We know that people who have experienced several previous episodes of depression are at high risk of relapse. It’s common practice (Geddes J. et al, 2003, Borges S et al, 2014) to keep taking the tablets after an episode to reduce the risk. However, while many who are at high risk of relapse understandably don’t want to do this, we also know that many more in primary care, who may not be at high risk, are doing so anyway (Kendrick T. et al 2015).
So, there’s much interest around the woodland in psychotherapy to prevent relapse (see the earlier blogs by fellow elves Sarah McDonald & Raluca Lucacel (2015)). Andre Tomlin blogged on the PREVENT study where there was no difference between mindfulness based cognitive therapy (MBCT) after remission with support to taper off or stop medication and continuing on antidepressants (Kuyken W. et al, 2015, Tomlin A, 2015). Unfortunately, another group could not replicate this (Cristea I, 2016) and also found that adding MBCT to maintenance antidepressants (compared with antidepressants alone) conferred no additional benefit (Huijbers MJ. et al, 2015).
This new study set out to discover whether:
- Staying on maintenance antidepressant treatment offered better protection against recurrence than receiving preventive cognitive therapy (PCT) while tapering off antidepressants
- Adding PCT to antidepressants was better at preventing recurrence than medication alone.
This was a single-blind, multicentre, parallel, three-group, randomised controlled trial in which participants recruited by general practitioners, pharmacists, secondary mental health care, or media were randomly assigned (in proportions of 10:10:8) to:
- Preventive cognitive therapy (PCT) and antidepressants
- Antidepressants alone, or
- PCT with antidepressant tapering
The researchers used computer-generated randomised allocation, which was stratified for number of previous depressive episodes and type of care.
PCT was provided in group or individual sessions (8 in total) by psychologists trained in cognitive behavioural therapy with some additional training. The main components of PCT are identification and evaluation of dysfunctional attitudes and schemas that activate positive affect and emotions, enhancement of memories of positive experiences and formulation of prevention strategies (Bockting C, et al 2015).
In the 2 groups that received maintenance (antidepressants alone) GPs and psychiatrists were advised to carry on prescribing at minimally required doses (≥ 20 mg fluoxetine equivalent). In the tapering group, they were advised to taper off over 4 weeks (NICE, 2009) but 60% took 6 months to do so as 4 weeks simply wasn’t feasible.
Eligible individuals had to have at least two previous episodes of major depressive disorder and have been in remission for at least 8 weeks, but no longer than 2 years. Additionally, recovery had to have been achieved with acute antidepressant treatment, and participants had to have been on antidepressants for at least the past 6 months.
Exclusion criteria were current mania or hypomania, a history of bipolar disorder, any history of psychosis, current alcohol or drug abuse, an anxiety disorder that requires treatment, psychological treatment more than twice a month, and a diagnosis of organic brain damage.
Participants were assessed for remission by standardised interview at 3, 9, 15 and 24 months. Assessors were masked to treatment allocation, whereas physicians and participants could not be masked.
The primary outcome was the time-related proportion of individuals with depressive relapse or recurrence in the intention-to-treat population, analysed in terms of time to recurrence.
2,486 participants were assessed for eligibility and 289 were randomly assigned to:
- PCT and antidepressants (n=104),
- antidepressants alone (n=100),
- PCT with antidepressant tapering (n=85).
Cumulative recurrence rates were:
- 42.6% for the PCT and antidepressants group
- 60.0% for the antidepressants alone group
- 63.3% for the PCT with antidepressant tapering group
Antidepressants alone were not superior to PCT while tapering off antidepressants, in terms of the risk of relapse or recurrence ((Cox regression analyses) hazard ratio [HR] 0·86, 95% CI 0·56 to 1·32; p=0·502).
Adding PCT to antidepressant treatment resulted in a 41% relative risk reduction, compared with antidepressants alone (0·59, CI 0·38 to 0·94; p=0·026).
Finally, the recurrence rate was lower with PCT plus antidepressants than with PCT while tapering off, but this is debatable (see below).
The authors concluded that:
Maintenance antidepressant treatment is not superior to PCT after recovery, whereas adding antidepressant treatment after recovery is superior to antidepressants alone.
PCT should be offered to recurrently depressed individuals on antidepressants and to individuals who wish to stop antidepressants after recovery.
Strengths and limitations
The main strengths of this study are that it is clearly a very high quality RCT carried out by a superbly qualified team over a substantial period of time (recruiting over 6 years).
However, a number of limitations are admitted by the team who carried out the study:
- Only participants with at least 2 previous episodes were included (for whom guidelines recommend continuation), so the results might not be generalisable to those with a single episode
- Because 81% used SSRIs it was not possible to distinguish effects for SSRIs from other antidepressants
- Sensitivity analyses showed a small reduction in the effect of adding PCT to antidepressants
- The sample size calculation (for the main treatment effects) was underpowered for subgroup and mediation analyses
- There were no control groups for pill-placebo or PCT.
Additionally, I would add that:
- Staying with the antidepressant protocol was problematic in all 3 groups
- The authors discuss the problems of distinguishing relapse from withdrawal symptoms. In his accompanying commentary, Fava (2018) says it’s unclear how many of the relapses in the tapering group were actually withdrawal and post-withdrawal syndromes. In this group, the rate of recurrence was higher during the first 140 days after tapering than in either of the groups in which antidepressants were continued. He therefore queried the claim that PCT and antidepressant continuation was superior to PCT and antidepressant discontinuation
- Participants were recruited widely (especially via the media) and may be less typical of a primary care setting, although 69% had received antidepressants from their GP.
Implications for practice
Preventive cognitive therapy should be offered to those who want to stay on or taper off antidepressants after recovery. As someone who is on long-term antidepressants I’ve benefited from cognitive therapy with some elements of PCT, and although it didn’t prevent relapse occurring it has helped me considerably. However, we lack the available trained personnel to offer it routinely.
What we now need is much more research into, and support for, tapering off antidepressants for those who neither need or want to continue them, such as in the REDUCE study currently being carried out by Tony Kendrick and his colleagues in Southampton. What we also need is a replication of this study, but based entirely in a primary care setting, where the majority of people are both prescribed and withdraw from antidepressants.
Conflicts of interest
Bockting CL, Klein NS, Elgersma H J et al. (2018) 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 controlled trial. The Lancet Psychiatry, 5(5), 401-410.[PubMed abstract]
Bockting CL, Hollon SD, Jarrett RB, et al. (2015) A lifetime approach to major depressive disorder: The contributions of psychological interventions in preventing relapse and recurrence. Clinical Psychology Review, 41, 16-26.[PubMed abstract]
Borges S, Chen YF, Laughren TP, et al. (2014) Review of maintenance trials for major depressive disorder: a 25-year perspective from the US Food and Drug Administration. The Journal of Clinical Psychiatry, 75, 205-214. [PubMed abstract]
Cristea I (2016) Mindfulness based therapy cannot substitute maintenance antidepressants for preventing depression relapse. The Mental Elf 6 April 2016.
Fava GA (2018) Time to rethink the approach to recurrent depression. The Lancet Psychiatry, 5(5), 380-381. No abstract available.
Geddes JR, Carney SM, Davies C et al. (2003) Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review. The Lancet, 361(9358), 653-661. [PubMed abstract]
Huijbers MJ, Spinhoven P, Spijker J, et al (2015) Adding mindfulness-based cognitive therapy to maintenance antidepressant medication for prevention of relapse/recurrence in major depressive disorder: randomised controlled trial. Journal of Affective Disorders, 187, 54-61. [PubMed abstract]
Kaymaz N, van Os J, Loonen AJ et al. (2008) Evidence that patients with single versus recurrent depressive episodes are differentially sensitive to treatment discontinuation: a meta-analysis of placebo-controlled randomized trials. Journal of Clinical Psychiatry, 69(9), 1423. [PubMed abstract]
Kendrick T, Stuart B, et al. (2015) Did NICE guidelines and the Quality Outcomes Framework change GP antidepressant prescribing in England? Observational study with time trend analyses 2003–2013. Journal of Affective Disorders, 186, 171-177. [PubMed abstract]
Kuyken W, Hayes R, Barrett B, et al. (2015) 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. The Lancet, 386(9988), 63-73.