Epilepsy & Behavior 23 (2012) 52–56

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Epilepsy & Behavior

journal homepage: www.elsevier.com/locate/yebeh

Cognitive-behavioral therapy for depression in patients with temporal lobe epilepsy:

A pilot study
D. Crail-Meléndez a,⁎, A. Herrera-Melo b, I.E. Martínez-Juárez c, J. Ramírez-Bermúdez a
a
Neuropsychiatry Unit, Mexico's National Institute of Neurology and Neurosurgery, México City, México
b
Fray Bernardino Alvarez Psychiatric Hospital, México City, México
c
Epilepsy Clinic, Mexico's National Institute of Neurology and Neurosurgery, México City, México

a r t i c l e i n f o a b s t r a c t

Article history: Depression has a high prevalence among patients with temporal lobe epilepsy (TLE). A pilot study was car-
Received 6 September 2011 ried out to evaluate group cognitive-behavioral therapy (CBT) as a treatment for depression in patients
Revised 21 October 2011 with TLE. Twenty-three outpatients with TLE and major depressive disorder, according to DSM-IV criteria,
Accepted 3 November 2011
were enrolled and divided into two groups to receive 16 weekly sessions of CBT. The primary outcome mea-
Available online 11 December 2011
sures were depression severity (assessed with the Beck Depression Inventory) and quality of life (measured
Keywords:
with the Quality of Life in Epilepsy-31). Sixteen patients (70%) completed at least 80% of the sessions. From
Cognitive-behavioral therapy week 8, CBT had a significant positive effect on severity of depression that lasted until the end of treatment. A
Group significant improvement in quality of life was also observed. CBT seems to be a useful intervention for treat-
Temporal lobe epilepsy ing depression and improving quality of life in patients with TLE.
Depression © 2011 Elsevier Inc. All rights reserved.
Quality of life

1. Introduction used in the treatment of poorly controlled seizures [18–20] and

Approximately 3% of the population will have epilepsy at some
point in their lives [1,2]. At Mexico City's National Institute of Neurol-
ogy and Neurosurgery (NINN), a tertiary care center, epilepsy is the
main cause of outpatient attention [3]. Depression is the illness
most frequently associated with epilepsy, occurring in 20 to 55% of
patients with recurrent seizures and in 3 to 9% of patients with con-
trolled epilepsy [4–6]. In Mexico, depression occurs in 42.7% of pa-
tients with epilepsy attended at tertiary centers [7]. Generally,
depression is more severe and frequent in patients with epilepsy
than in those with other neurological disorders [8,9]. Its treatment
is complicated by the risk of pharmacological interactions between
antiepileptic drugs and antidepressants and also by the false belief
that antidepressants significantly increase seizure risk [9,10].
Among the epilepsies, those causing seizures arising from the tem-
poral lobe are associated with the highest prevalence of depression
[9–12]. This can be explained by the dysfunction of limbic structures
such as the hippocampus, the amygdala, and the parahippocampal
cortex, which are also related to the neurobiology of depression
[4,10,13,14].
Major depression has a strong impact on the control and course of
epilepsy [15], and patients with both conditions have a reduced qual-
ity of life (QOL) [16,17]. Some psychological approaches have been
⁎ Corresponding author at: Neuropsychiatry Unit. National Institute of Neurology
and Neurosurgery, Insurgentes Sur 3877, México, D.F., 14269 México.
E-mail address: danielcrail@yahoo.com (D. Crail-Meléndez).
cognitive-behavioral therapy (CBT) has been supported as the treat-
ment of choice [19,21].
Cognitive-behavioral theory is a time-limited, structured, goal-
oriented therapy that is widely used to treat anxiety and depression
with an efficacy level similar to that of psychopharmacological treat-
ment [22–25], with positive cost-effective results [26]. Cognitive-
behavioral theory has been used to reduce seizure frequency in patients
with epilepsy [18,27–29] through behavioral or cognitive interventions
designed to counteract the level of arousal present at seizure onset
[30,31] and strategies to address psychological factors such as negative
emotional states (anxiety and depression) that are recognized as sei-
zure triggers [19,21,28]. Thus, there has been a preponderance of epi-
lepsy research on the use of CBT to reduce seizure severity or
frequency [32], but limited research on its use for the treatment of
comorbid depression [19,32,33], despite its high prevalence in pa-
tients with epilepsy [4–6]. Nevertheless, some evidence of the effec-
tiveness of this form of treatment does exist, in addition to the
advantage of avoiding pharmacokinetic and pharmacodynamic in-
teractions. This could be of particular interest for patients with
drug-resistant epilepsy.
This study was aimed at assessing the effectiveness of a 16-session
group CBT program designed for patients who have epilepsy and de-
pression. A secondary objective was to assess the impact of this CBT
program on quality of life. We specifically chose patients with TLE, be-
cause of the high comorbidity between TLE and depression and be-
cause TLE is the form of epilepsy most prevalent in the tertiary care
center where this study took place.

1525-5050/$ – see front matter © 2011 Elsevier Inc. All rights reserved.
doi:10.1016/j.yebeh.2011.11.001
 D. Crail-Meléndez et al. / Epilepsy & Behavior 23 (2012) 52–56
2. Methods
2.1. Patients and procedure
We designed a pilot clinical trial using a within-group design [34].
After approval by the institutional review board, the study was carried
out in a nonprobabilistic sample of outpatients from the epilepsy clinic
and the neuropsychiatry service at the NINN. Patients between 18 and
60 years of age were included in the sample. TLE was established using
the epilepsy diagnostic criteria of the International League Against Ep-
ilepsy [35], considering the clinical presentation of seizures and cor-
roborated by interictal and/or ictal EEG/video-EEG and MRI findings.
Diagnosis of TLE was made by an epileptologist. All patients had
major depressive disorder, but none of the patients was receiving,
nor had received in the past month, antidepressant therapy. Patients
who had already received CBT and those who had severe cognitive
problems, were illiterate, or had a physical or mental condition that
would not allow them to attend the sessions were excluded.
Evaluations were carried out before treatment, at the treatment
halfway point (session 8) and at the end of the study (session 16,
week 16).
We designed and implemented a structured, time-limited, short-
term, present-oriented, group CBT psychotherapy [36]. Each session
was given by two certified CBT therapists. The therapist who func-
tioned as the group leader has more than 10 years of experience in
group CBT for depression, and the co-therapist is a psychiatrist in
training on group psychotherapy with 5 years of experience in CBT
for affective disorders. To prevent “group process” [36,37], we set a
limit of 12 patients per group.
A total of 23 patients were enrolled and divided into two groups
(12 and 11 persons). Both groups received CBT from the same thera-
peutic team. Sixteen patients completed the treatment: 9 patients in
group 1 (8 females, 1 male) and seven patients in group 2 (all fe-
male). The overall dropout rate was 30% (n = 7). The most frequent
reasons for nonattendance were: lack of family support to attend
the sessions (n = 3) and lack of seizure control (n = 2). All of the non-
completers were lost at the beginning of treatment; the remaining
patients attended an average of 15 sessions. Antiepileptic treatment
was kept at stable doses from 6 weeks before the start of the study
until the end, except for one female patient who started topiramate.
The patients received 16 weekly 90-minute sessions (Table 1). The
first session was devoted to introduction of the group members, estab-
lishment of rules (number of sessions allowed to miss, ethics code,
Table 1
CBT sessions for depression in patients with TLE.
Session 1 Introduction: Group rules and presentation of the CBT approach
Session 2 Learning about epilepsy and depression (biopsychosocial model)
Relationship between mood and seizure control
Session 3 Goal setting and introduction to the mood/emotion rating system
Session 4 Modifying activities to improve mood (mastery and pleasure)
Session 5 Identifying mood shifts
Situation description and emotion identification (thought record)
Session 6 Reviewing thought records
Identification of automatic thoughts
Session 7 Reviewing thought records
Finding evidence
Session 8 Introduction to the thought distortion list
Identifying distortions in daily records
Session 9 Learning alternative thoughts
Sessions 10/11 Review of thought records
Session 12 Introduction to the concept of core beliefs
Downward arrow technique
Session 13 Evidence gathering, experiments, and problem-solving plans
Session 14 Coping strategies
Session 15 Integrative session: preparing for closing, Strategies for prevent
relapse
Session 16 Integrative session: closing.
Source. D. Crail-Melendez, National Institute of Neurology and Neurosurgery.
53
punctuality, etc.), and presentation of the cognitive-behavioral model.
Session 2 was devoted to providing information on and resolving
doubts about depression and epilepsy. Factors influencing how both ill-
nesses are controlled and the relationship between mood and seizure
control were explained to the patients. The importance of pharmacolog-
ical adherence, as well as the way antiepileptic drugs work and their ad-
verse effects, was also explained. During session 3, the group's goals and
objectives were established and the participants were taught how to
recognize and describe their mood using a mood/emotion rating sys-
tem. In sessions 4 and 5, the patients learned to recognize situations
leading to mood shifts; the importance of including mastery and plea-
sure activities in everyday life was explained.
The goal of the next part of the treatment (sessions 6–12) was to
teach the patients to use thought records to identify the relationship
between situation, thought, emotion, and behavior. In this stage they
learned to analyze and modify automatic thoughts, cognitive distor-
tions, and central beliefs. The records were collectively reviewed by
the group so that the patients could learn from each other, receive
feedback, and also help other members of the group.
Sessions 13 and 14 focused on the application of cognitive tech-
niques to gather evidence, implement behavioral experiments, and
learn to solve and confront problematic issues. The concept of asser-
tiveness and differentiation between assertive and nonassertive be-
haviors were explained. The final sessions were devoted to
reinforcing concepts and establishing strategies to prevent relapse
and to manage reactions in preparation for the end of treatment.
Examples and materials given during the therapy were designed to
address specific issues identified in patients with epilepsy. Patients
were provided with workbooks and printed information about TLE
and depression. The research team met after each session to monitor
progress of the study, review particular cases, and ensure protocol
adherence.
2.2. Measures
The Mini-International Neuropsychiatric Interview (MINI) [38]
was applied to diagnose depression and to ensure that no disorder
considered in the exclusion criteria was present. This diagnostic inter-
view is based on both the DSM-IV and the International Classification
of Disease (ICD) diagnostic criteria [39,40]. The mean administration
time is 15 minutes. For the diagnosis of major depressive disorder,
its κ values are 1 (interrater reliability) and 0.87 (test–retest reliabil-
ity); its sensitivity and specificity values are 0.86 and 0.84, respective-
ly; and its positive and negative predictive values are 0.75 and 0.92,
respectively [38].
Depression severity was assessed using the Beck Depression In-
ventory (BDI). This 21-item self-report questionnaire is used to mea-
sure depression symptoms and has been validated for its use in
Mexican patients [41]. In this Spanish version, the cutoff point is 14,
with a sensitivity of 0.86 and specificity of 0.86 in the Mexican popu-
lation. Scores of 14 to 20 denote mild- or moderate-severity depres-
sion. Scores above 20 denote severe depression.
The Spanish version of the Quality of life in Epilepsy-31 inventory
(QOLIE-31) [42,43] was applied to evaluate the secondary outcome
measure: quality of life. This is 31-item questionnaire comprising
seven subscales that measure health-related QOL in people with epi-
lepsy: Seizure Worry, Overall QOL, Emotional Well-Being, Energy/
Fatigue, Medication Effects, Social Functioning, and Cognitive Func-
tion. For this version, Cronbach's α coefficient is 0.92, and scores
range from 0 to 100, with higher scores denoting better quality of life.
2.3. Statistical analysis
Data were analyzed using SPSS Version 13 software. Central
tendency measures and percentages were used for the descriptive
analysis of continuous and nominal variables, respectively. The
54 D. Crail-Meléndez et al. / Epilepsy & Behavior 23 (2012) 52–56

Table 2 Table 3
Sociodemographic characteristics of the 16 patients who completed treatment. BDI and QOLIE-31 scores at baseline, week 8, and final assessment.

Mean SD % (n) Scale Mean (SD) P valuea

Demographics 34.1 8.9 Baseline Week 8 Week 16

Age (years)
BDI 30.5 (12.5) 12.5 (8.5) 12.8 (9.0) 0.001
Age at seizure onset 22 8.6
QOLIE-31
Education (years) 12 .80
Overall score 38.9 (14.9) 51.8 (14.5) 55.0 (19.6) 0.001
Gender (female) 98 (15)
Seizure Worry 33.2 (26.9) 45.7 (30.6) 48.8 (27.4) 0.02
Currently unemployed 56 (9)
Overall QOL 45.6 (17.3) 57.0 (14.0) 66.5 (20.6) 0.001
Marital status (single) 62 (10)
Emotional Well-Being 41.5 (21.3) 58.1 (15.5) 63.9 (21.8) 0.008
Family antecedent of epilepsy 25 (4)
Energy/Fatigue 38.9 (24.6) 51.7 (22.4) 55.8 (29.2) 0.02
Clinical diagnosis
Cognitive Function 35.5 (15.1) 43.8 (17.1) 43.7 (19.2) 0.1
Major depressive disorder 100 (16)
Medication Effects 37.3 (23.5) 58.0 (17.0) 55.2 (25.0) 0.009
Anxiety disorder 62.5 (10)
Social Functioning 44.4 (26.2) 54.8 (26.4) 49.5 (29.1) 0.41
Antiepileptic treatment
a
One antiepileptic drug 18.8 (3) Paired-sample t test between baseline and final scores. Boldface P values are signif-
Two antiepileptic drugs 43.7 (7) icant at α = 0.05.
More than two antiepileptic drugs 37.5 (6)

prescribed (75%, n = 12), followed by carbamazepine (44%, n = 7)

normality of continuous variables was tested using the Kolmogorov–
Smirnov test. BDI and QOLIE-31 scores before and after group CBT
were compared by means of paired-sample Student t tests. Scores at
week 8 were compared with baseline scores also using paired-
sample Student t tests. Repeated-measures ANOVA was used to com-
pare BDI and QOLIE-31 scores over the three assessments (baseline,
week 8, and end of treatment).
A post hoc analysis was carried out to compare depression remit-
ters versus nonremitters with respect to sociodemographic character-
istics (age, age at seizure onset, total years of education) and baseline
clinical variables (QOLIE-31, BDI scores, number of antiepileptic
drugs), using paired-sample Student t or χ 2 tests for quantitative
and categorical variables, respectively.
3. Results
3.1. Participants
Most of the 16 participants were female (n = 15), were an average
of 34 years of age, had at least a high school education (87%), were
unemployed (62%), and were single (62%). All patients met the cri-
teria for major depressive disorder, and 62% (n = 10) also met the cri-
teria for anxiety disorder.
Only three patients (18%) were on monotherapy (Table 2). Sodi-
um valproate was the antiepileptic drug (AED) most frequently
and clonazepam (43.7%, n = 7). Seven patients (43.7%) were using
two AEDs. Combinations most frequently used were sodium valpro-
ate with clonazepam (18.7%, n = 3) and valproate with carbamaze-
pine (18.7%, n = 3). The rest of the participants were using more
than two AEDs (Table 2).
Repeated-measures ANOVA showed that CBT had a significant
positive effect on BDI (F = 61.7, P = 0.000) and QOLIE-31 (F = 10.7,
P = 0.000) scores over the three assessments. As shown in Fig. 1, de-
pression severity, as measured by BDI scores, improved significantly
from the baseline to week 8 (P = 0.001), but there were no significant
differences between week 8 and week 16 (P = 0.77).
Remission rate was 62% (10 of 16 patients attained remission), as
measured by a BDI score b14. The number of AEDs taken was not re-
lated to remission: No significant differences in the number of remis-
sions were found between patients on monotherapy and those taking
two or more AEDs (χ 2 test, P = 0.719). All six patients who did not at-
tain remission were taking valproate—one as monotherapy, two in
combination with clonazepam, two in combination with carbamaze-
pine, and one in combination with lamotrigine and carbamazepine.
There were no significant differences in sociodemographic character-
istics (age, age at seizure onset, total years of education) and baseline
clinical variables (QOLIE-31, BDI scores, and number of AEDs) be-
tween depression remitters and nonremitters.
A statistically significant improvement in quality-of-life percep-
tion, as measured by the QOLIE-31, was observed throughout the
study (P = 0.001), with a final increase of 80% in the total score
(Fig. 1). The QOLIE-31 subscales on which there was significant im-
provement were: Emotional Well-Being (P = 0.008), Seizure Worry
(P = 0.02), Overall Quality of Life (P = 0.001), Energy/Fatigue
(P = 0.02), and Medication Effects (P = 0.009) (Table 3).

4. Discussion

Fig. 1. Changes over time in mean depression (Beck Depression Inventory [BDI]) and
quality-of-life (Quality of Life in Epilepsy-31 [QOLIE-31]) scores. The red line denotes
the changes in mean QOLIE-31 scores over the study period. The blue line denotes
the changes in mean BDI scores over the study period. *Significant at α = 0.05.
The aim of this study was to assess the effectiveness of a CBT pro-
gram in reducing depression and improving quality of life in a sample
of patients with TLE. Our results showed statistically significant im-
provements in depression and QOL measures, which were evident
from the treatment halfway point (week 8) and lasted until the end
of the study.
Although some previous studies have reported on the efficacy of
CBT in reducing depression [19,27,28,30,32,33,44–46], their primary
goal has usually been seizure reduction [18,20,46]. Our study is one
of the few [27,32,33] focusing on the treatment of depression in pa-
tients with epilepsy.
Our CBT approach differs from others previously reported
[19,27,28,32,33,44,46] in the number of treatment sessions provided:
16 sessions of 1.5 hours each, for a total of 24 hours of treatment. This
is higher than the median of 12 hours of treatment reported by
 D. Crail-Meléndez et al. / Epilepsy & Behavior 23 (2012) 52–56
Goldstein et al. [19], McLaughlin and McFarland [46], and Davis et al.
[33]; the 16 hours provided by Spector et al. [44] and Gillham [28];
and the 10 treatment sessions used in the study by Macrodimitris
et al. [32].
Depression scores of our patients were higher than those of pa-
tients participating in the studies by Davis et al. [33], Tan and Bruni
[27], Goldstein et al. [19], Gillham [28], Spector et al. [44], and
McLaughlin and McFarland [46], but similar to those reported by
Macrodimitris et al. [32]. Regardless of the severity of depression, a
statistically significant improvement was observed and the majority
of the patients (62%) attained remission. Although no statistically sig-
nificant differences were found between remitters and nonremitters
in sociodemographic characteristics and baseline clinical variables,
nonremitters had higher depression severity scores at baseline.
Quality of life was the secondary outcome measure of this study. It
has been shown that QOL is related not only to seizure control but
also to psychiatric comorbidity, especially to depression and anxiety
disorders [17,47–50]. In addition to having depression, most of our
patients were on antiepileptic polytherapy, which is an indicator of
seizure severity [51]. QOL is reduced in patients on polytherapy
[52,53] and in those with drug-resistant epilepsy [51,54,55]. The par-
ticipants showed significant improvements in QOL despite the pres-
ence of factors such as depression and polytherapy that are
associated with poor QOL. The only subscales on which no significant
improvement was observed were Social Functioning and Cognitive
Function. The former might be explained by the fact that many pa-
tients were dependent on other people to go out because of seizure
risk and because most of them did not have an income: only 38% of
our patients had a job. The lack of improvement on the Cognitive
Function scale could be due to the direct effect of TLE and AEDs on
learning and cognition [56–59].
The effects of antiepileptic drugs on mood and QOL in epilepsy pa-
tients have been extensively studied [59–64]. In fact, it has been
reported that some AEDs, such as vigabatrin, tiagabine, topiramate and
Phenobarbital, might induce or worsen depression symptoms [4,65,66].
Most of the participants in our study were on AEDs (such as carba-
mazepine, lamotrigine, valproate, or a combination of these) that are
known for their positive psychotropic profile [4,60,61,64]. We did not
find any significant relationship between the AEDs prescribed, the
number of AEDs used (monotherapy or polytherapy), and depression
or QOL scores. Although this was not the aim of this study and the
small sample size used precludes any firm conclusion in this regard,
these observations are in agreement with reports that do not support
the hypothesis that antiepileptic polytherapy, or any particular AED
by itself, might be the cause of depression [59,67].
We had a 30% dropout rate, which is lower than the reported av-
erage rate of dropouts [68]. The small sample size used in this study
admittedly constitutes a major shortcoming; however, this was a
pilot study, the main objective of which was to evaluate a specifically
oriented CBT model. Another caveat of our study is that we did not
evaluate changes in seizure frequency, although it is known that sei-
zure frequency and severity can influence depression and QOL.
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