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- Material and methods
A number of psychotherapies have been demonstrated to be effective adjunctive treatments in the management of bipolar disorder . Cognitive-behavioral therapy (CBT) is associated with fewer hospitalizations , longer time to depressive relapse , and fewer and shorter manic and depressive episodes . Interpersonal and Social Rhythm Therapy (IPSRT) is effective in improving occupational functioning , family therapy has been associated with longer time to relapse , while group-based psycho-education programs have also shown reduced rates of relapse over a 12-month follow-up period . Chronic care model programs, combining a range of psychological techniques along with structured follow-up, have also noted reduced mania symptoms at 2-year follow-up .
Despite this, some mixed results have been noted. Scott et al.  reported no significant difference in either postintervention relapse rates or symptom severity in a large trial of CBT compared with treatment as usual (TAU). However, a post hoc analysis demonstrated that CBT was more effective than TAU for those with <12 prior bipolar disorder episodes . Those with bipolar disorder have also been found to show less dysfunctional attitudes following CBT enhanced with emotive techniques , suggesting potential schematic changes from such psychological treatments.
Mindfulness-based approaches are a recent addition to the range of psychological therapies used to treat psychiatric conditions. Mindfulness has been described as ‘paying attention in a particular way: on purpose, in the present moment and non-judgmentally’  with therapies incorporating mindfulness including a range of techniques designed to train participants to cultivate a ‘mindful’ approach. These techniques include mindfulness meditation or more explicit instruction on how to relate to thoughts, emotions, and bodily sensations with mindful awareness.
Mindfulness-based Cognitive Therapy (MBCT) is an 8-week group therapy program developed to prevent depressive relapse in participants with a history of Major Depressive Disorder (MDD) . It is based on the Mindfulness-based Stress Reduction (MBSR) program  and is combined with cognitive therapy techniques including psycho-education on depression and relapse prevention strategies. MBCT has been found to be effective in preventing relapse to depression in MDD for those with three or more past episodes [13-16], in reducing current depressive symptoms [17, 18] and lowering comorbid anxiety .
Given the results at reducing depression and comorbid anxiety, a handful of provisional studies have examined MBCT in the treatment for bipolar disorder with mixed results. In a pilot study, Williams et al.  randomly allocated a mixed group of those with a history of unipolar depression (n = 14) and those with bipolar disorder in remission (n = 7) to either MBCT or a wait-list control condition. They reported that levels of depression decreased for all participants allocated to MBCT from baseline to post-treatment, and those with bipolar disorder returned lower anxiety scores compared with those allocated to the wait-list control condition .
Further study of bipolar disorder participants (n = 22) undertaken by Miklowitz et al.  reported improvements in depression from pre- to post-treatment with MBCT . However, a later study of MBCT for bipolar disorder (n = 15) reported no significant differences between pre- and post-treatment mania and depression scores . Another study examining the effects at 3-month follow-up noted improvements in depression symptoms, psychological wellbeing, and psychosocial functioning .
Despite these results, no studies have examined the effects of MBCT in a randomized controlled trial design over a longer follow-up period. The present study aimed to compare MBCT plus TAU to TAU alone in a randomized controlled trial of participants with bipolar disorder over a 12-month follow-up period. Given that MBCT has been reported to prevent depressive recurrences in those with major depressive disorder [13-15], we hypothesized that MBCT would reduce time to relapse and the number of depressive episodes in participants with bipolar disorder. It was also hypothesized that bipolar disorder participants allocated to MBCT would demonstrate lower depression scores over a 12-month follow-up period post-treatment.
Those with bipolar disorder have also been found to show less dysfunctional attitudes following CBT enhanced with emotive techniques , suggesting potential schematic changes from such psychological treatments.
Furthermore, as MBCT has been reported to reduce comorbid anxiety in major depressive disorder and bipolar disorder [19, 20], and given that anxiety may worsen the course of bipolar disorder [24, 25], a further aim of this trial was to investigate the effect of MBCT on comorbid anxiety in bipolar disorder, both in terms of categorically defined anxiety disorders and dimensional measures of anxiety. It was hypothesized that those allocated to MBCT plus TAU would report lower anxiety symptoms compared with TAU alone and that there would be corresponding changes in other outcome measures such as dysfunctional attitudes and response styles over a 12-month follow-up period.
Given the post hoc findings of Scott et al.  that CBT was more effective for those with fewer than 12 prior episodes, this study also examined for such differences in treatment outcome, hypothesizing that MBCT would be more effective than TAU alone for those with <12, compared with those with 12 or more prior episodes over a 12-month follow-up period.
In addition, given that psychotherapies such as CBT have been found in prior research to change cognitive styles such as by reducing dysfunctional attitudes , this study also aimed to examine any treatment effects on measures of response styles and dysfunctional attitudes. It was hypothesized that those allocated to MBCT plus TAU would show lower scores on these measures compared with those allocated to TAU alone.
Aims of the study
This study aims to compare mindfulness-based cognitive therapy to treatment as usual as an adjunctive treatment for bipolar disorder. It was hypothesized that those allocated to mindfulness-based cognitive therapy would return lower depression scores and experience fewer depressive episodes over the 12-month follow-up period than those allocated to treatment as usual. It was further hypothesized that there would be corresponding decreases in anxiety and dysfunctional attitudes as a result of mindfulness-based cognitive therapy treatment.
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- Material and methods
Of the 266 participants who were screened for the trial, 95 were eligible for inclusion. Forty-eight were randomized to MBCT and 47 to TAU. Figure 1 illustrates the flow of participants into the study. Reasons were noted when they were given by participants, such as dissatisfaction with treatment; however, some participants were not able to be contacted and were classified as declining to participate.
Fourteen participants (29%) (including 10 drop outs; see Fig. 1) did not complete the MBCT condition requirements, and 22 (47%) (including 18 drop outs; see Fig. 1) did not complete TAU requirements. Completers were defined as those who had completed both the post-treatment interview, and questionnaire assessments, and for those allocated to MBCT, had participated in a minimum of four group therapy sessions. There was a trend for those allocated to TAU to show higher drop-out and non-completion rates than those allocated to MBCT (χ2 = 3.14, P = 0.076). Participants allocated to the MBCT condition completed a mean number of seventreatment sessions (SD = 0.94; range: 4–8).
Nine participants in the MBCT condition and 11 in TAU had a change in medication initiated by their own physician during the 8-week trial. Changes were defined as any changes in dose, class, or type of medication that the participant indicated. One person in the MBCT condition did not provide information about medication use. There was no significant difference between the conditions on changes in medication during the trial period (χ2 = 1.575, P = 0.209).
Further demographic and clinical characteristics of the sample by treatment condition are described in Table 1. Using chi-square analyses, there were no significant differences between the conditions on any demographic variables. An anova found no significant difference between the conditions at baseline on the YMRS, MADRS, DASS subscales (depression, anxiety and stress), STAI (state/trait anxiety) subscales, RSQ subscales, DAS subscales, or MAAS (see Table 2).
Table 1. Demographic and clinical characteristics of the intention-to-treat sample at baseline
|N (%)||N (%)|
|Male||17 (35)||16 (34)|
|Female||31 (65)||31 (66)|
|Married||13 (29)||12 (26)|
|Never married||21 (47)||27 (57)|
|Separated/Divorced/Widowed||11 (24)||7 (15)|
|Country of birth|
|Australia||33 (70)||35 (74)|
|Other||14 (30)||12 (26)|
|Some secondary||3 (6)||4 (9)|
|Completed secondary||9 (19)||5 (11)|
|Vocational qualification||18 (38)||16 (34)|
|Bachelor degree or higher||16 (33)||19 (40)|
|Other||2 (4)||3 (6)|
|Full time||21 (45)||22 (47)|
|Part time||12 (26)||3 (6)|
|Casual||3 (6)||4 (9)|
|Unpaid||1 (2)||1 (2)|
|Unemployed/Retired||10 (21)||17 (36)|
|Illicit drug use|
|Past use||17 (35)||19 (40)|
|Current||7 (15)||4 (9)|
|No history of drug use||24 (50)||24 (53)|
|Lithium||13 (27)||18 (39)|
|Sodium Valproate||18 (38)||14 (31)|
|Lamotrigine||5 (10)||2 (4)|
|Other||9 (19)||11 (24)|
|Not stated||1 (2)||1 (2)|
|Not on medication||2 (4)||0 (0)|
|Number of previous episodes|
|1–11 episodes||18 (37)||20 (42)|
|12 or more||20 (42)||21 (45)|
|Unknown||10 (21)||6 (13)|
|Number of previous hospitalizations|
|None||14 (29)||16 (34)|
|1–3||21 (44)||20 (43)|
|4 or more||10 (21)||9 (19)|
|Unknown/not reported||3 (6)||2 (4)|
|Lifetime bipolar disorder diagnosis|
|Bipolar I||27 (56)||32 (68)|
|Bipolar II||21 (44)||14 (30)|
|Bipolar NOS||0 (0)||1 (2)|
|Any anxiety disorder||33 (69)||36 (77)|
|Panic disorder||18 (38)||15 (32)|
|Agoraphobia without panic||3 (6)||5 (10)|
|Social phobia||15 (31)||18 (38)|
|Generalized anxiety disorder||13 (27)||14 (30)|
|Specific phobia||18 (38)||23 (49)|
Table 2. Mean scores of outcome measures – intention-to-treat sample
| ||Baseline||Mid-treatment||Post-treatment||3-month follow-up||6-month follow-up||9-month follow-up||12-month follow-up|
|M (SD)||M (SD)||M (SD)||M (SD)||M (SD)||M (SD)||M (SD)||M (SD)||M (SD)||M (SD)||M (SD)||M (SD)||M (SD)||M (SD)|
|MADRS||11.71 (8.24)||14.57 (10.91)||9.81 (9.21)||12.74 (10.86)||7.14 (7.31)||11.07 (9.26)||4.58 (7.36)||11.61 (11.64)||6.67 (7.05)||6.33 (5.15)||8.60 (10.40)||10.55 (14.29)||9.60 (10.55)||8.00 (5.94)|
|YMRS||4.98 (4.49)||5.47 (4.36)||3.92 (4.16)||5.83 (5.57)||3.97 (4.57)||4.44 (4.38)||4.31 (5.47)||2.78 (2.58)||3.71 (3.65)||5.00 (5.66)||4.15 (6.55)||2.45 (2.46)||3.60 (4.13)||3.31 (5.39)|
|DASS – Depression||14.79 (12.11)||19.50 (14.16)||8.89 (8.12)||17.97 (13.73)||10.03 (9.49)||13.48 (11.26)||9.23 (8.81)||15.57 (13.70)||9.81 (7.86)||13.20 (12.20)||13.08 (12.91)||15.19 (14.30)||13.68 (11.94)||15.73 (14.65)|
|DASS – Anxiety||11.92 (10.39)||12.91 (11.18)||7.78 (6.08)||10.33 (9.83)||7.11 (6.30||7.74 (9.03)||6.68 (7.16)||9.48 (10.17)||5.81 (6.82)||6.80 (9.23)||8.62 (9.22)||9.10 (9.34)||9.73 (9.50)||5.40 (9.12)|
|DASS – Stress||21.13 (14.74)||22.35 (15.67)||15.05 (10.67)||19.07 (9.14)||15.14 (11.69)||16.30 (10.23)||12.00 (9.74)||17.48 (10.31)||11.38 (8.13)||13.27 (10.16)||13.54 (10.35)||14.38 (11.64)||15.36 (12.28)||13.80 (12.11)|
|STAI – State Anxiety||47.06 (16.42)||48.57 (13.87)||43.00 (13.22)||50.10 (11.55)||40.65 (13.21)||44.19 (12.50)||38.10 (12.82)||46.26 (15.17)||39.69 (11.64)||43.27 (16.04)||44.50 (16.51)||42.76 (11.70)||39.45 (14.03)||42.80 (7.64)|
|STAI – Trait Anxiety||51.72 (14.23)||54.59 (13.03)||48.24 (13.95)||52.43 (12.72)||45.57 (13.57)||51.07 (12.72)||43.97 (14.11)||49.96 (16.04)||44.12 (11.67)||47.47 (14.77)||49.19 (15.22)||46.90 (11.63)||47.82 (13.02)||49.73 (13.68)|
|RSQ – Rumination||32.94 (12.86)||39.38 (12.02)|| || ||33.93 (14.70)||34.95 (13.96)||33.93 (14.70)||34.95 (13.96)||29.56 (14.00)||35.86 (13.74)||32.31 (13.58)||31.57 (10.44)||30.64 (14.61)||34.80 (10.73)|
|RSQ – Adaptive||14.48 (7.82)||14.49 (7.10)|| || ||17.94 (7.98)||15.70 (5.62)||17.86 (7.31)||15.59 (6.91)||18.52 (7.74)||17.43 (7.65)||16.73 (6.00)||17.62 (7.02)||17.09 (6.13)||14.73 (6.85)|
|RSQ – Dangerous||3.09 (3.47)||5.13 (4.58)|| || ||3.03 (3.97)||4.48 (5.05)||2.89 (2.83)||2.86 (4.24)||3.17 (3.93)||2.71 (4.86)||2.88 (3.90)||2.76 (3.59)||2.59 (3.69)||1.40 (1.88)|
|DAS-24 – Goal Attainment||27.17 (7.18)||26.81 (7.60)|| || ||22.44 (7.53)||23.41 (8.12)||23.13 (6.80)||24.95 (8.40)||22.04 (8.54)||21.90 (9.15)||21.27 (8.15)||18.40 (7.54)||22.55 (9.83)||19.67 (10.45)|
|DAS-24 – Dependency||17.88 (5.20)||17.74 (5.51)|| || ||14.44 (5.18)||17.67 (5.84)||15.06 (4.85)||17.55 (6.05)||14.73 (4.84)||15.87 (5.76)||15.54 (5.04)||16.62 (6.58)||15.14 (5.92)||16.73 (7.16)|
|DAS-24 – Achievement||22.63 (5.78)||22.30 (6.99)|| || ||19.36 (7.18)||20.74 (5.30)||18.06 (6.48)||21.68 (6.46)||17.58 (7.58)||17.60 (6.16)||19.04 (6.72)||19.76 (7.22)||18.86 (7.22)||18.33 (6.44)|
|MAAS||3.32 (0.93)||3.30 (0.98)|| || ||3.87 (0.90)||3.49 (1.29)||3.95 (0.86)||3.45 (1.05)||3.88 (0.95)||3.65 (1.05)||3.78 (1.08)||3.52 (1.12)||3.82 (0.86)||3.61 (1.35)|
Thirty-two participants completed the 12-month follow-up interview assessments of the CIDI (MBCT N = 22; TAU N = 12) with 10 (46%) participants allocated to the MBCT condition and 4 (33%) participants in the TAU condition met diagnostic criteria for an anxiety disorder. Chi-square analysis found no significant difference between the conditions on whether or not the participant met criteria for a 12-month anxiety disorder diagnosis (χ2 = 0.083, P = 0.773).
Primary outcome measures: recurrence rates
Survival curves and recurrence rates were analyzed using the Cox proportion hazard regressions model to examine the time (weeks) to 12-month recurrence for hypo/manic (Fig. 2) and depressive episodes (Fig. 3). Data were utilized from 12-month interview assessments (MBCT N = 22; TAU N = 12) and self-reports at post-treatment, 3, 6, 9, and 12-month assessments (MBCT N = 12; TAU N = 17). Those who reported discontinuation from the trial due to symptoms (MBCT N = 3; TAU = 3) or significant clinical symptoms on the YMRS and MADRS at baseline (MBCT N = 4; TAU = 5) were included in the analysis. Last observation data at baseline was used for the remaining participants (MBCT = 7; TAU = 10).
Figure 2. Proportion of participants who survived without relapse to hypo/mania over 12 months by treatment condition.
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Figure 3. Proportion of participants who survived without relapse to depression over 12 months by treatment condition.
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Nineteen (59%) participants in the MBCT condition and 10 (48%) in the TAU reported a hypo/manic episode, while 20 (59%) in the MBCT condition and 17 (68%) in TAU reported a depressive episode over the 12-month follow-up period. Median time to hypo/mania relapse was 130 days for MBCT and 143 days for TAU. Median time to relapse for depression was 53 days for MBCT and 46 days for TAU.
There was no significant difference between the conditions on risk for recurrence or time to hypo/manic (hazard ratio = 1.813; 95% confidence interval 0.782–3.622; χ2 = 1.813, P = 0.183) or depressive (hazard ratio = 0.974; 95% confidence interval 0.509–1.864; χ2 = 0.006, P = 0.936) relapse.
Primary outcome measures: symptom severity scores
A MLM analysis was conducted on the MADRS and YMRS. Fixed effects added to the model were treatment condition, whether or not criteria were met for an anxiety disorder, and number of prior episodes (1–11 or 12 or more). There was no significant treatment by time interaction, nor treatment by time by number of prior episodes interaction for either MADRS or YMRS scores. Mean scores per condition are reported in Table 2.
Secondary outcome measures
A MLM analysis was conducted on the secondary outcome measures of the DASS subscales (depression, anxiety, and stress) and the STAI subscales (state and trait anxiety). Fixed effects added into the model were treatment condition, whether or not participants met DSM-IV criteria for an anxiety disorder and number of prior bipolar episodes.
For the DASS stress subscale, a trend was noted for a significant treatment by time interaction (F = 1.864, P = 0.088). The interaction of treatment by time by number of prior episodes interaction was not significant. No significant interactions were found for the DASS depression or anxiety subscales.
There was a significant treatment by time interaction for the STAI-state anxiety subscale (F = 2.158, P = 0.048) and a trend for the STAI-trait anxiety subscale (F = 1.944, P = 0.075). No treatment by time by number of prior episodes interaction was found. Mean scores for each condition are reported in Table 2.
A MLM analysis was conducted on the RSQ – Rumination, Dangerous Activities and Adaptive Functioning subscales, the DAS-24 – Dependency, Goal Attainment, and Achievement subscales and the MAAS. Fixed effects added into the model were treatment condition, whether or not participants met DSM-IV criteria for an anxiety disorder and number of prior bipolar episodes. A trend was found for the treatment by time interaction for the DAS-24 – dependency subscale (F = 2.186, P = 0.058). The DAS-24 – achievement subscale – demonstrated a significant treatment by time interaction (F = 2.534, P = 0.03) with a significant quadratic interaction being noted (t = 2.077, P = 0.039). The RSQ – rumination subscale – demonstrated a small trend for the treatment by time interaction (F = 1.894, P = 0.098). No other significant results were found (see Table 2).
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- Material and methods
In contrast to the findings of Teasdale et al.  on major depressive disorder, MBCT does not appear to offer a protective benefit in terms of delaying time to recurrence of an episode of depression or hypo/mania for those with bipolar disorder. There was also no significant treatment by time interaction for depressive or hypo/manic scores over the 12-month period, consistent with the findings of Weber et al. . This may not be surprising, given that some trials examining psychological interventions such as CBT have also found that the intervention did not reduce relapse to depression or hypo/mania in comparison to a TAU condition .
Those in the MBCT condition returned significantly lower scores on state anxiety than TAU, with similar trends also noted for trait anxiety – a finding that was consistent with that of Williams et al. . There was also a trend for self-reported stress scores to be lower in the MBCT condition than in TAU. These findings suggest that MBCT may offer some assistance in managing anxiety for those with bipolar disorder and in particular for managing state anxiety.
Although Scott et al.  reported that those with <12 prior bipolar episodes experienced reduced episode recurrence compared with those with 12 or more episodes, we did not replicate those results in this study. The number of prior episodes was also not associated with reductions in symptom severity measures.
Participants in the MBCT condition returned significantly lower scores on the Achievement subscale of the DAS over the 12-month follow-up period. The Achievement subscale assesses high personal standards of achievement, and it is possible that MBCT may address this through the non-judgmental nature of mindfulness practice and its emphasis on not striving to achieve a particular outcome. There was also a trend for lower scores on the Dependency subscale of the DAS in the MBCT condition. Lower scores on this measure indicate less reliance on others to achieve personal happiness. The emphasis on personal autonomy in mindfulness practice and the solitary nature of mindfulness meditation practice may reduce beliefs about personal happiness being dependent on others.
Rumination scores also showed a trend for an interaction of treatment by time, with MBCT participants returning lower scores than the TAU participants. However, as decreases in depression were not observed, and results were only at trend level, further research is required.
The small sample size and the drop-out rate at 12-month follow-up were high, with 22 participants allocated to MBCT and 12 allocated to TAU completing interview assessments. However, this study also utilized data that were obtained at other time points (3-, 6-, 9-month follow-up) for the survival analyses, and the additional use of a RCT design provides some confidence that these findings are robust. Other studies examining the protective benefits of MBCT in preventing relapse to depression in participants with major depressive disorder have assessed participants over an 18-month follow-up period , while this study utilized a 12-month follow-up period. It could be argued that a longer follow-up period is also required to best assess the outcome of MBCT in bipolar disorder. The group sizes in this study were also smaller than those in previously published studies of MBCT, which may also have influenced the result. Changes in medications that occurred throughout the trial may also have impacted on results, while self-reported episodes may also be not as reliable as other forms of measurement.
To conclude this is the first reported definitive RCT of MBCT in bipolar disorder. MBCT did not reduce time to recurrence of depressive or hypo/manic episodes over a 12-month follow-up period, nor was it associated with a reduction in mood symptom severity scores. However, MBCT was associated with a reduction in state and trait anxiety and levels of stress, indicating benefits to bipolar disorder patients with comorbid anxiety.
The project has been funded by National Health and Medical Research Council of Australia (NHMRC Program Grant 222708 and Program Grant 510135) and Rotary Australia.
Declaration of interest
Over the past 5 years, PM has received remuneration from AstraZeneca, Eli Lilly, Janssen-Cilag, and Lundbeck for lecture honoraria, consultancies, medico-legal reports, or advisory board membership. He has not been a member of an industry advisory board since late 2007 and has not accepted remuneration from industry since early 2009. The authors have no other conflicts of interest to declare.