A randomised controlled trial of
cognitive behaviour therapy in
adolescents with major depression
treated by selective serotonin
reuptake inhibitors. The ADAPT trial
IM Goodyer,1*B Dubicka,2P Wilkinson,1
R Kelvin,1C Roberts,3S Byford,4S Breen,2
C Ford,1B Barrett,4A Leech,2J Rothwell,2
L White2and R Harrington2†
1Developmental Psychiatry Section, Department of Psychiatry,
University of Cambridge, UK
2Department of Child and Adolescent Psychiatry,
University of Manchester, UK
3Trials Methodology Group, Medical Statistics,
University of Manchester, UK
4Centre for Economics of Mental Health, Institute of Psychiatry,
* Corresponding author
Health Technology Assessment
NHS R&D HTA Programme
Health Technology Assessment 2008; Vol. 12: No. 14
Cognitive behaviour therapy in adolescents with
Unipolar depression in adolescents is a serious
mental disorder with a high rate of recurrence
and relapse into adult life. Interventions
to treat the disorder, improve adult outcomes
and diminish subsequent healthcare costs
are much needed. To date there have been
no randomised control trials (RCTs) of
selective serotonin reuptake inhibitors
(SSRIs) carried out on moderate to severely
depressed adolescents attending NHS
The aim of this study was to determine if, in the
short term, depressed adolescents attending
routine NHS Child and Adolescent Mental
Health Services (CAMHS), and receiving ongoing
active clinical care, treatment with SSRIs plus
cognitive behaviour therapy (CBT) compared
with SSRI alone, results in better healthcare
outcomes. The specific research hypotheses
addressed were that compared with SSRIs alone,
combined treatment would over the length of
● result in greater psychosocial improvement
● diminish the overall level of depressive
● result in fewer patients meeting diagnostic
criteria at final evaluation
● decrease other public service use and be more
In order to achieve these objectives, an RCT of
adolescent patients fulfilling criteria for DSM-IV
major depression or with threshold major
depression (four symptoms) and marked
impairment was undertaken.
A pragmatic RCT was conducted on depressed
adolescents attending CAMHS who had not
responded to a psychosocial brief initial
intervention (BII) prior to randomisation.
Participants were recruited from two centres,
Manchester in the north-west and Cambridge in
the east of England. Six CAMHS participated:
four in Manchester (total population 831,000)
and two in Cambridge (total population
A total of 208 patients aged between 11 and
17 years were recruited and randomised.
All participants received active routine clinical care
in a CAMHS outpatient setting and an SSRI and
half were offered CBT.
The duration of the trial was a 12-week treatment
phase, followed by a 16-week maintenance phase.
Follow-up assessments were at 6, 12 and 28 weeks.
The primary outcome measure was the Health of
the Nation Outcome Scales for Children and
Adolescents (HoNOSCA). Secondary outcome
measures were self-report depressive symptoms,
interviewer-rated depressive signs and
symptoms, interviewer-rated psychosocial
impairment and clinical global impression of
response to treatment. Information on resource
use was collected in interview at baseline and at
the 12- and 28-week follow-up assessments
using the Child and Adolescent Service Use
Of the 208 patients randomised, 200 (96%)
completed the trial to the primary end-point at
12 weeks. By the 28-week follow-up, 174 (84%)
participants were re-evaluated. Overall, 193 (93%)
participants had been assessed at one or more
time points. Clinical characteristics indicated that
Executive summary: Cognitive behaviour therapy in adolescents with major depression
the trial was conducted on moderate to severely
depressed group. There was significant recovery
at all time points in both arms. The findings
demonstrated no difference in treatment
effectiveness for SSRI + CBT over SSRI
only for the primary or secondary outcome
measures at any time point. This lack of
difference held when baseline and treatment
characteristics where taken into account (age,
sex, severity, co-morbid characteristics, quality
and quantity of CBT treatment, number
of clinic attendances). The SSRI + CBT group
was somewhat more expensive over the 28 weeks
than the SSRI-only group (p = 0.057) and no
more cost-effective. Over the trial period there
was on average a decrease in suicidal thoughts
and self-harm compared with levels recorded at
baseline. There was no significant increase in
disinhibition, irritability and violence compared
with levels at baseline. Around 20% (n = 40) of
patients in the trial were non-responders. Of
these, 17 (43%) showed no improvement by
28 weeks and 23 (57%) were considered
minimally (n = 10) or moderately to severely
worse (n = 13).
For moderately to severely depressed adolescents
who are non-responsive to a BII, the addition of
CBT to fluoxetine plus routine clinical care in
moderate to severe depressions does not improve
outcome or confer protective effects against
adverse events and is not cost-effective. SSRIs
(mostly fluoxetine) are not likely to result in
harmful adverse effects.
The findings are broadly consistent with the
National Institute for Health and Clinical
Excellence guidelines on the treatment of
moderate to severe depression. Modification is
advised for those presenting with moderate
(6–8 symptoms) to severe (>8 symptoms)
depressions and in those with either overt suicidal
risk and/or high levels of personal impairment. In
such cases, the time allowed for response to
psychosocial interventions should be no more than
2–4 weeks, after which fluoxetine should be
Recommendations for future
Further research is recommended in the following
● Evaluate the efficacy of specific psychological
treatments against brief psychological
intervention. The current findings provide
anecdotal information for the putative
effectiveness of BII for some cases of
depression. BII can most likely be delivered
by all routine CAMHS services. It is not
clear if BII would be as safe and effective as
CBT, family or interpersonal psychotherapy
(IPT), for adolescents with moderate
● Determine the characteristics of patients with
severe depression who are non-responsive to
fluoxetine. It is likely that non-responders will
be heavy healthcare users into adult life.
Delineating their characteristics and their
pattern of healthcare use, including compliance
with treatment offered as adolescents, would be
a key study.
● A study into relapse prevention in severe
depressions. Preventing relapse will reduce the
risks associated with multiple depressive
episodes. Candidate models include assertive
outreach, dealing with non-health barriers to
rehabilitation (education, skills development
and work entry); CBT or IPT in healthcare
settings; family therapies to reduce negative
environments in the home; and befriending
techniques to re-engage adolescent peer group
often lost during a depressive episode. Relapse
prevention may improve outcome into adult life
and diminish healthcare cost in the medium
term. A longer term study with follow up for
2 years post-remission is required to address
● Improve the tools for determining treatment
responders and non-responders. A weakness in
all trials to date, including this study, is the
precision of measurement to assess both the
nature of the disorder and treatment response.
New tools are urgently required. These should
go beyond surface aspects of the clinical
phenotype. Such research must also determine
the most efficient delivery mode to the clinic of
any new and valid test procedure and its cost
benefits to the service.
Goodyer IM, Dubicka B, Wilkinson P, Kelvin R,
Roberts C, Byford S, et al. A randomised
controlled trial of cognitive behaviour therapy
in adolescents with major depression treated
by selective serotonin reuptake inhibitors.
The ADAPT trial. Health Technol Assess
Health Technology Assessment 2008; Vol. 12: No. 14 (Executive summary)
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