the follo$ing,

Asy!!etry of a!ygdala and anterior seg!ent of the hippoca!pus/0@1 2ule of hippoca!pal;a!ygdala co!ple' in pathogenesis of schizophrenia/0>1 )!aller gray !atter volu!e in the left and !iddle te!poral gyri and left posterior superior te!poral gyrus/0?1 2ule of bilateral !iddle frontal gyrus (prefrontal corte') in overt psychosis occurring $ith schizophrenia/0A1

)uperior te!poral corte' and dysfunction of corollary discharges in auditory hallucination/4:1

*atients $ith te!poral lobe epilepsy and psychosis of epilepsy have significantly s!aller brain volu!e than people $ith te!poral lobe epilepsy alone, and psychosis of epilepsy is a distinct nosologic entity differing fro! schizophrenia /401 Fanner states that various classifications have been proposed for the psychoses associated $ith epilepsy Ge asserts that for the neurologist, the !ost useful !ight be that $hich distinguishes a!ong psychoses closely lin%ed to seizures (ictal or postictal psychosis), those lin%ed to seizure re!ission (alternative psychosis), psychoses $ith a !ore stable and chronic course (eg, interictal psychosis), and iatrogenic psychotic processes related to antiepileptic drugs /441

ctal events
)tatus epilepticus (ie, co!ple' partial status epilepticus and absence status epilepticus) can !i!ic psychiatric disorders, including psychosis

Postictal events
)o and colleagues distinguished bet$een postictal psychosis, $hich is characterized by $ell; syste!atized delusions and hallucinations in a setting of preserved orientation and alertness, as $ell as postictal confusion They also distinguished bet$een self;li!ited postictal psychosis and the unre!itting chronic interictal psychosis seen in long;standing epilepsy /481 -riteria proposed by )tagno for postictal psychosis include the follo$ing/491 ,

*sychotic or other psychiatric sy!pto!s occur after a seizure or, !ore frequently, a series of seizures, after a lucid interval, or $ithin > days of the seizure(s) The event !ay be psychosis, depression, or elation or !ay be an an'iety;related sy!pto! The event is ti!e;li!ited, lasting days or, rarely, $ee%s# no significant clouding of consciousness occurs

Logsdail and Toone believe that clouding of consciousness, disorientation, or deliriu! !ay be noted, and, if consciousness is uni!paired, delusions and hallucinations are present# a !i'ture of both also !ay be noted /4=1 -louding should not be attributed to other !edical or psychiatric causes (eg, drug into'ication, co!ple' partial status epilepticus, !etabolic disturbance)

nterictal events
Interictal psychotic pheno!ena, particularly hallucinations and delusions, are co!!on in patients $ith epilepsy /4@, 4>, 4?1

Although !any etiologies of psychosis in epilepsy have been proposed, the significance of such factors as the type of seizure, epilepsy classification, lateralization of foci, and age at onset of epilepsy re!ains uncertain /4A, 8:, 80, 841 Tarulli et al docu!ented cases of patients $ho had !ultiple episodes of postictal psychosis before developing interictal psychosis /881 They concluded that a progression fro! postictal to interictal psychosis !ay be at play and that increased a$areness and pro!pt treat!ent of postictal psychosis !ay inhibit or prevent the develop!ent of so!e instances of interictal psychosis

Factors in the development of psychosis

The follo$ing variables are believed to have particularly strong lin%s to the develop!ent of psychotic pheno!ena in patients $ith epilepsy,

Ha!ily history of psychosis ; *atients $ho had a positive fa!ily history of psychosis $ere e'tre!ely susceptible to psychosis, so a genetic factor appears to be involved Age at onset of epilepsy ; *atients $ith interictal psychosis sho$ed a significantly earlier onset of epilepsy/89, 8=, 8@, 8>, 8?1 Type of seizure ; The e'istence of co!ple' partial seizure (!ostly te!poral lobe epilepsy) !ay be strongly associated $ith interictal psychoses /8A, 9:1 Intelligence ; *atients $ith borderline intellectual functioning tend to develop psychotic sy!pto!s relatively frequently/89, 8=1

The ris% factors for developing psychosis in epilepsy found in so!e studies also include the follo$ing/901 ,

*artial co!ple' seizures, especially $ith te!poral lobe foci The presence of 7alien tissue7 (eg, s!all tu!ors, ha!arto!as) &esial te!poral lobe ganglioglio!as Left;handedness, especially in $o!en

Bith regard to the first ite! above, so!e authors have noted a predo!inance of left;sided foci Hrontal lobe epilepsy is also co!!on )ch!itz et al studied ris% factors and classified the! by the follo$ing syste!,

Biologic factors Earlier onset of epilepsy &ore severe epilepsy *sychosocial factors

"isturbed fa!ily bac%ground Lac% of interpersonal relationships )ocial dependency *rofessional failure &ore frequent te!poral lobe and unclassifiable epilepsies and less frequent generalized epilepsies

Bith regard to the last ite! above, no significant differences in types of epilepsies bet$een patients $ith epilepsy and psychosis and patients $ith epilepsy $ithout psychiatric disease have been found Tri!ble and )ch!itz believe that the conclusions presented in the literature on ris% factors are highly controversial /901

!chi"ophrenia
In a revie$ study of patients $ith epilepsy $ho developed psychosis, Tandon and "eIuardo found that the patientsJ psychoses $ere usually a for! of schizophrenia, !ost co!!only paranoid schizophrenia /941 )tagno reported that persistent interictal psychoses of epilepsy and the schizophreniali%e psychoses of epilepsy are distinguishable fro! schizophrenia in the traditional psychiatric sense by the follo$ing/981 ,

Lac% of negative sy!pto!s of schizophrenia, particularly flattening of affect and personality deterioration Better pre!orbid personality *aranoid delusions "elusions of reference &ore benign and variable course

#reatment
)tatus epilepticus and ictal abnor!alities are treated in the sa!e $ay as nonpsychiatric epileptic events *ostictal events are treated by i!proving seizure control )o et al believe that postictal psychosis re!its spontaneously even $ithout treat!ent but that the use of effective neuroleptics !ay shorten the duration /991 Interictal psychosis is treated $ith antipsychotic drugs &edications that lo$er the seizure threshold should be avoided )o!e studies indicate that risperidone, !olindone, and fluphenazine !ay have better profiles than

older antipsychotic !edications# clozapine has been reported to confer a particularly high ris% of seizures Forced normalization Treat!ent of any of the psychoses of epilepsy should ta%e into consideration the pheno!enon ter!ed forced nor!alization, $hich is a concept described by Landolt in the 0A=:s Bhen the electroencephalogra! (EE() in psychotic patients is nor!alized, often $ith anticonvulsant !edicines, the psychiatric proble! $orsens Alternative psychosis, or antagonis! bet$een seizures and behavioral abnor!alities (ie, $orsening of behavior $ith i!prove!ent in seizure control), is a si!ilar pheno!enon that has been %no$n for a longer ti!e Horced nor!alization frequently is described in patients treated $ith ethosu'i!ide# anecdotally, ho$ever, forced nor!alization effects have been produced by treat!ent $ith !ost antiepileptic agents, including the ne$er agents The !echanis! underlying these interesting pheno!ena is not yet understood &any authors consider the idea of forced nor!alization to be so!e$hat controversial

$ipolar %ffective Disorders

Bipolar affective disorder is chronic psychiatric disease $ith severe changes in !ood $ith a $ide spectru! of clinical !anifestations A nu!ber of studies have de!onstrated that affective disorders in epilepsy represent a co!!on psychiatric co!orbidity# ho$ever, !ost of the neuropsychiatric literature focuses on depression, $hich is actually pro!inent /9=1 The incidence of developing bipolar affective disorder in epilepsy is 0 @A cases per 0::: persons;year, co!pared $ith : :> in the general population /9@1 Bipolar sy!pto!s $ere 0 @;4 4 ti!es !ore co!!on in sub.ects $ith epilepsy than $ith !igraine, asth!a, or diabetes !ellitus and are @ @ ti!es !ore li%ely to occur than in healthy sub.ects A total of 9A >< of patients $ith epilepsy $ho screened positive for bipolar sy!pto!s $ere diagnosed $ith bipolar disorder by a physician, nearly t$ice the rate seen in other disorders /9>1

Depression
"epression is a !ental state or chronic !ental disorder characterized by feelings of sadness, loneliness, despair, lo$ self;estee!, and self;reproach Acco!panying signs include psycho!otor retardation (or, less frequently, agitation), $ithdra$al fro! social contact, and vegetative states, such as loss of appetite and inso!nia "epression is the !ost frequent psychiatric co!orbidity seen in patients $ith epilepsy It is !ore li%ely to occur in patients $ith partial seizure disorders of te!poral and frontal lobe origin It is also !ore frequent in patients $ith poorly controlled seizures /9?1

T$o possibilities e'ist, (0) depression is a reaction to the epilepsy or (4) depression is a part of the epilepsy &endez et al co!pared patients $ith epilepsy to !atched controls $ithout epilepsy but $ith a si!ilar degree of disability fro! other chronic !edical diseases and found that $hile ==< of the patients $ith epilepsy reported depression, only 8:< of the !atched controls reported depression /9A1 &endez et al concluded that depression is related to a specific epileptic psychosyndro!e 3n the other hand, 2obertson concluded that $ith fe$ e'ceptions, the pheno!enology of the depression to a large degree is not attributed to neuroepilepsy variables# ho$ever, not all studies have found this difference /=:1 In patients $ith refractory epilepsy, the presence of depression is one of the !ost i!portant variables to have an i!pact on their quality of life, even !ore than the frequency and severity of the seizures )everal studies have docu!ented that the quality of life i!proves significantly in patients $ith epilepsy $ho are !ade seizure free If those patients are e'cluded, Boylan et al have found that the quality of life is related to depression but not to degree of seizure control /=01 "espite its high prevalence in patients $ith epilepsy, depression very often re!ains unrecognized and untreated The reasons for cliniciansJ failure to recognize depressive disorders in patients $ith epilepsy include the follo$ing/=41 ,

*atients tend to !ini!ize their psychiatric sy!pto!s for fear of being further stig!atized The clinical !anifestations of certain types of depressive disorders in epilepsy differ fro! depressive disorders in patients $ithout epilepsy and therefore are not recognized by physicians -linicians usually fail to inquire about psychiatric sy!pto!s *atients and clinicians tend to !ini!ize the significance of sy!pto!s of depression because they consider the! to be a reflection of a nor!al adaptation process to this chronic disease/=81 The concern that antidepressant drugs !ay lo$er the seizure threshold has generated a!ong clinicians a certain reluctance to use psychotropic drugs in patients $ith epilepsy

2is% factors for the develop!ent of depression in patients $ith epilepsy include the follo$ing,

Te!poral lobe (but not frontal lobe) partial co!ple' seizures Degetative auras Ha!ily history of psychiatric illness, particularly depression

Laterality effects, $hich are controversial

Physiologic factors associated ith e!ile!sy and de!ression "ecreased serotonergic, noradrenergic, and (ABAergic functions have been identified as pivotal etiologic !echanis!s in depression and have been the basis for antidepressant phar!acologic treat!ents /=91 "ecreased activity of these sa!e neurotrans!itters has been sho$n to facilitate the %indling process of seizure foci, to e'acerbate seizure severity, and to intensify seizure predisposition in so!e ani!al !odels of epilepsy Therefore, parallel changes of serotonin, norepinephrine, dopa!ine, and (ABA !ay be operant in the pathophysiology of depressive disorders and epilepsy Eobe et al have presented evidence that so!e types of depression and so!e types of epilepsy !ay be associated $ith decreased noradrenergic and serotonergic trans!ission in the brain /==1 Hlor;Genry speculated that depression !ight be related to right (nondo!inant) foci, a finding confir!ed by a fe$ other investigators /=@1 )o!e authors have suggested that elation is associated $ith right;sided lesions and depression or sadness $ith left;sided lesions &ost studies that find a relationship bet$een laterality and depression have found depression to be !ore co!!on $ith left;sided foci Lopez;2odriguez et al found that !a.or depressive episodes $ere statistically !ore frequent in patients $ith left te!poral lobe seizures than in patients $ith right te!poral lobe seizures /=>1 3ther authors report no laterality differences in depression rates "ther factors associated ith de!ression in e!ile!sy 3ne of the variables lin%ing depression and epilepsy is a fa!ily history of depression A greater frequency of depression has been found in patients $ith seizures originating in li!bic structures# also, a frontal lobe dysfunction has been associated $ith depression The quality of life is often subopti!al for patients $ith epilepsy, and this !ay adversely affect !ood /=?, =A, @:, @0, @41 Increased financial stress, life stressors, and poor ad.ust!ent to seizures are predictive of increased depression /@81 The lac% of control over the illness !ay be an additional ris% factor for depression /@9, @=1 "epression in epilepsy !ay also result fro! iatrogenic causes (phar!acologic and surgical) The AE"s !ost frequently associated $ith iatrogenic depressive sy!pto!s include the follo$ing/@@1 ,

*henobarbital *ri!idone Digabatrin Levetiraceta! Helba!ate Topira!ate

"epressive disorder can also occur follo$ing the discontinuation of AE"s $ith positive psychotropic properties, such as carba!azepine, o'carbazepine, valproic acid, and la!otrigine Fre#uency of de!ression in e!ile!sy In patients $ith epilepsy, the reported rates of depression range fro! ?;9?< (!ean 4A<, !edian 84<)# the prevalence of depression in the general population ranges in different epide!iologic studies fro! @;0>< /@>1 In a study of patients $ith epilepsy $ho $ere ad!itted to a psychiatric hospital, Betts found that depression $as the !ost co!!on psychiatric diagnosis Billia!s studied 4::: patients $ith epilepsy and found that depressed !ood $as part of the attac% in 40 According to Billia!s, depressed !ood $as the second !ost co!!on e!otion constituting part of the attac%, $ith fear being the !ost co!!on /@?1 3thers have found si!ilar results $haracteristics of de!ression in !atients ith e!ile!sy -haracteristics of patients $ith epilepsy $ho also have depression include the follo$ing,

He$er neurotic traits &ore psychotic traits Gigher trait and state an'iety scores &ore abnor!al affect and chronic dysthy!ic disorder Gigh hostility scores, especially for self;criticis! and guilt )udden onset and brief duration of sy!pto!s

*erhaps 0:;4:< of persons $ith epilepsy have a peri;ictal prodro!e consisting of depressed; irritable !ood, so!eti!es $ith an'iety or tension and headaches Although Billia!s noted in his patients that the !ood disturbance $ould persist for 0 hour to 8 days after the ictus, postictal affective syndro!es have received little attention in the literature /@?1

Blu!er has defined an interictal dysphoric disorder in patients $ith epilepsy in $hich sy!pto!s tend to be inter!ittent /@A1 3n average, the patients tend to have = of the follo$ing sy!pto!s (range 8;?),

"epressed !ood Anergia *ain Inso!nia Hear An'iety *aro'ys!al irritability Euphoric !oods

Fanner has noted that the sy!pto!s of depression in patients $ith epilepsy are different fro! those in patients $ithout epilepsy Ge believes that patients $ith epilepsy $ho are felt to $arrant antidepressant therapy often do not !eet for!al DSM criteria for a !ood disorder and concludes that the proble! of depression in epilepsy !ay be underesti!ated by using screening instru!ents designed for use in psychiatric patients />:1 Fanner continued $ith this research using the DSM-I% criteria &ost sy!pto!s presented $ith a $a'ing and $aning course, $ith sy!pto!;free periods Ge referred to this for! of depression as Kdysthy!ic;li%e disorder of epilepsy L -aplan et al believe that depression in children and adolescents $ith epilepsy tends to have a different presentation fro! that seen in adults $ith epilepsy, although so!e adolescents $ith depression !ay present $ith a syndro!e si!ilar to that seen in adults They reported that children $ith depression often do not appear sad and that the depression !ay be !anifested by the follo$ing/>01 ,

Irritability 3ppositionality Aggression Anger

Hor this reason, special instru!ents are used to assess depression in children Tho!e;)ouza et al reported that depression in children $ith epilepsy !ay be underdiagnosed and untreated for longer periods than in adults They found that >: =< of children and adolescents in the study had psychiatric disorders and that the !ost frequent psychiatric disorder

in children $as attention;deficitChyperactivity disorder (A"G") and the !ost frequent psychiatric disorder in adolescents $as depression They found that fa!ily history $as also an i!portant deter!inant in !ood disorders in children and adolescents />41 Preictal sym!toms of de!ression -ategorizing depression in patients $ith epilepsy as depression occurring peri;ictally (preictally, ictally, or postictally) and interictally !ay be useful *reictal sy!pto!s of depression are believed to present as sy!pto!s of irritability, poor frustration tolerance, !otor hyperactivity, and aggressive behavior in children $ith epilepsy Go$ever, very fe$ studies have been perfor!ed in the literature />81 Ictal sym!toms of de!ression Ictal sy!pto!s are the clinical e'pression of a si!ple partial seizure *sychiatric sy!pto!s occur in appro'i!ately 4=< of auras The !ost frequent sy!pto!s include feelings of anhedonia, guilt, and suicidal ideation />91 Postictal sym!toms of de!ression *ostictal sy!pto!s of depression have been recognized for a long ti!e, but they have been poorly studied in a syste!atic !anner />=1 Interictal sym!toms of de!ression Hor patients $ith epilepsy to e'perience depressive episodes that fail to !eet any of the DSM-I%TR criteria is not unusual Fraepelin and Bleuler $ere the first to describe affective sy!pto!s of pro!inent irritability, inter!i'ed $ith euphoric !ood, fear, and sy!pto!s of an'iety, as $ell as anergia, pain, and inso!nia />@, >>, >?1 In 0A?@, &endez et al used the ter! atypical depression in epilepsy patients using the DSM-III-R criteria Treatment The treat!ent of !ood disorders in patients $ith epilepsy includes reevaluation of the anticonvulsant regi!en, cautious but aggressive use of antidepressants, and psychotherapy Hirst and fore!ost, treat!ent involves seizure control $ith appropriate anticonvulsant therapies A pheno!enon analogous to alternative psychosis, $orsening of behavior $ith better seizure control, has been reported in epilepsy;associated !ood disorders There is evidence that so!e anticonvulsant therapies, including vagus nerve sti!ulation, valproate, gabapentin, carba!azepine, and la!otrigine, also have antidepressant effects and !ay

prove effective in treating depression in patients $ith epilepsy *henobarbital is %no$n to produce depression According to )ch!itz, vigabatrin has been lin%ed to psychoses and to !a.or depression, and phenytoin has been associated $ith to'ic encephalopathies />A1 &c-onnell and "uncan cite so!e patients in $ho! phenytoin had been lin%ed to depression and !ania A case has been !ade that the (ABAergic drugs !ay be associated $ith an increased incidence of psychiatric proble!s /?:1 Go$ever, antidepressants !ay be necessary to effectively treat depression in these patients Bhen an antidepressant is prescribed, the epileptogenic potential, adverse effects, and drug interactions !ust be evaluated )elective serotonin reupta%e inhibitors ())2Is) such as citalopra! (o$ing to its lac% of drug interactions) and !ultireceptor;active co!pounds such as nefazodone or venlafa'ine are suggested as first;line treat!ents Bupropion, !aprotiline, and clo!ipra!ine should be avoided Dirtually all nonM!onoa!ine o'idase inhibitor (&A3I) antidepressants have been reported to lo$er the seizure threshold In the treat!ent of epilepsy;related depression, priority should be given to opti!izing seizure control, since i!proved psychosocial functioning tends to acco!pany seizure re!ission Antidepressants !ay !anifest convulsant and anticonvulsant effects &aprotiline and a!o'apine have the greatest seizure ris%# do'epin, trazodone, and fluvo'a!ine appear to have the lo$est ris% Electroconvulsive therapy is not contraindicated and !ay prove effective for epilepsy patients $ith severe, treat!ent;resistant, or psychotic depression It is i!perative that depression be recognized and treated in patients $ith epilepsy Hurther prospective studies of ne$ treat!ent options for depression in this patient population are needed
/?01

&ania
In a carefully selected series of patients $ith epilepsy, Billia!s found that only 0@= of 4::: patients had co!ple', including e!otional, ictal e'periences /?41 3f those 0@= patients, only 8 described elation &ania and hypo!ania are rare in association $ith epilepsy &anic;depressive illness is also rare# of @@ patients $ith epilepsy and !a.or depression, only 4 had bipolar disorder This rarity is probably, to so!e degree, secondary to the anti!anic effect of drugs such as carba!azepine and valproate Go$ever, !ania $as unco!!only associated $ith epilepsy even before the use of !odern antiepileptic drugs

!uicidal $ehaviors

)uicidality (co!pleted suicide, suicide atte!pt, and suicidal ideation) is significantly !ore frequent a!ong people $ith epilepsy than in the general population /?0, ?8, ?9, ?=, ?@, ?>1 The ris% of suicide in the general population averages about 0 9< "epression is one of the psychiatric disorders that increases the ris% of suicide The ris% of suicide in depressed patients is believed to be around 0=< 3n average, the ris% of suicide in patients $ith epilepsy is about 08< (prevalence rate ranges fro! =;0: ti!es that of the general population) Although so!e authors question its !ethodological and patient selection techniques, !ost authors cite Barraclough6s !eta;analysis, $hich revealed that the ris% of suicide in patients $ith te!poral lobe epilepsy is increased to as !uch as 4=;fold that of the general population /??1 Even so, depression re!ains underrecognized and untreated The relationship bet$een epilepsy and suicidality is co!ple' and !ultifactorial *sychiatric adverse events, including sy!pto!s of depression and an'iety, have been reported $ith the use of several AE"s, particularly barbiturates (phenobarbital and pri!idone), topira!ate, tiagabine, zonisa!ide, vigabatrin, and levetiraceta! /?A, A:, A0, A41 The incidence of suicidal pheno!ena lin%ed to specific AE"s has not been syste!atically $ell studied These data !ay either reNect the natural course of an underlying, recurrent psychiatric illness $ith no real effect fro! AE"s or could suggest that AE"s lo$er the threshold for !anifesting psychiatric sy!pto!s in individuals $ho are vulnerable because of a genetic or historical predisposition to psychiatric disorders Hrequent ris%s associated $ith suicidality include the follo$ing/?01 ,

-urrent or past history of !ood and an'iety disorders Ha!ily psychiatric history of !ood disorders, particularly of suicidal behavior *ast suicidal atte!pts

In Eanuary 4::?, the O) Hood and "rug Ad!inistration (H"A) issued an alert regarding the association bet$een suicidality and AE"s, having concluded that there $as a statistically significant, 0 ?;fold increased ris% of suicidality $ith e'posure to AE"s This conclusion $as based on the results of a !eta;analysis that included data fro! 0AA rando!ized clinical trials of 00 AE"s, carba!azepine, felba!ate, gabapentin, la!otrigine, levetiraceta!, o'carbazepine, pregabalin, tiagabine, topira!ate, valproate, and zonisa!ide The !eta;analysis enco!passed 98,?A4 patients treated for epilepsy, psychiatric disorders, and other disorders, predo!inantly pain In the study, suicidality occurred in 9 8 of 0,::: patients treated $ith AE"s in the active ar!, co!pared $ith 4 4 of 0,::: patients in the co!parison ar! The results of this !eta;analysis !ust be considered $ith great caution, and !ore research is necessary /?0, A8, A91

The H"A has decided to insert suicide $arnings in the pac%age inserts of all AE"s# thus, physicians need to identify patients $ith increased ris% of suicide /A=1

%n'iety Disorders
An'iety is an e'perience of fear or apprehension in response to anticipated internal or e'ternal danger, acco!panied by !uscle tension, restlessness, sy!pathetic hyperactivity, andCor cognitive signs and sy!pto!s (hypervigilance, confusion, decreased concentration, or fear of losing control) An'iety is co!!on in patients $ith epilepsy# of 9A patients $ith epilepsy attending a tertiary epilepsy care center, =>< had high;level an'iety An'iety in patients $ith epilepsy can be ictal, postictal, or interictal (ABA is the !ost i!portant inhibitory trans!itter in the central nervous syste! Evidence suggests that the abnor!al functioning of (ABA receptors could be of great i!portance in the pathophysiology of epilepsy and an'iety disorders /?4, ?01 "ifferentiating bet$een spontaneous fear and reactive fear (ie, reaction to the %no$ledge that a seizure !ay occur) can be difficult *anic disorder can produce paro'ys!al sy!pto!s, $hich can be confused $ith epileptic events and !ay go unrecognized in patients $ith epilepsy An'iety also !ay be related to nonepileptic attac% disorder

!ymptoms of an'iety in epilepsy

)y!pto!s of an'iety in epilepsy !ay result or be e'acerbated by psychological reactions, including responses to the unpredictability of seizures and restrictions of nor!al activities This results in lo$ self;estee!, stig!atization, and social re.ection /0, ?8, ?91 According to (oldstein and Garden, epileptic events can produce sy!pto!s indistinguishable fro! those of pri!ary an'iety disorder /?=1 Hear and an'iety are often associated $ith si!ple partial seizures Torta and Feller esti!ated that fear occurs as an aura in as !any as 0=< of patients,/001 and (oldstein and Garden concluded fro! several studies that fear is one of the !ost co!!on ictal e!otions /?=1 Ictal an'iety sy!pto!s !anifest as fear or panic, so!eti!es $ith other characteristics of te!poral discharges, such as depersonalization and dP.Q vu, as $ell as other psychological and autono!ous pheno!ena /0, ?@1

%n'iety in association with type of epilepsy and frequency of sei"ures

The highest rates of psychiatric co!orbidities, including an'iety, are reported in patients $ith chronic, refractory seizure disorders /0, ?8, ?@, ?>1

Interestingly, ho$ever, (oldstein et al found that patients $ith epilepsy $ith high seizure frequency had lo$er an'iety scores than did patients $ith lo$er seizure frequency /??1 The ris% of an'iety is higher in focal (!ore frequent in te!poral lobe) epilepsy than in generalized epilepsy In patients $ith te!poral lobe epilepsy, Tri!ble et al reported that 0A< of the patients $ere diagnosed $ith an'iety and 00< $ere diagnosed $ith depression Edeh and Toone found that patients $ith te!poral lobe epilepsy scored higher for an'iety than did those $ith focal, nonte!poral lobe epilepsy /91 An'iety can also be seen in frontal lobe epilepsy

ctal and interictal an'iety

An'iety in epileptic patients !ay occur as an ictal pheno!enon, as nor!al interictal e!otion or as part of an acco!panying an'iety disorder, as part of an acco!panying depressive disorder, or in association $ith nonepileptic, seizureli%e events as part of an underlying pri!ary an'iety disorder Interictal an'iety has a great influence on the quality of life of patients, since !ost of the! have a per!anent fear of ne$ discharges Torta and Feller have esti!ated that as !any as @@< of patients $ith epilepsy report interictal an'iety (oldstein and Garden proposed 4 !a.or psychological !echanis!s for this, as follo$s,

Hear of seizure recurrence (seizure phobia) Issues surrounding locus of control

They concluded that docu!ented cases of actual seizure phobia are rare but that a sense of dispersed locus of control can cause profound proble!s in patients $ith epilepsy

#reatment
)everal studies have sho$n that pregabalin, used as an ad.unct for partial seizures, has been an effective, rapidly active, and safe treat!ent for generalized an'iety disorder

Research
Although, as sho$n above, studies loo%ing into the association bet$een an'iety and epilepsy have been perfor!ed, because of the difficulty in separating the an'iety that acco!panies a chronic disease fro! pathologic an'iety, studies investigating an'iety in epilepsy have nonetheless been relatively fe$

Personality Disorders

*ersonality disorders in epileptic patients can cause abnor!al behavior that can have a direct i!pact on seizure control and quality of life The question of the relationship has a long history and re!ains controversial In 0A>=, Bo'!an and (esch$ind described a syndro!e consisting of circu!stantiality (e'cessive verbal output, stic%iness, and hypergraphia), altered se'uality, and intensified !ental life in a patient $ith te!poral lobe epilepsy It $as called (esch$ind syndro!e /?A1 Bensan and Ger!an reported that data are insufficient to state $ith certainty that a consistent pattern of behavioral changes occur in patient $ith te!poral lobe epilepsy The co!ple' partial epilepsy should not be diagnosed on the basis of the presence of (esch$ind syndro!e $ithout any paro'ys!al episodes that can be proven to be epileptic /A:1 The lin% of personality disorders to epilepsy $as not only seen in te!poral lobe epilepsy Trin%a et al found that personality disorders $ere present in 48< of patients $ith .uvenile !yoclonic epilepsy /A01 Tri!ble has su!!arized the data and concluded that the personality profile of a patient $ith epilepsy can be e'plained by a co!ple' co!bination of the effect of (0) dealing $ith a chronic illnesses, (4) AE" effects, (8) and te!poral lobe pathology Ge supported that certain personality disturbances in epilepsies should be vie$ed as associated $ith cerebral abnor!alities that also lead to seizures /A41

%ttention(Deficit)*yperactivity Disorder
Attention;deficitChyperactivity disorder (A"G") is another psychiatric co!orbidity in patients $ith epilepsy and is !ore co!!on in children The co;occurrence !ay result fro! altered neurobiological !echanis!s involved in early brain develop!ent The incidence of A"G" is about > >@ cases per 0::: person;years in patients $ith epilepsy and 8 44 in patients $ithout epilepsy The incidence of epilepsy is 8 49 cases per 0::: person;year in patient $ith A"G" and : >? in those $ithout A"G" /A81 A neuropsychiatrist !ay find difficulty in differentiating i!paired attention secondary to absence of seizure and attention deficit as a phenotypical representation of A"G" &any AE"s can cause sy!pto!s !i!ic A"G", and the !ost co!!on i!plicated are the (ABAergic drugs such as barbiturates, benzodiazepines, and vigabatrin &ethylphenidate can cause aggravate seizures in patients $ith A"G", although generally it is considered safe in those $ho are seizure free /A91

Psychotropic Effects of %ntiepileptic Drugs

Fno$ledge about the psychotropic effects of AE"s is crucial and yet very li!ited in the epilepsy population Evidence suggests that la!otrigine and the vagal nerve sti!ulator !ay have antidepressant properties that could be of use in light of co!!on co!orbid depression -arba!azepine, valproate, la!otrigine, and possibly o'carbazepine !ay have !ood stabilizing properties (abapentin, pregabalin, and tiagabine !ay have an'iolytic benefits There is a ris% of depression related to barbiturates and topira!ate, and possibly to phenytoin Onderlying depression and an'iety sy!pto!s !ay be e'acerbated by levetiraceta!, $hile psychotic sy!pto!s, albeit rare, have been reported $ith topira!ate, levetiraceta!, and zonisa!ide /A=1

Psychiatric Disorders and Epilepsy !urgery

(enerally, psychiatric outco!es i!prove or no changes are noted $ith epilepsy surgery A history of psychiatric disorders before epilepsy surgery is associated $ith poorer chance of postsurgical seizure re!ission After resective surgery, only patients $ith good or e'cellent seizure control had sustained long;ter! i!prove!ent in !ood *ostsurgical patients had higher suicidal !ortality rate co!pared $ith the general population, and people $ho continue to have seizures after surgery had a higher suicidal !ortality rate, in contrast to those $ho $ere seizure free after surgery (9;= ti!es) /A@1 In a series of 4@ patients, ga!!a %nife radiosurgery for !esial te!poral lobe epilepsy sho$ed no significant psychiatric changes fro! preoperative baseline for up to 49 !onths /A>1 The ris% factors for depression after epilepsy surgery include preoperative history of !ood disorders and !esial te!poral lobe surgery "isturbed behavior !ay interfere $ith the preoperative evaluation, and the patient !ay not be able to provide infor!ed consent for investigation and surgery Dagus nerve sti!ulation sho$ed better responses in patients $ith chronic !a.or depressive disorders over 04 !onths of study /A?, AA1 In s!all studies, Elger et al and Garden et al sho$ed that treat!ent $ith vagal nerve sti!ulation i!proves depression in epileptics independent of effects on seizure frequency Dagal nerve sti!ulation is a useful therapeutic tool in treat!ent;resistant depression /0::1

Patient and Family Education

Hor patient education infor!ation, see Epilepsy, "epression, )chizophrenia, Bipolar "isorder, and An'iety The follo$ing Beb sites are useful patient and fa!ily education tools,

A!erican Epilepsy )ociety

-enters for "isease -ontrol and *revention, Epilepsy Epilepsy co! Epilepsy Houndation Epilepsy Houndation, -o!!unities &ayo-linic co!, Epilepsy &edline *lus, Epilepsy +ational Institute of +eurological "isorders and )tro%e, +I+") Epilepsy Infor!ation *age

Conclusion
*sychiatric co!orbidities in patients $ith epilepsy are relatively frequent "espite the high prevalence rates, fe$ data are available Because of this, the data used are fro! pri!ary psychiatric disorders, assu!ing it can be applicable to patients $ith epilepsy Early recognition and !anage!ent of psychiatric disorders in patients $ith epilepsy is e'tre!ely i!portant, because it i!proves the quality of life, decreases suicidality, and aids in better seizure control