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Half of people who stopped long term antidepressants relapsed within a year, study finds

BMJ 2021; 374 doi: (Published 30 September 2021) Cite this as: BMJ 2021;374:n2403

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Re: Half of people who stopped long term antidepressants relapsed within a year, study finds

Antidepressant discontinuation trial lacks consideration of evidence based psychological alternatives for continuation of antidepressants

Dear editor,
Lewis and colleagues (1) reported on the protective effect of maintenance of antidepressants versus discontinuing antidepressants for patients with depression in primary care as discussed in BMJ (BMJ 2021;374:n2403). In this RCT, the authors concluded that continuing antidepressants reduces the likelihood of relapse compared to discontinuing antidepressants over a 52-week follow-up. Patients who took part in the trial either had two previous episodes or took antidepressants for at least two years.

The study results may lead to the interpretation that long term use of antidepressant after remission of unipolar depression is the only evidence-based strategy to prevent relapse. However, the authors conclusion overlooks the robust evidence for psychological interventions as an alternative to long term use of antidepressant for relapse prevention in unipolar depression.

In the past decade there is accumulating robust evidence based on several RCT’s and meta-analyses for the effect of brief psychological interventions as relapse prevention strategy. That is, evidence shows that brief psychological interventions (i.e. Preventive Cognitive Therapy and Mindfulness Based Cognitive Therapy) are effective in reducing the risk for relapse in unipolar depression (2,3). Psychological interventions are also an alternative to antidepressants in recurrent unipolar depression. RCT’s and meta-analyses show that Preventive Cognitive Therapy (PCT) and Mindfulness Based Cognitive Therapy (MBCT) delivered during tapering and stopping antidepressants are an alternative for continuation of antidepressants, also in primary care (e.g., 3–5).

Furthermore, the latest Individual Patient Data meta-analysis on this topic demonstrated that brief psychological interventions (PCT, MBCT), delivered after remission, are an alternative for long-term use of antidepressants, also for those with high risk of relapse (3). The non-inferiority/preventative effect of psychological interventions was demonstrated for longer than one year (at least 15 months).

The evidence for alternative pharmaceutical strategies to stay well after a depression, is completely lacking in the article. However, the evidence for alternatives for medication is crucial for shared decision making with an individual that wishes to taper antidepressants in unipolar depression. These results open up the opportunity for individuals with recurrent unipolar depression that wish to taper antidepressants (as well as general practitioners and other clinicians) to choose between long term use of antidepressants or psychological interventions as alternative (that is PCT or MBCT).

prof. dr. Claudi Bockting, professor of Clinical Psychology in Psychiatry,
AmsterdamUMC/Centre for Urban Mental Health, University of Amsterdam

dr. Josefien Breedvelt, research director, National Centre for Social Research & AmsterdamUMC / @JosefienUMH

1. Lewis G, Marston L, Duffy L, Freemantle N, Gilbody S, Hunter R, et al. Maintenance or Discontinuation of Antidepressants in Primary Care. N Engl J Med [Internet]. 2021 Sep 29;385(14):1257–67. Available from:
2. Breedvelt JJF, Brouwer ME, Harrer M, Semkovska M, Ebert DD, Cuijpers P, et al. Psychological interventions as an alternative and add-on to antidepressant medication to prevent depressive relapse: systematic review and meta-analysis. Br J Psychiatry. 2020;0(1–8).
3. Breedvelt JJF, Warren FC, Segal Z, Kuyken W, Bockting CL. Continuation of Antidepressants vs Sequential Psychological Interventions to Prevent Relapse in Depression: An Individual Participant Data Meta-analysis. JAMA psychiatry. 2021 Aug;78(8):868–75.
4. Bockting CLH, Klein NS, Elgersma HJ, van Rijsbergen GD, Slofstra C, Ormel J, et al. Effectiveness of preventive cognitive therapy while tapering antidepressants versus maintenance antidepressant treatment versus their combination in prevention of depressive relapse or recurrence (DRD study): a three-group, multicentre, randomised control. The Lancet Psychiatry [Internet]. 2018;0366(18):1–10. Available from:
5. Kuyken W, Hayes R, Barrett B, Byng R, Dalgleish T, Kessler D, et al. Effectiveness and cost-effectiveness of mindfulness-based cognitive therapy compared with maintenance antidepressant treatment in the prevention of depressive relapse or recurrence (PREVENT): A randomised controlled trial. Lancet [Internet]. 2015;386(9988):63–73. Available from:

Competing interests: CLB is president of the European Association of Clinical Psychology and Psychological Treatment (EACLIPT) and co-developer of the Dutch multidisciplinary clinical guideline for depression, for which she receives no remuneration. She is also a member of the scientific advisory board of the National Insure Institute, for which she receives an honorarium, although this role has no direct relation to this topic. CLB has presented several keynote addresses at conferences, such as the European Psychiatry Association and the European Conference Association, for which she sometimes receives an honorarium. She has presented clinical training workshops on psychological interventions and wrote several books/co-edited books including a book on Preventive Cognitive Therapy , some of which include a fee or royalties. FB has no competing interests.

30 January 2022
Claudi L Bockting
Professor of Clinical Psychology in Psychiatrie and director Centre for Urban Mental Health
dr. Josefien Breedvelt
Amsterdam UMC, department of Psychiatry and Centre for Urban Mental Health, University of Amsterdam
Kromgouw, 16