Kuyken 2015.

Study characteristics
Methods	Design: multi‐centre single‐blind randomised controlled trial Prerandomisation phases: no Duration post randomisation: 104 weeks Aim: to determine whether MBCT with support to taper or discontinue antidepressant treatment (MBCT‐TS) was superior to maintenance antidepressants for prevention of depressive relapse or recurrence over 24 months
Participants	Country: UK Setting: community adults (from 4 general practices) Type of antidepressant: not described Treatment of antidepressant prerandomisation: on a therapeutic maintenance dose of maintenance treatment; mean not reported Treatment of antidepressant post stabilisation: on a therapeutic maintenance dose of maintenance treatment; mean not reported Primary diagnosis: recurrent depression Previous major depressive episodes: < 6 episodes: 57% discontinuation, 50% antidepressant; ≥ 6 episodes: 43% discontinuation, 50% antidepressant Total numbers of randomised participants: 424 (212 discontinuation, 212 antidepressant) Severity of depressive symptoms at randomisation GRID‐HAM‐D, n (SD): 4.8 (4.3) discontinuation; 4.6 (4.3) antidepressant Asymptomatic at randomisation (GRID‐HAM‐D < 8): 77% discontinuation, 76% antidepressant Symptomatic at randomisation (GRID‐HAM‐D ≥ 8): 23% discontinuation, 24% antidepressant Gender distribution (male): 71% discontinuation, 82% antidepressant Mean age, years (SD): 50 (12) discontinuation, 49 (13) antidepressant Inclusion criteria ‐ diagnosis of recurrent major depressive disorder (DSM‐IV criteria) in full or partial remission ‐ ≥ 3 previous major depressive episodes ‐ ≥ 18 years of age ‐ on a therapeutic dose of maintenance antidepressant drugs in line with BNF and NICE guidance Definition of remission ‐ full remission: GRID‐HAM‐D < 8, partial remission: GRID‐HAM‐D ≥ 8 Exclusion criteria ‐ current major depressive episode ‐ comorbid diagnosis of current substance misuse ‐ organic brain damage ‐ current or past psychosis, including bipolar disorder ‐ persistent antisocial behaviour ‐ persistent self‐injury needing clinical management or therapy ‐ formal concurrent psychotherapy
Interventions	Intervention: mindfulness‐based cognitive therapy (MBCT) with support to taper or discontinue antidepressant treatment (MBCT‐TS) (no placebo) Tapering: support to taper or discontinue maintenance antidepressants. Patients received support to support to taper or discontinue their antidepressant treatment both from the MBCT therapist and their GP. The study team provided guideline information to GPs and patients about typical tapering or discontinuation regimens and possible withdrawal effects. The guidelines recommended that patients begin a tapering regimen after 4 to 5 weeks of treatment; however, GPs and patients determined the tapering or discontinuation regimen. Letters signed by the chief investigator and the trial GP were sent to patients’ GPs and were copied to the patient, prompting the GP to have a discussion with the patient about a suitable tapering or discontinuation regimen after 4 to 5 weeks of MBCT‐TS group sessions. At the end of the 8 MBCT‐TS sessions, another letter was sent to remind the GP to ensure a tapering or discontinuation regimen was in place MBCT ‐ based on the protocol of Segal, Williams, and Teasdale ‐ a fully manualised psychosocial intervention with the treatment rationale for each session ‐ an 8‐week, group‐based programme (12 to 15 patients per group) designed to teach skills that prevent depressive relapse/recurrence ‐ consists of eight 2.25‐hour group sessions, normally over consecutive weeks, with 4 refresher sessions approximately every 3 months for the following year ‐ MBCT therapists are mental health professionals with extensive training in MBCT Compliance: during the trial, a rater assessed 2 sessions from each of the 21 MBCT‐TS courses using the MBCT‐Adherence Scale (AS), which indicated that the MBCT teaching was provided at required competency or adherence levels and above Intervention 2: maintenance antidepressants. Patients in the maintenance antidepressant group received support from their GP to maintain a therapeutic level of antidepressant medication in line with BNF and NICE guidelines for the 2‐year follow‐up period
Outcomes	Primary outcomes ‐ time to relapse/recurrence of depression according to the depression module of the Structured Clinical Interview for DSM–IV Axis I disorders (SCID‐I) at 5 separate intervals Definition of relapse or recurrence ‐ an episode meeting DSM‐IV criteria for a major depressive episode assessed by SCID‐I Secondary outcomes ‐ number of depression‐free days based on episode duration as assessed by the SCID‐I ‐ residual depressive symptoms assessed by the GRID‐HAM‐D and 21‐item self‐report BDI ‐ psychiatric and medical comorbidity using relevant SCID‐I modules and medical comorbidity using the Medical Symptom Checklist ‐ quality of life using the WHO Quality of Life instrument (WHO QoL‐BREF) and health‐related quality of life using the EQ‐5D‐3L (3‐level version) ‐ cost‐effectiveness Assessments for all outcomes at baseline, 1 month after the end of the 8‐week MBCT programme (or equivalent time in the maintenance antidepressant group), which varied between 12 and 24 weeks post randomisation, and at 9, 12, 18, and 24 months post randomisation
Notes	Funding: study supported by a grant from the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme and the NIHR Collaboration for Leadership in Applied Health Research and Care South West Peninsula COI: WK and AE are co‐directors of the Mindfulness Network Community Interest Company and teach nationally and internationally on MBCT. The other study authors declare no competing interests
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Comment: sequence generation by computer random number generator Quote: "participants were randomly assigned to either MBCT‐TS or maintenance antidepressants (in a 1:1 ratio) with a computer‐generated random number sequence with stratification by centre and symptomatic status"
Allocation concealment (selection bias)	Low risk	Comment: central allocation was used to conceal allocation Quote: "allocation was undertaken using a password‐protected website maintained by the Peninsula Clinical Trials Unit, independent of the trial. The trial administrator informed participants of the outcome of randomisation via a letter; research assessors remained masked to treatment allocation for the duration of the follow‐up period"
Blinding of participants and personnel (performance bias) All outcomes	High risk	Comment: blinding of participants and prescribing physician was not possible due to the nature of the intervention. Some outcomes are likely to be influenced by lack of blinding Quote: "in view of the nature of the interventions, patients and clinicians were aware of treatment allocation"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Comment: blinding of outcome assessment ensured; unlikely that the blinding could have been broken Quote: "research assessors remained masked to treatment allocation for the duration of the follow‐up period"
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: dropouts equal between groups and reported at each follow‐up stage of the study. 10% of participants were censored at their last follow‐up for the primary outcome
Selective reporting (reporting bias)	High risk	Comment: study protocol is available; all predefined primary and secondary outcomes were reported in pre‐specified way; only serious adverse events were monitored; other adverse events and withdrawal symptoms were not reported
Other bias	Low risk	None