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Effectiveness and cost-effectiveness of mindfulness-based
cognitive therapy compared with maintenance
antidepressant treatment in the prevention of depressive
relapse or recurrence (PREVENT): a randomised controlled trial
Willem Kuyken, Rachel Hayes, Barbara Barrett, Richard Byng, Tim Dalgleish, David Kessler, Glyn Lewis, Edward Watkins, Claire Brejcha,
Jessica Cardy, Aaron Causley, Suzanne Cowderoy, Alison Evans, Felix Gradinger, Surinder Kaur, Paul Lanham, Nicola Morant, Jonathan Richards,
Pooja Shah, Harry Sutton, Rachael Vicary, Alice Weaver, Jenny Wilks, Matthew Williams, Rod S Taylor, Sarah Byford
Summary
Background
Individuals with a history of recurrent depression have a high risk of repeated depressive relapse or recurrence.
Maintenance antidepressants for at least 2 years is the current recommended treatment, but many individuals are interested
in alternatives to medication. Mindfulness-based cognitive therapy (MBCT) has been shown to reduce risk of relapse or
recurrence compared with usual care, but has not yet been compared with maintenance antidepressant treatment in a
definitive trial. We aimed to see whether MBCT with support to taper or discontinue antidepressant treatment (MBCT-TS)
was superior to maintenance antidepressants for prevention of depressive relapse or recurrence over 24 months.
Methods
In this single-blind, parallel, group randomised controlled trial (PREVENT), we recruited adult patients with
three or more previous major depressive episodes and on a therapeutic dose of maintenance antidepressants, from
primary care general practices in urban and rural settings in the UK. Participants were randomly assigned to either
MBCT-TS or maintenance antidepressants (in a 1:1 ratio) with a computer-generated random number sequence with
stratification by centre and symptomatic status. Participants were aware of treatment allocation and research assessors
were masked to treatment allocation. The primary outcome was time to relapse or recurrence of depression, with
patients followed up at five separate intervals during the 24-month study period. The primary analysis was based on
the principle of intention to treat. The trial is registered with Current Controlled Trials, ISRCTN26666654.
Findings
Between March 23, 2010, and Oct 21, 2011, we assessed 2188 participants for eligibility and recruited
424 patients from 95 general practices. 212 patients were randomly assigned to MBCT-TS and 212 to maintenance
antidepressants. The time to relapse or recurrence of depression did not di er between MBCT-TS and maintenance
antidepressants over 24 months (hazard ratio 0·89, 95% CI 0·67–1·18; p=0·43), nor did the number of serious
adverse events. Five adverse events were reported, including two deaths, in each of the MBCT-TS and maintenance
antidepressants groups. No adverse events were attributable to the interventions or the trial.
Interpretation
We found no evidence that MBCT-TS is superior to maintenance antidepressant treatment for the
prevention of depressive relapse in individuals at risk for depressive relapse or recurrence. Both treatments were associated
with enduring positive outcomes in terms of relapse or recurrence, residual depressive symptoms, and quality of life.
Funding
National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme, and
NIHR Collaboration for Leadership in Applied Health Research and Care South West Peninsula.
Copyright
© Kuyken et al. Open Access article distributed under the terms of CC BY.
Lancet
2015; 386: 63–73
Published
Online
April 21, 2015
http://dx.doi.org/10.1016/
S0140-6736(14)62222-4
This online publication has been
corrected. The corrected version
first appeared at thelancet.com
on September 30, 2016
See
Comment
page 10
Department of Psychiatry,
University of Oxford, Oxford, UK
(W Kuyken PhD);
Mood Disorders
Centre, Psychology, University of
Exeter, Exeter, UK
(W Kuyken,
R Hayes PhD, E Watkins PhD,
C Brejcha BSc, J Cardy BSc,
A Causley BSc, S Cowderoy MSc,
A Evans MSc, F Gradinger PhD,
J Richards BSc, P Shah, H Sutton,
R Vicary PhD, A Weaver BSc,
J Wilks MSc, M Williams MSc);
Centre for the Economics of
Mental and Physical Health,
King’s College London, London,
UK
(B Barrett PhD, S Byford PhD);
Primary Care Group, Plymouth
University Peninsula Schools of
Medicine and Dentistry,
Plymouth, UK
(R Byng PhD);
Medical Research Council
Cognition and Brain Sciences
Unit, Cambridge, UK
(T Dalgleish PhD);
School of Social
and Community Medicine,
University of Bristol, Bristol, UK
(D Kessler PhD, S Kaur BSc);
Division of Psychiatry, University
College London, London, UK
(G Lewis PhD);
Clifton,
Bedfordshire, UK
(P Lanham);
Department of Psychology,
University of Cambridge,
Cambridge, UK
(N Morant PhD);
and Exeter Medical School,
University of Exeter, Exeter, UK
(R S Taylor PhD)
Correspondence to:
Dr Willem Kuyken, Department
of Psychiatry, Warneford
Hospital, University of Oxford,
Oxford OX3 7JX, UK
[email protected]
Introduction
Depression typically has a relapsing and recurrent course.
Without ongoing treatment, individuals with recurrent
depression have a high risk of repeated depressive relapses
or recurrences throughout their life with rates of relapse or
recurrence typically in the range 50–80%.
2
Major inroads
into the substantial health burden attributable to
depression could be offset through interventions that
prevent depressive relapse or recurrence in people at
highest risk. If the factors that make people susceptible to
depressive relapse or recurrence can be attenuated, the
recurrent course of depression could potentially be broken.
1
Currently, most depression is treated in primary care,
and maintenance antidepressants are the mainstay
approach for the prevention of relapse or recurrence. The
UK’s National Institute for Health and Care Excellence
(NICE) recommends that, to stay well, people with
a history of recurrent depression should continue
maintenance antidepressants for at least 2 years.
3
However, adherence rates tend to be poor, maintenance
antidepressant treatment is only protective for as long as
it is taken
4
and is contraindicated for some groups, and
many patients express a preference for psychosocial
interventions that provide long-term protection against
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relapse or recurrence. Patients at increased risk of relapse
show less protection from maintenance antidepressants
than do patients at low risk and many patients express a
preference for psychosocial interventions that provide
long-term protection against relapse or recurrence.
Mindfulness-based cognitive therapy (MBCT) was
developed as a psychosocial intervention for teaching
people with recurrent depression the skills to stay well in
the long term.
5
A systematic review and meta-analysis
6
of
six randomised controlled trials (n=593) suggests that
MBCT significantly reduces the rates of depressive relapse
or recurrence compared with usual care or placebo,
corresponding to a relative risk reduction of 34% (risk ratio
0·66, 95% CI 0·53–0·82). Evidence is accumulating that
MBCT might confer most benefit to patients at greatest
risk, for example those reporting childhood adversity.
7,8
A
key remaining uncertainty is whether MBCT provides an
alternative for people wishing to discontinue
antidepressants.
9
On the basis of our pilot trial,
10
we tested
whether MBCT with support to taper or discontinue
antidepressant treatment (MBCT-TS) was better than
maintenance antidepressants in terms of: a primary
outcome of prevention of depressive relapse or recurrence
over 24 months; and secondary outcomes of depression-
free days, residual depressive symptoms, psychiatric and
medical comorbidity, quality of life, and cost-effectiveness
over 24 months.
GPs had the opportunity to exclude patients they felt
would be unsuitable and a letter of invitation was sent to
the remaining identified patients. Patients who expressed
an interest in the trial were screened over the telephone to
establish potential eligibility and if suitable were invited
to attend a baseline interview.
The study was approved by the UK National Health
Service South West Research Ethics Committee
(09/H0206/43) and we obtained research governance
approval from the local primary care trusts or health
boards. The trial was conducted and reported in
accordance with CONSORT guidelines.
14,15
Randomisation and masking
Participants were randomly allocated (in a 1:1 ratio) to
receive either maintenance antidepressant treatment or
an 8-week MBCT class that included support to taper or
discontinue their maintenance antidepressant medication
(MBCT-TS).
Patients were randomly assigned to the two groups with a
computer-generated random number sequence stratified
according to recruitment centre and participants’ symp-
tomatic status at randomisation using the GRID-Hamilton
Rating Scale for Depression (GRID-HAMD)
16
cutoff of less
than 8 being asymptomatic and greater than or equal to 8
being partially symptomatic.
17
Allocation was undertaken
using a password-protected website maintained by the
Peninsula Clinical Trials Unit, independent of the trial. The
trial administrator informed participants of the outcome of
randomisation via a letter; research assessors remained
masked to treatment allocation for the duration of the
follow-up period. The fidelity of this masking was moderate
with assessors correctly guessing allocation for 56% of
assessments. In view of the nature of the interventions,
patients and clinicians were aware of treatment allocation.
Method
Study design and participants
PREVENT was a multicentre, pragmatic, single-blind,
parallel randomised controlled trial examining MBCT-TS
versus maintenance antidepressants. The study design
and procedures are presented in full in in the published
trial protocol.
11,12
Participants were recruited from general practices in
urban and rural settings in four UK centres: Bristol,
Exeter and east Devon, north and mid Devon, and south
Devon. Inclusion criteria were a diagnosis of recurrent
major depressive disorder in full or partial remission
according to the Diagnostic and Statistical Manual of
Mental Disorders-IV (DSM-IV); three or more previous
major depressive episodes; age 18 years or older; and on a
therapeutic dose of maintenance antidepressant drugs in
line with the British National Formulary (BNF)
13
and
NICE guidance. Exclusion criteria were a current major
depressive episode, comorbid diagnoses of current
substance misuse; organic brain damage; current or past
psychosis, including bipolar disorder; persistent antisocial
behaviour; persistent self-injury needing clinical manage-
ment or therapy; and formal concurrent psychotherapy.
All participants gave written informed consent.
Most participants were identified through searches of
computerised general practitioner (GP) practice databases
to identify patients who were currently being prescribed a
therapeutic dose of antidepressants. PREVENT was also
advertised locally and interested patients could self-refer.
64
Procedures
MBCT is a manualised, group-based skills training
programme designed to enable patients to learn skills that
prevent the recurrence of depression.
18
It is derived from
mindfulness-based stress reduction, a programme with
proven efficacy in ameliorating distress in people with
chronic disease, and cognitive-behavioural therapy for
acute depression, which has shown efficacy in prevention
of depressive relapse or recurrence. MBCT is intended to
enable people to learn to become more aware of their bodily
sensations,
thoughts,
and
feelings
associated
with depressive relapse or recurrence and to relate
constructively to these experiences. Participants learn
mindfulness practices and cognitive-behavioural skills both
in session and through homework assignments. Therapists
provide support to patients in learning to respond
adaptively to thoughts, feelings, and experiences that might
otherwise have triggered depressive relapse. The
programme consists of eight 2·25 h group sessions,
normally over consecutive weeks, with four refresher
sessions offered roughly every 3 months for the following
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year. Four therapists delivered 21 MBCT-TS groups in
various settings including research clinical facilities,
hospital sites, and the community.
Before therapists progressed to running trial groups, an
independent check on their competency was established.
An experienced MBCT therapist independent of the trial
rated at least two videotapes for every potential therapist
using the Mindfulness-Based Interventions Teacher
Assessment Criteria
19
and MBCT Adherence Scale
(MBCT-AS).
20
She made an overall judgment as to whether
the therapists were competent and adhered to the MBCT
manual, and therapists only progressed once competency
in all domains was clearly established. During the trial, the
same rater assessed two sessions from each of the
21 MBCT-TS courses using the MBCT-AS, which indicated
that the MBCT teaching was at required competency or
adherence levels and above. The sessions second rated
were randomly selected by the trial team before the start of
the intervention, and therapists were unaware which of
their sessions would be assessed. During the trial,
therapists received group supervision every 2 weeks for 3 h.
Patients in the MBCT-TS group received support to
taper or discontinue their maintenance antidepressants
both from the MBCT-TS therapist and their GPs. The
study team provided guideline information to GPs and
patients about typical tapering or discontinuation
regimens and possible withdrawal effects. The guidelines
recommended that patients began a tapering regimen
after 6 weeks of treatment; however, GPs and patients
determined the tapering or discontinuation regimen.
Letters signed by the chief investigator and trial GP (RB)
were sent to patients’ GPs and copied to the patient,
prompting the GP to have a discussion with the patient
about a suitable tapering or discontinuation regimen
after 4–5 weeks of the MBCT-TS group sessions. At the
end of the eight MBCT-TS sessions, another letter
was sent reminding the GP to ensure a tapering or
discontinuation regimen was in place.
Patients in the maintenance antidepressant group
received support from their GPs to maintain a therapeutic
level of antidepressant medication in line with BNF
13
and
NICE guidelines for the 2-year follow-up period.
As described fully in the trial protocol,
11,12
we encouraged
all participants to adhere to medication for the full length
of the trial by writing to all trial participants and their
GPs after every follow-up reminding them that the trial
was seeking to compare staying on antidepressants for
2 years with taking part in mindfulness classes and
tapering or discontinuation of antidepressant treatment.
However, patients remained in the trial whatever
treatment choices they made.
Participants were assessed at six timepoints: baseline
(before randomisation), 1 month after the end of the
8-week MBCT-TS programme (or the equivalent time in
the maintenance antidepressant group), which varied
between 12 and 24 weeks post-randomisation, and at
9, 12, 18, and 24 months post-randomisation.
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Outcomes
The primary outcome measure was time to relapse or
recurrence of depression, with patients followed up at
five separate intervals during the 24-month period of
study. We assessed the time between assessments
retrospectively according to the depression module of
the Structured Clinical Interview for DSM–IV (SCID).
21
We defined relapse or recurrence as an episode meeting
DSM-IV criteria for a major depressive episode.
11,21
The secondary outcomes were number of depression-
free days, residual depressive symptoms, psychiatric and
medical comorbidity, quality of life, and cost-effectiveness.
At each follow-up we recorded the number of depression-
free days based on episode duration as assessed by the
SCID, residual depressive symptoms as assessed by the
GRID-HAMD
22
and the 21-item self-report Beck
Depression Inventory (BDI),
23
psychiatric comorbidity
using the relevant SCID modules and medical
comorbidities using the Medical Symptom Checklist
(MSCL), quality of life using the WHO Quality of Life
instrument (WHOQOL-BREF),
24
and health-related quality
of life using the EQ-5D-3L (three level version).
25,26
The economic perspective included all hospital and
community health and social services, plus productivity
losses, known to be a substantial cost in depression.
27
We
obtained MBCT group data from therapist records. We
obtained data on indirect time related to MBCT delivery,
including preparation and supervision, from trial
therapists. We obtained data on drugs and use of all other
services using the Adult Service Use Schedule (AD-SUS) at
each follow-up, modified and successfully used in our
previous MBCT trial.
10
We confirmed ADM prescriptions
and GP contacts via GP records. We measured productivity
losses as a result of time off work or reduced productivity at
work due to illness using the absenteeism and presenteeism
questions of the WHO’s Health and Work Performance
Questionnaire (HPQ).
28
All unit costs were for the financial year 2011–12, and
costs and quality-adjusted life-years (QALYs) incurred in
the second year were discounted by 3·5% as recommended
by NICE.
29
We calculated the cost of MBCT-TS directly from
salaries using a micro-costing approach used in our
previous trial.
10
We applied national UK unit costs to
medication and all other health and social services. We
calculated productivity losses using the friction cost
approach for absenteeism
30
and using the method set out
by Kessler and colleagues
28
for presenteeism. The appendix
shows full details of all unit costs.
At an early Trial Management Group Meeting we
decided on the final list of measures to assess these
constructs, and the WHOQOL was selected as secondary
outcome measure quality of life (Aug 19, 2009). An
oversight meant that this change was not included in the
published protocol or in the ISRCTN register
(ISRCTN26666654), although the full list of primary and
secondary outcomes were logged at the first Trial Steering
Committee (Dec 1, 2009) and in the CONSORT diagram
See
Online
for appendix
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28 597 participants identified on search
8989 GP excluded
19 608 invites sent
1881 declined further contact
14 756 no response
872 could not contact back
2188 assessed for eligibility
1764 excluded
1120 not eligible
644 declined
89 self-referred
424 randomised
212 assigned to MBCT-TS
176 completed 4 or more sessions
30 initiated treatment but attended less than 4 sessions
6 did not initiate treatment
212 assigned to maintenance antidepressant medication
162 remained on a BNF therapeutic dose of
antidepressant medication
50 did not remain on a BNF therapeutic dose of
antidepressant medication
17 lost to follow-up
9 withdrew
20 lost to follow-up
8 withdrew
186 completed MBCT+ 1 follow-up
184 completed MBCT+ 1 follow-up
23 lost to follow-up
11 withdrew
32 lost to follow-up
10 withdrew
178 completed 9-month follow-up
176 completed 9-month follow-up
15 lost to follow-up
13 withdrew
18 lost to follow-up
11 withdrew
184 completed 12-month follow-up
183 completed 12-month follow-up
20 lost to follow-up
15 withdrew
2 died
20 lost to follow-up
16 withdrew
1 died
175 completed 18-month follow-up
175 completed 18-month follow-up
10 lost to follow-up
17 withdrew
2 died
10 lost to follow-up
17 withdrew
2 died
183 completed 24-month follow-up
183 completed 24-month follow-up
Figure 1:
Trial profile
GP=general practitioner.
MBCT-TS=mindfulness-based
cognitive therapy with support
to taper or discontinue
antidepressant medication.
212 included in the intention-to-treat population
212 included in the intention-to-treat population
66
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reported in the Data Monitoring Committee (DMC)
charter (dated May 24, 2010), which was signed by all
DMC members. There is therefore a discrepancy between
the published protocol that does not list the WHOQOL as
a secondary outcome (Kuyken et al, 2010) and this
outcome paper, which does report it. This discrepancy has
no impact on the interpretation of the findings.
MBCT-TS (n=212)
Demographic characteristics
Women
White ethnic origin
Age, years
Mean (SD)
Range
Marital status
50 (12)
22–78
42 (20%)
125 (59%)
44 (21%)
1 (<1%)
10 (5%)
36 (17%)
84 (40%)
77 (36%)
5 (2%)
133 (63%)
10 (5%)
68 (32%)
1 (<1%)
£19 930 (13 387)
£1200–£72 000
96 (45%)
53 (25%)
22 (10%)
5 (2%)
0
35 (17%)
1 (<1%)
151 (71%)
210 (99%)
m-ADM (n=212)
174 (82%)
210 (99%)
49 (13)
20–79
38 (18%)
140 (66%)
33 (16%)
1 (<1%)
10 (5%)
45 (21%)
92 (43%)
61 (29%)
4 (2%)
139 (66%)
4 (2%)
68 (32%)
1 (<1%)
£18 024 (13 582)
£792–£80 000
76 (36%)
52 (25%)
38 (18%)
6 (3%)
2 (1%)
37 (17%)
1 (<1%)
Statistical analysis
The study was powered to detect a hazard ratio of 0·63
between the two treatments at 24 months for the primary
outcome, with 90% power, two-sided 5% α level, assuming
a small clustering effect (intraclass correlation=0·01) and
allowing for 20% loss to follow-up, producing a target
sample size of 420 (210 per group). All analyses were
prespecified in a detailed statistical analysis plan that was
reviewed by the independent Trial Data Monitoring and
Steering Committees. Analyses were undertaken according
to the intention-to-treat principle except where stated.
The primary analysis was a between group comparison
of time to relapse or recurrence at 24 months using a
Cox regression proportional hazards model adjusted for
stratification variables. We did two predefined secondary
analyses of the primary outcome comparing groups
according to whether participants had received an adequate
dose of treatment and adhered to treatment as invited. We
defined an adequate dose of treatment for MBCT-TS as
attending four or more group sessions and for maintenance
antidepressants as a BNF therapeutic dose of
antidepressants during the 24-month follow-up period. We
defined adherence to treatment as invited for MBCT-TS as
attending four or more classes and at some point
discontinuing or reducing antidepressants; for
maintenance antidepressants, we defined adherence as a
BNF therapeutic dose throughout the 24-month follow-up.
We compared secondary outcomes across all timepoints
using repeated measures mixed regression models.
Missing data were assumed missing at random and
sensitivity analysis examined the effect of missing data
using multiple imputations.
31
We report between group
inference for secondary outcome analyses based on
complete case and imputed datasets.
We used interaction terms to undertake predefined
exploratory subgroup analyses on the primary outcome,
across the stratification variables (recruitment centre and
baseline depression severity) and reported childhood
abuse.
12,32
Participants in the high abuse group reported
experiencing childhood physical or sexual abuse or scored
above the median score for the Measure of Parenting
Scale (MOPS)
33
abuse subscale. Participants completed
the MOPS at baseline as part of an embedded process-
outcome study.
11
The abuse subscale asks participants to
indicate how true they felt certain statements about their
parents’ behaviour were: for example, “parent was
physically violent or abusive of me; parent made me feel
unsafe”. Participants in the low reported childhood abuse
group scored below the median score for the MOPS abuse
10
Single
Married, cohabiting, or civil partnership
Separated, divorced, or widowed
Missing
Education
No educational qualification
O levels or GCSEs
AS and A levels or vocational qualification
University training
Missing
Religion
Christian
Other
None
Missing
Salary (£)
Mean (SD)
Range
Social class
Class 0
Class 1
Class 2
Class 3
Class 4
Class 5
Not classified
Stratification variables
Depressive symptomology at randomisation
Asymptomatic
Symptomatic
Recruitment site
Bristol
Exeter and east Devon
North and mid-Devon
South Devon
Psychiatric characteristics
Current depressive symptomology GRID-HAMD
Current depressive symptomology BDI-II score
Previous major depressive episodes
<6 episodes
≥6 episodes
Age (years) at first depression onset
Time (months) since last depressive episode
Number of comorbid DSM-IV axis I psychiatric
diagnoses
163 (77%)
49 (23%)
33 (16%)
72 (34%)
55 (26%)
52 (25%)
4·8 (4·3)
13·8 (10·2)
120 (57%)
92 (43%)
24·4 (11·5)
21·2 (27·0)
0·5 (0·9)
162 (76%)
50 (24%)
31 (15%)
76 (36%)
54 (25%)
51 (24%)
4·6 (4·3)
14·5 (10·1)
106 (50%)
106 (50%)
25·4 (13·3)
17·1 (23·0)
0·7 (0·9)
(Table 1 continues on next page)
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MBCT-TS (n=212)
(Continued from previous page)
Received outpatient psychiatric or psychological
treatment
Attempted suicide
Number of previous attempts
Severity of reported childhood abuse
High
Low
Missing
Quality of life
How would you rate your quality of life?
How satisfied are you with your health?
Physical
Psychological
Social
Environment
Health-related quality of life (EQ-5D tariffs)
3·7 (0·8)
2·9 (1·0)
14·5 (6·5)
12·6 (2·6)
13·4 (3·4)
15·0 (2·4)
0·760 (0·268)
105 (50%)
105 (50%)
2 (1%)
103 (49%)
48 (23%)
1·7 (1·1)
m-ADM (n=212)
108 (51%)
53 (25%)
1·9 (1·5)
111 (52%)
101 (48%)
0
3·7 (0·8)
3·1 (1·0)
14·4 (5·1)
12·3 (2·6)
13·1 (3·4)
15·1 (2·6)
0·778 (0·211)
productivity losses. Cost-effectiveness was explored using
the net benefit approach
36
with effectiveness measured in
terms of the primary outcome measure (depressive relapse
or recurrence) and QALYs calculated with the EQ-5D.
Uncertainty around the cost and effectiveness estimates
was represented by cost-effectiveness acceptability curves.
37
All analyses were undertaken using Stata v.13.
38
Role of the funding source
The funder of the study had no role in study design, data
collection, data analysis, interpretation of data, or writing
of the paper. The corresponding author had full access to
all the data in the study and had final responsibility for
the decision to submit for publication.
Results
Between March 23, 2010, and Oct 21, 2011, of
2188 participants assessed for eligibility, we recruited
424 patients from 95 general practices. Of these,
212 participants were allocated to receive MBCT-TS
and 212 participants to maintenance antidepressant
treatment (figure 1). Primary outcome data were obtained
for 189 (89%) participants in the MBCT-TS group and
194 (92%) participants in the maintenance
antidepressants group; the remaining participants’ data
were censored at their last follow-up. We retained
366 (86%) of 424 participants over the 24-month follow-up
period. At 24 months, we obtained secondary outcome
data for 173 (82%) participants in the MBCT-TS group
and for 175 (83%) in the maintenance antidepressants
group. The pattern of collected secondary outcomes was
similar for each group throughout the whole follow-up
period, 84% MBCT-TS and 83% maintenance
antidepressants. The data available for analysis were
comfortably within the margin required by the power
calculation.
Baseline characteristics were balanced between the
two groups with the possible exception of gender (table 1).
Because no evidence exists that patients’ gender moderates
MBCT treatment outcome,
10
we did not add gender in the
primary analysis model. Table 2 shows treatment adherence
and the extent to which patients followed invitations to
discontinue maintenance antidepressants; more than 75%
of patients adhered to treatment as intended.
We observed little or no clustering in primary or
secondary outcomes by therapist. Because model results
accounting for clustering by therapist were identical to
those obtained for the primary intention-to-treat analysis,
we report outcome findings without consideration of
therapist clustering.
Primary analysis of the primary outcome showed no
evidence of a reduction in the hazard of relapse or
recurrence with MBCT-TS compared with maintenance
antidepressant treatment in the intention-to-treat
analysis (hazard ratio [HR] 0·89, 95% CI 0·67–1·18,
p=0·43), with 94 (44%) of 212 patients in the MBCT-TS
group relapsing compared with 100 (47%) of 212 in
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Data are number of participants (%) or mean (SD), unless otherwise specified. Quality of life assessed using the WHO
quality of life assessment with higher scores indicating a higher quality of life. MBCT-TS=mindfulness-based cognitive
therapy with support to taper or discontinue antidepressant medication. m-ADM=maintenance antidepressant
medication. GCSE=general certificate of secondary education. GRID-HAMD=Hamilton Rating Scale for Depression set out
in a grid. BDI-II=Beck Depression Inventory-II. DSM-IV=Diagnostic and Statistical Manual of Mental Disorders, 4th Edn
.
Table 1:
Baseline characteristics of participants for the intention-to-treat population
Number of patients
(%)
m-ADM treatment adherence
Remained on therapeutic dose
Did not remain on therapeutic dose
MBCT-TS treatment adherence
Participants who did not initiate MBCT treatment
Participants who initiated MBCT treatment
Mean number of sessions attended
Mode number of sessions attended
Standard deviation sessions attended
Completed four or more MBCT sessions
No reduction to their ADM dose
Reduced their ADM
Discontinued their ADM
6 (3%)
206 (97%)
6
8
2·4
176 (83%)
23 (13%)
29 (17%)
124 (71%)
162 (76%)
50 (24%)
ADM use in patients who attended four or more sessions of MBCT-TS
m-ADM=maintenance antidepressant medication. MBCT-TS=mindfulness-based
cognitive therapy with support to taper or discontinue antidepressants.
Table 2:
Adherence to treatment in each trial group
subscale and did not report childhood physical or sexual
abuse.
We analysed differences in mean costs using standard
parametric
t
tests with the validity of results confirmed
using bias-corrected, non-parametric bootstrapping
(repeat re-sampling).
34,35
The primary economic analysis
compared MBCT-TS and maintenance antidepressant
treatment from the health and social care perspective
preferred by NICE;
29
secondary analyses included
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the maintenance antidepressants group, log-rank
c² (1)=0·67, p=0·41 (figure 2).
Another assessor rated every first actual or borderline
relapse or recurrence and we recorded 90% agreement
between the raters (κ=0·62, 95% CI 0·48–0·77, p<0·0001).
A subset of 112 SCID interviews were also second rated by
an experienced rater who was independent of the trial with
96% agreement being recorded (κ=0·90, 0·82–0·98,
p<0·0001).
Secondary analyses on our primary outcome exploring
the effect of adherence to treatment showed a non-
significant reduction in the hazard of relapse or recurrence
with MBCT-TS compared with maintenance antidepressant
treatment at 24 months in participants who received an
adequate dose of treatment (HR 0·79, 95% CI 0·58–1·08,
p=0·14), with 81 (46%) of 176 patients in the MBCT-TS
group relapsing compared with 80 (49%) of 162 in the
maintenance antidepressants group, log-rank c²(1)=2·3,
p=0·13 (appendix). There was a non-significant reduction
in the hazard of relapse or recurrence with MBCT-TS
compared with maintenance antidepressant treatment at
24 months in participants who followed the invited
treatment with respect to use of antidepressants (HR 0·77,
0·56–1·06, p=0·10), with 70 (46%) of 153 patients in the
MBCT-TS relapsing compared with 80 (49%) of 162 in the
maintenance antidepressants group, log-rank c²(1)=2·7,
p=0·10 (appendix). In view of their non-randomised
nature, these secondary analyses are prone to selection
bias and confounding (appendix).
We did not note a difference in treatment effect on the
primary outcome across either stratification variable
subgroup of depression severity at baseline or centre
(table 3). However, we noted a significant interaction
between severity of reported childhood abuse and
treatment group. Specifically, compared with maintenance
antidepressant treatment, MBCT-TS reduced the risk of
relapse or recurrence for participants with high severity of
reported childhood abuse (49 [47%] of 105
vs
65 [59%] of 111)
whereas there was a slightly higher risk of relapse with
MBCT-TS in the low severity of childhood abuse subgroup
(44 [42%] of 105
vs
35 [35%] of 101) compared with the
maintenance antidepressants group (table 3). We noted
several differences in the baseline characteristics of
participants with high and low severity of reported
childhood abuse. Individuals who reported a more abusive
childhood had had more previous psychiatric treatments
including more hospital admissions, had had more
previous episodes of depression and made more suicide
attempts, had a greater chance of a family history of both
suicide and mental illness, and were more likely to smoke
than were participants who reported a less abusive
childhood (appendix).
With respect to our secondary outcomes, we noted no
evidence of the superiority of MBCT-TS over main-
tenance antidepressants (table 4). Furthermore, none of
the secondary outcome treatment effects at any follow-up
points exceeded a standardised mean difference of 0·4.
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Vol 386 July 4, 2015
Survival proportion (non-relapse or recurrence; %)
100
m-ADM
MBCT-TS
75
50
25
0
0
5
154
167
10
128
134
15
108
113
20
99
101
25
0
0
Analysis time (months)
Number at risk
m-ADM 212
MBCT-TS 212
Figure 2:
Survival curves (of not relapse or recurrence) over a 24-month follow-up period for the
intention-to-treat population
m-ADM=maintenance antidepressant medication. MBCT-TS=mindfulness-based cognitive therapy with support
to taper or discontinue antidepressant medication.
MBCT-TS
Depression severity
Asymptomatic
(HRSD <8)*
Symptomatic
(HSRD ≥8)
Centre
South Devon*
Bristol
Exeter and east
Devon
North and
mid-Devon
Childhood abuse
Lower risk*
Higher risk
105 (50%)
105 (50%)
52 (25%)
33 (16%)
72 (34%)
55 (26%)
163 (77%)
49 (23%)
Maintenance
Stratified HR
antidepressants (95% CI)
162 (76%)
50 (24%)
0·83 (0·60–1·15)
1·06 (0·62–1·18)
Interaction HR (95% CI);
p value
1·27 (0·68–2·39); 0·46
52 (24%)
31 (15%)
76 (36%)
54 (25%)
0·61 (0·33–1·13)
1·60 (0·54–2·12)
1·10 (0·68–1·81)
0·84 (0·49–1·43)
1·75 (0·70–4·39)
1·81 (0·83–3·96)
1·37 (0·61–3·08); 0·47†
101 (48%)
111 (52%)
1·31 (0·83–2·04)
0·69 (0·47–1·00)
0·53 (0·29–0·95); 0·03
Data are number of participants (%) unless otherwise stated. HR=hazard ratio. HRSD=Hamilton Rating Scale for
Depression. MBCT-TS=mindfulness-based cognitive therapy with support to taper or discontinue antidepressants.
*Reference subgroup. †p value for treatment-centre interaction across centres.
Table 3:
Subgroup analyses of treatment effect on days to relapse
MBCT-TS group attendance was estimated to cost
£112 per participant (table 5). Use of other health-care and
social care services differed little between groups
(appendix) and hence total health and social care cost per
participant did not differ significantly between the MBCT-
TS and the maintenance antidepressants group (mean
difference £124, 95% CI –749·98 to 972·57, p=0·80).
Results including patient costs (productivity losses and out
of pocket expenditure) were also non-significant (table 5).
Cost-effectiveness analysis (appendix) suggests a
trade-off between MBCT-TS and maintenance anti-
depressants when effects are measured in terms of relapse
(costs higher and outcomes better), implying improve-
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Baseline
Mean (SD)
Depression
Depression-free days
m-ADM
MBCT-TS
Residual depressive symptoms
BDI
m-ADM
MBCT-TS
GRID-HAMD
m-ADM
MBCT-TS
Psychiatric comorbidities
m-ADM
MBCT-TS
MSCL
m-ADM
MBCT-TS
Quality of life
WHO-QoL: Q1—overall
perception of quality of life
m-ADM
MBCT-TS
WHO-QoL: Q2—overall
perception of health
m-ADM
MBCT-TS
WHO-QoL physical health
domain
m-ADM
MBCT-TS
WHO-QoL psychological
domain
m-ADM
MBCT-TS
WHO-QoL social relationships
domain
m-ADM
MBCT-TS
WHO-QoL environment domain
m-ADM
MBCT-TS
EQ-5D tariff
m-ADM
MBCT-TS
0·778
(0·211)
0·760
(0·268)
202
209
15·1 (2·6)
15·0 (2·4)
205
209
13·1 (3·4)
13·4 (3·4)
205
209
12·3 (2·6)
12·6 (2·6)
205
209
12·3 (2·6)
12·6 (2·6)
205
209
3·1 (1·0)
2·9 (1·0)
205
209
3·7 (0·8)
3·7 (0·8)
205
209
21·7 (13·8)
22·8 (14·0)
206
210
0·7 (1·0)
0·5 (0·9)
212
212
4·6 (4·3)
4·8 (4·3)
212
212
14·4 (10·1)
13·8 (12·4)
206
210
··
··
··
··
N
MBCT + 1 month
Mean (SD)
N
9 months
Mean (SD)
N
12 months
Mean (SD)
N
18 months
Mean (SD)
N
24 months
Mean (SD)
N
p value*
p value†
0·66
··
··
··
··
··
··
··
··
··
··
··
··
··
··
··
··
607·4
(196·4)
607·4
(203·7)
212
212
0·63
0·18
13·9 (10·9)
9·9 (9·7)
7·4 (6·3)
6·3 (5·6)
174
174
183
186
10·5 (9·7)
11·0 (10·5)
5·6 (6·4)
6·0 (5·5)
142
151
175
177
11·3 (9·2)
10·7 (10·0)
4·7 (5·2)
5·7 (5·7)
157
167
181
184
11·3 (10·7)
11·7 (10·6)
5·3 (6·1)
5·7 (5·7)
149
142
174
174
11·9 (10·7)
167
0·76
4·7 (5·7)
4·7 (4·8)
183
183
0·91
··
··
··
··
··
··
··
··
··
··
··
··
··
··
··
··
0·1 (0·4)
0·1 (0·3)
19·3 (13·7)
21·0 (14·0)
196
196
156
167
··
··
··
··
··
··
··
··
0·3 (0·6)
0·3 (0·7)
21·7 (16·3)
183
183
0·42
167
22·2 (14·6) 169
0·07
3·8 (0·9)
3·8 (0·8)
173
174
3·9 (0·8)
3·7 (0·9)
141
151
3·9 (0·9)
3·7 (0·9)
157
166
3·9 (0·9)
3·7 (0·9)
149
141
3·8 (1·0)
3·7 (0·9)
167
169
0·97
3·2 (1·0)
3·1 (1·0)
173
174
3·2 (1·0)
3·1 (1·1)
141
151
3·3 (1·0)
3·2 (1·1)
157
166
3·3 (1·1)
3·2 (1·0)
149
141
3·2 (1·0)
3·1 (1·0)
167
169
0·07
14·3 (3·0)
14·3 (3·3)
173
174
14·8 (3·2)
14·2 (3·3)
141
151
14·7 (3·3)
14·1 (3·4)
157
166
14·7 (3·3)
13·9 (3·5)
149
141
14·9 (5·5)
13·9 (3·5)
167
169
0·55
12·6 (2·8)
13·4 (2·6)
173
174
13·4 (2·7)
13·3 (3·0)
141
151
13·3 (2·7)
13·3 (2·9)
157
166
13·3 (3·0)
12·9 (2·8)
149
141
13·1 (3·0)
13·1 (2·9)
167
169
0·96
13·3 (3·4)
13·8 (2·9)
15·3 (2·5)
15·21 (2·4)
0·760
(0·226)
0·727
(0·295)
173
174
173
174
173
174
14·0 (3·4)
13·7 (3·4)
15·7 (2·3)
15·4 (2·6)
0·773
(0·234)
0·735
(0·256)
141
151
141
151
142
151
14·2 (3·3)
13·9 (3·5)
15·6 (2·6)
15·2 (2·6)
0·764
(0·248)
0·721
(0·293)
157
166
157
166
156
167
14·2 (3·4)
14·0 (3·4)
15·7 (2·6)
15·3 (2·6)
0·768
(0·243)
0·723
(0·282)
148
141
149
141
149
142
13·9 (3·5)
13·7 (3·3)
15·7 (2·7)
14·9 (2·6)
0·757
(0·266)
0·715
(0·310)
167
169
0·14
167
169
0·13
166
169
11·6 (10·9) 169
0·21
0·55
Psychiatric and medical comorbidity
0·90
0·43
0·03
0·90
0·02
0·68
0·81
0·04
0·07
m-ADM=maintenance antidepressant medication. MBCT-TS=mindfulness-based cognitive therapy with support to taper or discontinue antidepressant medication. BDI=Beck Depression Inventory.
GRID-HAMD=GRID Hamilton Rating Scale for Depression. MSCL=medical symptom checklist. WHO-QoL=WHO Quality of Life. *p values reported are the treatment group-time interaction contrasts of marginal
linear predictions for observed data. †p values reported are the treatment group-time interaction contrasts of marginal linear predictions for including imputed data. All models adjusted for baseline depression
severity category on Hamilton scale and centre.
Table 4:
Intention-to-treat repeated measures amalyses at 1 month after treatment, and follow-up at 9, 12, 18, and 24 months for secondary outcomes
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MBCT-TS (n=181)
MBCT
Antidepressants
Hospital and community services
Total health-care PSS
Out of pocket costs to patients
Productivity losses (n=265)
Societal costs (n=252)
112·00 (0·00)
40·10 (72·13)
2332·43 (4065·88)
2484·52 (4077·31)
56·76 (168·29)
504·26 (1881·49)
3204·05 (4011·91)
Maintenance
antidepressants (n=180)
0·00 (0·00)
69·79 (168·48)
2290·62 (4190·65)
2360·41 (4205·58)
83·33 (283·12)
310·54 (761·06)
2754·92 (4465·07)
Mean difference (95% CI)*
p value*
124·11 (–749·98 to 972·57)
0·800
449·14 (–842·18 to 1286·26)
0·681
Data are mean (SD) unless otherwise stated. MBCT-TS=mindfulness-based cognitive therapy with support to taper or discontinue antidepressant medication.
MBCT=mindfulness-based cognitive therapy. PSS=personal social services. *Adjusted for stratification variables.
Table :
Mean cost per participant over the 24-month follow-up period (£)
ments in the percentage of participants who relapse can
only be gained with additional expenditure. In terms of
QALYs, MBCT-TS is dominated by maintenance
antidepressant treatment (MBCT-TS costs higher and
outcomes poorer, on average, than maintenance
antidepressant treatment). Irrespective of measure of
effect, exploration of statistical uncertainty suggests that
the probability of MBCT-TS being more cost effective than
maintenance antidepressants does not rise above 52%.
Serious adverse events were monitored and a total of ten
serious adverse events were reported, four of which
resulted in the death of the participant. These adverse
events were evenly split between the two trial groups
(three non-fatal and two fatal serious adverse events in
each group) and reported to the Trial Steering and Data
Monitoring Committees who concluded that there was no
reason to believe that any of the serious adverse events
were related to either the intervention or the trial.
Discussion
We noted no evidence for the superiority of MBCT-TS
compared with maintenance antidepressants for patients
with recurrent depression in terms of the primary outcome
of time to depressive relapse or recurrence over 24 months
or any of the secondary outcomes. Cost-effectiveness
analysis does not support the hypothesis that MBCT-TS is
more cost effective than maintenance antidepressants, in
terms of either relapse or recurrence or QALYs.
Before this study, only two small studies
10,39
had
compared MBCT-TS with maintenance antidepressants
(panel). In our pilot trial,
10
MBCT-TS (n=62) was
compared with maintenance antidepressant treatment
(n=61) over a 15-month follow-up, and relapse or
recurrence rates were 47% for MBCT-TS, compared with
60% for maintenance antidepressants.
10
In the second
study,
39
84 patients with recurrent depression who had
remitted on antidepressants were randomly assigned to
MBCT-TS, maintenance antidepressants, or pill placebo.
Relapse or recurrence rates noted over 18 months of
follow-up did not differ for MBCT-TS (28%, n=5/18) and
maintenance antidepressants (27%, n=3/11), but both
were lower than with placebo (71%, n=10/14).
39
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Vol 386 July 4, 2015
Relapse or recurrence rates in people with three or
more previous episodes are as high as 80% over 2 years.
2
Moreover, results from meta-analyses consistently
suggest that maintenance antidepressant treatment
reduces the odds of relapse by two-thirds or a halving of
absolute risk compared with usual care or placebo.
4
Future research should therefore examine the hypothesis
that MBCT-TS would provide benefits over and above
either usual care, no treatment, or pill placebo.
Across both treatment groups, outcomes were
comparatively good over the 2 years of follow-up in terms
of relapse or recurrence, residual symptoms, and quality
of life (table 4).
Consistent with an emergent pattern of findings,
7
MBCT
might confer most benefit to patients at greatest risk of
relapse. A randomised trial
7
of patients with a history of
three or more episodes of depression (n=274) compared
MBCT, psycho-education, and usual care over a 12-month
follow-up. MBCT provided significant protection against
relapse or recurrence for participants with increased risk
due to history of childhood abuse, but showed no significant
advantage over the whole group.
7
Findings from trials of
psychosocial approaches have shown that more intensive
psychosocial treatments confer protection for those most at
risk. For example, in a two-arm randomised trial over a
21-month follow-up, relapse or recurrence rates were 51%
for maintenance cognitive behavioural therapy (CBT) and
60% for psycho-education, but in those at greatest risk,
CBT
conferred
greater
protection
than
did
40
psycho-education. A reported history of abuse and
adversity is associated with worse outcomes in people who
have depression.
41
Perhaps MBCT confers resilience in this
group at highest risk because patients learn skills that
address some of the underlying mechanisms of relapse or
recurrence, a question we will explore in a subsequent
publication from this trial. Studies are needed that have the
primary aim of establishing the effectiveness and
mechanism of MBCT for those at differing levels of risk of
relapse, with robust measures of risk.
This largest trial of any mindfulness-based approach to
date answered an important clinical question of high
relevance to GPs and patients at risk for depressive relapse
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Panel:
Research in context
Systematic review
A 2011 meta-analysis identified two small trials comparing the effectiveness of
mindfulness-based cognitive therapy with support to taper or discontinue antidepressant
medication (MBCT-TS) with maintenance antidepressants in prevention of relapse or
recurrence, following up participants for 60 weeks.
6
We did some searches of electronic
databases (Embase, PubMed, PsycINFO, Web of Science, Scopus, and the Cochrane
Controlled Trials Register) from the first available year to Nov 22, 2014, using keywords
(mindfulness-based cognitive therapy) OR (mindfulness based cognitive therapy) OR
(MBCT) AND depress*). No language or other limitations were imposed. We screened
abstracts to retrieve full-text articles for assessment of eligibility. We also checked reference
lists of relevant studies and reviews for additional references to potentially relevant studies.
This search identified no further published trials. The combined relative risk ratio of MBCT-
TS versus maintenance antidepressants was 0·80 (95% CI 0·60–1·08,
z=1·45,
p=0·15),
corresponding to a non-significant risk reduction of 20%. We extended these findings with
a large pragmatic superiority trial of MBCT-TS compared with maintenance antidepressants
for people with a history of three or more previous episodes of depression. The primary
outcome was relapse or recurrence over 2 years of follow-up. MBCT-TS was not superior to
maintenance antidepressant medication in terms of time to depressive relapse or
recurrence over the 24 months (hazard ratio 0·89, 0·67–1·18). We pooled our trial data with
the equivalent MBCT-TS and maintenance antidepressant medication groups of the
previous two randomised controlled trials (n=123
10
and n=54
39
), and used the equivalent
60-week follow-up point available across all three studies. The combined relative risk ratio
of MBCT-TS versus maintenance antidepressants was 0·76 (95% CI 0·59–0·98), a risk
reduction of 24%. There was no evidence of statistical heterogeneity.
Interpretation
We found no evidence that MBCT-TS is superior to maintenance antidepressant treatment
for the prevention of depressive relapse. However, when considered in the context of the
totality of randomised controlled data, we found evidence from this trial to support
MBCT-TS as an alternative to maintenance antidepressants for prevention of depressive
relapse or recurrence at similar costs. It allows such individuals to stay well and maintain
good quality of life. In patients who report childhood abuse, MBCT-TS might confer greater
benefit than maintenance antidepressants in prevention of depressive relapse or recurrence.
or recurrence. The internal validity of the trial was
established through the fidelity of MBCT-TS delivery, high
rates of treatment adherence, excellent retention, and
through masked outcome assessment. The external validity
was maximised by the relatively long follow-up (24 months),
and good adherence rates in both treatment groups.
The study had several limitations. The sample consisted
of a group of people at high risk of depressive relapse or
recurrence,
42
currently taking antidepressants, and who
were open both to considering a group-based psychosocial
treatment and to discontinuing or continuing
antidepressant medication. This characteristic is both
a strength and limitation of the study. The findings
are therefore only generalisable to the subgroup of
individuals in equipoise about type of preventive treatment.
Moreover, our recruitment strategy consisted of searching
primary care databases and inviting patients who were
currently taking maintenance antidepressants rather than
recruiting patients who were discussing their options for
preventing relapse or recurrence with their GP.
72
The design included neither a usual care nor an attention
control group. The absence of an attention control group
means any effects of MBCT cannot be inferred to be
specific to MBCT; ongoing studies of mechanisms of
action in MBCT from our group will address this question.
Finally, the pragmatic nature of the trial means that a
subgroup of patients in both groups did not comply with
the study invitation to discontinue antidepressant
medication. This characteristic is both a strength
(pragmatism and generalisability) and limitation (the
antidepressant medication was not fully controlled).
In a large rigorous, yet pragmatic randomised trial we
have shown that MBCT-TS is not superior to maintenance
antidepressants over 2 years of follow-up for patients with
recurrent depression. Benchmarked against epidemio-
logical data, both treatments were associated with enduring
positive outcomes in terms of relapse or recurrence,
residual depressive symptoms, and quality of life. This
study, combined with previous studies, provides important
evidence that MBCT-TS might confer ongoing protection
for patients who would like an alternative to maintenance
antidepressant medication. The results further suggest that
psychosocial treatments such as MBCT and CBT
7,40,43
offer
added value for patients who need them most (ie, those at
highest risk of depressive relapse or recurrence). However,
studies have tended to operationalise risk in somewhat
different ways (such as early adversity, unstable remission,
more previous episodes, early age of onset) and although
these risk factors overlap, future research should examine
how and through what mechanism risk is conferred and
resilience learned. In the interim, the implication is that for
patients at low risk, treatments such as psycho-education or
maintenance antidepressants, which require less patient
commitment and cost, might be indicated, whereas for
patients at highest risk, more intensive treatments such as
MBCT could be indicated. This implication has substantial
potential to improve prevention by maximising the delivery
of treatments through stratified approaches, which also
have the potential to improve patient choice.
Contributors
WK, SB, RB, TD, GL, RST, EW, PL, DK, and NM were responsible for the
original proposal, securing funding for the trial, and drafting the original
protocol. WK as chief investigator had overall responsibility for the
management of the study and the Exeter site, and as co-investigators GL
and DK had responsibility for the Bristol site. Trish Bartley, AE, and WK
provided training and supervision for the trial therapists (CB, SC, AE, and
JW). RB also provided support for intervention development and delivery.
JC, AC, FG, RH, SK, JR, PS, HS, RV, AW, and MW were responsible for
data collection. RH, WK, RST, and SB wrote the statistical analysis plan.
AC, BB, RH, PS, and MW did the data cleaning and BB and RST did the
analyses. SB, RH, WK, and RST wrote the initial draft of the manuscript.
All authors contributed to, and approved, the final manuscript.
Declaration of interests
WK and AE are co-directors of the Mindfulness Network Community
Interest Company and teach nationally and internationally on MBCT.
The other authors declare no competing interests.
Acknowledgments
This research was funded by the National Institute for Health Research
Health Technology Assessment (NIHR HTA) programme (project number:
08/56/01). The views expressed in this publication are those of the authors
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and do not necessarily reflect those of the HTA programme, NIHR, NHS,
or the Department of Health. We thank all the practitioners and GP surgery
staff who took part in this research and Trish Bartley for her input to MBCT
therapist training and MBCT fidelity checks. We thank Beverley Herring
and other service users who brought their personal lived experience of
depressive illness to advise on the direction of the trial and provide training
for the research assessors. We acknowledge the SCID and GRID-HAMD
training that Sandra Kennell-Webb provided to our research staff. We thank
the members of our Trial Steering Committee (Chris Leach, Richard Moore,
and Glenys Parry) and Data Monitoring Committee (Paul Ewings,
Andy Field, and Joanne MacKenzie) for their valuable advice and support
during the project and Shadi Beshai who completed some of the final
research assessments. We acknowledge the additional support that has been
provided by the Mental Health and Primary Care Research Networks, and
the support provided by the Department of Health and local Primary Care
Trusts in meeting the excess treatment and service support costs associated
with the trial. Most importantly, we are grateful to the participants for their
time in taking part in this trial. Finally, we also thank the following
colleagues who have contributed to the PREVENT study, through
recruitment and retention of patients or provision of administrative support:
Rebecca Amey, Miriam Cohen, Alice Garrood, Nora Goerg, Anna Hunt,
Sarah Lane, Mary Sharkey, Cara Simmance, Holly Sugg, Lucy Wootton, and
other undergraduates and researchers who provided support to the trial.
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