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Original Investigation | Meta-analysis

Efficacy of Mindfulness-Based Cognitive Therapy in Prevention of Depressive Relapse An Individual Patient Data Meta-analysis From Randomized Trials

Willem Kuyken, PhD1; Fiona C. Warren, PhD2; Rod S. Taylor, PhD2; Ben Whalley, PhD3; Catherine Crane, PhD1; Guido Bondolfi, MD, PhD4; Rachel Hayes, PhD5; Marloes Huijbers, MSc6; Helen Ma, PhD1,7; Susanne Schweizer, PhD8; Zindel Segal, PhD9; Anne Speckens, MD6; John D. Teasdale, PhD8; Kees Van Heeringen, PhD10; Mark Williams, PhD1; Sarah Byford, PhD11; Richard Byng, PhD12; Tim Dalgleish, PhD7,8,13
[+] Author Affiliations
1Department of Psychiatry, University of Oxford, Prince of Wales International Centre, Warneford Hospital, Oxford, England
2Institute of Health Research, Primary Care Research Group, Exeter Medical School, Exeter, England
3School of Psychology, Faculty of Health and Human Sciences, University of Plymouth, Plymouth, England
4Department of Psychiatry, University Medical Centre, University of Geneva, Geneva, Switzerland
5Institute of Health Research, Child Health Group, Exeter Medical School, Exeter, England
6Department of Psychiatry, Radboud University Nijmegen Medical Centre, Radboud University Nijmegen, Nijmegen, The Netherlands
7Hong Kong Centre for Mindfulness, Hong Kong
8Medical Research Council Cognition and Brain Sciences Unit, Cambridge, England
9Department of Psychology, University of Toronto Scarborough, Toronto, Ontario, Canada
10University Department of Psychiatry, University Hospital, Gent, Belgium
11King’s Health Economics, King’s College London, London, England
12Peninsula School of Medicine, Plymouth University, Plymouth, England
13Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, England
JAMA Psychiatry. 2016;73(6):565-574. doi:10.1001/jamapsychiatry.2016.0076.
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Importance  Relapse prevention in recurrent depression is a significant public health problem, and antidepressants are the current first-line treatment approach. Identifying an equally efficacious nonpharmacological intervention would be an important development.

Objective  To conduct a meta-analysis on individual patient data to examine the efficacy of mindfulness-based cognitive therapy (MBCT) compared with usual care and other active treatments, including antidepressants, in treating those with recurrent depression.

Data Sources  English-language studies published or accepted for publication in peer-reviewed journals identified from EMBASE, PubMed/Medline, PsycINFO, Web of Science, Scopus, and the Cochrane Controlled Trials Register from the first available year to November 22, 2014. Searches were conducted from November 2010 to November 2014.

Study Selection  Randomized trials of manualized MBCT for relapse prevention in recurrent depression in full or partial remission that compared MBCT with at least 1 non-MBCT treatment, including usual care.

Data Extraction and Synthesis  This was an update to a previous meta-analysis. We screened 2555 new records after removing duplicates. Abstracts were screened for full-text extraction (S.S.) and checked by another researcher (T.D.). There were no disagreements. Of the original 2555 studies, 766 were evaluated against full study inclusion criteria, and we acquired full text for 8. Of these, 4 studies were excluded, and the remaining 4 were combined with the 6 studies identified from the previous meta-analysis, yielding 10 studies for qualitative synthesis. Full patient data were not available for 1 of these studies, resulting in 9 studies with individual patient data, which were included in the quantitative synthesis.

Results  Of the 1258 patients included, the mean (SD) age was 47.1 (11.9) years, and 944 (75.0%) were female. A 2-stage random effects approach showed that patients receiving MBCT had a reduced risk of depressive relapse within a 60-week follow-up period compared with those who did not receive MBCT (hazard ratio, 0.69; 95% CI, 0.58-0.82). Furthermore, comparisons with active treatments suggest a reduced risk of depressive relapse within a 60-week follow-up period (hazard ratio, 0.79; 95% CI, 0.64-0.97). Using a 1-stage approach, sociodemographic (ie, age, sex, education, and relationship status) and psychiatric (ie, age at onset and number of previous episodes of depression) variables showed no statistically significant interaction with MBCT treatment. However, there was some evidence to suggest that a greater severity of depressive symptoms prior to treatment was associated with a larger effect of MBCT compared with other treatments.

Conclusions and Relevance  Mindfulness-based cognitive therapy appears efficacious as a treatment for relapse prevention for those with recurrent depression, particularly those with more pronounced residual symptoms. Recommendations are made concerning how future trials can address remaining uncertainties and improve the rigor of the field.

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Figure 1.
Preferred Reporting Items for Systematic Reviews and Meta-analyses Flow Diagram From Record Identification to Study Inclusion
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Figure 2.
Random Effects Meta-analyses Comparing Mindfulness-Based Cognitive Therapy (MBCT) With Other Variables

Forest plot of 2-stage meta-analysis of aggregate data on hazard ratio scale comparing (A) risk of relapse of depression in participants receiving MBCT with participants not receiving MBCT; (B) risk of relapse of depression in participants receiving MBCT with participants receiving an alternative active therapy; and (C) risk of relapse of depression in participants receiving MBCT with participants receiving antidepressant medication. Weights are from random effects analyses.

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Figure 3.
Interactive Effect Between Mindfulness-Based Cognitive Therapy (MBCT) Status and Baseline Depression With Regard to the Relative Hazard of Depressive Relapse

Predictive margins for the relative hazard of depressive relapse comparing participants receiving MBCT with those not receiving MBCT at baseline depression z scores, derived from a model including MBCT status, baseline depression z score, the interaction between MBCT status and baseline depression z score, baseline mindfulness z score, age at onset of depression, and number of past episodes of depression (5 or more/4 or fewer).

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Efficacy of Mindfulness-Based Cognitive Therapy in Prevention of Depressive Relapse
Posted on June 29, 2016
Sergio Zaderenko MD
Hearltland Psychiatric Medicine, LLC. Prairie Village, Kansas USA. Clinical Assisstant Professor of Psychiatry, University of Missouri-Kansas City School of Medicine, USA
Conflict of Interest: None Declared
In their meta-analysis of Mindfulness Based Cognitive Therapy (MBCT), Kuyken et al (1) present a fairly rigorous assessment of the methodology of the individual studies. However, the degree of the limitations may not have been fully acknowledged by the authors.

Kuyken et al assessed the overall risk of bias as low based, mostly, on the lack of double blinding which the authors considered to be of “moderate”concern. A recent systematic review by Hróbjartsson et al (2), looking at risk of bias in studies of similar characteristics to the ones reviewed by Kuyken et al, finds that “non-blinded patients exaggerated the standardized mean difference by an average of 0.56 standard deviation, but with considerable variation; in trials with a true moderate effect size of –0.5, non-blinded patients thus cause an exaggeration of the estimated effect by 112%”, a substantial overestimation of results and risk of bias. Another factor that increases the risk of bias is the presence of subjective outcomes which is particularly problematic in studies lacking double blind design (3). Even though the assessors may be blinded to treatment condition, a strategy that may reduce the risk of bias in non-blinded studies where the assessors subjectively assess the results, the recurrence of depression in the studies reviewed by Kuyken et al was assessed based on patient's report via responses to a depression tool. Another element that can contribute to risk of bias, and acknowledged by two of the studies reviewed in the Meta-analysis (4,5) and the authors of the meta-analysis itself (1), is the fact that four out of the nine studies included in the meta-analysis were authored by the developers of MBCT who have a vested interest in the success of MBCT. The authors of the other studies are also practitioners of MBCT which may also present a conflict of interest.

There is substantial clinical heterogeneity in the studies reviewed in the meta-analysis. For instance, in one study(5) the subjects recruited had a particular interest in MBCT. In another study (6) 25% of subjects in the MBCT group stayed on some dose of antidepressant medications (ADM's). In the study by Huijbers et al. (7), that did a direct comparison by adding MBCT to ADM's , MBCT did not improve outcomes compared to using ADM's alone.

The risk of publication bias, based on asymmetry in the funnel plot, is acknowledged by the authors and adds another element of concern regarding the quality of the evidence.
When the above mentioned limitations are evaluated using the GRADE method and integrated into the GRADEpro GDT tool (8), the quality of the evidence of the studies comprising the meta-analysis by Kuyken et al would be estimated as low.

Recurrence of major depression, especially if the episode is severe, carries considerable morbidity and mortality (9). Kuyken et al make helpful recommendations for improving the quality of future studies. However, at the present time, it is questionable whether recommending MBCT, as a single intervention for the prevention of major depressive episodes, would be clinically prudent.


1.- Kuyken W et al. Efficacy of Mindfulness-Based Cognitive Therapy in Prevention of Depressive Relapse: An Individual Patient Data Meta-analysis From Randomized Trials. JAMA Psychiatry. 2016 Jun 1;73(6):565-574.

2.-Hróbjartsson A, Emanuelsson F, Skou Thomsen AS, et al . Bias due to lack of patient blinding in clinical trials: A systematic review of trials randomizing patients to blind and non-blind sub-studies. Int J Epidemiol 2014;43:1272–83
3.-Jelena Savović, PhD; et al. Influence of Reported Study Design Characteristics on Intervention Effect Estimates From Randomized, Controlled Trials. Ann Intern Med. 2012;157(6):429-438
4.- Bondolfi  G, Jermann  F, der Linden  MV,  et al.  Depression relapse prophylaxis with mindfulness-based cognitive therapy: replication and extension in the Swiss health care system. J Affect Disord. 2010;122(3):224-231.
5.-Godfrin  KA, van Heeringen  C.  The effects of mindfulness-based cognitive therapy on recurrence of depressive episodes, mental health and quality of life: a randomized controlled study. Behav Res Ther. 2010;48(8):738-746.
6.- Kuyken  W, Byford  S, Taylor  RS,  et al.  Mindfulness-based cognitive therapy to prevent relapse in recurrent depression. J Consult Clin Psychol. 2008;76(6):966-978.
7.- Huijbers  MJ, Spinhoven  P, Spijker  J,  et al.  Adding mindfulness-based cognitive therapy to maintenance antidepressant medication for prevention of relapse/recurrence in major depressive disorder: randomised controlled trial. J Affect Disord. 2015;187:54-61.

8.- Schünemann H, Brożek J, Guyatt G, Oxman A, editors. GRADE handbook for grading quality of evidence and strength of recommendations. Updated October 2013. The GRADE Working Group, 2013. Available from guidelinedevelopment.org/handbook
9.- Hardy P. Severe depression : morbidity-mortality and suicide. Encephale. 2009 Dec;35 Suppl 7:S269-71.


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