A total of 280 potential trials were identified. After duplications removed, 247 papers were screened by title and abstracts, and 32 papers were retrieved for full-text review. Of these, 6 trials[36–41] were identified eligible and were included in meta-analysis (excluded studies with reasons were listed in Supplementary file 3). Figure 1 shows the progress of selection.
Characteristics of included studies
The included trials were conducted in the UK(n = 3), Canada(n = 2), and the USA(n = 1), between 2008 to 2018. One trial conducted a follow-up of 8 months, while the other 5 trials had over 1 year of follow-up, of which 1 study[41] conducted a 26-month follow-up[39]. A total of 1061 participates were recruited, with the size of individual trials ranged from 54 to 424. Of these participants, about 70% were female. Most trials recruited participants with history of at least 3 depressive episodes according to DSM-IV[42], although 3 studies[38, 39, 41] included participants with more than 1 or 2 episodes. All trials defined relapse of depression as a return of symptoms meeting the criteria for major depression on Module A of the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (SCID) [43]. In the intervention groups, 4 studies[36–40] chose MBCT for treatment, while 2 trials[37, 41] used MBCT with discontinuation of antidepressant medication. During the discontinuation, patients were asked and recommended to withdraw gradually from their antidepressants over a period of 4–5 weeks. The program of MBCT was based on the protocol by Segal, Williams & Teasdale[44], across 8 weekly group meetings of 2 ~ 2.5 hours duration with or without a retreat day held between 6th and 7th session. The control groups 6 studies used ACCs. ACCs including mADM [37, 40, 41] and program comprised most of elements of MBCT except mindfulness meditation[36, 38, 39]. In mADM group, patients were monitored and treated by their physicians with an adequate dose of antidepressants, and recommendations were provided to manage side-effects. Key characteristics of included trials are shown in Table 1.
Table 1
Author, year, country | Sample | Age Mean (SD) | Female(%) | Previous episodes Mean (SD) | Age of first onset Mean (SD) | Intervention (frequency,duration) | Intervention(n/drop outs/analysis) | Control | Control(n/drop outs/analysis) | Follow-up period | AEs/SAEs |
Kuyken 2008 UK | Participants with three or more previous episodes of depression with mADM over the last 6 months and were in full or partial remission. (N = 123) | 49.16(11.17) | 76 | 6.39(2.96) | 26.22(12.14) | MBCT (8, weekly, 2 h) | (61/2/61) | mADM | (62/6/62) | 15 months. | No AEs |
Segal 2010 Canada | Participants with 2 previous episodes of depression. (N = 54) | 45.32(10.40) | 61 | 4.70(2.40) | 31.80(11.75) | Discontinuation + MBCT (8, weekly,2 h with a retreat day held between sessions 6 and 7) | (26/5/26) | mADM | (28/8/28) | 8 months | NR |
Williams 2014 UK | Patients with at least 3 episodes of major depression and remission for the previous 8 weeks. (N = 274) | 43.82(12.17) | 72 | ≥ 5:77% | 21.26 (10.93) | MBCT (8, weekly, 2 h) | (108/9/99) | CPE program | (110/7/103) | 12 months; follow-up classes taking place 6 weeks and 6 months posttreatment | Participants reported 15 SAEs to the research team, five arising from MBCT and 10 from CPE. |
Kuyken 2015 UK | Patients with diagnosis of recurrent major depressive disorder in full or partial remission and three or more previous major depressive episodes. (N = 424) | 49.50(12.50) | 77 | ༜6:53.3%;≥6:46.7% | 24.9(12.42) | MBCT (8, weekly, 2·25 h) + taper or discontinue antidepressant treatment | (212/46/212) | mADM | (212/50/212) | 24 months | A total of ten SAEs were reported, four of which resulted in the death of the participant. |
Frab 2018 Canada | Patients were absence of a diagnosis of depression, with 1 previous episode. (N = 166) | 40.63(11.77) | 67 | 3.86(2.33) | 22.43(10.66) | MBCT (8, weekly, 2 h) | (82/33/82) | CT | (84/37/84) | 24 months | NR |
Shallcross 2018 USA | Patients with minimum of 1 prior episode of depression, current remission from depression for at least 1 month. (N = 92) | 34.90(11.40) | 76 | ≥ 3:95% | 16.10(7.00) | MBCT (8, weekly, 2.5 h) | (46/24/46) | ACC was based on the validated and manualized Health Enhancement Program | (46/17/46) | 26 months | NR |
N, number; MBCT, mindfulness-based cognitive therapy; mADM, maintenance antidepressant medication; NR, no report; CPE, cognitive psychological education; CT, cognitive therapy; ACC, active control condition. |
AE, adverse event; SAE, serious adverse event |
Risk of bias assessment
The Cochrane Collaboration Risk of Bias Tool[45] was used to assess risk of bias across studies. Of the 6 included studies, all described the details of random sequence generation by computer software[37–41] or a dynamic type of treatment allocation[36, 46] and all trials conducted proper allocation concealment. Research assessors were blinded to treatment allocation in five trials[36, 37, 39–41], while 1 trial did not report the blinding method[38]. All studies reported drop-outs and 2[40, 41] with reasons, and all trials carried out the intention-to-treat analysis. In selective reporting, all studies were registered advanced and 1 study[37] published a prior-protocol, while 1[39] failed to provide a registration number.(Fig. 2, Fig. 3)
Relapse rate of MBCT versus. ACCs
This is a dichotomous outcome and defined as the proportion of participants who had a return of symptoms meeting the SCID. All the included studies reported the relapse rate after intervention and follow-up. The pooled results showed that there was no statistical difference between the MBCT group and the ACCs group in reducing relapse of depressive disorder (RR = 0.90, 95% CI 0.79 to 1.03, P = 0.13). There was no heterogeneity (χ2 = 0.97, P = 0.97, I2 = 0%) across these studies. Subgroup analysis was carried out based on different controls. No significant difference of relapse rate was found between patients received MBCT versus program comprised most of elements of MBCT except mindfulness meditation (RR = 0.80, 95% CI 0.60 to 1.08, P = 0.15) and MBCT versus mAMD (RR = 0.93, 95% CI 0.79 to 1.08, P = 0.13). No heterogeneity was found in both subgroup analyses (I2 = 0%). (Fig. 4)
Trail sequential analysis
To determine the required sample size of MBCT versus ACCs in reducing relapse rate in recurrent depressive patients, we assumed a 46.15% relapse rate in control group and a relative risk reduction of 10% based on our meta-analysis. The cumulative Z-curve for trials with low bias risk did not cross any of the boundaries, which showed that we need a sample of 3622 to detect a plausible effect of MBCT on relapse rate (with 80% power and α = 0.05). (Fig. 5)
Safety assessment
Three studies reported AEs during experiments. Kuyken[40] found no AEs through the oversight of the Trial Steering Committee in the study of 2008. Williams[36] reported 15 SAEs to the research team, 5 arising from MBCT group and 10 from control group. Of these, only 1 was adjudged to be a serious adverse reaction potentially arising from a trial treatment. In the 2015 study, Kuyken[37] reported a total of 10 SAE, 4 of which resulted in the death of the participant, and the Trial Steering and Data Monitoring Committees concluded that there was no reason to believe that any of the SAEs were related to either the intervention or the trial.
Publication bias
As less than 10 studies were included, the Begg's Test and Egger's test would have no valuable reference.
Evidence rating
The assessment of evidence would offer a clear, precise illustration of decision-making progress with the GRADE tool. The quality of evidence was moderate. The reason for downgrading was that the sample size was lower than the optimal information size. The outcome from the meta-analysis was presented in Table 2.
Table 2
Grade evidence profile of MBCT versus ACCs
Certainty assessment | № of patients | Effect | Certainty | Importance |
№ of studies | Study design | Risk of bias | Inconsistency | Indirectness | Imprecision | Other considerations | MBCT | ACC | Relative (95% CI) | Absolute (95% CI) |
relapse rate (follow up: range 8 months to 26 months) |
6 | randomised trials | not serious | not serious | not serious | serious a | none | 219/528 (41.5%) | 246/533 (46.5%) | OR 0.90 (0.79 to 1.03) | 46 fewer per 1,000 (from 97 fewer to 14 more) | ⨁⨁⨁◯ MODERATE | Critical |
CI, Confidence interval; OR, Odds ratio |
a. The pooled (cumulative) sample size was lower than the optimal information size (OIS) and/or the total enrollment was less than 300 (dichotomous data). |