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

Marloes J Huijbers, Philip Spinhoven, Jan Spijker, Henricus G Ruhé, Digna J F van Schaik, Patricia van Oppen, Willem A Nolen, Johan Ormel, Willem Kuyken, Gert Jan van der Wilt, Marc B J Blom, Aart H Schene, A Rogier, T Donders, Anne E M Speckens, Marloes J Huijbers, Philip Spinhoven, Jan Spijker, Henricus G Ruhé, Digna J F van Schaik, Patricia van Oppen, Willem A Nolen, Johan Ormel, Willem Kuyken, Gert Jan van der Wilt, Marc B J Blom, Aart H Schene, A Rogier, T Donders, Anne E M Speckens

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.

Conflict of interest statement

Declaration of interest

None.

© The Royal College of Psychiatrists 2016.

Figures

Fig. 1
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
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
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
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.

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