Psychiatric outcomes of epilepsy surgery: a systematic review.

Abstract

The objective of this systematic review was to identify: (1) prevalence and severity of psychiatric conditions before and after resective epilepsy surgery, (2) incidence of postsurgical psychiatric conditions, and (3) predictors of psychiatric status after surgery.
A literature search was conducted using PubMed, EmBase, and the Cochrane database as part of a larger project on the development of an appropriateness and necessity rating tool to identify patients of all ages with potentially resectable focal epilepsy. The search yielded 5,061 articles related to epilepsy surgery and of the 763 articles meeting the inclusion criteria and reviewed in full text, 68 reported psychiatric outcomes. Thirteen articles met the final eligibility criteria.
The studies demonstrated either improvements in psychiatric outcome postsurgery or no changes in psychiatric outcome. Only one study demonstrated deterioration in psychiatric status after surgery, with higher anxiety in the context of continued seizures post-surgery. One study reported a significantly increased rate of psychosis after surgery. The two main predictors of psychiatric outcome were seizure freedom and presurgical psychiatric history. De novo psychiatric conditions occurred postsurgery at a rate of 1.1-18.2%, with milder psychiatric issues (e.g., adjustment disorder) being more common than more severe psychiatric issues (e.g., psychosis).
Overall, studies demonstrated either improvement in psychiatric outcomes postsurgery or no change. However, there is a need for more prospective, well-controlled studies to better delineate the prevalence and severity of psychiatric conditions occurring in the context of epilepsy surgery, and to identify specific predictors of psychiatric outcomes after epilepsy surgery.

Full text

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Psychiatric outcomes of epilepsy surgery: A systematic review
*ySophiaMacrodimitris,yzElisabethM. S. Sherman,ySamanthaForde,xJoseF. Tellez-Zenteno,
y{AmyMetcalfe, xLizbeth Hernandez-Ronquillo, y{Samuel Wiebe,andy{NathalieJette ´
Departmentsof *Psychology, andyClinicalNeurosciences,Universityof Calgary,Calgary,Alberta,Canada;zAlbertaChildren’s
Hospital,AlbertaHealthServices,Calgary,Alberta,Canada;xDepartmentof Medicine, University of Saskatchewan,Saskatoon,
Saskatchewan,Canada;and{Departmentof CommunityHealthSciences,Universityof Calgary,Calgary,Alberta,Canada
SUMMARY
Purpose: The objective of this systematic review was to
identify: (1) prevalence and severity of psychiatric condi-
tions before and after resective epilepsy surgery, (2) inci-
dence of postsurgical psychiatric conditions, and (3)
predictors ofpsychiatric status aftersurgery.
Methods: A literature search was conducted using Pub-
Med, EmBase, and the Cochrane database as part of a lar-
ger project on the development of an appropriateness
and necessity rating tool to identify patients of all ages
with potentially resectable focal epilepsy. The search
yielded 5,061 articles related to epilepsy surgery and of
the 763 articles meeting the inclusion criteria and
reviewed in full text, 68 reported psychiatric outcomes.
Thirteen articles metthe finaleligibility criteria.
Key Findings: The studies demonstrated either improve-
ments in psychiatric outcome postsurgery or no changes
in psychiatric outcome. Only one study demonstrated
deterioration in psychiatric status after surgery, with
higher anxiety in the context of continued seizures post-
surgery. One study reported a significantly increased rate
of psychosis after surgery. The two main predictors of
psychiatric outcome were seizure freedom and pre-
surgical psychiatric history. De novo psychiatric condi-
tions occurred postsurgery at a rate of 1.1–18.2%, with
milder psychiatric issues (e.g., adjustment disorder) being
more common than more severe psychiatric issues (e.g.,
psychosis).
Significance: Overall, studies demonstrated either im-
provement in psychiatric outcomes postsurgery or no
change. However, there is a need for more prospective,
well-controlled studies to better delineate the prevalence
andseverityofpsychiatric conditions occurring inthecon-
text of epilepsy surgery, and to identify specific predictors
ofpsychiatric outcomes afterepilepsy surgery.
KEY WORDS: Epilepsy surgery, Psychiatric outcomes,
Systematicreview, Depression, Anxiety, Psychosis.
The psychiatric outcomes of epilepsy surgery are of par-
ticular interest (Foong & Flugel, 2007; Garcia-Morales
et al., 2008; Spencer & Huh, 2008) given the high overall
prevalence of psychiatric conditions in persons with epi-
lepsy (Ertekin et al., 2009; Guarnieri et al., 2009; Sperli
et al., 2009). Population-based studies demonstrate that
those with epilepsy have a higher prevalence of lifetime
psychiatric disorders (35%) than the general population
(20.7%) (Tellez-Zenteno et al., 2007). Mood and anxiety
disorders are the most frequent psychiatric conditions in
persons with epilepsy, with lifetime prevalence rates of
24.4% (vs. 13.2% general population) and 22.8% (vs.
11.2% general population), respectively (Tellez-Zenteno
et al., 2007). Other population-based studies (Qin et al.,
2005) demonstrate that persons with epilepsy are two and a
half times more likely to develop schizophrenia and three
times more likely to develop a schizophrenia-like psychosis
than the general population. In addition, rates of suicidal
ideation are significantly higher in persons with epilepsy
(25%) than in the general population (13.3%) (Tellez-Zent-
eno et al., 2007). Higher rates of depression have also been
reported among patients with epilepsy compared to patients
with other neurologic conditions (e.g., migraines) (Mendez
et al., 1993).
Psychiatric comorbidity has been recognized as a signifi-
cant predictor of seizure outcome after surgery, with
research demonstrating that the presence of psychiatric
disorders may be associated with worse prognosis post-
surgery (Kanner et al., 2009). There have been multiple
nonsystematic reviews of the psychiatric outcomes of epi-
lepsy surgery (Foong & Flugel, 2007; Garcia-Morales et al.,
2008; Spencer& Huh, 2008). Inone review, mood and anxi-
ety disorders were determined to be common after epilepsy
surgery, particularly among those with a lifetime history of
these disorders (Garcia-Morales et al., 2008). Spencer and
AcceptedJanuary9,2010;Early ViewpublicationXxxxxXX,20XX.
Address correspondence to Nathalie Jett?, MD, MSc, FRCPC, Depart-
ment of Clinical Neurosciences, Foothills Medical Center, 1403 29 St NW,
Calgary, Alberta, T2N 2T9 Canada. E-mail: nathalie.jette@albertahealth-
services.ca
WileyPeriodicals, Inc.
ª2011International LeagueAgainstEpilepsy
Epilepsia,**(*):1–11,2011
doi:10.1111/j.1528-1167.2011.03014.x
FULL-LENGTH ORIGINAL RESEARCH
1

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Huh (2008) reported similar results, adding that the stron-
gest predictor of psychiatric outcome was seizure control
postsurgery. Although psychiatric outcomes after epilepsy
surgery have been documented, there are no systematic
reviews, to ourknowledge, on this topic.
The purpose of this article was to conduct a systematic
review of the existing literature on psychiatric outcomes
associated with resective epilepsy (both temporal and extra-
temporal lobe) surgery. Specifically, the aims were to (1)
determine prevalence and severity of psychiatric problems
pre- and postsurgery; (2) determine the incidence of de novo
psychiatric problems after surgery; and (3) review predic-
tors ofpsychiatric statusafter surgery.
Methods
Literature searchstrategy andstudy selection
A literature search was conducted using PubMed, Em-
Base, and the Cochrane database until June 2008. The full
search strategy (June 2008) is appended (Appendix). Inclu-
sion criteria for the initial search were partial epilepsy, focal
resections (e.g., lesionectomy, lobectomy, corticectomy,
selective amygdalohippocampectomy), English language,
and sample size ‡20. Initial exclusion criteria were hypotha-
lamic hamartoma, subpial transections, hemispherectomies,
callosotomies, other palliative procedures, stimulation stud-
ies, neonates, and abstracts not published as full papers.
Additional inclusion criteria specific to this review were:
reported pre- and postsurgery data; provided prevalence
estimates of psychiatric problems and/or provided some
information about possible predictors of psychiatric out-
comes; used Diagnostic and Statistical Manual of Mental
Disorders (DSM; American Psychiatric Association, 2000)
criteria or International Classification of Diseases (ICD;
World Health Organization, 1992) criteria for psychiatric
diagnoses orusedaclear psychometricallysound self-report
symptom scale; and used a systematic method for obtaining
information (e.g., review by psychiatrist, structured clinical
interview, rating scales). All nonsystematic literature
reviews were excluded, although their reference lists were
reviewed to ensure that no additional studies were missed.
Studies using retrospective chart review as the primary
information collection method were excluded unless the
data obtained met the above criteria (e.g., psychiatrist
recorded DSM diagnoses for all patients pre- and postsur-
gery in the chart). We did not exclude studies based on time
of follow-up because many studies had follow-up times of
<2 years. All abstracts and articles were reviewed by an epi-
lepsyclinical psychologistand a neuropsychologist.
Analysis
Data from studies meeting inclusion criteria were col-
lected, including number of participants, age group, study
type (prospective or retrospective; controlled or noncon-
trolled), region of surgical resection, time to follow-up,
assessment type (e.g., diagnostic interview, self-report mea-
sure), psychiatric variables studied, psychiatric diagnostic
system used,overall psychiatric outcome, whether psychiat-
ric outcome was related to seizure freedom, other predictors
of psychiatric outcome, and number or percent with de novo
psychiatric problems. The extracted data were then checked
again foraccuracy by a research assistant.
Results
Description of included studies
Our original search using PubMed, EmBase, and the
Cochrane database yielded 5,061 articles related to epilepsy
surgery (see Fig. 1). Of these, 68 studied psychiatric comor-
bidity as an outcome of epilepsy surgery. Thirteen met all
inclusion criteria and none of the exclusion criteria and thus
were includedin this systematic review.
All studies and key findings are listed in Table 1. Six
studies included only adults, five studies included both
adults and children, and two studies included only children.
Six studies included only individuals with temporal lobe
resections, whereas seven included both temporal and extra-
temporal resections. Of the studies reviewed, it was unclear
in some cases whether the studies were prospective or retro-
spective, but most of the studies (n = 10) appeared to be
prospective noncontrolled;two were prospective controlled,
and one was retrospective controlled. The majority of the
studies (n = 8) had follow-up times in the 6–12 month
range. The other five studies had 24 months or greater fol-
low-up interval.
Depression (eight studies), anxiety (eight studies), and
overall psychological adjustment or presence/absence of
any psychiatric disorder (six studies) were the most
commonoutcomesexplored. These outcomeswereassessed
primarily through psychiatric assessment/diagnosis, struc-
tured interview, and/or self-report symptom measures.
Psychosis (one study), anger (one study), and interictal
dysphoric disorder (IDD) were less commonly measured.
IDD is generally a less serious psychiatric condition charac-
terized by a constellation of at least three emotional symp-
toms (depression, lack of energy, irritability, insomnia, fear,
anxiety, and/or euphoria), which are intermittent (lasting a
few hours to a few days) and do not meet full criteria for
a mood or anxiety disorder (Blumer et al., 1998). One
pediatric study explored pediatric psychiatric diagnoses,
whereas the other pediatric study explored parent-rated
child psychopathology, family adjustment, and child self-
reportedself-esteem.
The following describes the results for each of the differ-
ent psychiatric outcomes inmore detail.
Depression
Across studies (Table 1), the preoperative base rate of
depressive symptoms in surgical patients was high (24–
38%) (Spencer et al., 2003; Reuber et al., 2004; Meldolesi
2
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et al., 2007), but no higher than epilepsy patients treated
medically (39%, Reuber et al., 2004). The majority of stud-
ies comparing depression (including IDD) pre- and postsur-
gery demonstrated improvements in depression after
surgery, defined either as reduced prevalence of patients
meeting clinical criteria for depression, or significant
improvements on rating scales measuring depressive symp-
toms (Blumer et al., 1998; Spencer et al., 2003; Reuber
et al., 2004; Cankurtaran et al., 2005; Devinsky et al.,
2005; Pintor et al., 2007). In the only prospective controlled
study on depression included in this review, Reuber et al.
(2004) reported that a control group of medically treated
patients had significantly higher rates of depression than the
surgical group at 12 months of follow-up. Notably, half of
the patients in the control group were surgical candidates
who decided against surgery rather than patients who were
waiting for surgery or deemed ineligible for surgery. In a
prospective noncontrolled study, Spencer et al. (2003)
reported that 24% of temporal lobe patients had clinically
elevated depression scores presurgery, compared to only
13% at24 months postsurgery.
Incontrasttothesestudiesdemonstratingreduceddepres-
sion postsurgery, three studies (Altshuler et al., 1999;
Mattsson et al., 2005; McLellan et al., 2005) reported no
change or equivocal prevalence rates for patients with
depression pre- and postsurgery. Although depression
improved for some patients in these studies, these improved
cases were balanced by de novocases of depression postsur-
gically. Meldolesi et al. (2007) used the reliable change
index method to demonstrate few changes in self-reported
depression pre- versus postsurgery.
Prevalence of de novo depression cases (i.e., new cases of
depression in previously nondepressed patients) was
reported in five studies (Blumer et al., 1998; Altshuler
et al., 1999; Reuber et al., 2004; Cankurtaran et al., 2005;
Devinsky et al., 2005). Prevalence rates ranged from a high
of 18.2% of IDD cases 10 months postsurgery (Blumer
et al., 1998) to a low of 4% de novo depression cases 1 year
postsurgery (Reuber et al., 2004). The well-designed study
of Devinsky et al. (2005) demonstrated a de novo depres-
sion rate of 6.1% at 24 months postsurgery. Generally, de
novo cases of depression appeared to occur in individuals
with continued seizures postsurgery (Blumer et al., 1998;
Reuber et al., 2004; Devinsky et al., 2005).
In terms of predictors of postoperative depression,
studies found no laterality effects (Altshuler et al., 1999;
Figure 1.
Systematic literature review search results—general search refers to partial epilepsy and epilepsy surgery search strategy (aimed par-
ticularly at identifying all surgical series). The review search was broader and included all review articles as well (rather than only origi-
nal research articles).
Epilepsia
ILAE
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Table 1. Summary of psychiatric outcomes
Study
n
subjects
Age
group
Study type
Region of
resection
Follow-up
Assessment
type
Psychiatric
variables
Overall outcomea
Outcome
related
to seizure
freedom?
Other
predictors
ofpsychiatric
outcomeb
Percentage
ofde novo
cases
Altshuler
et al. (1999)
49surgical,
13 control
Adult and
children
Retrospective
controlled
Temporal
Mean = 10.9
years
Structured
interview:
SCID,
DSM-III-R
Depression
Equivocal
Presurgery (n = 49
surgical): 17(35%)
depressed
Postsurgery (n = 17
depressed presurgery):
8 (47%)of previously
depressed patients had
no depression postsurgery; 9(53%)had adepression
recurrence postsurgery
Yes– seizures
were controlled
in 7/8(88%)
patients without
depression
recurrence
postsurgery
Surgical group
had ahigher lifetime history of
depression than
controls
4/5 (80%) ofde
novo depression
cases had surgicalcomplications
5(10.2%)
depression
Blumer et al.
(1998)
50surgical
Adult and
children
Prospective
noncontrolled
44 temporal
6frontal
10 months
Structured
interview:
epilepsy
questionnaire
and
neurobiology
inventory
IDD
Psychosis
Majority improved
Presurgery (n = 44):
25 (57%) IDD
Postsurgery (n = 25 IDD
presurgery): 5 (20%) no IDD and no ADD; 9 (36%)no IDD but on
ADD; 11 (44%)still had
IDD but6 (55%)
stabilized on double
ADD
Yes
6/8(75%) de
novo IDD
cases had continued
seizures
Psychotropic
medication (ADD)
required to
maintain
improvement
n = 42with
‘‘reliable
follow-up’’
8(18.2%) IDD6(14%)psychosis
Cankurtaran
et al. (2005)
22surgical
Adult
Prospective
noncontrolled
Temporal
3and
6 months
Structured
interview:
SCID, DSM-IV
Self-report:
BPRS, HDRS,
HARS
Anxiety
Depression
Psychiatric
diagnosis
Majority improved at
6 months
Presurgery (n = 22)
presence of apsychiatric diagnosis:6 (27%)
Postsurgery (n = 22)
presence of apsychiatric diagnosis:
3 months: 6(27%)6 months: 2(9%)
Patients with
psychiatric
comorbidity had
more seizures
in the last
monthprior
tosurgery
Psychotropic
medications
required in 4 (18%)
at3-month
follow-up and
7(32%) at 6-month
follow-up
3 months:
anxiety: 2(9%)
depression:
4 (18.2%)
6 months:
depression
1 (5%)
Devinsky
et al. (2005)
358surgical
Adult and
children
Prospective
noncontrolled
89.1%
temporal
10.9% frontal
24 months
Structured
interview:
CIDI,ICD10
andDSM-IV
Self-report:
BDI; BAI
(‡16
moderate-
severesymptoms)
Anxiety
Depression
Psychosis
Majority improved
Presurgery Psychiatric
Diagnoses (CIDI)
(n = 336)c:
Anxiety Disorder:
59 (18%)
Depression: 75 (22%)
Other: 12 (4%)
Postsurgery (n = 278)
Psychiatric Diagnoses
(CIDI):
Anxiety Disorder:
29 (10%)
Depression: 26 (9%)
Other: 3(1%)
Yes– moderate
tosevere
depression
symptoms
postoperatively
in 17.6%with
continued
seizures versus
8.2% whowere
seizure-free
Psychiatric
diagnosis
presurgerypredictedpostsurgical
symptoms
Gender: women
more likely to
have apsychiatric
diagnosis
Depression: 6.1%
Anxiety: 6.9%
Psychosis: 1.1%
Continued
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Table 1. Continued
Study
n
subjects
Age
group
Study type
Region of
resection
Follow-up
Assessment
type
Psychiatric
variables
Overall outcomea
Outcome
related
to seizure
freedom?
Other
predictors
ofpsychiatric
outcomeb
Percentage
of denovo
cases
Hermann
et al. (1992)
97surgical
Adult
Prospective
noncontrolled
Temporal
6–8 months
Self-report:
MMPI, WPSI,
GHQ
Total
psychological
adjustment
(rank sum
ofthree
measures)
N/A (this study
focused on predictors
oftotal psychological
adjustment)d
Yes– being
totally
seizure-free
predicted overallpostoperative psychological
adjustment
Preoperative
total
psychological
adjustment
–
Hermann
et al. (1989)
41surgical
Adult
Prospective
noncontrolled
Temporal
1, 3 and
6 months
Self-report:
MHI
Anxiety
Depression
Psychological
distress
Loss of
emotional/
behavioral
control
Mixedd
Seizure-free patients
only demonstrated
significant decreases
in psychopathology
andimprovements
in mental health by
3 month follow-up
Yes– no
change group
had continued
seizures;
improved group
was seizure-free
at 6 months
Time by seizure
freedom interaction
(i.e., psychological
status improved
over time) for
seizure-free group
only
–
Mattsson
et al. (2005)
57surgical
Adult
Prospective
noncontrolled
47temporal10
extratemporal
2–8 years
Self-report:
KSP
Anxiety
proneness/ neuroticism
No change in
degree of
anxiety proneness
postsurgeryd
No significant
differences
between
seizure-free
and
continued-
seizures groups
–
–
McLellan
et al. (2005)
60surgical
Children
Prospective
noncontrolled
Temporal
1 year
Clinical
diagnosis
(psychiatric;
chart review)
DSM-IV
One or
more DSM-IV
psychiatric
diagnosis
Equivocal
Presurgery (n = 60):
43 (72%)had apsychiatric diagnosis
Postsurgery (n = 57):
41 (72%)had apsychiatric diagnosis;9(16%) diagnosis
resolved, but 7(12%)
denovo cases
No
–
7(12%) all
diagnoses
Meldolesi
et al. (2007)
52surgical
Adult
Prospective
noncontrolled
Temporal
Extratemporal
24 months
Self-report:
BDI, STAI,
MMPI, STAXI
Anxiety Anger
Depression
Mixed
Anxiety, anger:
statistically significant
improvementsd
Depression: reduced
but not statistically
significant
No
Younger age,
shorter
epilepsy
duration =
improved anger
–
Continued
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Table 1. Continued
Study
n
subjects
Age
group
Study type
Region of
resection
Follow-up
Assessment
type
Psychiatric
variables
Overall outcomea
Outcome
related
to seizure
freedom?
Other
predictors
of psychiatric
outcomeb
Percentage
of denovo
cases
Pintor
et al. (2007)
70 surgical
Adult
Prospective
noncontrolled
Temporal
1, 6, and
12 months
Structured
interview:
SCID, DSM-IV
Anxiety
Depression
Psychiatric
disorder
Majority improved
Pre surgery (n = 70)
presence ofa psychiatric disorder:33 (47%)
Post surgery (n = 70)
presence ofapsychiatric disorder
1 month: 30 (43%)6 months: 23 (33%)12 months: 18 (26%)
No
Any psychiatric
history, morepsychiatricproblemspost-surgery
Gender: women
more likely to
have psychiatricproblems
3(4.3%) all
diagnoses
Reuber
et al. (2004)
76 surgical,
18control
(medical
treatment)
Adult and
children
Prospective
controlled
75%
temporal
25%
extratemporal
12 months
Self-report:
BDI, SRAS
Anxiety
(SRAS
> 35 =
abnormalanxiety)
Depression
(BDI > 12 =
probable
depression)
Mixed: anxiety:
no change; depression:
surgical – majority
improved; control –
majority worsenede
Pre-surgery
Surgical (n = 76):
Anxiety: 36 (48%)
Depression: 22 (29%)
Presurgery
Controls (n = 18):
Anxiety: 7(39%)
Depression: 3(18%)
Postsurgery
Surgical (n = 76):
Anxiety: 30 (39%)
Depression: 12 (16%)
Postsurgery
Controls (n = 18):
Anxiety: 10 (56%)
Depression: 7(41%)
Yes –improved
symptoms of
depression and
anxiety if
seizure-free at
follow-up for
both surgical
andcontrolgroups
Those with
higher presurgical
depression scoresdemonstrated
most depression
improvement if
they were
seizure-free
postsurgery
Anxiety:
Surgical
(n = 76):
10 (13%)
Controls
(n = 18):
4(22%)
Depression:
Surgical
(n = 76):3(4%)
Controls
(n = 18):6(35%)
Smith
et al. (2004)
30 surgical,
21control
Children
Prospective
controlled
18 temporal8extratemporal 4multilobar
12 months
Collateral
rating: CBCL,
family
adjustment
Self-report:
PHCSC
Normal
versus
Abnormal
(1 standard
deviation)
Independence
promotion
No changed
No differences
between surgical
and control groups
No
Yes
Age: younger
more improved
onCBCL total
behavior score;
older more
improved on
self-conceptsubscale
–
Continued
6
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Table 1. Continued
Study
n
subjects
Age
group
Study type
Region of
resection
Follow-up
Assessment
type
Psychiatric
variables
Overall outcomea
Outcome
related
toseizure
freedom?
Other
predictors
of psychiatric
outcomeb
Percentage
of denovo
cases
Spencer
et al. (2003)
360surgical
Adult and
children
Prospective
noncontrolled
Temporal
Extratemporal
2, 12, and
24 months
Self-report:
BDI, BAI
(‡16 =
moderate-severe
symptoms)
Anxiety
Depression
Majority
improved
Presurgery
(BAI n = 360;
BDI n = 358):
Anxiety: 94 (26%)
Depression: 86 (24%)
Postsurgery
(BAI n = 251;
BDI n = 249):
Anxiety:
2 months 25 (10%)12 months 25 (10%) 24 months 33 (13%)
Depression:
2 months 25 (10%) 12 months 32 (13%) 24 months 32 (13%)
No
–
–
ADD, antidepressant drugs; BAI, Beck Anxiety Inventory; BDI, Beck Depression Inventory; BPRS, Brief Psychiatric Rating Scale; CBCL, Child Behavior Checklist; CIDI, Composite International Diagnostic Inventory; DSM, Diagnos-
tic and Statistical Manual of Mental Disorders; GHQ, General Health Questionnaire; HARS, Hamilton Anxiety Rating Scale; HDRS, Hamilton Depression Rating Scale; ICD, International Classification of Diseases; IDD, interictal dys-
phoric disorder; KSP, Karolinska Scales of Personality; MHI, Mini Health Inventory; MMPI, Minnesota Multiphasic Personality Inventory; N/A, not applicable; PHCSC, Piers–Harris Children’s Self Concept Scale; SCID, Structured
Clinical Interview for the DSM;SRAS, Self Rating Anxiety Scale; STAI, State-Trait Anxiety Inventory; STAXI, State-Trait AngerInventory; WPSI,Washington Psychosocial Seizure Inventory.
aOutcome grouped based on nochange, majority improved, mixed, majority worsened, or equivocal.
bOnly listed if itwas astatistically significant predictor.
cThe total sample did not receive the structured diagnostic interview.
dSpecific data for presurgery and postsurgery psychiatric prevalence rates were not reported.
eSample size calculations were conducted from percentages reported in the study. Thus,sample size proportions may not always equal the exact percentage.
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Meldolesi et al., 2007), and no effects of age, sex, or age at
epilepsy onset (Spencer et al., 2003). Four of the studies
demonstrating improvements in depression after surgery
specified that improvements were related to seizure free-
dom (Hermann et al., 1989; Altshuler et al., 1999; Reuber
et al., 2004; Devinsky et al., 2005; see Spencer et al.,
2003, for an exception). For example, Devinsky et al.
(2005) reported that 17.6% of their sample with continued
seizures met criteria for moderate to severe depression
compared to 8.2% of seizure-free patients postsurgery.
Two studies demonstrated that patients with a preexisting
history of depression were more likely to experience
depression postsurgery (Devinsky et al., 2005; Pintor et al.,
2007). In one study, psychotropic medications were
required to maintain reduced depression scores in surgical
patients (Blumer et al., 1998).
Anxiety
Anxietyalsoappearedtohavehighbaseline prevalencein
epilepsy surgery candidates (e.g., 48%, Reuber et al., 2004)
as shown in Table 1. Similar to the results for depression,
most of the studies exploring anxiety pre- and postsurgery
demonstrated reduced prevalence of anxiety postsurgery
(Spencer et al., 2003; Cankurtaran et al., 2005; Devinsky
et al., 2005; Meldolesi et al., 2007; Pintor et al., 2007). For
example, Meldolesi et al. (2007) applied the reliable change
index to anxiety changes pre- and postsurgery. The percent-
age of patients with reliable improvements in anxiety after
surgery was twice the percentage of patients showing reli-
able worsening of anxiety postsurgery (13–23% improved
anxiety vs. 4–6% worsened anxiety). They concluded that
anxietygenerallydecreasesovertimepostsurgically.
Three studies demonstrated no change in anxiety scores
(Hermann et al., 1989; Reuber et al., 2004; Mattsson et al.,
2005) postsurgery. Although overall anxiety scores did not
significantly reduce in the surgical group of Reuber et al.
(2004), a control group comparison revealed that there were
significantly fewer patients with clinically elevated anxiety
in a surgical group compared to a medically managed con-
trolgroup at 12-monthfollow-up(39% vs. 56%).
Although studies seem to suggest improvements in anxi-
ety postsurgery, three studies report de novo anxiety cases,
with prevalence rates of 6.9% (Devinsky et al., 2005), 9.1%
(Cankurtaran et al., 2005), and 13% (Reuber et al., 2004),
at 24-month, 6-month, and 12-month postsurgical follow-
up, respectively.
In terms of predictors of postsurgical anxiety, Devinsky
et al. (2005) found that having an anxiety disorder presur-
gery increased the likelihood that an anxiety disorder
would be diagnosed postsurgery. Another study (Reuber
et al., 2004) reported a significant relationship between
anxiety and seizure freedom. In this study, patients who
had <50% improvement in seizure frequency, or an
increase in seizures postsurgery, also demonstrated an
increase in anxiety.
Overall psychological adjustment andprevalence of
psychiatric disorders
Six studies explored more general psychological adjust-
ment, distress, or overall prevalence of psychiatric disorders
pre– and post–epilepsy surgery (Hermann et al., 1989,
1992; Blumer et al., 1998; Cankurtaran et al., 2005; McLe-
llan et al., 2005; Pintor et al., 2007). Four studies reported
improvements (Hermann et al., 1992; Blumer et al., 1998;
Cankurtaran et al., 2005; Pintor et al., 2007) and one
reported no change postsurgery (Hermann et al., 1989;
McLellan et al., 2005). The final study demonstrated mixed
results (Hermann et al., 1989), with overall improvement in
psychological distress occurring only in the context of sei-
zure freedom. In this study, 33% of patients with continued
seizures experienced a worsening of psychological well-
being 6 months postsurgery compared with only 7% of the
seizure-free group.
Blumer et al. (1998) found that 41% of surgical patients
have psychiatric complications in the first 8 months after
surgery, either in the form of exacerbations of preexisting
conditions, or de novo psychiatric problems. In the study of
Pintor et al.(2007),where the majority ofpatientsimproved
psychiatrically postsurgery, having a psychiatric history
and/or a specific psychiatric diagnosis at presurgical assess-
ment predicted an increased likelihood of a psychiatric dis-
order postsurgery.
Thesestudiessuggestthatepilepsypatients withapsychi-
atric history are at higher risk for poor psychiatric outcomes
postsurgery but de novo psychiatric problems and psycho-
logical adjustment issues also occur, particularly in the con-
text of continuedseizures postsurgery.
Anger andpsychosis
Only one study explored anger symptoms pre- and post-
surgery. In this study, Meldolesi et al. (2007) reported
improved scores on a self-report scale of anger symptoms
postsurgery. Results demonstrated that 17%, 19%, and 15%
showed reliable improvements on state anger, trait anger,
and inside-directed anger, respectively. This was in contrast
to 4%, 6%, and 4% who showed reliable worsening of state
anger,trait anger, and inside-directed anger, respectively.
Psychosis was also only explored in depth in one study.
However, this study by Devinsky et al. (2005) was a well-
designed prospective studyoftemporalandfrontalresection
cases with 24-month follow-up but no control group. This
study demonstrated a 1.1% prevalence rate of de novo psy-
chosis cases postsurgery. Blumer et al. (1998) found a
higher rate of de novo psychosis (6 of 42 or 14% of patients)
at 10 months postsurgery also in a mixed surgical group pri-
marily characterizedby temporal lobectomy patients.
Pediatric studies including psychiatric outcomes
Two studies examined psychiatric disorders or psycho-
logical adjustment in pediatric patients. McLellan et al.
(2005) specifically explored rates of psychiatric diagnoses
8
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Page 9

in children and adolescents pre- and postsurgery. Although
this was a retrospective chart review, all participants had a
formal, documented psychiatric assessment and the assess-
ment occurred within the same timeframe pre- and postsur-
gery (12 months). In addition, a psychiatristwas involved in
the chart review. The rate of ‘‘one or more psychiatric diag-
nosis’’ in the sample remained at 72% postsurgery, with
16% of participants’ psychiatric problems resolving but
12% receiving a de novo psychiatric diagnosis. The second
pediatric study (Smith et al., 2004) was a prospective,
matched,controlled study.Parent-rated andself-reportmea-
sures were used in this study to quantify behavioral,
self-esteem, and family adjustment changes pre- and post-
surgery. There were no differences between the groups on
behavioral and self-esteem scales. Overall, there were few
changes postsurgery, and the prevalence of behavioral and
psychosocial difficulties remained high in both the surgical
and control groups after 1 year (i.e., >50%; Smith et al.,
2004). However, family-based independence promotion
improved in surgical cases as compared to controls. Age
predicted behavior changes, with parent-rated behavior of
younger surgical patients being more favorable postsurgery
compared to parent behavior ratings of older patients. In
contrast, older surgical patients were more likely to report
improved self-concept postsurgery than younger surgical
patients. However, given that the majority of areas were
unchanged after surgery, the authors concluded that
improvements maytaketime toemerge inpediatricepilepsy
surgery patients.
Discussion
The studies included in this systematic review demon-
strate either improvements in psychiatric problems postsur-
gery or no changes/equivalent rates of psychiatric issues
postsurgery. Only one study demonstrated deterioration in
psychiatric status after surgery, with higher anxiety in the
context of continued seizures postsurgery (Reuber et al.,
2004). One study also reported a high rate of postsurgical
psychosis(Blumeret al.,1998),butthiswasnotreplicatedin
alargerstudywithlongerfollow-up(Devinskyet al.,2005).
The two main predictors of psychiatric outcomes identi-
fied were seizure freedom and presurgical psychiatric his-
tory. Based on our systematic review, studies generally
demonstrate that seizure freedom is an important predictor
of psychiatric outcomes postsurgery, with some studies
reporting that de novo psychiatric issues occurred primarily
in patients with continued seizures after surgery. Similarly,
surgical patients with a history of psychiatric issues are
more likely to experience psychiatric problems postsurgery.
However, other studies reviewed concluded that preexisting
depression should not be a contraindication for surgery
(Altshuler et al., 1999), and that depression can be
improved by successful surgical treatment of epilepsy (Reu-
ber et al., 2004), although continued psychotropic medica-
tion may be required to maintain reduced depression
postsurgery (Blumer et al., 1998). Other predictors, such as
laterality, age at epilepsy onset, gender, and age appear to
have minimal predictive value in psychiatric outcomes after
epilepsy surgery. However, other important predictors of
psychiatricstatus,suchasfamilyhistory,levelofsocialsup-
port, and life stress, were generally not considered in the
studies reviewed. Expanding the scope of predictors of psy-
chiatric status included in epilepsy surgery studies is an
important consideration forfutureresearch.
Our review also demonstrated that de novo psychiatric
conditions occur postsurgery at a rate of anywhere from
1.1–18.2%, with the increased likelihood generally being
inversely related to the severity of the psychiatric issue (i.e.,
1.1% de novo psychosis vs. 18.2% IDD). Unfortunately, the
studiesreviewedheredidnotprovidesignificantinsightinto
the possible predictors of de novo psychiatric issues other
than continued seizures. In one study, Altshuler et al.
(1999) demonstrated that de novo depression cases were
more likely to have experienced surgical complications. In
the only study (Reuber et al., 2004) reviewed here that
clearly comparedde novo depression and anxiety symptoms
in surgical cases versus nonsurgical controls, surgical cases
were much less likely to experience de novo depression or
anxiety than medical treatment controls at 12-month fol-
low-up. Overall, the literature reviewed here suggests that
de novo psychiatric issues are relatively rare postsurgery
and more likely to occur in the context of continued sei-
zures, surgical complications, or continued medical (rather
than surgical) seizure management. Future research includ-
ing medically managed control groups and exploration of
other factors, such as area of resection, specifically in rela-
tion to de novo psychiatric conditions, is required to
improve our understanding of the occurrence of de novo
psychiatric conditions postsurgery.
Only two pediatric studies met our inclusion criteria for
this review. Overall, there were few postoperative behav-
ioral and psychosocial changes postepilepsy surgery in the
pediatric population.
This systematic review highlights the diversity of assess-
ment techniques employedto establish the psychiatric status
of patients in epilepsy surgery studies. The studies included
for review assessed psychiatric status through structured
diagnostic interviews, a series of psychometrically tested
symptom questionnaires, or a combination of both assess-
ment methods. Generally, studies that included a structured
diagnostic interview produced more definitive positive
results (i.e., improved psychiatric status) compared to stud-
ies that employed only symptom scales, which generally
demonstrated more mixed or equivocal results. This sug-
gests that, although patients may not meet full criteria for a
psychiatric disorder postsurgery, they may still struggle
meaningfully with symptoms of a psychiatric disorder post-
surgery. This also highlights the importance of having both
symptom scales and diagnostic assessments included as part
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Page 10

of the psychiatric screen for patients undergoing epilepsy
surgery infutureresearch.
Conclusions
This review demonstrates the need for more prospective,
well-controlled studies to better delineate the prevalence
and severity of psychiatric conditions occurring in the con-
text of epilepsy surgery, and to identify specific predictors
of psychiatric outcomes after epilepsy surgery. One of the
main challenges in this area is the paucity of studies using
established psychiatric diagnostic criteria (i.e., DSM-IV).
Theuseofdiverseassessmentmethods andtools,anddiffer-
ent clinical cutoffs, also complicates interpretation across
studies. Furthermore, the majority of studies have short-
term follow-ups. Current efforts toward developing multi-
center surgical trials, including standardized assessment
procedures, may alleviate some of these problems in future
studies designed to assess psychiatric outcomes of epilepsy
surgery. A systematic psychiatric or psychological assess-
ment, including both a structured diagnostic interview and
psychometrically sound symptom measures that incorporate
established cutoff scores (e.g., Beck Depression Inventory
scores ‡ 16, Devinsky et al., 2005) and conducted both
prior to and after epilepsy surgery, should be considered in
all surgical candidates. The results of this review suggest
that the majority of psychiatric changes occur within the
first year of surgery, suggesting that the assessment should
be completed by 1 year postsurgery.
Acknowledgments
Dr. N. Jett? holds salary awards from the Alberta Heritage Foundation
for Medical Research (AHFMR; Population Health Investigator) and from
the Canadian Institutes of Health Research (CIHR; New Investigator
Award). This study was in part supported by a Clinician Scientist award
to N. Jett? from the American Epilepsy Society and the Milken Family
Foundation and operating grants and or funds from AHFMR, Alberta
Health Services, CIHR, the Hotchkiss Brain Institute and the University of
Calgary.
Disclosure
None of the authorshave any conflict of interest to disclose. We confirm
that we have read the Journal’s position on issues involved in ethical publi-
cationandaffirmthatthisreportis consistent withthoseguidelines.
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Appendix—Full Search Strategy
1. epilep*.mp.
2. (surger* or surgi*).mp. [mp = title, abstract, subject
headings, heading word, drug trade name, original title,
device manufacturer, drug manufacturername]
3. (epilepsy and surgery).mp. [mp = title, abstract, subject
headings, heading word, drug trade name, original title,
device manufacturer, drug manufacturer name]
4. (incidence or mortality or follow-up studies or prognosis
or prognos* or predict* or course or outcome or psycho-
logy or quality of life or memory or survival analysis or
seizure*or utilization or cost or efficacy or complications
or effectiveness or sudep).mp. [mp = title, abstract,
subject headings, heading word, drug trade name, origi-
nal title, device manufacturer, drugmanufacturername]
5. (1 and 2) or 3
6. 4and 5
7. (randomized controlled trial or random* or (double and
blind) or placebo or drug therapy or therapeutic or cohort
studies or risk or (odds and ratio) or (relative and risk) or
case control or case-control studies or clinical trial or ran-
dom allocation or case series or decision analysis or eco-
nomic).mp. [mp = title, abstract, subject headings,
heading word, drug trade name, original title, device
manufacturer, drug manufacturer name]
8. 6and 7
9. limit 8to (human and English)
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