Randomized Controlled Trial

. 2016 Apr;208(4):366-73.

doi: 10.1192/bjp.bp.115.168971. Epub 2016 Feb 18.

Discontinuation of antidepressant medication after mindfulness-based cognitive therapy for recurrent depression: randomised controlled non-inferiority trial

Affiliations

¹ Marloes J. Huijbers, MSc, Department of Psychiatry, Radboud University Medical Center, Nijmegen, The Netherlands; Philip Spinhoven, PhD, Institute of Psychology, Leiden University, Leiden and Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands; Jan Spijker, PhD, MD, Pro Persona Nijmegen, Nijmegen, The Netherlands; Henricus G. Ruhé, PhD, MD, Department of Psychiatry, University Medical Center Groningen, Groningen, The Netherlands; Digna J. F. van Schaik, PhD, MD, Patricia van Oppen, PhD, GGZ InGeest and Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands, Willem A. Nolen, PhD, MD, Johan Ormel, PhD, Department of Psychiatry, University Medical Center Groningen, Groningen, The Netherlands; Willem Kuyken, PhD, Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, UK; Gert Jan van der Wilt, PhD, Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands; Marc B. J. Blom, PhD, MD, Parnassia Bavo Psychiatric Institute, The Hague, The Netherlands; Aart H. Schene, PhD, MD, Department of Psychiatry, Radboud University Medical Center, Nijmegen, The Netherlands; A. Rogier T. Donders, PhD, Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands; Anne E. M. Speckens, PhD, MD, Department of Psychiatry, Radboud University Medical Center, Nijmegen, The Netherlands marloes.huijbers@radboudumc.nl.
² Marloes J. Huijbers, MSc, Department of Psychiatry, Radboud University Medical Center, Nijmegen, The Netherlands; Philip Spinhoven, PhD, Institute of Psychology, Leiden University, Leiden and Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands; Jan Spijker, PhD, MD, Pro Persona Nijmegen, Nijmegen, The Netherlands; Henricus G. Ruhé, PhD, MD, Department of Psychiatry, University Medical Center Groningen, Groningen, The Netherlands; Digna J. F. van Schaik, PhD, MD, Patricia van Oppen, PhD, GGZ InGeest and Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands, Willem A. Nolen, PhD, MD, Johan Ormel, PhD, Department of Psychiatry, University Medical Center Groningen, Groningen, The Netherlands; Willem Kuyken, PhD, Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, UK; Gert Jan van der Wilt, PhD, Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands; Marc B. J. Blom, PhD, MD, Parnassia Bavo Psychiatric Institute, The Hague, The Netherlands; Aart H. Schene, PhD, MD, Department of Psychiatry, Radboud University Medical Center, Nijmegen, The Netherlands; A. Rogier T. Donders, PhD, Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands; Anne E. M. Speckens, PhD, MD, Department of Psychiatry, Radboud University Medical Center, Nijmegen, The Netherlands.

PMID: 26892847
PMCID: PMC4816973
DOI: 10.1192/bjp.bp.115.168971

Randomized Controlled Trial

Discontinuation of antidepressant medication after mindfulness-based cognitive therapy for recurrent depression: randomised controlled non-inferiority trial

Marloes J Huijbers et al. Br J Psychiatry. 2016 Apr.

. 2016 Apr;208(4):366-73.

doi: 10.1192/bjp.bp.115.168971. Epub 2016 Feb 18.

Authors

Affiliations

¹ Marloes J. Huijbers, MSc, Department of Psychiatry, Radboud University Medical Center, Nijmegen, The Netherlands; Philip Spinhoven, PhD, Institute of Psychology, Leiden University, Leiden and Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands; Jan Spijker, PhD, MD, Pro Persona Nijmegen, Nijmegen, The Netherlands; Henricus G. Ruhé, PhD, MD, Department of Psychiatry, University Medical Center Groningen, Groningen, The Netherlands; Digna J. F. van Schaik, PhD, MD, Patricia van Oppen, PhD, GGZ InGeest and Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands, Willem A. Nolen, PhD, MD, Johan Ormel, PhD, Department of Psychiatry, University Medical Center Groningen, Groningen, The Netherlands; Willem Kuyken, PhD, Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, UK; Gert Jan van der Wilt, PhD, Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands; Marc B. J. Blom, PhD, MD, Parnassia Bavo Psychiatric Institute, The Hague, The Netherlands; Aart H. Schene, PhD, MD, Department of Psychiatry, Radboud University Medical Center, Nijmegen, The Netherlands; A. Rogier T. Donders, PhD, Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands; Anne E. M. Speckens, PhD, MD, Department of Psychiatry, Radboud University Medical Center, Nijmegen, The Netherlands marloes.huijbers@radboudumc.nl.
² Marloes J. Huijbers, MSc, Department of Psychiatry, Radboud University Medical Center, Nijmegen, The Netherlands; Philip Spinhoven, PhD, Institute of Psychology, Leiden University, Leiden and Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands; Jan Spijker, PhD, MD, Pro Persona Nijmegen, Nijmegen, The Netherlands; Henricus G. Ruhé, PhD, MD, Department of Psychiatry, University Medical Center Groningen, Groningen, The Netherlands; Digna J. F. van Schaik, PhD, MD, Patricia van Oppen, PhD, GGZ InGeest and Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands, Willem A. Nolen, PhD, MD, Johan Ormel, PhD, Department of Psychiatry, University Medical Center Groningen, Groningen, The Netherlands; Willem Kuyken, PhD, Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, UK; Gert Jan van der Wilt, PhD, Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands; Marc B. J. Blom, PhD, MD, Parnassia Bavo Psychiatric Institute, The Hague, The Netherlands; Aart H. Schene, PhD, MD, Department of Psychiatry, Radboud University Medical Center, Nijmegen, The Netherlands; A. Rogier T. Donders, PhD, Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands; Anne E. M. Speckens, PhD, MD, Department of Psychiatry, Radboud University Medical Center, Nijmegen, The Netherlands.

PMID: 26892847
PMCID: PMC4816973
DOI: 10.1192/bjp.bp.115.168971

Abstract

Background: Mindfulness-based cognitive therapy (MBCT) and maintenance antidepressant medication (mADM) both reduce the risk of relapse in recurrent depression, but their combination has not been studied.

Aims: To investigate whether MBCT with discontinuation of mADM is non-inferior to MBCT+mADM.

Method: A multicentre randomised controlled non-inferiority trial (ClinicalTrials.gov:NCT00928980). Adults with recurrent depression in remission, using mADM for 6 months or longer (n= 249), were randomly allocated to either discontinue (n= 128) or continue (n= 121) mADM after MBCT. The primary outcome was depressive relapse/recurrence within 15 months. A confidence interval approach with a margin of 25% was used to test non-inferiority. Key secondary outcomes were time to relapse/recurrence and depression severity.

Results: The difference in relapse/recurrence rates exceeded the non-inferiority margin and time to relapse/recurrence was significantly shorter after discontinuation of mADM. There were only minor differences in depression severity.

Conclusions: Our findings suggest an increased risk of relapse/recurrence in patients withdrawing from mADM after MBCT.

PubMed Disclaimer

Conflict of interest statement

Declaration of interest

None.

Figures

**Fig. 1**
Flow of participants from screening to analysis, comparing mindfulness-based cognitive therapy (MBCT) followed by discontinuation of maintenance antidepressant medication (MBCT+discontinuation) with MBCT plus maintenance antidepressant medication (MBCT+mADM). a. Patients with a relative preference for MBCT were included in the current trial, whereas patients with a relative preference for mADM were included in a parallel trial (MBCT+mADM v. mADM alone).

**Fig. 2**
Plot showing the differences in relapse/recurrence rates and corresponding one-sided 95% confidence intervals exceeding the non-inferiority margin, for patients with recurrent depression receiving either mindfulness-based cognitive therapy (MBCT) followed by discontinuation of maintenance antidepressant medication (MBCT+discontinuation group, n = 128) or MBCT plus maintenance antidepressant medication (MBCT+mADM, n = 121).

**Fig. 3**
Survival curves over 15-month follow-up (65 weeks) for patients with recurrent depression receiving either mindfulness-based cognitive therapy (MBCT) followed by discontinuation of maintenance antidepressant medication (MBCT+discontinuation, n = 128) or MBCT plus maintenance antidepressant medication (MBCT+mADM, n = 121). (a) Intention-to-treat analysis, (b) per-protocol analysis.

**Fig. 4**
Severity of (residual) depressive symptoms over 15-month follow-up for patients with recurrent depression receiving either mindfulness-based cognitive therapy (MBCT) followed by discontinuation of maintenance antidepressant medication (MBCT+discontinuation, n = 128) or MBCT plus maintenance antidepressant medication (MBCT+mADM, n = 121). (a) Intention-to-treat analysis, (b) per-protocol analysis. Inventory of Depressive Symptomatology – Clinician rated (IDS-C) cut-off points for depression severity: 0–11 none, 12–23 mild, 24–36 moderate, 37–46 severe and 47–84 very severe.

See this image and copyright information in PMC

References

1. Richards D. Prevalence and clinical course of depression: a review. Clin Psychol Rev 2011; 31: 1117–25. - PubMed
1. Kaymaz N, van Os J, Loonen AJ, Nolen WA. Evidence that patients with single versus recurrent depressive episodes are differentially sensitive to treatment discontinuation: a meta-analysis of placebo-controlled randomized trials. J Clin Psychiatry 2008; 69: 1423–36. - PubMed
1. Borges S, Chen YF, Laughren TP, Temple R, Patel HD, David PA, et al. Review of maintenance trials for major depressive disorder: a 25-year perspective from the US Food and Drug Administration. J Clin Psychiatry 2014; 75: 205–14. - PubMed
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Discontinuation of antidepressant medication after mindfulness-based cognitive therapy for recurrent depression: randomised controlled non-inferiority trial

Affiliations

Discontinuation of antidepressant medication after mindfulness-based cognitive therapy for recurrent depression: randomised controlled non-inferiority trial

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

Associated data

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical