Combined Cognitive-Behavioural Therapy and Pharmacotherapy for Adolescent Depression

Combined Cognitive-Behavioural Therapyand Pharmacotherapy for AdolescentDepressionDoes it Improve Outcomes Compared with Monotherapy?

Benedetto Vitiello

National Institute of Mental Health, Bethesda, Maryland, USA

Abstract Adolescent depression can be effectively treated with selective serotoninreuptake inhibitors (SSRIs), such as fluoxetine, or with specific forms ofpsychotherapy, such as cognitive-behavioural therapy (CBT) and inter-personal therapy. A single course of any of these treatments, however, leavesbetween one-third and one-half of patients insufficiently improved and stilldepressed. In an effort to increase effectiveness, medication and CBT havebeen combined (COMB). A few controlled clinical trials have recently com-pared COMB with monotherapy. TADS (Treatment for Adolescents withDepression Study) randomly assigned 439 adolescents with major depressivedisorder to fluoxetine, CBT, COMB or clinical management with placebo.After 12 weeks of treatment, both fluoxetine and COMB reduced depressionmore than CBT or placebo did, but only COMB was effective in inducingremission, achieving functional recovery and reducing suicidal ideation. After36 weeks of treatment, there was no difference in improvement amongtreatments, but more suicidal events occurred in the medication only groupthan in the CBT only group. However, in another trial, ADAPT (AdolescentDepression and Psychotherapy Trial), involving 208 youths, no advantagesof COMB over usual care with an SSRI could be detected. In a third trial,TORDIA (Treatment of Resistant Depression in Adolescence), which ran-domized 334 patients with an major depression unresponsive to previousSSRI treatment, COMB produced a greater response rate than medicationmonotherapy. These and other, smaller trials of COMB in adolescent de-pression are reviewed in this article. It is concluded that, while there is nounivocal support for the superiority of COMB, two controlled trials indicatethat COMB has a more favourable benefit/risk balance than monotherapy inadolescent depression. It remains to be determined for which patient sub-groups and in which clinical settings COMB may be most advantageous.

1. Depressive Disorders in Adolescence

Mood disorders are a major cause of morbid-ity in adolescence. In the US, these disorders rank

first among the causes of hospitalization betweenthe ages of 13 and 17 years,[1] and constitute amajor risk factor for suicide, which is the thirdleading cause of death in the teenage years.[2]

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Depression impairs functioning at home, schooland in peer relationships, increases the risk forsubstance abuse, and portends adult depressionand associated dysfunction.[3,4]

As is currently the case for most psychiatricdisorders, there are no diagnostic biologicalmarkers for depression, which remains a clini-cally defined condition. According to the currentnosology, depressive disorders include majordepressive disorder (MDD), dysthymic disorderand depressive disorder not otherwise specified.[5]

The diagnostic criteria for MDD are substan-tially the same across the lifespan, although thediagnostic process needs to be developmentallyappropriate. Depression is uncommon and diffi-cult to diagnose in preschool years, and remainsinfrequent until puberty when its prevalence ra-pidly increases to reach adult levels in the teenageyears. It is estimated that MDD affects, at anytime, about 4–6% of adolescents between 13 and17 years of age.[6]

MDD is characterized by a distinct episode ofdepressed or irritable mood causing significantdistress and/or functional impairment, lasting atleast 2 weeks and occurring in a patient who doesnot have a history of mania.[5] An episode of de-pression can last months, occasionally years.[7]

Even when depression eventually abates, residualsymptoms can persist and functional recoveryremain incomplete. Furthermore, recurrence iscommon. In one study, about 40% of youths whohad recovered from one episode of MDD hadanother episode in the following 12 months.[8]

Thus, despite the tendency of depression towardsspontaneous improvement in at least one-third ofthe cases, especially those with milder symptoms,there is general agreement that youths withmoderate to severe depression should be vigor-ously treated.[9]

2. Evidence-Based Treatments ofAdolescent Depression

Effective treatments of adolescent depressionexist. In particular, randomized controlled clin-ical trials support the efficacy of selective ser-otonin reuptake inhibitors (SSRIs) and two typesof psychotherapy, cognitive-behavioural therapy

(CBT) and interpersonal therapy, for the treat-ment of adolescents with MDD.[10,11] Fluoxetinewas found to be better than placebo in threeclinical trials,[7,12,13] and is currently the onlySSRI approved by the US FDA for the treatmentof depression in children aged ‡8 years. For otherSSRIs, such as sertraline and citalopram, theevidence is less strong, being limited to onecontrolled trial each.[14,15] CBT, a form of psy-chotherapy that attempts to correct cognitivedistortions associated with depression and topromote healthy behaviours, is the best in-vestigated specific therapy for depression and hasbeen found to be of greater efficacy than non-specific supportive psychotherapy and familytherapy.[11]

CBT can be delivered either individually or asgroup therapy, and several CBT manuals for thetreatment of depressed adolescents are available.In fact, the term CBT indicates a psychother-apeutic approach that is essentially based oncognitive restructuring and behavioural activa-tion, although there is considerable variabilityamong the various treatment manuals. Mostcommonly, CBT includes an acute treatmentconsisting of 12–15 hourly sessions, usually de-livered on a weekly basis, followed by bi-weeklysessions for a 2-month consolidation phase and agradual termination with monthly sessions.

Though effective, SSRIs and CBT have, onaverage, a small effect size when used as mono-therapy,[10,11] and still leave between one-thirdand one-half of patients insufficiently improvedand still depressed. Therefore, there has beeninterest in combining pharmacological andpsychotherapeutic interventions in an attempt toenhance effectiveness. In fact, for adult depres-sion, combined treatment was found to be moreeffective than medication or CBT alone.[16,17]

However, combined treatment also has its draw-backs. Combined treatment obviously requiresmore resources and is more expensive.[18] It alsooften requires the involvement of two separateclinicians, one prescribing and monitoring themedication treatment and the other providing thepsychotherapy, so that good co-ordination be-tween clinicians is needed for optimal success. Inconsequence, implementation of this approach

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ª 2009 Adis Data Information BV. All rights reserved. CNS Drugs 2009; 23 (4)

may not be practically possible because of adearth of CBT-trained clinicians in many com-munities and the higher cost of combined treat-ment versus monotherapy.

This article briefly examines and discusses theavailable data comparing SSRI medication andCBT monotherapy with their combination in thetreatment of adolescent depression.

3. Methodological Challenges inEvaluating Combined Treatment

Clinical trials that compare pharmacotherapy,psychotherapy and their combination are by ne-cessity rather complex, methodologically challeng-ing and expensive to conduct. First, the expecteddifference in outcome between active treatmentsis smaller than that between an active treatmentand placebo. Thus, the sample size must be largeenough to ensure adequate statistical power andavoid false-negative conclusions (i.e. statisticaltype II error). Second, the inclusion of a placeboarm is desirable because this can help with theinterpretation of the results.[19] If there is nodifference between the active treatments, butthe active treatments are better than placebo, onecan be reassured of the assay sensitivity of thestudy and thus conclude that both treatments aresimilarly effective. Third, while medication canbe fully masked with a matched placebo pill,psychotherapy cannot be administered underdouble-blind conditions. Adding a pill placebo topsychotherapy creates problems by introducingan artificial and extraneous element in thepatient-therapist relationship. Clearly, differentlevels of compromise are possible, none of whichis completely satisfactory in removing potentialbiases. Fourth, this type of study requires inter-disciplinary collaborations between investigatorswith expertise in psychopharmacology and re-searchers in psychotherapy. Industry has littleinterest in sponsoring these studies, which areusually funded with public funds.

Thus, it is not surprising that relatively fewlarge, controlled, clinical trials have beenconducted to compare the effectiveness of com-bination versus monotherapy in adolescentdepression. In recent years, three such studies

have been reported and will be briefly reviewedhere together with other, smaller, randomizedcontrolled trials (table I). These studies wereidentified by a MEDLINE search for publishedrandomized clinical trials of antidepressantmedication versus a combination of medicationand CBT in adolescent depression.

4. TADS (Treatment for Adolescents withDepression Study)

TADS (Treatment for Adolescents with De-pression Study) was a publicly funded controlledtrial that directly compared the effectiveness offluoxetine, CBT and their combination (COMB)with clinical management with pill placebo.[20]

TADS was conducted at 13 clinical sites in theUS, of which most were university clinics. A littlemore than half of the patients were recruitedthrough direct advertising to the public. Inclusioncriteria were quite broad, and common co-morbid-ities, such as anxiety disorders and attention-deficit hyperactivity disorder, were allowed.However, patients who were actively suicidal,abusing alcohol or drugs, psychotic, with severeconduct problems or in need of hospitalizationwere excluded.

In the fluoxetine and placebo groups, patientswere treated by a pharmacotherapist, while COMBpatients each had two clinicians, a pharmaco-therapist and a CBT therapist. There was ongoingcommunication and co-ordination of treatmentbetween the two clinicians. Fluoxetine and placebowere delivered under double-blind conditions,but CBT and COMB were not masked. Thus, ashappens when comparing pharmacological andpsychotherapeutic interventions, there was animbalance in masking across treatment groups,with a potential bias in favour of the psy-chotherapy containing conditions.[29] To attenu-ate potential biases, all primary outcomes wereassessed by independent evaluators blinded totreatment assignment.

After 12 weeks of treatment, a statistically signi-ficantly greater rate of improvement was observedwith fluoxetine (62%) or COMB (73%) thanwith CBT (48%) or placebo (35%) [figure 1].[7,20]

While fluoxetine and COMBwere not statistically

Combined CBT and Pharmacotherapy for Adolescent Depression 273


Table I. Randomized controlled clinical trials of combination vs monotherapy in adolescent depression

Study Inclusion Exclusion Design and treatments Duration Primary outcome

measures

Response rate and main findings

TADS[7,20] 439 outpatients

Age: 12–17 y

Major depressive

disorder

Psychosis

Bipolar disorder

Mental retardation

Substance abuse

Recent suicidal

attempt

Suicidal intention

Four parallel groups:

fluoxetine, placebo,

CBT and COMB

Multi-site

Flexible dose

Individual CBT

12wks of acute treatment

followed by a 24-wk

continuation

CDRS-R

CGI-I

Response:

CGI-I = 1 or 2

At wk 12:

COMB: 73%Medication: 62%CBT: 48%Placebo: 35%At wk 36:

COMB: 86%Medication: 81%CBT: 81%Medication, but not COMB,

increased risk for suicidal events

ADAPT[21] 208 outpatients

Age: 11–17 y

Major depressive

disorder

Bipolar disorder

Schizophrenia

Mental retardation

Need for

hospitalization

Two parallel groups:

SSRI and COMB

Multi-site

Flexible dose

Individual CBT

12 wks of acute treatment

followed by 16 wks of

continuation

HoNOSCA

Response:

CGI-I = 1 or 2

At wk 12:

COMB: 42%Medication: 44%At wk 28:

COMB: 53%Medication: 61%No difference on HoNOSCA

TORDIA[22] 334 outpatients

Age: 12–18 y

Major depressive

disorder unresponsive

to one SSRI treatment

Psychosis

Bipolar disorder

Pervasive

developmental

disorder

Substance abuse

Factorial with four

parallel groups: other

SSRI or venlafaxine,

with or without CBT

Multi-site

Flexible dosing

Individual CBT

12 wks of acute treatment

followed by 12-wk

continuation

CDRS-R

CGI-I

Response: ‡50%decrease in

CDRS-R and

CGI-I = 1 or 2

At wk 12:

COMB: 55%Medication: 41%No difference on CDRS-R

Clarke et al.[23] 152 outpatients

Age: 12–18 y

Major depressive

disorder

Schizophrenia

Mental retardation

Two parallel groups:

SSRI vs COMB

Multiple practice

settings

Flexible dosing

Individual CBT

52wks CES-D

Response:

no current major

depression

episode

At wk 12:

COMB: 77%Medication: 72%At wk 52:

COMB: 89%Medication: 94%

Continued next page

274Vitiello

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different in improvement rate, COMB was supe-rior in inducing remission of depression, decreas-ing suicidal ideation and improving functioning,global health and feelings of well being (figures 2and 3). Only COMB resulted in greater rates ofremission (37%) and normalization of function-ing (35%) than placebo (17% and 19%, respec-tively).[31,32] At the end of the 36-week treatment,the rate of clinical response was similar acrossfluoxetine, CBT and COMB, indicating that thebenefit of COMB is in accelerating the improve-ment process.[30]

An added benefit was that COMB-treatedpatients achieved a high rate of response on alower dose of fluoxetine (28mg/day) than thosetaking fluoxetine monotherapy (32mg/day).[7]No suicide occurred in TADS, but some patientshad episodes of suicidal ideation or attemptsduring the 36-week trial.[33] These episodes weremore common in the fluoxetine group (14.7%)than in the COMB (8.4%) or CBT (6.3%) groups.Thus, overall, COMB showed a more favourablebenefit/risk ratio than medication monotherapy.The mechanism through which CBT, given con-comitantly with SSRI medication, may attenuatethe risk for suicidal behaviour is unknown, al-though it is possible that it provides patients withskills that help diffuse tension and cope withstressful situations in more appropriate, non-destructive ways.

Exploratory secondary analyses of the TADSdatabase at week 12 suggested that certain typesof patientmay bemore likely to benefit fromCOMBthan from monotherapy.[34] The advantage ofCOMB over fluoxetine was evident in the sub-groups with less severe depression or a greaterdegree of cognitive distortion, while for the mostsevere patients there was no apparent benefit fromadding CBT. These results should be consideredwith caution as they stem from secondary analysesand require prospective studies for confirmation.

An analysis of the TADS data has indicatedthat, while both fluoxetine alone and COMB canbe considered cost effective using standard cri-teria for healthcare, fluoxetine is much more costeffective, at least after 12 weeks of treatment.[18]

Thus, the relative advantages of COMB in termsof efficacy and safety must be weighed against aT

able

I.Contd

Study

Inclusion

Exclusion

Designandtreatm

ents

Duration

Primary

outcome

measures

Responserate

andmain

findings

Melvin

etal.[24]

73outpatients

Age:12–18y

Majordepressive

disorder,dysthymia

ordepressionnot

otherw

isespecified

Psychosis

Bipolardisorder

Mentalretardation

Substanceabuse

Activesuicidality

Threeparallelgroups:

sertraline,CBTand

COMB

Multi-site

Flexible

dosing

IndividualCBT

12wkswitha6-m

onth

follow-up

DSM-IVdiagnosis

Response:

remissionorpartial

remission

Atwk12:

COMB:52%

Medication:46%

CBT:86%

Riggsetal.[25]

126outpatients

Age:13–19y

Majordepressive

disorderand

substanceabusewith

history

ofconduct

disorder

Psychosis

Bipolardisorder

Highriskfor

suicidality

Twoparallelgroups:

CBTplusfluoxetinevs

CBTplusplacebo

Single-site

Fixeddose

(20mg/day)

IndividualCBT

(focusedonsubstance

abuse)

16wks

CDRS-R

CGI-I

Response:

CGI-I=

1or2

Atwk16:

COMB:76%

CBT:67%

COMBbetterthanCBTon

CDRS-R

ADAPT=AdolescentDepression

And

Psychotherapy

Trial;

CBT=cognitive-behaviouraltherapy

(differentmanuals

were

used);

CDRS-R

=Child

Depression

Rating

Scale-

Revised;[2

6]CES-D

=CenterforEpidemiologicalStudiesDepressionScale;CGI-I=

ClinicalGlobalIm

pression-Improvement;[27]COMB=combinationofmedicationandCBT;

HoNOSCA=Health

ofthe

Nation

Outcome

ScalesforChildren

and

Adolescents;[28]SSRI=

selective

serotonin

reuptake

inhibitor;

TADS=Treatm

ents

forAdolescents

with

DepressionStudy;TORDIA

=Treatm

entOfResistantDepressionIn

Adolescents.



substantially greater cost and complexity of treat-ment. If, however, the protective effect of COMBagainst suicidal behaviour is confirmed by futurestudies, COMB may be considered also econom-ically advantageous given the high costs oftenassociated with suicidal events.

5. ADAPT (Adolescent Depression andPsychotherapy Trial)

ADAPT (Adolescent Depression and Psycho-therapy Trial) was a randomized, controlledtrial of SSRI medication versus the combinationof SSRI plus CBT.[21] The study, which was pri-marily funded by the National Health System inthe UK, was conducted in community clinicalsettings. Patients were clinically referred andtreatment was delivered using routine care prac-tices. All patients received an initial brief psycho-therapeutic intervention, and only those whodid not show improvement were randomized intothe trial. Thus, all patients in ADAPT receivedsome type of psychotherapy, although not ne-cessarily CBT. The fact that only non-respondersto the initial psychotherapy were randomized

into the trial might have selected not only themore severe patients, but also those less respon-sive to psychotherapy. A total of 208 outpatientsaged 11–17 years were randomly assigned toroutine care with an SSRI medication (primarily,but not exclusively, fluoxetine) or the same butwith the addition of CBT. The acute treatmentphase lasted 12 weeks and was followed by a lessintensive 16-week maintenance phase. At the endof the 28-week treatment, patients in both groupswere improved, with no differences betweentreatment arms in terms of symptom reduction,remission or incidence of suicidal behaviour.[21]

The response rate was 61% in the usual care withfluoxetine group compared with 53% in thecombined fluoxetine plus CBT group, a non-significant difference. Obviously, adding CBTresulted in a higher cost for the combination withno evidence of greater cost effectiveness.[35]

ADAPT was a pragmatic trial, conducted in‘real world’ clinical practices, as opposed to aca-demic settings, using typical clinicians rather thanresearch staff. The sample of ADAPT wassomewhat more severe than that of TADS, andalso included patients with recent suicidal behav-iour (who were excluded from TADS). Thus, thedifferent conclusions emerging from TADS andADAPT may be due to differences in severity ofdepression, co-morbidity or treatment delivery.

COMBFLXCBTPBO

0

10

20

30

40

50

60

70

80

90

100

Wk 12 Wk 36

Treatment groups

Res

pons

e ra

te (

%)

Fig. 1. Response rates in TADS (Treatment for Adolescentswith Depression Study).[7,30] Response was defined as a score of‘much’ or ‘very much’ improved on the Clinical Global Impression-Improvement scale. At week 12, COMB and FLX were betterthan PBO and CBT (p <0.001). Treatment groups did not differ atweek 36. Last available observation was carried forward. PBOtreatment continued for 12 weeks. CBT = cognitive-behaviouraltherapy; COMB = combination (FLX plus CBT); FLX = fluoxetine;PBO = placebo.

37%

23%

17%16%

0

5

10

15

20

25

30

35

40

CBT PBO FLX COMB

Pat

ient

s in

rem

issi

on (

%)

Fig. 2. Remission from depression in TADS (Treatment for Ado-lescents with Depression Study) after 12 weeks of treatment.[31]

Remission was defined as a total score of £28 on the Child De-pression Rating Scale-Revised.[26] Only COMB was significantlybetter than PBO (p =0.0009). CBT = cognitive-behavioural therapy;COMB= combination (FLX plus CBT); FLX= fluoxetine;PBO=placebo.

276 Vitiello


6. TORDIA (Treatment of ResistantDepression in Adolescents)

TORDIA (Treatment of Resistant Depressionin Adolescents) was also a publicly funded, con-trolled clinical trial in 12- to 17-year-old youthswith MDD.[22] In this study, which was con-ducted at six sites in the US, including a managed-care practice setting, patients had been previouslytreated unsuccessfully with an SSRI medicationand were still depressed. The patients wererandomly assigned to receive a different anti-depressant medication either alone or togetherwith CBT. On a random basis, the medicationconsisted of another SSRI or venlafaxine. Acutetreatment lasted 12 weeks and was followed byanother 12-week continuation phase. At the endof the first 12 weeks, more patients met responsecriteria in the COMB group (54.8%) than in themedication alone group (40.5%; p = 0.009). Inaddition to the responder rate, the trajectory ofdepressive symptoms during TORDIA was alsoanalysed: symptoms significantly declined overtime, but without differences between treatmentgroups.

Unlike TADS, but in agreement withADAPT, there was no indication that CBT had asuperior effect in decreasing suicidal ideation orpreventing suicidal events compared with medi-cation-only treatment. Patients who participatedin TORDIA and ADAPT were more severe be-cause of greater co-morbidity, suicidality or pre-vious treatment resistance at study entry. These

differences in study sample might have accountedfor the observed differences in outcome.

TORDIA is a unique study that addresses theimportant issue of which treatment to use fordepressed adolescents for whom SSRI mono-therapy has not been helpful. The results of thestudy are remarkable in indicating that there is anapproximate 50% likelihood of improvement withsubsequent treatment and that COMB worksbetter than monotherapy for these patients.

7. Other Randomized Studies

Three other controlled comparisons of CBTplus medication versus medication alone havebeen recently reported in depressed adoles-cents.[23-25] Similar to the previously describedtrials, these too were mainly funded by publicresearch agencies or not-for-profit foundations.Only a weak effect of CBT was found in a ran-domized trial of brief CBT added to a back-ground of antidepressant medication in practicesettings in the US.[23] This study had a relativelysmall sample size (total number = 152), whichmay explain the difficulty in finding statisticallysignificant differences. As with ADAPT, thisstudy was a pragmatic trial that enrolled clini-cally referred patients and maintained usualpractice treatment as background for the experi-ment. It is interesting, and perhaps not entirelycoincidental, that neither this study nor ADAPTcould find added benefit from CBT over existingclinical care with SSRIs. A possible conclusion isthat it may be difficult to ‘export’ successfullyspecialized psychotherapies such as CBT intousual practice settings.

Another, smaller, controlled study was con-ducted in community clinics in Australia.[24]

A total of 73 adolescents aged 12–18 years witha diagnosis of MDD, dysthymia or depressivedisorder not otherwise specified were randomlyassigned to CBT, sertraline or their combination.The primary outcome was the presence of de-pressive diagnosis assessed by the clinician usinga standard semi-structured interview. There wasno evidence of superiority of the combinationover monotherapy. In fact, the CBT mono-therapy group had a lower rate of depression at

45

50

55

60

65

70

Baseline Wk 6 Wk 12

Mea

n C

GA

S s

core

COMBFLXCBTPBO

Fig. 3. Level of functioning in TADS (Treatment for Adolescentswith Depression Study).[32] COMB was superior to PBO and CBT(p<0.0001), and to FLX (p< 0.05). FLX was better than PBO and CBT(p<0.05).[29] CBT= cognitive-behavioural therapy; CGAS=Children’sGlobal Assessment Scale; COMB= combination (FLX plus CBT);FLX= fluoxetine; PBO= placebo.



the end of the first 3 months of treatment. Ser-traline dosage was rather low, however, and thismight have been a disadvantage for the SSRIarm. The result of this study is apparently at oddswith that obtained in TADS, where CBT was notbetter than clinical management with placebo at3 months.[7] However, moderator analyses ofTADS have indicated that there was substantialindividual variability in treatment response, andthat CBT worked best for certain patient sub-groups characterized by milder depression andhigher family income.[34]

The third trial has unique features that makeit substantially different from the previousstudies.[25] This study, which was funded by theNational Institute of Drug Abuse, enrolled 126youths aged 13–19 years who met diagnostic cri-teria for both MDD and substance abuse dis-order (other than tobacco use) in addition tohaving a history of conduct disorder. Patientswere randomized to receive a 16-week treatmentof CBT plus fluoxetine or CBT plus placebo.However, it is important to note that the CBTwas primarily addressed to the substance abuseand not to the depression. Analyses of continuousratings of depression showed a significantly great-er decline in depressive symptoms with COMBthan with CBT alone. At the end of treatment,76% of patients receiving COMB were deemedimproved with respect to their depression versus67% receiving CBT alone, but the difference wasnot statistically significant. No treatment effecton self-reported substance use was detected, andthe CBT-only group was more likely to have asubstance-free urine screen than the COMBgroup. Clearly, the study population of this trialis substantially different from that of other stud-ies, and these results cannot be generalized oreasily integrated into those from other trials innon-substance abusing, depressed teenagers.

8. Conclusions

There has been much interest in developingand testing treatments for depressed adolescentsthat combine pharmacological and psychosocialinterventions. Recently, a number of well designedand carefully conducted clinical trials have been

reported. The studies are rather heterogeneouswith respect to patient characteristics, treatmentsettings and outcome measures, and these differ-ences make comparisons across studies difficult.Perhaps not surprisingly, the picture that emergesfrom these studies is not amenable to univocalinterpretations, but likely reflects the consider-able heterogeneity of clinical situations andtreatment delivery. Despite these limitations, anumber of informative conclusions can be drawn.

The results of two large trials provide supportfor the superior efficacy of the combinationSSRI medication plus CBT for adolescents withmoderately severe depression and in those whohave not improved on SSRI monotherapy.[7,22]

Trials conducted in usual practice settings, how-ever, could not find evidence of added benefitfrom CBT over standard clinical care with SSRImedication.[21,23,24]

The finding from TADS that CBT decreasedsuicidal ideation and protected against the emer-gence of suicidal behaviour is especially im-portant vis-a-vis the increased incidence ofsuicidality events with SSRIs compared withplacebo.[36] The fact that this effect was not de-tected in other trials suggests that multiple, stillunrecognized, clinical and contextual variablesinfluence the relationship between treatment andsuicidal behaviour in youth.

The rate of progress achieved in testing com-bined treatments for depressed adolescents isindeed remarkable, with several large multi-sitetrials having been reported in the last few years.It remains to be clarified which patients tendto do better with combined treatment than withmonotherapy, and which sequential treatmentapproaches are most effective and under whichcircumstances. There are suggestions that clinicalcharacteristics, such as severity of illness or de-gree of cognitive distortions, moderate treatmentresponse, and further research aimed at develop-ing more personalized approaches to treatment iswarranted.

Acknowledgements

No sources of funding were used to assist in the prepara-tion of this article. The author is Chief of the Child and

278 Vitiello


Adolescent Treatment and Preventive Intervention ResearchBranch at the National Institute of Mental Health, Bethesda,MD, USA, and Adjunct Professor of Psychiatry at the JohnsHopkins University, Baltimore, MD, USA. The opinions andassertions contained in this article are the private views of theauthor and are not to be construed as official or as reflectingthe views of the National Institute of Mental Health, theNational Institutes of Health or the USDepartment of Healthand Human Services. The author has no conflicts of interestthat are directly relevant to the content of this article.

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Correspondence: Dr Benedetto Vitiello, National Institute ofMental Health, Room 7147, 6001 Executive Blvd, Bethesda,MD 20892-9633, USA.E-mail: [email protected]

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Combined Cognitive-Behavioural Therapy and Pharmacotherapy for Adolescent Depression