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Psychological Medicine (2012), 42, 1429–1439. f Cambridge University Press 2011
doi:10.1017/S0033291711002522
O R I G I N A L AR T I C LE
Cognitive behaviour therapy and supportive therapy
for bipolar disorders: relapse rates for treatment
period and 2-year follow-up
T. D. Meyer1,2* and M. Hautzinger1
1
2
Department of Clinical and Developmental Psychology, Institute of Psychology, Eberhard Karls Universität Tübingen, Germany
Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK
Background. The efficacy of adjunctive psychosocial interventions such as cognitive behaviour therapy (CBT) for
bipolar disorder (BD) has been demonstrated in several uncontrolled and controlled studies. However, these studies
compared CBT to either a waiting list control group, brief psycho-education or treatment as usual (TAU). Our
primary aim was to determine whether CBT is superior to supportive therapy (ST) of equal intensity and frequency
in preventing relapse and improving outcome at post-treatment. A secondary aim was to look at predictors of
survival time.
Method. We conducted a randomized controlled trial (RCT) at the Department of Psychology, University of
Tübingen, Germany (n=76 patients with BD). Both CBT and ST consisted of 20 sessions over 9 months. Patients were
followed up for a further 24 months.
Results. Although changes over time were observed in some variables, they were not differentially associated with
CBT or ST. CBT showed a non-significant trend for preventing any affective, specifically depressive episode during
the time of therapy. Kaplan–Meier survival analyses revealed that 64.5 % of patients experienced a relapse during the
33 months. The number of prior episodes, the number of therapy sessions and the type of BD predicted survival
time.
Conclusions. No differences in relapse rates between treatment conditions were observed, suggesting that certain
shared characteristics (e.g. information, systematic mood monitoring) might explain the effects of psychosocial
treatment for BD. Our results also suggest that a higher number of prior episodes, a lower number of therapy
sessions and a diagnosis of bipolar II disorder are associated with a shorter time before relapse.
Received 23 March 2011 ; Revised 12 October 2011 ; Accepted 13 October 2011 ; First published online 21 November 2011
Key words : Bipolar disorder, cognitive behaviour therapy, predictors, randomized controlled trial, relapse prevention.
Introduction
Bipolar disorders (BDs) are more frequent and disabling than originally thought, with many patients
showing significant impairment or subsyndromal
symptoms between episodes (e.g. Judd et al. 2002 ;
Judd & Akiskal, 2003 ; Solomon et al. 2010). Although
medication is needed, the role of psychosocial factors
in the onset and course of BD has become obvious (e.g.
Alloy et al. 2005 ; Johnson, 2005) and has led to the
development of several psychosocial interventions.
Cognitive behaviour therapy (CBT) relies on the
assumption that the interaction of thoughts, behaviours
* Address for correspondence : T. D. Meyer, Ph.D., Doctorate in
Clinical Psychology, Institute of Neuroscience, Newcastle University,
Ridley Building, Newcastle upon Tyne NE1 7RU, UK.
(Email : [email protected])
and emotions is the underlying psychopathology, including depression and mania. Indeed, empirical
evidence has demonstrated the role of cognitive vulnerability factors such as dysfunctional attitudes or
attributional style for BD and mania (e.g. Johnson,
2005 ; Jones et al. 2005 ; Alloy et al. 2009). Several reviews have looked at the efficacy of psychotherapy
for BD (e.g. Beynon et al. 2009 ; Miklowitz & Scott,
2009 ; Szentagotai & David, 2010), and in summary
indicate that CBT for BD works better than waiting for
treatment (Scott et al. 2001), is more beneficial than
brief psycho-education (Zaretsky et al. 2008) and has
mostly proved to be superior to treatment as usual
(TAU) with respect to functioning and relapse prevention (e.g. Lam et al. 2003 ; Ball et al. 2006). Focusing
on overall relapse rates from four randomized controlled trials (RCTs) in their meta-analysis, Lynch et al.
(2010) concluded that CBT is not effective for BD.
1430
T. D. Meyer and M. Hautzinger
Although Scott et al. (2006) did not find an overall
effect for CBT with regard to relapse prevention for
severe BD, they did report that individuals with fewer
episodes benefited from receiving CBT. Despite these
encouraging results, there are limitations, for example
the amount of attention patients in the control groups
had received has not been controlled. Waiting for
treatment also has its own negative effects, with 30 %
of patients dropping out (Scott et al. 2001). By contrast,
TAU mostly included regular visits to the psychiatrist
and crises management. This was usually provided to
all study participants, so that in effect CBT was an
add-on intervention. Therefore, the patients treated
with CBT received much more attention and support
of any kind compared to those in the control conditions. This renders interpretations ambiguous
(e.g. Goldfried & Wolfe, 1998).
The primary aim of our study was therefore to
examine whether the positive results with regard to
relapse rates and post-treatment improvements in
former studies are still evident if people are randomized to CBT or another treatment condition that is
matched in frequency and intensity of contact (i.e.
supportive therapy, ST). We used relapse rates as the
main outcome variable but also considered symptom
levels and indicators of cognitive vulnerability (e.g.
locus of control). It was expected that CBT would lead
to lower relapse rates, decrease symptoms levels and
cognitive vulnerability (e.g. increased internal locus of
control). A secondary aim was to test whether illnessrelated variables that have been identified in other
studies predict survival time, specifically length of
treatment, number of prior episodes, age of onset,
medication, psychosocial functioning and type of BD
(e.g. Miklowitz et al. 2003 ; Scott et al. 2006, 2007 ;
Zaretsky et al. 2008).
Method
Participants
Recruitment took place in the Department of Psychology, University of Tübingen, Germany, between
August 1999 and September 2004. The patients were
either referred by local hospitals, psychiatrists or were
self-referrals due to public information in newspapers
or on the radio. Participants were invited to a screening session in which they were informed about the
study and gave written informed consent. Baseline
assessment consisted of at least three consecutive
sessions, in which clinical interviews (e.g. SCID-I
and SCID-II) and self-ratings (e.g. the Beck Depression
Inventory, BDI) were completed.
The inclusion criteria for the study were (a) a primary
disorder of BD according to DSM-IV (APA, 1994),
(b) age between 18 and 65 years, and (c) willingness to
continue current or start medication. Exclusion criteria
were : (a) the primary diagnosis is a non-affective disorder including schizo-affective disorder, (b) current
major affective episode (depressed, mixed or mania
according to SCID-I) or Bech–Rafaelsen Melancholia
Scale (BRMS ; Bech & Rafaelsen, 1980) score >14 or
Bech–Rafaelsen Mania Rating Scale (BRMAS ; Bech
et al. 1978) score >9, (c) substance-induced affective
disorder, or affective disorder due to a general medical
condition, (d ) current substance dependency requiring
detoxification (abuse did not qualify for exclusion),
(e) serious cognitive deficits (IQ <80), and ( f ) being
currently in psychological treatment.
Treatment conditions
Patients were randomly allocated to individual CBT or
ST using a stratified randomization strategy controlling for gender, bipolar I or II disorder, and age of
onset (before/after age of 20 years). Treatment started
within 2–4 weeks after the assessments. Both treatments consisted of 20 sessions (50–60 min) distributed
over 9 months. The first 12 sessions were provided on
a weekly basis, then biweekly sessions were offered
for the next 2 months and the remaining sessions were
scheduled monthly. Manuals were provided for both
treatments ; with the CBT one being published (Meyer
& Hautzinger, 2004). Both treatment conditions included information (e.g. symptoms, aetiology, medication) and mood monitoring in the form of a mood
diary. The difference between therapies was such that,
in the ST condition, therapists adopted a client-centred
focus, meaning that whatever problems the patient
presented were dealt with by providing emotional
support and general advise. If no specific topic was
mentioned by the patient, information about BD and
medication was delivered by the therapist without
referring to written or any other material. In contrast
to the CBT, no efforts were made to specifically link
this information to the individual’s biography or experience. The mood diary was checked by the therapist who provided brief feedback (e.g. regularity of
medication, of sleep and overall mood) or probed for
missing information but without using any CBTrelated techniques such as guided discovery, problem
solving or reality testing.
CBT covered (a) an information and motivation
module (providing and jointly elaborating on information and an understanding of BD, its symptoms,
aetiology, course, triggers and pharmacotherapy
based on and linked to the individual’s experience, but
also addressing, for example in this context, potentially dysfunctional beliefs about BD and medication),
(b) an individual relapse module (including life chart
CBT versus ST for BD
analysis, identification and monitoring of individual
early warning symptoms for mania and depression,
functional behaviour analysis or risky behaviours,
coping with prodromal symptoms), (c) cognitive and
behavioural strategies dealing with depression and
mania (e.g. cognitive restructuring, activity schedule/
daily routine, planning pleasurable activities), and
(d) training of communication skills and/or problemsolving skills depending on the individuals strengths
and deficits.
Therapists (n=8, one being T.D.M.) had a least
1-year postgraduate training in CBT and had attended
a specific 2-day workshop about CBT and ST for
BD with role plays and video training. All therapy
sessions were video-taped and weekly supervision
was provided.
Materials and procedures
SCID-I and SCID-II (First et al. 1996, 1997) were used
by trained clinical psychologists to diagnose mental
health problems at baseline and in the follow-up
period. All interviews were videotaped, and a random
sample of 53 patients was used to estimate reliability,
which proved to be excellent (k=0.93 for bipolar I,
k=0.89 for bipolar II). Relapse was defined as any
mood episode that fulfilled DSM-IV criteria. Throughout the therapy period recordings were made of hospitalizations and episodes obtained by the clinicians’
notes and from the patients’ mood diaries [including
also weekly assessments using the Center for Epidemiologic Studies Depression Scale (CES-D ; Radloff,
1977 ; Meyer & Hautzinger, 2003)]. Severity of symptoms and functioning was also assessed repeatedly
throughout the study period using the BRMS, the
BRMAS and the Global Assessment Scale (GAS), with
good reliability : intraclass correlation coefficient
(ICC)=0.87, 0.77 and 0.81 respectively. Several selfrating measures were used, such as the BDI (Beck &
Steer, 1987 ; a=0.89) and the Self-Rating Mania
Inventory (SRMI ; Shugar et al. 1992 ; a=0.94). In
addition, the Locus of Control for health and illness
(LC ; Lohaus & Schmitt, 1989) and the Disease Concept
Scale [‘ Krankheitskonzeptskala ’ (KK) ; Linden et al.
1988] were used. The 21 items of the LC are rated on a
scale from 1 (totally true) to 6 (not at all true) and three
composite scores can be calculated : internal LC
(a=0.89), external LC – powerful others (a=0.76),
and external LC – chance (a=0.88). The KK is so far
the only existing German scale that has been evaluated
to assess subjective illness concepts of patients. All 29
items are rated on a five-point scale (from 0=do not
agree at all to 4=totally agree). Seven subscales were
derived through factor analysis : trust in medication,
trust in psychiatrist, negative expectations, guilt,
1431
chance, vulnerability, and idiosyncratic assumptions
[0.67 (chance) <a <0.85 (trust in medication)]. The LC
and KK scales were assumed to be psychological concepts related to adherence and to reflect effects of
psychotherapy. To estimate adherence to medication,
the Somatotherapy Index (Bauer, 2001) was used. The
best available data were used (mostly blood serum
levels) to ensure the most accurate reporting of the
maximum level of somatotherapy across medication
types (i.e. ‘ 0 ’ no or very low levels of medication ; ‘ 4 ’
indicating optimal pharmacotherapy). Cognitive testing was undertaken to ensure that intellectual functioning was sufficient, using the intelligence test
(Leistungsprüfsystem, LPS) devised by Horn (1983).
After baseline assessment (t0), participants were
randomly assigned to CBT or ST. Immediately following treatment, the post-treatment assessment (t1)
took place with raters who were blind to the treatment
conditions. Further follow-up assessments took place
every 3 months for the first year and one further
assessment after 2 years. The analysis reported here
focuses on the immediate effects of CBT on symptoms
and psychological variables comparing pre- (t0) and
post-treatment assessment (t1) and also relapse rates
for the total 33-month period.
Statistical analysis
In the original planning stage, a power analysis assuming a large effect size (with power=0.80, p<0.05)
suggested a required sample size of 2r20 patients
to detect mean differences and 2r26 for detecting
differences in x2 tests (Cohen, 1988). According to
Chambless & Hollon (1998), such a sample size should
reveal differences that are clinically meaning.
Baseline comparisons were made if appropriate
parametrically, using t tests for dimensional measures
and x2 for categorical variables. All main analyses are
presented as intent-to-treat (ITT) analyses. Using SPSS
version 17.0 (SPSS Inc., USA), treatment effects were
analysed with an ANOVA with repeated measurements including the factors time, treatment condition
and their interaction. For the analyses, exact p values
were reported up to p=0.15. The primary hypothesis
referring to survival time (in weeks) was analysed
using Kaplan–Meier curves with significance tests
based on the log rank test. The secondary hypothesis
was tested by running Cox proportional regressions to
estimate the effects of the specified covariates for the
whole sample including therapy condition : number of
prior episodes, diagnosis (coded as ‘ 1 ’ for bipolar
I and ‘ 2 ’ for bipolar II), age of onset, medication adherence (Somatotherapy Index, 0 to 4), number of
therapy sessions, and baseline overall functioning
(GAS). Skew, kurtosis and univariate outliers were
1432
T. D. Meyer and M. Hautzinger
Total sample
n = 141
n = 11 just phone contact
n = 23 baseline assessment incomplete
(e.g. in psychotherapy)
n = 107
Baseline
assessment
completed
n = 20 No bipolar disorder diagnosis
n = 1 opiate dependency
n = 1 alcohol dependency
n = 9 ‘informed consent’
withdrawn
n = 76
randomized
CBT
n = 38
ST
n = 38
Episodes during treatment:
any mood: n = 12
depressed: n = 7
(hypo)manic: n = 10
Episodes during treatment:
any mood: n = 20
depressed: n = 14
(hypo)manic: n = 8
n = 33 completers
n = 5 dropouts
n = 32 completer
n = 6 dropouts
Fig. 1. Flowchart of recruitment of patients. CBT, Cognitive behaviour therapy ; ST, supportive therapy.
checked, and the ‘ number of episodes ’ was
transformed using the natural logarithm (ln). No
transformation improved the skew of the ‘ number of
therapy sessions ’ so the original raw scores were used.
Two multivariate outliers were identified (both men in
their sixties with a co-morbid personality disorder,
one CBT/one ST), but because their inclusion did not
change the results, they were included in the analyses.
Analyses were conducted separately for any new affective episode, and also for depressive and manic episodes (including hypomanic and mixed episodes).
Results
Patient characteristics
Overall, 141 patients contacted us (Fig. 1). In some
cases the only contact was by telephone. Twenty individuals did not have a primary BD. Two patients
were excluded because they had a current substance
dependency. Nine patients withdrew their informed
consent prior to start of treatment (mainly because of
the required videotaping of the therapy sessions).
Comparing the randomized patients to the nonparticipating patients revealed no differences with
respect to gender, type of BD, lifetime diagnosis of
alcohol- or substance-related disorders, personality or
anxiety disorders (all x2 or Fisher’s exact tests p>0.10).
The same was true for age, age of onset, current
medication adherence or current level of depression
(all t <j1.15j). Patients who participated had low but
significantly higher manic ratings (BRMAS) than those
who discontinued [t(77.76)=2.73, p<0.008, d=0.41,
mean=1.68 (S.D.=3.22) v. 0.50 (S.D.=0.86)]. Despite
their higher subsyndromal manic symptoms, their
current psychosocial functioning was considered significantly higher than those who did not continue with
the study [t(90)=2.10, p<0.05, d=0.58, mean=69.59
(S.D.=12.64) v. 62.31 (S.D.=12.45)].
Fifty-three (69.7 %) out of the 76 patients were taking
at least one mood stabilizer (and in 17 cases this was
accompanied by antidepressant medication). Seven
(9.2 %) were only on antidepressant medication and 16
(21.1 %) did not take any medication at the beginning
of the study. Of the 53 receiving mood stabilizers, the
majority (51.3 %, n=39) had one, 13 (17.1 %) had a
combination of two and one individual (1.3 %) had
three mood stabilizers (lithium : n=30 ; valproate :
n=16 ; carbamazepine : n=9 ; antipsychotics : n=13).
The groups did not differ in whether they had a mood
stabilizer or antidepressant medication [all x2f1.27,
N.S. (data not shown)].
CBT versus ST for BD
1433
Table 1. Baseline characteristics of patients before treatment (t0) and recurrence rates during follow-up
Treatment condition
Cognitive
behaviour
therapy (n=38)
Supportive
therapy
(n=38)
Gender : female, n ( %)
Age (years), mean (S.D.)
Age of onset (years), mean (S.D.)
Number of episodes, median (range)
18 (47.4)
44.4 (11.0)
26.6 (9.2)
6 (1–60)
20 (52.6)
43.5 (12.7)
29.8 (12.4)
6 (1–40)
16 (42.1)
15 (39.5)
7 (18.4)
16 (41.0)
16 (41.0)
7 (17.9)
x2(2, n=76)=0.11, N.S.
30 (78.9)
8 (21.1)
30 (78.9)
8 (21.1)
x2(1, n=76)=0.00, N.S.
8 (21.1)
6 (15.8)
8 (21.1)
14 (38.9)
7 (18.4)
13.50 (9.8)
17.7 (11.0)
6.08 (4.70)
2.34 (3.69)
67.4 (12.4)
2.7 (1.5)
56.9 (7.2)
12 (31.6 %)
9 (23.7)
4 (10.5)
10 (26.3)
14 (36.18
8 (21.1)
11.03 (7.60)
19.3 (11.2)
5.55 (5.24)
1.03 (2.56)
71.8 (12.6)
2.6 (1.3)
59.6 (6.2)
20 (52.6 %)
x2(1, n=76)=0.08, N.S.
x2(1, n=76)=0.46, N.S.
x2(1, n=76)=0.29, N.S.
x2(1, n=76)=0.03, N.S.
x2(1, n=76)=0.08, N.S.
t(74)=1.29, N.S.
t(73)=0.63, N.S.
t(74)=0.46, N.S.
t(74)=1.81, N.S.
t(74)=1.55, N.S.
t(74)=0.15, N.S.
t(74)=x1.58, N.S.
x2(1, n=76)=3.46, p=0.06
19 (50)
16 (42.1)
10 (26.3)
10 (26.3)
0 (0.0)
26 (68.4)
17 (44.7)
11 (28.9)
5 (13.2)
7 (18.4)
1 (1.3)
23 (60.5)
Marital status, n ( %)
Single
Married
Divorced
Diagnosis, n ( %)
Bipolar I
Bipolar II
Co-morbid Axis I diagnosis, n ( %)
Alcohol abuse/dependency
Substance abuse/dependency
Anxiety disorders
Psychotic mood-related symptoms, n ( %)
Personality disorder, n ( %)
Beck Depression Inventory (BDI)
Self-Rating Mania Scale (SRMS)
Bech–Rafaelsen Melancholia Scale (BRMS)
Bech–Rafaelsen Mania Scale (BRMAS)
Global Assessment Scale (GAS)
Somatotherapy Indexa
Cognitive functioningb
Recurrence (9 months treatment)
Recurrence (9 months plus 24 months
follow-up), n ( %)
Major depressive episode
Any manic episodes
Hypomanic episode
Manic episode
Mixed episode
Any affective episode
Statistics
x2(1, n=76)=0.61, N.S.
t(74)=0.32, N.S.
t(74)=x1.28, N.S.
Mann–Whitney U=708.5,
Z=x0.14, N.S.
S.D.,
a
Standard deviation ; N.S., not significant.
The Somatotherapy Index is a score varying between 0 and 5 to describe the quality of prescribed and taken medication
based primarily on blood serum levels (M. Bauer et al., unpublished manuscript).
b
Cognitive functioning was assessed with an intelligence test (Leistungsprüfsystem, Horn, 1983), which provide
standardized t scores (mean=50, S.D.=10).
Table 1 displays the baseline characteristics of the
final sample. No significant baseline differences between CBT and ST were found for any of the variables,
suggesting successful randomization. Completers
were those patients who attended at least 16 out of
20 sessions. A total of 11 patients attended less than
16 sessions and were considered drop-outs (14.5 %).
Most patients (82 %) dropped out before session 10.
Dropping out was not related to treatment condition,
sex, marital status, type of BD or co-morbid substance
use or anxiety disorders (all x2 f1.81 or Fisher’s exact
test p>0.15). The same was true for age, current
symptoms of depression, number of episodes or
psychosocial functioning according to the GAS (all
t<1.58). Drop-outs were more likely to have a personality disorder diagnosis (54.5 %) than completers
(13.8 %) (Fisher’s exact test p=0.006). When excluding
drop-outs, the average number of sessions attended
was 18.53 (S.D.=1.09) for CBT and 19.28 (S.D.=1.17)
for ST.
1434
T. D. Meyer and M. Hautzinger
Table 2. Symptoms and indicators of psychosocial functioning pre- (t0) and post-intervention (t1)
Outcome
Drop-outs
Beck Depression Inventory
(BDI)
Self-Rating Mania Inventory
(SRMS)
Bech–Rafaelsen Melancholia Scale
(BRMS)
Bech–Rafaelsen Mania Scale
(BRMAS)
Global Assessment Scale
(GAS)
Medication adherence
(Somatotherapy Index)a
LC : internal
LC : external – powerful others
LC : external – chance
Trust in medication
(KK)
Trust in psychiatrist
(KK)
Negative expectations
(KK)
Feeling of guilt
(KK)
Chance
(KK)
Personal vulnerability
(KK)
Idiosyncratic assumptions
(KK)
Cognitive behaviour therapy
Supportive therapy
n ( %)
n ( %)
Mean
S.D.
5 (13.2)
t0
t1
t0
t1
t0
t1
t0
t1
t0
t1
t0
t1
t0
t1
t0
t1
t0
t1
t0
t1
t0
t1
t0
t1
t0
t1
t0
t1
t0
t1
t0
t1
37
38
38
38
37
38
38
Mean
S.D.
Statistics
7.60
4.35
11.22
10.09
5.24
4.53
2.56
1.19
12.62
16.79
1.41
1.47
5.60
5.59
5.72
5.36
7.29
7.02
4.05
4.48
2.90
2.39
3.42
3.31
2.27
2.48
3.72
3.95
2.68
2.85
3.57
3.01
x2(1, n=76)=0.11
T : F=17.81, p<0.001
TrI : F=1.86
T : F=7.07, p<0.01
TrI : F=1.05
T : F=10.26, p<0.005
TrI : F=0.06
T : F=2.14
TrI : F=0.53
T : F=8.90, p<0.01
TrI : F=0.17
T : F=0.00
TrI : F=0.03
T : F=12.68, p<0.011
TrI : F=0.17
T : F=0.13
TrI : F=0.84
T : F=10.29, p<0.01
TrI : F=0.10
T : F=0.00
TrI : F=2.63, p=0.11
T : F=0.89
TrI : F=3.55, p=0.06
T : F=4.559, p<0.05
TrI : F=0.02
T : F=0.02
TrI : F=1.56
T : F=3.23, p=0.08
TrI : F=0.74
T : F=0.35
TrI : F=0.68
T : F=4.82, p<0.05
TrI : F=0.00
6 (15.8)
13.50
10.93
17.65
15.83
6.08
4.29
2.34
1.64
67.37
73.29
2.55
2.53
26.42
28.13
24.24
24.92
20.34
18.03
13.14
13.78
9.95
10.58
7.53
6.79
4.71
5.03
7.27
6.92
6.13
6.45
6.92
6.21
9.38
9.17
10.98
11.66
4.70
5.08
3.69
3.37
12.43
14.11
1.59
1.45
7.54
5.15
5.34
4.88
7.74
7.10
3.77
4.10
2.78
3.22
4.17
3.43
3.04
2.40
3.53
3.70
3.21
3.06
3.66
4.02
38
38
38
38
38
38
37
11.03
6.00
19.27
15.18
5.55
3.47
1.03
0.79
71.82
76.32
2.50
2.53
26.24
28.41
25.59
25.30
22.66
20.76
13.21
12.61
10.05
9.84
8.00
7.36
5.34
4.95
8.63
7.63
6.11
6.05
8.30
7.62
KK, Krankheitskonzeptskala (Disease Concept Scale) ; LC, Locus of Control ; S.D., standard deviation ; T, F value for main effect
of time ; I, F value for main effect of treatment condition ; IrT, F value for the interaction term of time and treatment condition.
a
The Somatotherapy Index is a score varying between 0 and 5 to describe the quality of prescribed and taken medication
based primarily on blood serum levels (M. Bauer et al., unpublished manuscript).
Primary outcomes : post-treatment effects and
relapse rates
Post-treatment effects
Descriptive data for baseline and post-treatment
symptoms and indicators for psychosocial functioning
are presented in Table 2. This table shows that symptoms of depression decreased significantly over time,
but there was no significant timertreatment interactions for self-ratings or observer ratings. Self-rated but
not clinician-rated manic symptoms decreased significantly over time. Psychosocial functioning (GAS)
improved, but this was not specific to either treatment
condition. Using the Somatotherapy Index to quantify
current medication adherence based on blood levels of
different medications, there was no evidence for any
change.
Internal LC increased significantly over time and
external LC (chance) decreased but no significant
timertreatment interaction was observed. External
LC (powerful others) did not change over time. Some
of the illness-related cognitions (e.g. negative expectations, idiosyncratic assumptions) changed over time
in the expected direction, but no significant effect
CBT versus ST for BD
1435
was found favouring CBT. There was only a nonsignificant trend for CBT-treated patients to trust their
clinicians more after therapy.
decrease in risk for a recurrence compared to bipolar II
patients. Examination of the logarithm of the number
of episodes for each increase of one point increased
the risk for relapse by 7 %. However, risk for relapse
decreased by 10 % with each therapy session.
Analysis of survival time until first depressive episode indicates that again the covariates contributed
significantly to the prediction [log likelihood x2(df=
7)=20.68, p<0.005, R2=0.24], with bipolar I versus II
and the number of therapy sessions being significant
predictors. More therapy sessions were again associated with longer time until a depressive episode,
and bipolar II was associated with increased risk for
a depressive relapse. A different picture emerged
for manic-like episodes. Although the number of prior
episodes emerged as a significant predictor of shortened survival time, overall the set of covariates did
not significantly predict survival time [log likelihood
x2(df=7)=8.11, N.S., R2=0.10 (Table 3)].
Relapse rates
Discussion
Overall, 64.5 % (n=49) of the patients had at least one
recurrence within the 33 study months (see Table 1).
On average, the first recurrence occurred 67.53 (S.E.=
9.21) weeks after treatment had started for the CBT
group and 66.25 (S.E.=10.58) weeks for the ST group.
Kaplan–Meier analyses revealed that survival times
until first recurrence of any affective episode did not
differ significantly between therapy conditions [log
rank (Mantel–Cox) x2=0.004, N.S. (Fig. 2)]. With regard
to first depressive recurrence, the mean survival times
were 86.05 (S.E.=9.75) and 88.86 (S.E.=11.15) weeks
for CBT and ST respectively (log rank x2=0.02, N.S.).
The corresponding survival times for any hypomanic,
manic or mixed episode were 95.85 (S.E.=10.05)
and 113.60 (S.E.=0.97) weeks, again revealing no significant difference in survival time (log rank x2=1.33,
N.S.).
Several reviews have concluded that, overall, studies
have shown that adjunctive psychotherapy has
beneficial effects for patients with BD (e.g. Beynon
et al. 2009 ; Miklowitz & Scott, 2009 ; Szentagotai &
David, 2010). However, at least when focusing on the
studies evaluating CBT, it is only justified to conclude
that adjunctive CBT is mostly more effective than
TAU, waiting for treatment or a brief psychoeducation. We therefore addressed the question of
whether CBT shows any evidence for post-treatment
benefits and relapse prevention that go beyond those
of an ST equal in number and duration of sessions and
including information and a mood diary.
Disregarding any trends, the general picture is that
the changes observed over time in both CBT and ST in
subsyndromal symptoms and cognitive factors such
as LC were the same, but that the treatments did not
differ on post-treatment outcome. The same was true
for rates of recurrence and time to recurrence. Partially
in line with prior studies (e.g. Scott et al. 2006 ;
Zaretsky et al. 2008), higher risk for any recurrence was
predicted by a greater number of prior episodes, a
lower number of therapy sessions and bipolar II disorder. The pattern for depressive and manic recurrence was different but it is not clear whether this is
due to low power for distinct episodes or evidence for
polarity-specific predictors (e.g. Johnson & Meyer,
2004).
Our results contrast with other studies that have
shown that psychosocial treatments significantly reduced relapse rates (e.g. Lam et al. 2003 ; Miklowitz
et al. 2003). However, most studies either used
a waiting list control group, TAU or fewer sessions
Cumulative proportion without
any episode
1.00
CBT (n = 38)
ST (n = 38)
.80
.60
.40
.20
.00
0
20
40
60
80
100
120
140
160
Time untill first recurrence (in weeks)
Fig. 2. Cumulative survival functions with regard to
recurrence of any affective episode for cognitive behaviour
therapy (CBT) and supportive therapy (ST).
Secondary outcomes : predictors of survival time
Proportionality of hazards was tested and was given
for all but ‘ number of prior episodes (ln) ’ so that
its interaction with time was included in the analysis.
The results of the Cox regression model are displayed
in Table 3. Confirming the prior analysis, there was
no statistically significant effect of therapy condition
after adjusting for the seven covariates [x2 log likelihood x2(df=1)=0.11, p=0.75, R2=0.001]. Survival
time till any mood episode was, however, predicted
by the set of covariates [log likelihood x2(df=7)=
20.12, p<0.005, R2=0.23], with three predictors being
significant and not including 1.00 in the confidence
interval. Patients with bipolar I disorder had a 60 %
1436
T. D. Meyer and M. Hautzinger
Table 3. Predictors in the Cox regression models for recurrence of depression, mania and any affective episode
Variables
Any affective episode
Diagnosis
Medication adherence
Age of onset
Psychosocial functioning (GAS t0)
Number of episodes
Number of episodesrtime
Number of therapy sessions
Treatment condition
Recurrence of depression
Diagnosis
Medication adherence
Age of onset
Psychosocial functioning (GAS t0)
Number of episodes
Number of episodesrtime
Number of therapy sessions
Treatment condition
Recurrence of mania
Diagnosis
Medication adherence
Age of onset
Psychosocial functioning (GAS t0)
Number of episodes
Number of episodesrtime
Number of therapy sessions
Treatment condition
B (S.E.)
Wald
OR
95 % CI
x0.91 (0.37)
0.04 (0.11)
0.20 (0.01)
x0.01 (0.01)
0.57 (0.25)
x0.16 (0.01)
x0.11 (0.04)
0.10 (0.30)
6.07**
0.00
2.13
0.39
5.27**
6.77***
6.45**
0.11
0.40
1.00
1.02
0.99
1.77
0.98
0.90
1.10
0.20–0.83
0.81–1.25
0.99–1.05
0.97–1.02
1.09–2.87
0.97–1.00
0.83–0.98
0.61–1.96
x1.05 (0.41)
x0.07 (0.12)
0.03 (0.02)
x0.02 (0.02)
0.47 (0.29)
x0.02 (0.01)
x0.11 (0.05)
x0.01 (0.01)
6.65***
0.30
3.81*
1.16
2.70
4.70**
4.95**
0.00
0.35
0.94
1.03
0.98
1.60
0.98
0.90
0.99
0.16–0.78
0.73–1.19
1.00–1.06
0.96–1.01
0.91–2.81
0.07–1.00
0.81–0.98
0.97–1.00
x0.60 (0.48)
x0.06 (0.15)
x0.02 (0.02)
0.00 (0.02)
0.71 (0.32)
x0.01 (0.01)
x0.07 (0.08)
0.51 (0.40)
1.57
0.19
0.82
0.03
4.95**
2.36
0.96
1.62
0.55
0.94
0.98
1.00
2.04
0.99
0.93
1.66
0.21–1.40
0.71–1.25
0.95–1.02
0.97–1.04
1.09–3.81
0.98–1.00
0.80–1.08
0.98–1.00
GAS, Global Assessment Scale ; S.E., standard error ; OR, odds ratio ; CI, confidence interval.
Diagnosis coded ‘ 1 ’ as bipolar I and ‘ 2 ’ as bipolar II. Number of prior episodes were logarithmically transformed (ln).
Medication adherence was scored according to the Somatotherapy Index : 0=no medication and 4=optimal level of medication.
Treatment condition coded ‘ 0 ’=supportive therapy (ST), ‘ 1 ’=cognitive behaviour therapy (CBT).
* p<0.10, ** p<0.05, *** p<0.01.
(e.g. Zaretsky et al. 2008). As Colom et al. (2003) used
an unstructured group setting as a control condition,
their study and ours are not directly comparable ; they
focused on group treatment whereas we had an individual therapy setting. Furthermore, our ST included
information and daily mood monitoring. Most closely
resembling our ST condition is the ‘ intensive clinical
management ’ used by Frank et al. (2005) as a control
group in their RCT evaluating interpersonal and social
rhythm therapy (IPSRT). Initial analyses revealed that
it is not the specific kind of treatment per se but the
continuity of the treatment condition from the acute to
the maintenance phase that was beneficial (Frank et al.
1999).
What do our results imply ? Time effects do not
necessarily reflect treatment effects because other factors could also contribute to or account for those
changes. Non-significant differences in relapse rates
can indicate either a lack of efficacy for both CBT and
ST or equal effectiveness. The pattern of results
(decreases in depression, increases in psychosocial
functioning, no changes in medication adherence,
specific changes in LC) does resemble other studies
(e.g. Scott et al. 2001 ; Lam et al. 2003). Very few other
studies have included such a long follow-up of 2 years
in addition to the treatment period, but the overall
relapse rate of 64.5 % for 33 months is still within
the range of relapse rates reported by some others
(e.g. Colom et al. 2003 : 66.7 % v. 91.7 % ; Lam et al. 2005 :
63.8 % v. 84 %). We therefore conclude that the observed effects are unlikely in the absence of any treatment added to medication.
The question remains : why did CBT and ST lead to
these comparable outcomes ? First, information was
incorporated in both conditions and is generally considered essential in all psychosocial treatments for BD
(Scott et al. 2007 ; Miklowitz & Scott, 2009). Second,
the mood diary was originally used to increase the
CBT versus ST for BD
credibility of our ‘ control condition ’ and to disguise
the outcome of the randomization process. However,
we consider that the self-monitoring proved to be
central for many patients and triggered in many
patients self-management and self-regulation processes regardless of the treatment condition.
Before drawing any final conclusions, some limitations should be considered. First, the sample size
might be considered small. Although we acknowledge
that this study is smaller than others (e.g. Lam et al.
2003, 2005 ; Scott et al. 2006), the sample was larger
than needed according to our original power analysis.
Additionally, the effect size of R2=0.001 for treatment
effects with regard to recurrences implies that only an
enormous sample would potentially find any evidence
for differential effects or moderators for CBT versus ST.
Second, we did not formally assess adherence to the
treatment manuals. We cannot totally rule out that this
could have affected the results, but the training and
especially the weekly video-based supervision were
aimed at reducing risk of deviating from the manuals.
Third, a potential bias in participation and drop-out
was observed, which affects generalizability of the
results but this is not surprising (e.g. Shea et al. 1990 ;
McFarland & Klein, 2005). However, we were less restrictive in our inclusion criteria than other studies
trying to increase external validity.
In summary, our study adds to the complex picture
that CBT might work better when there is nothing
else in place (e.g. waiting, TAU), but we did not find
much evidence for specific effects of CBT for BD.
Given that there are several psychological approaches
for BD, future research should focus on the question
of matching patients to treatments. Furthermore, with
regard to depression, different treatments have been
developed so that treatment options now differ for
acute depression, chronic depression and recurrent
depression (e.g. McCullough, 2000 ; Segal et al. 2002 ;
Barton et al. 2008). A similar approach might be needed
for improving outcomes in patients with bipolar I or II
disorder or those with different co-morbidities.
Acknowledgements
This research was supported by a grant provided by
the Deutsche Forschungsgemeinschaft (DFG ME
1681/6-1 to 6-3). We are indebted to all the therapists
and independent raters, especially Drs P. Peukert and
K. Salkow, and also the research assistants for all their
work, support and help. We also especially thank
Professor J. Scott (Newcastle University) who provided very helpful and highly valued comments on an
earlier draft of this paper with regard to the analyses,
and Dr J. Rogers (Newcastle University) for final
editing and proofreading.
1437
Declaration of Interest
None.
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