Cognitive behavior therapy for depression in people with epilepsy: A systematic review

Cognitive behavior therapy for depression in people with

epilepsy: A systematic review*†MilenaGandy, *Louise Sharpe, and ‡KathrynNicholson Perry

Epilepsia, **(*):1–10, 2013doi: 10.1111/epi.12345

SUMMARY

Cognitive behavioral therapy (CBT) is a recommended treatment for depression in people with epilepsy (PWE); how-

ever, a recent Cochrane review found that there was insufficient evidence that any psychological therapy is effective.

This conclusion provides little help to clinicians who provide interventions for depressed PWE. The aim of this review

was to systematically and qualitatively review the literature on the efficacy of CBT for depression in PWE based on

randomized controlled trials (RCTs) and case series.We aim to determine patterns in the literature to inform the type

of CBT, if any, that should be offered to PWE who are depressed. Databases MEDLINE, PsycINFO, and the Cochrane

EBM Reviews were searched via OVID. Selection criteria included the following: (1) participants with epilepsy; (2) use

of CBT; (3) valid depression outcome measure; and (4) published in peer-reviewed journal in English. Inclusions of

studies were assessed by two independent researchers. We identified 14 outcome papers for 13 CBT trials including 6

randomized controlled trials (RCTs) and 7 case series. Positive effects of CBT on depression were reported in three of

six RCTs. A review of their content revealed that all effective RCTs specifically tailored CBT to improve depression.

Conversely, two of three RCTs that failed to find depression-related effects focused on improving seizure-control. This

pattern was also observed in the case series. Although limited in number and having methodologic limitations, the

treatment studies included in our review suggest that interventions tailored toward improving depression are possibly

efficacious, whereas those that focus on improving seizure control do not appear to be. However, this review highlights

that there is need for further RCTs in this area in order to confirm the possible efficacy of CBT for depression in PWE.

KEYWORDS: Mood, Psychotherapy, Seizure.

Despite the high prevalence and significant consequencesof comorbid depression in people with epilepsy (PWE), itoften remains untreated (Hermann et al., 2000; Jones et al.,2003; Barry et al., 2008; Kanner, 2011). Physician reluc-tance to place PWE on antidepressant medication, due tofears of lowering seizure threshold and adverse drug interac-tions between antidepressants and antiepileptic drugs, hasbeen identified to be a major barrier for the treatment ofdepression in PWE (Barry et al., 2008; Cotterman-Hart,2010; Noe et al., 2011). As a result, effective psychologicaltherapies aimed at improving depression in PWE would be

of particular value (Barry et al., 2008; Ramaratnam et al.,2008; Kerr et al., 2011).

A recent Cochrane review assessed the findings of16 randomized controlled and quasi-randomized trials ofpsychological treatment in PWE (Ramarantnam et al.,2008). The review found no reliable evidence that anypsychological treatment—including relaxation therapy,electroencephalography (EEG) biofeedback, and cognitivebehavioral therapy (CBT)—led to significant improve-ment in seizure control or improvement in quality of life(QoL). The treatments included in the review were variedin therapeutic content, rated as methodologically weak,and yielded mixed results (Ramarantnam et al., 2008).Despite the lack of conclusive evidence for effective treat-ments for depression in PWE, the recent internationalconsensus clinical practice statement for the treatment ofneuropsychiatric conditions associated with epilepsy rec-ommended CBT as the psychological treatment of choicefor depression in PWE (Kerr et al., 2011).

CBT has been found to be an effective treatment fordepression in the general population (Tolin, 2010; Hofmannet al., 2012) as well as in a number of health populations,

Accepted July 16, 2013.*The School of Psychology, University of Sydney, Sydney, New South

Wales, Australia; †The Centre for Emotional Health (CEH), Departmentof Psychology, Macquarie University, Sydney, New South Wales,Australia; and ‡Centre for Health Research, School of Social Sciencesand Psychology, University of Western Sydney, Bankstown, New SouthWales, Australia

Address correspondence to Milena Gandy, The School of Psychology,University of Sydney, Brennan MacCallum Bld (A18), Sydney, NSW2006, Australia. E-mail: [email protected]

Wiley Periodicals, Inc.© 2013 International League Against Epilepsy

1

CRITICALREVIEWAND INVITEDCOMMENTARY

including multiple sclerosis (Mohr et al., 2001), chronicpain (Eccleston et al., 2003), rheumatoid arthritis (Sharpeet al., 2001), and chronic obstructive pulmonary disease(COPD; Livermore et al., 2010). One of the significant ben-efits of CBT as a form of therapy is its ability to be adaptedto address specific issues for different health populations(Krishnamoorthy, 2003). However, despite these numerousrecommendations, the effectiveness of CBT to improvedepression in PWE remains unclear.

The recent Cochrane review was limited to randomizedcontrolled trials (RCTs) and included only three RCTs ofCBT for depression. An additional three trials have sincebeen conducted in this area. Therefore, the first aim ofthis systematic review was to provide the first review ofall the published evidence for CBT interventions for PWEto improve depression outcomes. The second aim was toassess whether the literature allows any recommendationsas to which CBT strategies are most strongly empiricallysupported for the treatment of depression in PWE, whichcould help clinicians provide treatments for PWE whohave mood disturbances that are more strongly evidencebased.

MethodsUsing the Meta-analysis of Observational Studies in

Epidemiology (MOOSE) criteria as a guide (Stroup et al.,2000), we conducted a literature search of published studies

in April 2012. The electronic databases MEDLINE,PsycINFO, and the Cochrane EBM Reviews—CochraneCentral Register of Controlled Trial were searched viaOVID using different combinations of the following words:epileps*, seizure, depression, depressive symptoms, mood,cognitive therapy, behaviour therapy, problem solving ther-apy, mindfulness therapy, and psychotherapy. The searchstrategy modeled but expanded upon the Cochrane reviewof psychological treatment in epilepsy search strategies(Ramarantnam et al., 2008). There were no limits placed onthe years for searched articles. All medical Subject Heading(MeSH) terms were exploded to broaden the search for rele-vant studies. In addition, the ancestry method, whichinvolves hand searching the reference list of empirical stud-ies and reviews, was used to identify further studies. Tomeet the inclusion criteria, the study needed to: (1) involveparticipants with a diagnosis of epilepsy, (2) use a form ofCBT, (3) use established measures of depression as outcomemeasures, and (4) be published in a peer-reviewed journal inEnglish.

Figure 1 displays the process of study selection for thereview. We identified 133 articles. All titles and abstractswere reviewed to determine their relevance, by one reviewer(MG), who is a registered psychologist and PhD candidate.Reasons for exclusion are outlined in Box A. A randomselection of 25% (33) of abstracts was assessed by anindependent assessor (LS), who is a professor of clinicalpsychology, to ensure interrater reliability, where there was

Figure 1.

Search process utilized and the

outcomes obtained in identifying

articles for the review. CBT,

cognitive, behavioral therapy, PNES,

psychogenic nonepileptic seizures,

PWE, people with epilepsy.

Epilepsia ILAE


2

M. Gandy et al.

100% agreement. Following this, 32 abstracts wereretained, and full copies of the articles were reviewed. Tworaters (MG and LS) independently assessed each article foreligibility, as outlined in Box B. Three additional articleswere retrieved via the ancestry method. A list of excludedRCTs is included in Table S1. Disagreement betweenreviewers was resolved by consensus; interrater reliabilityhad a kappa coefficient of 0.86.

All RCTs were rated using the PEDro-P scale. ThePEDro-P is a modified version of the PEDro scale, whichwas initially developed to rate the quality of RCTs for thepurpose of systematic reviews, on the Physiotherapy Evi-dence Database (Maher et al., 2003). The scale has beenmodified by researchers who manage the PsychologicalDatabase for Brain Impairment Treatment Efficacy (Psych-bite), to tailor it to the analysis of treatment trials in the areaof brain impairment, including epilepsy. The PEDro-P wasselected because it provides a quality score based on strictinternal validity criterion for RCTs, which were establishedby strict Delphi technique procedures (Verhagen et al.,1998). The PEDro-P quality score allows for comparisonbetween RCTs and has been found to have good reliability(Maher et al., 2003). The scale contains 11 items, one ques-tion assesses external validity and the remaining 10 assessinternal validity. The PEDro-P items are scored as yes (1)or no (0). A copy of the items and the PEDro-P scores foreach RCT have been reported in Table S2.

Given that case series provide only Level IV Evidencefor the efficacy of an intervention, according to the NationalHealth and Medical Research Council (NHMRC) of Austra-lia definitions (2009), we include them in this review inorder to determine whether the patterns that are identifiedfrom RCTs are also supported in the case series that appearin the literature. However, we have not assessed case seriesfor quality, since by definition internal and external validityare likely to be relatively low.

ResultsTrial design

Fourteen articles reporting 13 CBT studies were identi-fied. One paper was a long-term follow-up analysis of oneof the RCTs (Chaytor et al., 2011), and was therefore notconsidered as a separate study. A detailed summary of thestudies is provided in Table 1. Six of the studies wereRCTs (Davis et al., 1984; Tan & Bruni, 1986; Martinovi�cet al., 2006; Ciechanowski et al., 2010; Thompson et al.,2010; McLaughlin & McFarland, 2011), thus providingNHMRC Level II Evidence (NHMRC, 2009). Four of thesix RCT designs employed simple comparisons of CBTwith a waitlist control (WLC) or treatment as usual(TAU). One trial compared CBT with both WLC andTAU and another compared CBT with relaxation. Theremaining seven articles were treatment trial case seriesdesigned studies (n = 7).

Trial qualityAll trials had a total score of 1 for external validity on the

PEDro-P, as they each specified their trial eligibility crite-ria. For internal validity, the PEDro-P scores ranged from 2to 7 (M = 5, standard deviation [SD] = 1.8). All trials usedrandom allocation, with only one failing to conceal alloca-tion (Tan & Bruni, 1986). Two studies failed to report base-line comparability between their treatment groups (Daviset al., 1984; Tan & Bruni, 1986). Only two studies usedblind assessors to assess at least one key outcome measure(Tan & Bruni, 1986; Ciechanowski et al., 2010). Three haddropout rates in excess of 12% (Davis et al., 1984; Ciecha-nowski et al., 2010; Thompson et al., 2010). Only two trialsreported an intention-to-treat analysis (Tan & Bruni, 1986;Ciechanowski et al., 2010). Between-group statistical com-parisons were reported in all but one trial (Davis et al.,1984). Point estimates and variability for treatment effectswere reported in only half of the trials (Martinovi�c, 2001;Ciechanowski et al., 2010; McLaughlin & McFarland,2011).

Randomized controlled trial details

ParticipantsWhen the six RCTs are considered, a total of 247 partici-

pants entered these trials (mean 41 (SD 22); range 15–80);of these 219 (89%) completed the majority of treatment(mean 37 (SD 23); range 13–80). The mean percentage ofmale participants in CBT groups was only 25% (SD 15;range 12.5–52.5). The sample had a mean age of 38 years(SD 17; range 17–68).

Only three trials stipulated specific epilepsy criteria. Oneincluded participants with newly diagnosed epilepsy (Marti-novi�c et al., 2006), another excluded newly diagnosedpatients (Thompson et al., 2010), and one included onlypatients with inadequate seizure control (Tan & Bruni,1986). One study specifically treated adolescent patients(13–19 years old; Martinovi�c et al., 2006) and another olderadults (≥60 years old) only (McLaughlin & McFarland,2011).

Treatment deliveryOf the six RCTs, four examined group therapy (Davis

et al., 1984; Tan & Bruni, 1986; Thompson et al., 2010;McLaughlin & McFarland, 2011), one using “virtualgroups” via the internet or telephone (Thompson et al.,2010). Of the four programs that described the qualifica-tions of facilitators, one used lay therapists (Thompsonet al., 2010), one used psychologists (McLaughlin &McFarland, 2011), and the remaining two were facilitatedby social workers (Davis et al., 1984; Ciechanowski et al.,2010).

The mean total treatment duration for the RCTs was9 weeks (SD =5, range 6–19 weeks) and the mean numberof hours in treatment was 11 h (SD 3, range 8–16 h). All


3

CBT for Depression in PWE

Table

1.Summary

ofRCTsreviewed

Author

(year,country)

Participants

Conditionandintervention

Assessed

Significantgroup9

time

interactiona

p-Valueb

Sample

CBT

male(%)

CBT

age(years)

Mean

(SD)

Studydesign

Therapydelivery

Totalperiod

andam

ount

Depression

outcome

measure

Dropout

rate

(%)

McLaughlin

&McFarland

(2011,A

ustralia)

N=37;C

BT

n=18,≥

60yearsold

44

68(7)

CBTvs.

Relaxation

Groupsrunby

psychologist

6weekly

92hsessions=12h

CID

I-Auto

(depressionand

dysthym

ia)

GDS

0Pre,post,

3-m

oFU

No3/3measures

atpostand

3-m

oFU

6

Ciechanowski

etal.

(2010,U

.S.A.)

Long-term

FUChaytor

etal.(2011)

N=80;

CBTn=40

52.5

43(11)

CBTvs.U

CIndividual

homebased

bymasterslevel

socialworkers

89

1hvisitsover

19weeks=8h+c

5–1

0minphonecalls

Monthlyover

12months

HSC

L-20

HSC

LSuicide

items

(measuredat

12months)

12.5at6and

12moFU

Pre,6

and

12-m

oFU

No1/1

(p=0.096)

at6-m

oYes2/2HSC

L(p

=0.003)

Suicideitems

(p=0.025)

at12mo:

No2/2

measuresat

18-m

o

7

Thompsonetal.

(2010,U

.S.A.)

N=32,

CBTn=NR

23

36(N

R)

CBTvs.W

LC

Home-based

groupsvia

netorphone

runbylayperson

withepilepsy

andRA

8weekly

91hsessions=8hd

BDIe

36

Pre,post

(8wk)

Yes1/1

measure

(p=0.001)

atpost

4

Martinovi� cetal.

(2006,Serbia)

N=30;

CBTn=15

40

17(3)

CBTvs.T

AU

IndividualbyNR

89

1hsessionsover

2months=8h+

49

1hboosters

sessions

monthly

=4h

BDI

CES-D

HAMD

6Pre,6

and

9-m

oFU

Yesfor3/3

measures

(p≤0.050)

at6mo:

Yes3/3

measures

(p≤0.050)

at9-m

o

6

Tan

&Bruni

(1986,C

anada)

N=27;

CBTn=8

37.5

33(11)

CBTvs.

SCvs.W

LC

Groupsrun

byNR

8weekly

92h=16hf

BDI

10

Pre,post,

4-m

oFU

No1/1

measure

atpostand4-m

o

5

Davisetal.

(1984,U

.S.A.)

N=13;

CBTn=8

12.5

33(11)

CBTvs.W

LC

Grouprunby

socialworkers.

6weekly

92h=12

BDIg

13

Pre,post,

6-w

kFU

No1/1

(p=0.100)

2

BDI,Beck

DepressionInventory;C

BT,cognitivebehavioraltherapy;CESD

,CentreforEpidemiologicalStudyofDepressionScale;C

IDI-Auto,C

omposite

InternationalDiagnosticInterview-C

omputerized;FU

,fol-

low-up;G

DS,GeriatricDepressionScale;H

AMD,H

amiltonDepressionScale;H

SCL,H

opkinsSymptom

Checklist;h,hours;m

o,M

onth;M

DD,m

ajordepressivedisorder;N,number;NR,notreported;R

A,research

assistant,SC

,standardcare;T

AU,treatmentas

usual;U

C,usualcare;vs.,versus;wk,w

eek;W

LC,w

aitlistcontrol.

aThere

was

somediscrepancy

betw

eenstudiesinthereportingofstatistics.W

here

reported,w

eincludetheactualp-values,butwhere

notavailablewehavesimplyincludedreference

towhetherornottheyaresig-

nificant.

bPedro-P

ratings

scoredoutof10.

c Mean

visitsforPEARLSinterventionwas

6.2visits

=6.2

h(SD

=3;m

edian=8,range

=0–8

;fourhad

novisits,72.5%had

≥6visits).

dThirty-twoparticipantstookpartinatleasthalfo

fthesessions=4h.

eThisstudyalso

usedamodifiedversionofthemeasure

oftheBDI,whichincludedapositive

response

category

foreachitem.A

sthismeasure

containedthesameinform

ationas

theBDI,andproducedthesameout-

comes,itwas

notconsideredas

aseparatemeasure.

f Participantsattendedan

average

of7.4sessions=14.8

h.

gAlthough

thisstudyalso

usedtheDepressionAdjectiveChecklistandGeneralisedContentScale,these

arenotvalidatedmeasuresofdepressionandthusexcludedforthereview.


4

M. Gandy et al.

trials offered weekly or every two week therapy. Two trialsprovided booster sessions and support for rehearsal of skillslearned in the primary intervention phase (Martinovi�c et al.,2006; Ciechanowski et al., 2010).

Depression measuresThree (of six) RCTs specified depression status criteria.

One only included participants with a formal diagnosis ofdepression (Ciechanowski et al., 2010). Another includedparticipants defined as having “subthreshold depression,”whereby patients reported elevated symptoms of depressionon measures (Beck Depression Inventory [BDI], or the Cen-ter for Epidemiological Study of Depression measure [CES-D], and Hamilton Depression Scale [HAMD]), but did notnecessarily meet diagnostic criteria for depression (Marti-novi�c et al., 2006). The third trial selected participantsbased on their scores on the CES-D (Ciechanowski et al.,2010; Thompson et al., 2010), such that only those withscores in the range of >13 to <38 were included (Thompsonet al., 2010). Only one of the six studies used a diagnosticinterview (McLaughlin & McFarland, 2011), althoughanother used the HAMD to assess clinician-rated symptomseverity (Martinovi�c et al., 2006). The remainder relied onpatient self-report scales, including the BDI (4/6; Daviset al., 1984; Tan & Bruni, 1986; Martinovi�c et al., 2006;Thompson et al., 2010), CES-D (1/6; Martinovi�c et al.,2006), Hopkins Symptom Checklist-20 (HSCL-20 [1/6];Ciechanowski et al., 2010), and the Geriatric DepressionScale (GDS; [1/6]; McLaughlin et al., 2008). Only one ofthe six studies assessed suicidal ideation (Ciechanowskiet al., 2010).

RCT CBT components focusTable 2 provides a detailed description of the CBT com-

ponents in each of the treatment trials. Five (of the six) trialsexplicitly noted that the aim of the study was to evaluate thebenefits of CBT for improving depression outcomes (Daviset al., 1984; Martinovi�c et al., 2006; Ciechanowski et al.,2010; Thompson et al., 2010; McLaughlin & McFarland,2011); one trial instead referred to improvements in psycho-pathology (Tan & Bruni, 1986). Three (of six) trials alsoaimed to evaluate the benefits of CBT to improve seizurecontrol (Tan & Bruni, 1986; Martinovi�c et al., 2006;McLaughlin & McFarland, 2011) and four (of six) toimprove quality of life or psychosocial wellbeing (Tan &Bruni, 1986; Martinovi�c et al., 2006; Thompson et al.,2010; McLaughlin & McFarland, 2011). Thompson et al.(2010) also aimed to assess the effects of CBT for increasingknowledge/skills and self-efficacy. An important distinctioncan be made in terms of the primary focus of these CBTinterventions. Four (of six) RCTs primarily tailored CBT toimprove depression and coping in PWE (Davis et al., 1984;Martinovi�c et al., 2006; Ciechanowski et al., 2010; Thomp-son et al., 2010), whereas the remaining two focused onseizure control.

Effects of the intervention on depressionBecause of the poor reporting of some trials we were

unable to perform a meta-analysis. Instead the results aresummarized in relation to those that reported significantand nonsignificant effects on depression outcome mea-sures. Across the six RCTs, there were 11 outcomes ofdepression reported. Positive results were described in 6of 11 of these measures at one or more assessment point.The six observations came from three (of six) trials. Thefirst RCT found significant positive long-term effects ofCBT compared to TAU (Martinovi�c et al., 2006). Largetreatment effects were found for the BDI (d = 0.85), theCES-D (d = 0.86), and the HAMD (d = 1.5) at 6 and9 months (BDI [d = 0.85], HAMD [d = 1], CES-D[d = 0.65]). The second RCT also found a large treatmenteffect (d = 0.75) in HSCL-20 scores at posttreatment, andin suicidal ideation at 12-month follow-up (Ciechanowskiet al., 2010), but not at 6- or 18-month follow-up(Chaytor et al., 2011). The final RCT to report positivefindings reported significant improvements on the BDIfollowing a group based CBT program compared to WLC(Thompson et al., 2010).

Of the three RCTs with nonsignificant effects of treat-ment on their depression measures, the most recent failedto find significant changes on three measures of depres-sion in older adults who had received a CBT programcompared to those who received a relaxation program(McLaughlin & McFarland, 2011). This included theGDS immediately and 3 months posttreatment, and theComposite International Diagnostic Interview (CIDI-Auto) for a diagnosis of depression and dysthymia at3 months. The trial did, however, report main effects fortime, whereby both the CBT and relaxation programexperienced significant improvements on the GDS andCIDI dysthymia diagnosis. The other two RCTs failed tofind significant differences in BDI scores in participantswho received CBT compared with control groups (Daviset al., 1984; Tan & Bruni, 1986).

Comparison of effective and noneffective trialsAs displayed in Table 2, a significant pattern emerges

when the CBT intervention focus of effective and ineffec-tive RCTs is compared. It is important to note that all threeeffective RCTs were focused primarily on improvingsymptoms of depression as opposed to seizure control(Martinovi�c et al., 2006; Ciechanowski et al., 2010;Thompson et al., 2010). On the other hand, two (of thethree) ineffective RCTs were focused primarily on seizurecontrol (Tan & Bruni, 1986; McLaughlin & McFarland,2011). Also displayed in Table 1, all three RCTs that failedto find significant effects were group-based interventions(Davis et al., 1984; Tan & Bruni, 1986; McLaughlin &McFarland, 2011), whereas two (of three) effective RCTsused an individual therapy approach (Martinovi�c et al.,2006; Ciechanowski et al., 2010). There were no systematic


5


differences in length of therapy, and it is important to high-light that two (of three) effective RCTs utilized boostertherapy sessions. Although overall there were no clear dif-ferences in PEDro-P scores between effective and ineffec-tive trials, it is notable that the only trial to tailor CBT toimprove depression that subsequently failed to find anytherapeutic benefit was the lowest quality of all the trials(Davis et al., 1984).

Case series detailsA summary of the case series studies is included in

Table 3.

ParticipantsThe characteristics of participants in the case series were

similar to those within the RCTs. There were 89 participantsrecruited into seven studies (mean 12 (SD 6); range 6–23)with a 19% dropout rate. A similar proportion of males(26%; SD 21; range 0–55.5) of a similar age (32 years;range 13–41) was evident. Most studies (n = 4) includedparticipants with specific epilepsy criteria, temporal lobeepilepsy (TLE; Crail-Melendez et al., 2012), and poorlycontrolled epilepsy (Spector et al., 1999; Goldstein et al.,2003; Elsas et al., 2011). Recruitment was usually throughtertiary referral services (6/7). Two studies excluded partici-pants with depressive disorders (Wagner et al., 2010; Elsas

et al., 2011), whereas one only included participants withmajor depressive disorder (MDD) not currently taking an-tidepressants (Crail-Melendez et al., 2012).

TreatmentIn terms of the treatments administered, the majority were

group interventions (5/7) of slightly longer duration than inthe RCTs (12 sessions over 16 h). Two (of seven) specifi-cally targeted children with epilepsy and their parents(Snead et al., 2004; Wagner et al., 2010), and the remainder(5/7) targeted adults.

All studies relied on symptom measures of depression,including the BDI (n = 2; Macrodimitris et al., 2011; Crail-Melendez et al., 2012), the Hospital Anxiety DepressionScale (HADS [n = 2]; Spector et al., 1999; Goldstein et al.,2003), the Children’s Depression Inventory (CDI; [n = 2];Snead et al., 2004; Wagner et al., 2010), and the Profile ofMood States (POMS; [n = 1]; Elsas et al., 2011).

Case seriesEach of the seven case series had a single depression out-

come measure point. Positive effects of CBT were reportedin three of seven studies (Elsas et al., 2011; Macrodimitriset al., 2011; Crail-Melendez et al., 2012), a proportion sim-ilar to that of the RCTs. There were no clear patterns interms of participant characteristics or length of intervention.

Table 2. CBT components of RCT

RCT

Significant

effects on

depression CBT seizure-focused content CBT depression-focused content

1 N Reiter behavioral intervention: Self-monitoring; psychoed of physical

and emotional healthy lifestyle and medication issues;

understanding epilepsy and identifying auras; identifying, avoiding

and controlling seizure triggers; CBT and seizures

2 Y Physical activity scheduling PEARLS program: problem-solving therapy; Social and

Physical activity scheduling

3 Y Project UPLIFT (MBCT): psychoed for depression and

epilepsy, thought monitoring; identifying cognitive

distortions; self-esteem; problem identification; goal

setting; identifying supports; relaxation exercises;

mindfulness activities, e.g., attention to breath

4 Y Activity plans; relaxation; identifying and challenging thought

distortions; social skills and problem-solving training

5 N Self-monitoring of stressful events and seizures; relaxation and

coping skills training for stress and seizure control (stress

inoculation approaches; cognitive restructuring; assertiveness

and social skills rehearsal; problem-solving; discussion of future

plans and vocational issues

Reading about coping with depression and stress

6 N Increasing pleasant events and physical exercise, increasing

assertiveness; identifying self-talk (fault thinking);

thought-stopping; increasing positive cognitions and

coping statements

CBT, cognitive behavioral therapy; MBCT, mindfulness based cognitive therapy; N, no; Psychoed, psychoeducation; RCT, randomized controlled trial; UPLIFT,using practice, learning to increase favorable thoughts; Y, yes.

1 = McLaughlin & McFarland (2011); 2 = Ciechanowski et al. (2010); 3 = Thompson et al. (2010); 4 = Martinovi�c et al. (2006); 5 = Tan & Bruni (1986);6 = Davis et al. (1984).


6

M. Gandy et al.

However, case series studies were explored to determinewhether the same pattern of results was evidenced as dis-cussed above. Two (of three) effective case series weredepression-focused CBT interventions (Macrodimitriset al., 2011; Crail-Melendez et al., 2012), whereas, only one(of five; Elsas et al., 2011) that focused on seizure frequencywas effective (Spector et al., 1999; Goldstein et al., 2003;Snead et al., 2004; Wagner et al., 2010). Furthermore, thisstudy involved a high dose of CBT (6 months) and effectswere lost at 6 months posttreatment (Elsas et al., 2011).

DiscussionAlthough previous systematic reviews have concluded

that there is insufficient evidence to support psychosocialtreatments for depression in PWE (Ramarantnam et al.,2008), this is the first review to focus exclusively on CBT

recently recommended for use in PWE (Kerr et al., 2011).This systematic review draws slightly more optimistic con-clusions. We found a pattern of results that suggested thatthere was limited support for any beneficial effects ondepression from CBT that focused on seizure control. Thatis, of the two RCTs and five case series that tested this var-iant of CBT, only one case series demonstrated positiveeffects on depressive symptoms. Furthermore, this effectwas found following a significantly higher dose of CBT(6 months) compared to other trials where effects failed toremain 6 months posttreatment. On the other hand, CBTfocusing specifically on depression did appear, based onthe majority of RCT studies (three of four), to result inimprovements in depressive symptoms for patients withepilepsy. Furthermore, this pattern of results was supportedfrom the available case series. It should be noted that theseobservations are tentative and require further investigation.

Table 3. Summary of case reviews

Author

(year, country) Sample Male (%)

Age (years)

Mean (SD) Therapy delivery Period and amount

Depression

outcome

measure

Significant

improvements in

depression

Crail-Melendez

et al.

(2012, Mexico)

N = 16 TLE

outpatients

with MDD

6 34 (9) Group run by

CBT therapist

and psychiatrist

16 weekly 9 1.5 h

sessions = 24 h a

BDI Yes 1/1 measure

from pre- to

mid-treatment

(session 8;

p = 0.0001) and

posttreatment

(session 16;

p = 0.001)

Elsas et al.

(2011, U.S.A.)

N = 8 25 41 (8) Individual by

epilepsy therapist

1 h weekly meetings

over 6

months = 24 h

POMS Yes for 1/1 measure

pre to post

(p ≤ 0.001),

including the

depression-

dejection scale

(p ≤ 0.05) but not

pre to FU

(6 months)

Macrodimitris

et al.

(2011, Canada)

N = 18 39 41 (11) Groups run by

clinical psychologist

and social worker

10 weekly 9

2 h = 20 hbBDI-II Yes in 1/1 measure

between pre and

post (p ≤ 0.001)

Wagner

et al.

(2010, U.S.A.)

N = 9 children

and parents

55.5 13 (2) Child group run by

pediatric psychologist

and parent groups

by social worker

8 weekly 9 1 h +combined

session = 8.5 h

CDI Nil 1/1 measure

Snead et al.

(2004, U.S.A.)

N = 7 adolescents 43 15 (18) Adolescent group

and Parent group

run by a psychologist

6 weeks 9 1 h 6 h CDI Nil 1/1 measure

Goldstein

et al. (2003,

United Kingdom)

N = 6 poorly

controlled

seizures

0 39 (16) Individual run by

clinical nurse specialist

12 weekly 9

1 h = 12 h

HADS-D Nil 1/1 measure

Spector et al.

(1999,

United Kingdom)

N = 7 14.3 40 (NR) Groups run by

psychologist and

occupational therapist

8 weekly 9

2 h = 16 h

HADS-D Nil 1/1 measure

AED, antiepileptic drug; BDI, Beck Depression Inventory; CBT, cognitive behavioral therapy; CDI, Children’s Depression Inventory; FU, follow-up; GDS, Geri-atric Depression Scale; HADS-D, Hospital Anxiety and Depression Scale-Depression; h, hours; JME, juvenile myoclonic epilepsy; MDD, major depressive disorder;N, number; NR, not reported; POMS, profile of mood states; TLE, temporal lobe epilepsy.

aParticipated attended an average of 15 session = 22.5 h.bParticipants required to attend 6 of 10 sessions = 12 h.


7


Before considering these findings in further detail, a com-ment on limitations of the literature need to be acknowl-edged, since they render any conclusions preliminary.

The RCTs included in this systematic review had a rangeof limitations. On average, trials were rated as being ofmoderate quality on the PEDro-P. Sample sizes were small,with some studies including fewer than 10 participants inthe CBT arm (Davis et al., 1984; Tan & Bruni, 1986), withan underrepresentation of male participants. Dropout rateswere variable, and in some studies were quite large (e.g.,36%). Within a few studies, participants often failed toattend all treatment sessions, resulting in questions aboutwhether all completers were exposed to a sufficient dosageof the therapy. The trials also failed to comment on adher-ence protocols relating to their CBT interventions. Further-more, only two (of six) trials reported intention-to-treatanalyses, and no studies systematically investigated thecharacteristics of those who dropped out during treatment.In addition, it is possible that the findings of this review areinfluenced by a publication bias toward studies reportingpositive outcomes, meaning that the results inflate the likeli-hood of positive results.

In addition, there was a range of differences in the therapythat was provided, includingmode of administration, qualifi-cations of the facilitators, provision of booster sessions, anddifferent session content. In fact, in one study, CBT wasaugmented with antidepressant medication review whereparticipants failed to respond to the initial course of therapy(Ciechanowski et al., 2010). It is therefore difficult to confi-dently ascribe differences in outcome to a single factor. It isimportant to note that the majority of trials utilized symptommeasures of depression as opposed to a clinical diagnosis.The effects of CBTonwell-defined depression criteria there-fore are lacking.

Notwithstanding these issues, the fact that there weresome consistent differences between those RCTs that foundpositive benefits for participants and those that did not isimportant in guiding clinicians and researchers. Our reviewindicated a relatively consistent finding, that the majority ofCBT trials (n = 2 of 2) and case series (n = 4 of 5) that werefocused on improving seizure control were ineffective inimproving depression. This finding is not surprising whenconsidered among research reviews that suggest the rela-tionship between depression and epilepsy variables, includ-ing seizure frequency and severity, is weak (Lambert &Robertson, 1999; Hermann et al., 2000; Marsh & Rao,2002; Seethalakshmi & Krishnamoorthy, 2007). Given thecurrent poor evidence of a strong relationship between sei-zure frequency and depression in PWE, it is not surprisingthat treatment aimed at reducing seizures would fail toimprove depression-related outcomes.

In contrast, the relatively consistent pattern that effectiveRCTs (n = 3 of 3) and case series (n = 2 of 2) were thosethat tailored CBT to improving depression in PWE suggeststhat these forms of CBT intervention are likely efficacious.

This is particularly supported by the finding of medium tolarge effects for CBT interventions on various depressionoutcomes over long-term follow-up periods in two of thethree effective RCTs (Martinovi�c et al., 2006; Ciechanow-ski et al., 2010). However, before firm conclusions aboutthe effectiveness of depression-related CBT programs inPWE can be made, further RCTs in this area are necessary.Of importance, CBT was found to be effective in adultsand adolescents with and without depressive disordersacross the three effective trials (Martinovi�c et al., 2006;Ciechanowski et al., 2010; Thompson et al., 2010). This isimportant, because many PWE experience postictal, atypi-cal, or subclinical symptoms of depression that fail to meetdiagnostic criteria for a formal depressive disorder or areshort-lived, but may still contribute to poorer QoL or placethem at risk for developing clinically identifiable depressionif left unmanaged (Kanner, 2009). Unfortunately, becausethe trials reviewed here did not provide diagnostic informa-tion, it is unknown whether these varying presentationsrespond equally to intervention and future research isneeded to address this issue.

The findings of Martinovi�c et al. (2006) suggest thatCBT can prevent the occurrence of future depressive disor-ders in adolescents with new-onset epilepsy. Reserving theuse of treatment protocols for depressive symptoms onlyamong those meeting diagnostic criteria is not indicatedaccording to the available evidence. Furthermore, the poten-tial preventative role of CBT in adults with epilepsy needsto be assessed further.

Our comparison of effective and ineffective trials alsosuggests that CBT may be more effective if delivered indi-vidually, and that long-term benefits are most likely withthe inclusion of booster sessions. Booster sessions provideopportunities to revise and practice CBT skills, which maybe particularly important for adults with epilepsy who areknown to be at a high risk of memory impairments that mayaffect the retention of CBT skills delivered in therapy (Elgeret al., 2004; Vingerhoets, 2006).

ConclusionsDepression in PWE is a highly prevalent and disruptive

condition that often goes undetected and untreated. Ourreview suggests that CBT interventions aimed at seizurecontrol are unlikely to confer depression-related benefits.Alternatively, our review suggests that interventions tai-lored toward improving depression are likely efficacious,thus providing some support for the recent internationalclinical practice recommendations that CBT be used to treatdepression in PWE (Kerr et al., 2011). However, it shouldbe noted that these suggestions are preliminary and requireadditional research support before firm conclusions regard-ing the potential superiority of depression-focused CBTover seizure-control focused can be established. The patternof results also suggests that individual therapy with booster


8

M. Gandy et al.

sessions is most likely to be effective for PWE. Although amore optimistic conclusion than the recent Cochrane review(Ramarantnam et al., 2008), we also found that the treat-ment trials reviewed had numerous methodologic limita-tions that preclude definitive conclusions as to the currentlevel of effectiveness of CBT for improving depression.These limitations must be addressed in future trials beforefirm conclusions about the efficacy of CBT for depressionin CBT can be reached. In particular, trials are needed thathave larger sample sizes (with equal numbers of men andwomen), well-defined depressed data via the use of diagnos-tic interviews, and that provide intention- to-treat and effectsize data.

AcknowledgmentsMs Milena Gandy is supported by the generous scholarships of the

National Health Research Council of Australia and the Molly McDonnellFoundation of the Epilepsy Society of Australia for this research.

DisclosureNone of the authors has any of interest to disclose. We confirm that we

have read the Journal’s position on issues involved in ethical publicationand affirm that this report is consistent with those guidelines.

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Supporting InformationAdditional Supporting Information may be found in the

online version of this article:Table S1. Excluded RCTs following review.Table S2. PEDro-P ratings for RCTs.


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Cognitive behavior therapy for depression in people with epilepsy: A systematic review