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doi:10.1017/S0033291711002054
O R I G I N A L AR T I C LE
Background. The aim of this study is to examine the ecacy of mindfulness-based cognitive therapy (MBCT)
in addition to treatment as usual (TAU) for recurrent depressive patients with and without a current depressive
episode.
Method. A randomized, controlled trial comparing MBCT+TAU (n=102) with TAU alone (n=103). The study
population consisted of patients with three or more previous depressive episodes. Primary outcome measure was
post-treatment depressive symptoms according to the Hamilton Rating Scale for Depression. Secondary outcome
measures included the Beck Depression Inventory, rumination, worry and mindfulness skills. Group comparisons
were carried out with linear mixed modelling, controlling for intra-group correlations. Additional mediation analyses
were performed. Comparisons were made between patients with and without a current depressive episode.
Results. Patients in the MBCT+TAU group reported less depressive symptoms, worry and rumination and
increased levels of mindfulness skills compared with patients receiving TAU alone. MBCT resulted in a comparable
reduction of depressive symptoms for patients with and without a current depressive episode. Additional analyses
suggest that the reduction of depressive symptoms was mediated by decreased levels of rumination and worry.
Conclusions. The study ndings suggest that MBCT is as eective for patients with recurrent depression who are
currently depressed as for patients who are in remission. Directions towards a better understanding of the
mechanisms of action of MBCT are given, although future research is needed to support these hypotheses.
Received 27 December 2010 ; Revised 29 July 2011 ; Accepted 6 September 2011
Key words : Depression, MBCT, mindfulness, recurrence.
Introduction
Major depression is serious health problem. Its lifetime prevalence is 16.2 % and the 12-month prevalence
is 6.6 % (Kessler et al. 2003). The probability of relapse
increases with every depressive episode (Eaton et al.
2008). Consequently, the development of eective strategies to prevent relapse is very important. The usual
treatment oered is antidepressant medication, which
often yields unwanted side eects, compromising
patient compliance (Hollon et al. 2002, 2005).
Mindfulness-based cognitive therapy (MBCT) is
an alternative, psychological intervention designed
Method
Design
A randomized, controlled design was used comparing
MBCT plus TAU with TAU alone. Patients in the TAU
condition participated in the MBCT training after a
3-month waiting list period. In order to investigate
the stability of the eects of MBCT, patients in both
conditions were followed for 1 year after completing
MBCT. The results at 1-year follow-up will be presented separately.
Statistical analysis
All analyses were carried out using the intention
to treat sample. As <3 % of the data was missing, reported results are based on complete data. Sensitivity
analysis based on worse case imputation revealed no
dierence in direction nor signicance for all outcomes.
Post-measurement scores were compared between
the two groups, controlling for baseline depression
levels. Additional analyses were performed within
subgroups with and without a current depressive
episode. To account for possible dierences between
therapy groups, we added a random group eect. All
analyses were performed using linear mixed models
including an exploratory moderation analyses. A
Cohens d eect size was calculated based on the
complete group (n=205) baseline standard deviation
to avoid a contamination of standard deviation due to
therapy eects.
Additional information about reliable change for
the HAMD scores is provided, calculated and visually
presented based on the work of Jacobson & Truax,
(1991), using testretest reliability to correct for
measurement errors of the HAMD, again using the
complete group baseline standard deviation.
For the mediation analysis, we followed the recommendations of Preachers and Hayes for multiple
mediation models (Preacher & Hayes, 2008). In all
mediation analyses, HAMD post-measurement scores
were controlled for baseline depression by using premeasurement HAMD scores as a covariate. Residual
change scores for all potential mediators were calculated (MacKinnon, 2008). To explore whether the
mediators (partly) eected the relation of condition on
post-treatment depression levels, the model including
the potential mediators was compared with the model
without mediators for both univariate and multivariate models. An advantage of a multivariate model
over several univariate models is the possibility of
determining the relative contribution of each indirect
Enrolment
Randomization
(n = 219)
Allocation
Analysis
Results
Study population
Of the 258 patients interviewed, 33 were excluded and
six refused to participate. Reasons for exclusion were :
(1) not having three or more previous depressive
episodes (n=19) ; (2) change in medication within 6
weeks before the start of the study (n=4) ; (3) previous
(hypo)manic episodes (n=2) ; (4) current substance
abuse (n=3) ; (5) acute need of psychiatric treatment
(n=2) ; (6) problems to participate in a group therapy
(n=2) ; (7) cognitive impairments (n=1).
A total number of 219 patients were included
and eventually 205 patients were analysed (MBCT
n=102 ; TAU n=103), see Fig. 1 for a detailed description of the patient ow. Within each condition,
the groups were divided into subgroups with and
without a major depressive episode based on the MINI
Table 1. Baseline characteristics of mindfulness-based cognitive therapy (MBCT) and treatment as usual (TAU) conditions for the total group of participants and the two subgroups without and with a
current depressive episode
Total group
No current depression
Currently depressed
MBCT
(n=102)
TAU
(n=103)
Sig.b
MBCT
(n=68)
TAU
(n=68)
Sig.b
MBCT
(n=34)
TAU
(n=35)
Sig.b
Female
Married/Cohabiting
Care for children
Employed
Tertiary education
Antidepressant medication
Previous cognitive behavioural therapy
Recent meditation experiencea
71 (70)
66 (64)
43 (42)
52 (51)
67 (66)
53 (52)
61 (60)
49 (48)
74 (72)
66 (64)
36 (35)
51 (50)
55 (53)
48 (47)
58 (56)
48 (47)
p=0.73
p=0.57
p=0.40
p=0.66
p=0.44
p=0.62
p=0.56
p=0.94
48 (71)
19 (59)
28 (43)
34 (52)
45 (68)
35 (57)
45 (71)
33 (50)
52 (77)
44 (68)
23 (35)
41 (64)
39 (60)
32 (53)
40 (65)
30 (46)
p=0.56
p=0.61
p=0.37
p=0.37
p=0.79
p=0.59
p=0.41
p=0.66
23 (68)
22 (65)
13 (42)
18 (53)
22 (34)
18 (58)
18 (67)
16 (49)
22 (63)
22 (71)
15 (44)
10 (32)
16 (52)
16 (57)
16 (64)
18 (55)
p=0.68
p=0.67
p=0.86
p=0.29
p=0.37
p=0.94
p=0.84
p=0.62
8.0 (5.7)
11.9 (7.3)
27.2 (9.9)
39.6 (12.7)
7.8 (6.3)
13.8 (7.6)
28.3 (9.5)
43.0 (11.9)
Sig.c
p=0.81
p=0.15
p=0.52
p=0.10
12.4 (6.3)
20.7 (9.8)
29.4 (8.7)
48.6 (9.1)
12.1 (6.4)
21.3 (10.8)
28.7 (10.0)
45.2 (12.4)
Sig.c
p=0.83
p=0.81
p=0.76
p=0.21
9.5 (6.2)
14.9 (9.2)
28.0 (9.5)
42.6 (12.3)
9.2 (5.6)
16.2 (9.4)
28.4 (9.6)
43.7 (11.5)
Sig.c
p=0.79
p=0.30
p=0.74
p=0.50
19.0 (7.5)
18.4 (8.2)
15.9 (6.1)
18.4 (6.2)
18.7 (7.4)
18.3 (7.8)
16.8 (5.6)
18.0 (6.4)
p=0.76
p=0.91
p=0.31
p=0.63
19.3 (7.2)
19.7 (7.3)
16.7 (5.8)
19.2 (6.5)
18.0 (6.9)
18.7 (7.4)
17.4 (5.6)
19.0 (6.3)
p=0.31
p=0.45
p=0.51
p=0.86
18.6 (8.0)
15.9 (9.5)
14.4 (6.4)
16.8 (5.5)
20.1 (8.2)
8.6 (17.4)
15.6 (5.7)
15.8 (6.0)
p=0.44
p=0.50
p=0.43
p=0.49
22.0 (5.5)
18.2 (3.5)
9.7 (2.3)
20.8 (4.9)
18.2 (3.4)
10.3 (2.2)
p=0.14
p=0.99
p=0.12
23.7 (5.4)
18.9 (3.3)
9.7 (1.9)
22.1 (4.5)
18.0 (3.1)
10.4 (2.0)
p=0.09
p=0.94
p=0.05
18.8 (4.2)
16.6 (3.3)
9.7 (1.9)
18.1 (4.6)
16.5 (3.5)
9.8 (2.7)
p=0.56
p=0.92
p=0.88
HAMD, Hamilton Rating Scale for Depression ; BDI, Beck Depression Inventory ; RSS, Rumination on Sadness Scale ; PSWQ, Penn State Worry Questionnaire ; KIMS, Kentucky
Inventory of Mindfulness ; WHOQOL-Bref, World Health Organization Quality of Life, self-report questionnaire.
a
Meditation and/or body focused experience <6 months ago.
b 2
x tests.
c
Independent sample t tests.
d
Measured in a subsample : MBCT [n=89 (non-depressed, n=59 ; depressed, n=30)] ; TAU [n=74 (non-depressed, n=51 ; depressed, n=23)].
Baseline characteristics ; n ( %)
Table 2. Depressive symptoms, rumination, mindfulness skills and quality of life at post-treatment of mindfulness-based cognitive
therapy (MBCT) and treatment as usual (TAU) conditions, controlling for baseline levels of symptoms
Total group
Post-measurement results ;
mean (S.D.)a
MBCT
(n=102)
TAU
(n=103)
Group dierence
(95 % CI)b
Depression (HAMD)
Depression (BDI)
Rumination (RSS)
Worry (PSWQ)
7.5 (5.8)
10.3 (7.8)
22.0 (8.6)
36.8 (12.0)
10.5 (6.8)
16.2 (9.8)
27.3 (10.6)
42.5 (10.7)
22.8 (7.4)
19.7 (7.6)
20.0 (5.6)
22.3 (5.5)
18.2 (7.1)
17.9 (7.2)
16.1 (6.0)
18.6 (6.7)
0.65
0.20
0.74
0.51
23.6 (5.3)
19.9 (3.4)
10.2 (2.1)
21.6 (5.1)
18.4 (3.7)
10.0 (2.3)
0.19
0.36
0.13
Cohens d
0.53
0.50
0.50
0.43
HAMD, Hamilton Rating Scale for Depression ; BDI, Beck Depression Inventory ; RSS, Rumination on Sadness Scale ; PSWQ,
Penn State Worry Questionnaire ; KIMS, Kentucky Inventory of Mindfulness ; WHOQOL-Bref, World Health Organization
Quality of Life, self-report questionnaire.
a
Unadjusted condition means and standard deviations (S.D.).
b
Dierences between conditions, corrected for baseline values.
c
Measured in a subsample : MBCT [n=89 (non-depressed, n=59 ; depressed, n=30)] ; TAU [n=74 (non-depressed, n=51 ;
depressed, n=23)].
d
Statistical signicant dierence for p<0.05.
Ecacy of MBCT
Depressive symptoms
Table 3. Depressive symptoms, rumination, mindfulness skills and quality of life at post-treatment of mindfulness-based cognitive therapy (MBCT) and treatment as usual condition (TAU),
controlling for baseline levels of symptoms, for both subgroups without and with a current depressive episode respectively
No current depression
MBCT
(n=68)
TAU
(n=68)
Depression (HAMD)
Depression (BDI)
Rumination (RSS)
Worry (PSWQ)
6.2 (4.7)
8.6 (6.3)
21.3 (8.6)
34.6 (11.3)
9.1 (5.6)
14.0 (8.0)
26.4 (10.4)
41.6 (10.2)
22.8 (7.4)
20.4 (7.1)
20.7 (5.4)
23.2 (5.4)
17.8 (7.1)
18.2 (7.0)
16.7 (5.6)
16.7 (5.6)
25.0 (4.8)
20.2 (3.3)
10.2 (2.2)
22.5 (4.7)
18.9 (3.3)
10.3 (2.1)
Cohens d
MBCT
(n=34)
TAU
(n=35)
0.58
0.56
0.46
0.45
10.2 (6.7)
13.7 (9.5)
23.4 (8.6)
41.1 (12.5)
13.4 (8.1)
20.4 (11.7)
29.2 (10.9)
44.4 (11.5)
0.62
0.19
0.77
0.52
22.9 (7.5)
18.3 (8.5)
18.7 (6.0)
20.4 (4.8)
19.0 (7.1)
17.5 (7.7)
15.0 (6.8)
16.9 (7.1)
0.64
0.20
0.74
0.49
0.23
0.33
0.01
20.6 (5.3)
19.2 (3.5)
10.1 (2.0)
19.7 (5.3)
17.3 (4.2)
9.5 (2.6)
0.22
0.46
0.17
Group dierence
(95 % CI)b
x2.9 (x4.6 to x1.3)d
x4.2 (x6.2 to x2.2)d
x4.4 (x7.6 to x1.3)d
x5.4 (x8.2 to x2.5)d
Group dierence
(95 % CI)b
x3.3 (x6.6 to x0.1)d
x5.3 (x10.0 to x0.6)d
x5.4 (x9.5 to x1.3)d
x4.8 (x9.8 to 0.1)d
Cohens d
0.53
0.53
0.59
0.49
HAMD, Hamilton Rating Scale for Depression ; BDI, Beck Depression Inventory ; RSS, Rumination on Sadness Scale ; PSWQ, Penn State Worry Questionnaire ; KIMS, Kentucky
Inventory of Mindfulness ; WHOQOL-Bref, World Health Organization Quality of Life, self-report questionnaire.
a
Unadjusted condition means and standard deviations (S.D.).
b
Dierences between conditions, corrected for baseline values.
c
Measured in a subsample : MBCT [n=89 (non-depressed, n=59 ; depressed, n=30)] ; TAU [n=74 (non-depressed, n=51 ; depressed, n=23)].
d
Statistical signicant dierence (p<0.05).
Post-measurement results ;
mean (S.D.)a
Currently depressed
20
TAU
MBCT
15
b
10
a
0
0
10
15
20
25
To further investigate whether depressive symptoms at baseline inuenced the ecacy of MBCT, we
performed an interaction analysis adding an interaction term between baseline depression levels (HAMD)
and condition. We found no signicant interaction
for any of the outcome variables, indicating that the
ecacy of MBCT is independent of baseline level of
depression. Using split-le analyses for patients with
and without a current depressive episode, no signicant interactions were found between baseline
depression levels (HAMD) and any of the outcome
measures. The result for the interaction analysis between baseline depression levels and end of treatment
levels of depression (HAMD) is graphically presented
in Fig. 2, showing baseline and end of treatment levels
of depression in both conditions. From this gure it
becomes apparent that the reduction of depressive
symptoms as a result of MBCT is independent from
the baseline level of depression.
Clinically signicant change
A clinically signicant change of the HAMD scores,
the primary outcome measure, is presented in Table 4,
using both the JacobsonTruax reliable change index
and the absolute cut-o level of HAMD 10 as criteria
Table 4. Numbers and percentages of depression change based on the JacobsonTruax Reliable Change Index (RCI), calculated for
HAMD scores, pre- and post-measurement of the MBCT and TAU conditions, stratied for amount of depressive symptoms, also
displayed in Fig. 3
Depression diagnosis
at baseline
Past cut-o
RCI criterion
Improved (.)
+
+
Changed (,)
+
x
Deteriorated (+)
+
+
No current depression, n ( %)
MBCT (n=68)
TAU (n=68)
MBCT (n=34)
TAU (n=35)
MBCT (n=102)
TAU (n=103)
10 (14.7)
4 (5.9)
5 (14.7)
4 (11.4)
15 (14.7)
8 (7.8)
3 (4.4)
2 (2.9)
2 (5.9)
2 (5.7)
5 (4.9)
4 (3.9)
52 (76.5)
50 (73.5)
25 (73.5)
23 (65.7)
77 (75.5)
73 (70.9)
3 (4.4)
12 (17.6)
2 (5.9)
6 (17.1)
5 (4.9)
18 (17.5)
Current depression, n ( %)
Total, n ( %)
HAMD, Hamilton Rating Scale of Depression ; MBCT, mindfulness-based cognitive therapy ; TAU, treatment as usual.
TAU
MBCT
35
type of change
improved
changed positively
30
not changed
deteriorated
25
20
15
10
0
0
10
15
20
25
30
35 0
10
15
20
25
30
35
Mediation analysis
Rumination, worry and the four separate mindfulness
skills were expected to be mediators between the
MBCT training and post-measurement levels of depression (HAMD). Predicted mediators were rst
analysed using a univariate model and, if shown to be
a contributing factor, were entered into a multivariate
model.
The main analyses revealed that all the suggested
mediators were related to condition (MBCT versus
10
and improvement in mindfulness skills. Most importantly, we found no dierences between patients
with and without a current depressive episode in
terms of reduction of depressive symptoms. The
amount of formal practice seems to have some relation
with decrease in depressive symptoms. The results
suggest that post-measurement levels of depressive
symptoms were mediated by a decrease in worry and
rumination.
This study presents the rst large-scale, randomized, controlled study showing MBCT to be ecacious in reducing depressive symptoms for patients
with recurrent depression suering from a current
depressive episode. These results are in line with previous studies including one randomized, controlled
[Barnhofer et al. 2009 (n=28)], one controlled but not
randomized study [Kingston et al. 2007 (n=19)] and
three uncontrolled studies with a range of 13 to 79
participants (Finucane & Mercer, 2006 ; Kenny &
Williams, 2007 ; Eisendrath et al. 2008). These studies
showed that patients with current depressive symptoms might also benet from MBCT. Note that the
eect sizes found in our study were smaller than in the
study by, for example, Barnhofer et al. (2009). One
explanation for the reduced eect sizes study might be
the inclusion of patients with recent meditation experience, since this was shown to be a moderating
variable.
The fact that recent meditation experience was
shown to moderate the level of depressive symptoms
supports the idea that the meditation component plays
a key role in the eects of MBCT but this has yet to be
proven (Williams et al. 2010).
Additional analyses and gures, especially Fig. 3,
illustrate that not only more patients improved, but
also fewer patients deteriorated in the MBCT condition compared with TAU alone. This is congruent
with the prophylactic results of MBCT for depression
shown in previous studies (e.g. Ma & Teasdale, 2004 ;
Kuyken et al. 2008).
Our nding that patients without a current
depressive episode also showed reduced levels of depressive symptoms is encouraging, considering the
clinical relevance of residual symptoms in the prediction of relapse and recurrence of depression. Kennedy
et al. (2004) showed that subsyndrome levels of
depression are common and persistent after severe
episodes of depression. Residual depressive symptoms have been repeatedly shown as a predictor of
depressive relapse (e.g. Paykel et al. 1995 ; Rush et al.
2006 ; Hardeveld et al. 2010). This may contribute to the
ecacy of MBCT preventing relapse.
The exploratory mediation analysis lends valuable
insights towards a better understanding of the
working mechanism of MBCT. Congruent with our
11
Conclusions
The greatest merit of this study is that it shows that
MBCT is also ecacious in recurrent depressive
patients with a current depressive episode. The study
also gives some directions toward a better understanding of the mechanisms of action of MBCT.
However, the exploratory nature of this justies further investigation.
Acknowledgements
We thank the trainers Noud de Haas and Hetty
Janssen for providing the MBCT training, Cobie
Wijsman, Dorien Verplak and Geert Schattenberg for
their help with the data collection and Poppy
Schoenberg for her comments. We also thank the following students for their contribution to the study :
Lissy van de Laar ; Tom Wingens ; Robert de Boer ;
Milou Johan ; Gitte Janssen Steenberg ; Karlijn Peer ;
Sara Al Shamma ; Joelle Terlouw ; Tessa Bronkhorst.
Finally, we are grateful to the patients for their willingness to participate in the study. (The trial is registered at Clinical Trials.gov ; ID : NCT01038765.)
Declaration of Interest
The corresponding author is nancial supported by
Fonds Psychische Gezondheid ; Grant Number : 2005
6028 and part of the Spinoza prize 2002 of Professor
H. P. Barendregt.
References
Baer RA, Smith GT, Allen KB (2004). Assessment of
mindfulness by self-report : The Kentucky Inventory of
Mindfulness Skills. Assessment 11, 191206.
Baer RA, Smith GT, Hopkins J, Krietemeyer J, Toney L
(2006). Using self-report assessment methods to explore
facets of mindfulness. Assessment 1, 2745.
Barnhofer T, Crane C, Hargus E, Amarasinghe M, Winder
R, Williams JMG (2009). Mindfulness-based cognitive
therapy as a treatment for chronic depression : a
preliminary study. Behaviour Research and Therapy 47,
366373.
Baum C, Kuyken W, Bohus M, Heidenreich T, Michalak J,
Steil R (2010). The psychometric properties of the
Kentucky Inventory of Mindfulness Skills in clinical
populations. Assessment 17, 220229.
Bech P, Kastrup M, Rafaelson OJ (1989). Mini-compendium of
Rating Scales for States of Anxiety, Depression, Mania and
Schizophrenia with Corresponding DSM-III Syndromes
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