172 http://neuro.psychiatryonline.

org J Neuropsychiatry Clin Neurosci 17:2, Spring 2005

Clinical Assessment of
Axis I Psychiatric
Morbidity in Chronic
Epilepsy: A Multicenter
Investigation
Jana E. Jones, Ph.D.
Bruce P. Hermann, Ph.D.
John J. Barry, M.D.
Frank Gilliam, M.D.
Andres M. Kanner, M.D.
Kimford J. Meador, M.D.
Received June 24, 2003; revised December 15, 2003; accepted August
30, 2004. From the Department of Neurology, University of Wisconsin-
Madison, Madison, Wisconsin; the Department of Psychiatry, Stanford
University, Stanford, California; the Department of Neurology, Rush-
Presbyterian St. Lukes Medical Center, Chicago, Illinois; the Depart-
ment of Neurology, Columbia University, NY, New York; and the De-
partment of Neurology, University of Florida, Gainesville, Florida.
Address correspondence to Dr. Jones, University of Wisconsin-
Madison, H4/680 CSC, 600 Highland Ave., Madison, WI 53792-6180;
jejones@neurology.wisc.edu (E-mail).
Copyright 2005 American Psychiatric Publishing, Inc.
This study characterizes the rate of current Axis I
DSMIV disorders using a brief standardized
psychiatric interview procedure, the Mini Interna-
tional Neuropsychiatric Interview (v5.0) (MINI),
and determined the validity of MINI diagnoses of
current depressive episodes to the research stan-
dard (Structured Clinical Interview for DSMIV
Disorders [SCID]). One hundred seventy-four pa-
tients with chronic epilepsy from ve tertiary
medical centers were interviewed using the MINI
and the mood disorders module of the SCID. Cur-
rent Axis I disorders were evident in one-half the
sample (49%), with prevalent anxiety (30.4%)
and mood (21.8%) disorders. Major depressive ep-
isode was the most common individual diagnosis
(17.2%). Concordance was high between the
MINI and SCID for diagnoses of current depres-
sion, especially for major depression. Of those
with current major depression, less than one-half
were treated with antidepressant medications.
Current Axis I DSMIV diagnoses can be effec-
tively and accurately identied in clinical settings
using shorter standardized psychiatric interview
techniques. Issues regarding recognition and
treatment of psychiatric morbidity in epilepsy are
discussed.
(The Journal of Neuropsychiatry and Clinical
Neurosciences 2005; 17:172179)
D
espite an extensive literature indicating that de-
pression is a frequent psychiatric complication of
chronic epilepsy,
15
reports continue to indicate that
mood disorders in particular, and psychiatric comorbid-
ity more generally, continue to go unrecognized or un-
treated in both children
6
and adults with epilepsy,
79
further eroding health-related quality of life.
9,10,11
Rec-
ognition of comorbid psychiatric disorders in epilepsy
needs to be improved in routine clinical settings. Stan-
dardized psychiatric interview procedures provide one
avenue to comprehensively characterize the presence
and nature of current Axis I DSMIV disorders. How-
ever, these procedures, such as the Structured Clinical
Interview for DSMIV Axis I Disorders-Research Ver-
sion (SCID-I),
12
can be too time consuming for routine
clinical use. Even the research literature contains a mod-
J Neuropsychiatry Clin Neurosci 17:2, Spring 2005 http://neuro.psychiatryonline.org 173
JONES et al.
TABLE 1. Demographics and Clinical Seizure Features (N174)
Age (years) 39.04 (11.9)
WRAT (Reading Score) 97.31 (13.2)
Gender
women 115 (66.1%)
men 59 (33.9%)
Age of epilepsy onset (years) 21.1 (13.7)
Seizure duration (years) 17.9 (12.7)
Medications
monotherapy 94 (54%)
polytherapy 80 (46%)
Seizure Types*
simple partial 53 (30.5%)
complex partial 96 (55.2%)
secondarily generalized 55 (31.6%)
primarily generalized 72 (41.4%)
*Individuals may have more than one seizure type.
WRATWide-Range Achievement Test
est number of studies using this methodology with the
majority occurring in specialized surgical settings.
1318
Standardized psychiatric interview procedures that
are more time efcient yet reliable, valid, and compre-
hensive, would offer the potential to be of greater clini-
cal utility as well as to facilitate clinical research in this
important area. The Mini International Neuropsychiat-
ric Interview (MINI) represents an effort of this type,
focusing predominantly on current Axis I DSMIV dis-
orders with an efcient series of probe questions.
19
The
reliability and validity of this interview procedure have
been investigated in some clinical groups, but, to date,
the MINI has not been used in the investigation of psy-
chiatric morbidity in epilepsy.
The purpose of this multicenter investigation was to
use the MINI to examine the nature and distribution of
Axis I DSMIV disorders in an unselected population of
patients with epilepsy attending university-based epi-
lepsy clinics. Patients also underwent interviews with
the Mood Disorders Module of the SCID-I to determine
the validity of MINI-based diagnoses compared to the
research standard. Mood disorders, major depression in
particular, were of special interest given the known in-
creased prevalence of these diagnoses and the associ-
ated elevated mortality due to suicide in epilepsy.
20
METHOD
Subjects
Patients with a diagnosis of epilepsy, regardless of sei-
zure type, were recruited through tertiary outpatient ep-
ilepsy centers from ve universities (Medical College of
Georgia, Rush Presbyterian St. Lukes Medical Center,
Stanford University, Washington University, University
of Wisconsin-Madison). Inclusion criteria includedchro-
nological age 18 years and older, treated only with an-
tiepilepsy medications (excluding patients who under-
went surgery or were implanted with vagal nerve
stimulator), on stable antiepilepsy medications for the
previous 30 days, and intact reading ability with Wide
Range Achievement Test-3 (WRAT-3) reading scores
69.
One hundred seventy-four individuals met all selec-
tion criteria, proceeded through informed consent pro-
cedures, and fully completed all interviews and ques-
tionnaires. Table 1 summarizes the demographic and
clinical epilepsy characteristics of the study sample.
Overall, patients in this investigation suffered from
chronic epilepsy (approximately 18 years of epilepsy),
almost one-half were on polytherapy (46%), and the ma-
jority (55%) had complex partial seizures.
Procedures
Trained investigators at each site interviewed study par-
ticipants with the Mini International Neuropsychiatric
Interview (MINI) in order to identify current DSMIV
Axis I disorders.
19
Additionally, each subject also un-
derwent an interviewusing the Mood Disorders module
of the Structured Clinical Interview for DSMIV Axis I
Disorders-Research Version (SCID-I)
12
in order to iden-
tify lifetime-to-date and current DSMIV Axis I mood
disorders. The SCID-I represented the research standard
to which MINI diagnoses of depression were compared.
Study interviewers at each site were experiencedin stan-
dardized psychiatric assessment. However, for the pur-
poses of this investigation all interviewers underwent
centralized training in the use of the MINI and mood
disorders module of the SCID-I by experienced psychi-
atric research clinical interviewers. Finally, the Beck De-
pression Inventory-II
21
and Center for Epidemiological
Studies-Depression Scale (CES-D)
22
were completed by
each participant in order to capture symptoms of current
depressive symptoms. Further details regarding these
measures are provided below.
MINI
The MINI was developed as a short and efcient diag-
nostic interview to be used in clinical as well as research
settings.
19
It follows DSMIV and the ICD-10 criteria for
psychiatric disorders, screening for 17 Axis I disorders,
174 http://neuro.psychiatryonline.org J Neuropsychiatry Clin Neurosci 17:2, Spring 2005
AXIS I PSYCHIATRIC MORBIDITY IN EPILEPSY
TABLE 2. MINI: Axis I Current Diagnoses (N174)
Mood DisordersCurrent 24.0%
Depressive Disorders 21.2%
Major Depressive Episode 17.2%
Dysthymia 4.0%
Bipolar Disorders 2.8%
Manic Episode 1.7%
Hypomanic Episode 1.1%
Anxiety DisordersCurrent 52.1%
Panic Disorder 3.4%
Agoraphobia 15.5%
Social Phobia 10.9%
Obsessive-Compulsive 3.4%
Posttraumatic Stress Disorder 5.7%
Generalized Anxiety Disorder 13.2%
Schizophrenia & Other Psychotic DisordersCurrent
Psychotic Disorders 0.6%
A large number of participants had more than one diagnosis
(N59).
Percentages across the Axis I disorders exceeded 100%, reecting
co-morbidity.
MINIMini International Neuropsychiatric Interview
with brief suicidality and antisocial personality mod-
ules. The Axis I disorders included in the MINI were
selected based upon the 12-month prevalence reported
in the Epidemiologic Catchment Area Study
23
and the
National Comorbidity Survey.
24
The MINI has been val-
idated in the U.S. and Europe and is available in 20 lan-
guages.
25
Administration time ranges from approxi-
mately 1520 minutes for individuals with few
positively endorsed symptoms to 2030 minutes for in-
dividuals who meet criteria for current diagnoses.
SCIDIResearch Version
The Structured Clinical Interview for DSMIV Axis I
Disorders-Research Version is a well known semistruc-
tured interview that provides a framework upon which
to make DSMIV Axis I diagnoses.
12
Only the Mood
Disorders module of the SCID-I was administered in
this study in order to determine the validity of MINI
mood diagnoses. The interview required approximately
1525 minutes in order to complete the module. The
SCID-I is arguably the standard semistructured psychi-
atric interview procedure most used for research pur-
poses. The MINI and SCID-I were administered in a sin-
gle session, and each subject was interviewed privately
and independently.
Beck Depression Inventory- (BDI) II
The Beck Depression Inventory II is a well-known self-
report instrument designed to assess and detect the se-
verity of current (past 2 weeks) depressive symptoms in
clinical, medical and community settings.
21
The BDI-II
contains 21 descriptive statements regarding depressive
symptoms frequently reported by individuals diag-
nosed with depression. Each of the items contains a
four-point severity rating scale, with administration
time ranging from 5 to 10 minutes. Scores above 19 in-
dicated moderate severity of depressive symptoms.
21
CES-D
Self-rated depressive symptoms were also assessed us-
ing the CES-D. The CES-D is a 20-item scale developed
to screen for depression in primary care settings.
22
It has
been shown to be a valid and reliable instrument
22,26,27
and scores of 16 are most frequently used to indicate
depression.
RESULTS
MINI Diagnoses
A summary of current MINI Axis I DSMIV disorders
among the epilepsy patients is provided in Table 2.
Nearly one-half of the sample had no current axis I di-
agnosis (N89 or 51.1%), while the remaining half
(N85 or 48.9%) exhibited current diagnoses. Comor-
bidity across diagnoses was frequent. The results re-
ported in Table 2 reect this comorbidity in that the per-
centages across the Axis I disorders exceed 100%
indicating that a large number of participants have more
than one disorder (N59).
Among the mood disorders, and in fact among all in-
dividual diagnoses, major depression was the most
common disorder (17.2%), with a considerably smaller
proportion meeting criteria for current dysthymia
(4.0%) or bipolar disorders (2.8%).
Current anxiety disorders were especially prevalent
with 91 of diagnoses falling in this category. Agorapho-
bia (15.5%), generalized anxiety disorder (13.2%), and
social phobia (10.9%) were the most common diagnoses
among the anxiety disorders.
Within the anxiety disorders a substantial proportion,
25 of 52 persons or 48.1%, met criteria for two or more
anxiety disorders. There was also considerable comor-
bidity between mood and anxiety disorders. Of those
patients with current depressive disorders, the majority
(27 of 37 or 72.9%) were also diagnosed with a current
anxiety disorder. Schizophrenia and other psychotic dis-
orders were uncommon (N1 or 0.6%).
SCID-I Diagnoses
Using the mood disorders module of the SCID, 45.4%
of the sample was diagnosed with lifetime-to-date mood
J Neuropsychiatry Clin Neurosci 17:2, Spring 2005 http://neuro.psychiatryonline.org 175
JONES et al.
TABLE 4. Concordance Between MINI and SCID Diagnoses
DSM-IV Diagnosis
Major Depressive Episode-Current 0.86*
Manic Episode-Current 0.49*
Manic Episode-Past 0.79*
Hypomanic Episode-Current
Hypomanic Episode-Past 0.48*
Dysthymia-Current 0.31*
*Kappa value is signicant at the 0 .001 level; MINIMini
International Neuropsychiatric Interview; SCIDStructured Clinical
Interview for DSM
TABLE 3. MINI Versus SCID-I Results
Mood Disorders
MINI
(n174)
SCID
(n174)
Major Depressive Episode
Current 30 (17.2%) 29 (16.7%)
Manic Episode
Current 3 (1.7%) 1 (0.6%)
Past 5 (2.9%) 5 (2.9%)
Hypomanic Episode
Current 2 (1.1%) 0 (0.0%)
Past 10 (5.7%) 6 (3.4%)
Dysthymia
Current 7 (4.0%) 5 (2.9%)
MINIMini International Neuropsychiatric Interview; SCID-
IStructured Clinical Interview for Diagnostic and Statistical
Manual for Mental Disorders
FIGURE 1. Comparison Self-Report Depression Inventories with
MINI and SCID
S
c
o
r
e
Current MDE-SCID Current MDE-MINI
5
10
15
20
0
Yes No Yes No
25
30
35
CES-D BDI-II
MINIMini International Neuropsychiatric Interview
SCIDStructured Clinical Interview for DSM
CESCenter for Epidemiological Studies Depression Scale
BDIBeck Depression Inventory
disorders of any type, 27.0% with a past major depres-
sive episode (39.7% lifetime-to-date [includes current]).
MINI Versus SCID-I Diagnoses
Mini International Neuropsychiatric Interview and
SCID-I diagnoses were compared using the mood dis-
order modules of each instrument, including current
and past diagnoses where applicable. As shown in Table
3, current major depressive episodes were identied
with similar frequency by the MINI (17.2%) and SCID-
I (16.7%). Table 4 demonstrates signicant concordance
(Kappa) between the MINI and SCID-I for all DSMIV
mood diagnoses captured by both instruments. The
highest concordance was evident for major depressive
episodes-current (0.86) and manic episodes-past (0.79)
(Table 5). While signicant, considerably lower concor-
dance between MINI and SCID-I was seen for other di-
agnostic categories due, at least in part, to low frequen-
cies of diagnosis in this population.
The degree of concordance for major depressive epi-
sode was also examined for individual subjects. Twenty-
three of 30 (76.7%) individuals with a major depressive
episode were diagnosed by both instruments, with 7
subjects diagnosed by one or the other interview pro-
cedure (4 on MINI only, 3 on SCID only).
Treatment With Antidepressant Medications
Less than one-half of the individuals identied as meet-
ing criteria for a current major depressive episode were
being treated with antidepressant medications. Only 13
or 43.3% of subjects diagnosed with a current major de-
pressive episode by the MINI were taking an antide-
pressant medication, and only 14 or 48.3% of subjects
identied by the SCID-I as experiencing a current major
depressive episode were taking antidepressants. These
results underscore previous reports that current depres-
sion is undertreated in this population. Interestingly, 20
(11.5%) individuals who did not meet criteria for a cur-
rent major depressive episode were taking antidepres-
sant medications. Of this group, 60% had a past major
depressive episode based on the SCID-I.
Self-Reported Depression
Subjects diagnosed with a current major depressive ep-
isode had signicantly (p0.01) higher scores on the
BDI and the CES-D as would be expected (Figure 1). For
individuals identied with a current major depressive
episode by the MINI and SCID-I, the mean CES-D,
scores were 30.96 and 29.38, respectively. Similar results
were noted on the BDI-II, with essentially equal mean
scores for individuals with MINI and SCID-I diagnoses
176 http://neuro.psychiatryonline.org J Neuropsychiatry Clin Neurosci 17:2, Spring 2005
AXIS I PSYCHIATRIC MORBIDITY IN EPILEPSY
of current major depressive episode (28.27 and 27.68,
respectively).
DISCUSSION
This multicenter investigation assessed a sample of out-
patients with epilepsy followed at university-basedclin-
ics using standardized psychiatric interviewprocedures
in order to characterize the rate of current major Axis I
DSMIV disorders. Patients were interviewed with a
standardized protocol (MINI) that is more economical
in its time demands and therefore of potential utility in
clinical settings. Additionally, the mood disorder mod-
ule of the SCID-I was administered in order to deter-
mine the validity of MINI diagnoses of depression com-
pared to the research standard. The discussion that
follows reviews the rates and distribution of current
Axis I DSMIV disorders using the MINI, and the valid-
ity of MINI mood disorder diagnoses compared to the
research standard, and concludes with a brief review of
issues related to the comorbidity, recognition, and treat-
ment of current DSMIV disorders in patients with
chronic epilepsy.
Rates of Current Axis I DSMIV Disorders
Rates of current Axis I DSMIV disorders using the
MINI were found to be common, affecting essentially
one-half of the sample. This rate of current Axis I dis-
orders is elevated compared to ndings derived from
population-based studies such as the National Comor-
bidity Survey in which 48% of patients had a lifetime
history of Axis I disorders.
24
Most but not all investigations using standardized
DSM-based structured interviews in the epilepsy liter-
ature have involved patients who were candidates for
epilepsy surgery, most often with intractable temporal
lobe epilepsy (e.g., references 1318). Comparatively
less research has been devoted to characterizing the dis-
tribution of Axis I disorders in the general population
of patients with epilepsy attending specialty clinics.
Nonetheless, the rate reported here (49%) is within the
range (19%62%) of current Axis I disorders in the few
other available studies of patients with epilepsy that
have reported this statistic.
17,28,29
Overall, these ndings
warrant a heightened index of concern for psychiatric
morbidity in comparable specialty clinic settings.
Of the epilepsy patients with identied current dis-
orders, 21.2% met criteria for depressive disorders, in-
cluding current major depression (17.2%). Interestingly,
anxiety disorders were unexpectedly common current
disorders, with agoraphobia (15.5%), generalized anxi-
ety disorders (13.2%), and social phobia (10.9%) being
the most common. As noted previously, most studies
examining patients with temporal lobe epilepsy, have
reported lifetime-to-date mood disorders to be more
common than anxiety disorders. This pattern has been
reported by several investigators including Victoroff
30
(63% mood versus 32% anxiety), Altshuler et al.
13
(44%
versus 5%), Silberman et al.
18
(62% versus 15%), and
Hermann et al.
4
(46% versus 13%). The rate of current
major depression in these epilepsy subjects (17.2%) is
considerably higher than that reported in the general
population (10%).
24
The high rate of anxiety disorders found here was un-
expected. This sample included individuals with a range
of seizure types. Individuals studied here did not un-
dergo ictal monitoring as part of the research protocol,
so the relationship between mood versus anxiety dis-
orders and seizure type could not be directly addressed
in this investigation. However, there were no signicant
differences between individuals with complex partial
seizures with and without secondary generalized sei-
zures in terms of the frequency of mood (p0.74) and
anxiety (p0.20) disorders in general or more speci-
cally major depression (p0.57).
In summary, in this sample of individuals with
chronic epilepsy, major depression (17%) was the most
common current Axis I DSMIV diagnosis, followed by
agoraphobia (15%), generalized anxiety disorder (13%)
and social phobia (11%). The broader trend, however,
revealed overrepresentation of anxiety (52.1%) com-
pared to mood disorders (24.0%).
Patterns of Psychiatric Comorbidity
In the epilepsy literature there has been very little ex-
amination of the degree of comorbidity across psychi-
atric diagnoses. Interestingly, the rate of comorbid MINI
current mood and anxiety disorders was high in this
sample, with 27 of 37 (73%) patients with depressive
disorders also diagnosed with a comorbid current anxi-
ety disorder. This combination of comorbid major de-
pression and anxiety was more common than depres-
sive disorders alone (10 of 37 or 27.0%). In addition,
within the anxiety disorders there were a large number
of comorbid diagnoses. A substantial proportion, 25 of
52 persons or 48.1%, met criteria for two or more current
anxiety disorders. Patterns of comorbidity are of consid-
J Neuropsychiatry Clin Neurosci 17:2, Spring 2005 http://neuro.psychiatryonline.org 177
JONES et al.
erable interest in the general psychiatric literature,
24
but
remain to be fully characterized among patients with
epilepsy.
Recognition and Treatment of Psychiatric Morbidity
Consistent with previous reports,
2,6,79
we found that
mood disorders in epilepsy, including current major de-
pression, often went untreated. Fewer than one-half
(43%) of the patients with current major depression in
this investigation were treated with antidepressant
medications. The reasons for the undertreatment of de-
pression in the general population have been reviewed
previously,
31
but remain to be characterized in epilepsy.
While high rates of untreated depression typically raise
the index of suspicion that psychiatric comorbidity is
inadequately screened for by attending physicians,
31
one interesting nding suggests that epilepsy specialists
were concerned about and looking for comorbid mood
disorders. A subset of 20 (11.5%) individuals was iden-
tied who were prescribed antidepressant medications,
but they did not meet criteria for current major depres-
sion or a current mood disorder more generally. The na-
ture of this subset of individuals remains uncertain and
could reect persons with subsyndromal depressive dis-
orders, mood disorders that are adequately treated and
no longer clinically manifest, or perhaps receiving anti-
depressant treatment that is not clinically warranted.
Review of SCID-Iata for these 20 individuals, however,
revealed that 60%suffered a past (but not current) major
depressive episode, suggesting that treatment may have
been appropriately targeted in the majority of cases.
This subset of patients also raises the possibility that
mood disorders may be even more common than our
gures indicate.
Another interesting consideration is related to the in-
dividuals (43%) with current major depression who
were treated with antidepressant medications. Despite
receiving treatment, these individuals continued to meet
criteria for major depression, suggesting that their de-
pression had not responded to adequate treatment, the
antidepressant treatment was suboptimal, patients suf-
fered from drug resistant depression, or perhaps pa-
tients were noncompliant with their antidepressant
treatment.
Overall, these results suggest that treating physicians
are attempting to identify and treat comorbid mood dis-
orders in particular, but they overlook one-half of the
existing cases with current signicant mood disorders,
the vast majority of whom also suffer from comorbid
anxiety disorders, and apparently are having difculty
controlling depressive symptoms in treated patients.
Several investigative groups in the epilepsy literature
have pointed to the need for improved recognition of
depression, unquestionably an important goal. How-
ever, the primary care literature has demonstrated that
attempts to improve recognition of depression do not
invariably translate to improved treatment of depres-
sion.
31
In the epilepsy literature, intervention papers
typically focus on the standard of care for the treatment
of depression in epilepsy,
2,32
with the assumption that
this information will be incorporated into the usual and
typical care of patients with epilepsy by their primary
physicians, subsequently improving psychiatric out-
comes. However, randomized treatment trials in other
(non-neurological) health care settings have challenged
this assumption. These studies have demonstrated the
cost-effective and treatment-effective superiority of pro-
grams of so-called collaborative care (e.g., combined
psychiatry and primary medical) over improved usual
care for the management of major depression.
3336
Such
issues have yet to be examined seriously in epilepsy, as
do issues related to the additional health care costs and
associated functional disabilities
37,38
that have been
demonstrated to be associated with major depression in
other patient populations. Finally, anxiety disorders ap-
pear especially common in this population, and similar
data collection regarding the recognition and adequacy
of treatment of these disorders remains an important
task for the future.
Limitations/Future Directions
Several limitations of this investigation, as well as op-
portunities for future research, should be recognized.
First, the sample investigated here consisted of individ-
uals with chronic epilepsy recruited from tertiary care
centers. Findings regarding rates of Axis I disorders
therefore cannot be assumed to generalize to the general
population of persons with better-controlled epilepsy in
the community. Second, this investigation did not focus
on predictors of current mood disorders (e.g., localiza-
tion and lateralization of seizure onset), but the reliabil-
ity of MINI diagnoses may make such efforts feasible in
clinical settings. Third, irritability and anger related to
interictal dysphoric disorder
40
were not evaluated in
this study and are not specically addressed in the
MINI. Finally, the high rate of anxiety disorders, either
alone or in combination with mood disorders, suggests
178 http://neuro.psychiatryonline.org J Neuropsychiatry Clin Neurosci 17:2, Spring 2005
AXIS I PSYCHIATRIC MORBIDITY IN EPILEPSY
that directed study of these disorders remains an im-
portant task for the future.
This study was presented in abstract form at the annual
meetings of the American Epilepsy Society, Seattle, December
2002 and the American Psychiatric Association, San Fran-
cisco, May 2003.
This study was supported by a research grant from
GlaxoSmithKline and NIMH F32 MH64988-01A2 (J. Jones,
Inc.).
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