Kuyken 2008.

Study characteristics
Methods	Design: randomised controlled trial Prerandomisation phase: no Duration post randomisation: 64 weeks Aim: to examine whether MBCT provides an alternative approach to maintenance ADM in preventing depressive relapse/recurrence
Participants	Country: UK Setting: community adults (primary care practices across a range of urban and rural locations; primary care physicians then screened the list of selected patients and wrote letters to potential participants describing the study, enclosing the study information sheet, and stating that unless they decided to opt out, they would be contacted by a member of the study team) Type of antidepressant: SSRI (58%), TCA (22%), or combination (20%) Duration of antidepressant treatment prerandomisation: 6 months or longer of maintenance treatment; mean time 340 days Duration of antidepressant treatment post stabilisation: not described Primary diagnosis: recurrent depression Number of previous episodes, median: discontinuation 6, antidepressant 6; with more than 10 episodes: 38% discontinuation, 31% continuation Total numbers of randomised participants: 123 (61 discontinuation, 62 antidepressant) Severity of depressive symptoms at randomisation, HDRS score, mean (SD): 5.62 (4.3) discontinuation, 5.76 (4.69) antidepressant In full remission (HDRS < 8), n (%): discontinuation 42 (69%), 41 (66%) antidepressant In partial remission (HDRS ≥ 8), n (%): discontinuation 19 (31%), 21 (34%) antidepressant Gender distribution (male): 77% discontinuation, 76% antidepressant Mean age, years (SD): 48.95 (10.55) discontinuation, 49.37 (11.84) antidepressant Inclusion criteria ‐ ≥ 18 years ‐ recurrent depression (history of ≥ 3 previous episodes) (DSM–IV criteria) ‐ treated with a therapeutic dose of maintenance antidepressant treatment in line with the British National Formulary ≥ previous 6 months ‐ currently in full or partial remission from the most recent episode of depression Definition of remission ‐ full remission: asymptomatic: HDRS < 8, partial remission: HDRS ≥ 8 Exclusion criteria ‐ comorbid diagnoses of current substance dependence ‐ organic brain damage ‐ current/past psychosis ‐ bipolar disorder ‐ persistent antisocial behavior ‐ persistent self‐injury requiring clinical management/therapy ‐ unable to engage with MBCT for physical, practical, or other reasons (e.g. very disabling physical problem, unable to comprehend materials) ‐ formal concurrent psychotherapy
Interventions	Intervention: mindfulness‐based cognitive therapy (MBCT) and support to taper/discontinue antidepressant (no placebo) Tapering scheme: tapering/discontinuation regimens were determined by physicians and patients. Patients and physicians were initially prompted to begin to discuss a tapering/discontinuation regimen after 4 to 5 weeks of MBCT. At the end of MBCT, patients were reminded to ensure a tapering/discontinuation regimen was in place MBCT ‐ mindfulness‐based cognitive therapy was delivered in primary care settings with MBCT groups of 9 to 15 patients following the treatment protocol (Segal, Williams, & Teasdale, 2002) ‐ 2‐hour sessions over 8 consecutive weeks, followed by 4 follow‐up sessions in the following year ‐ session content included guided mindfulness practices (i.e. body scan, sitting meditation, yoga); inquiry into patients’ experience of these practices; review of weekly homework (i.e. 40 minutes of mindfulness practice per day and generalisation of session learning); and teaching/discussion of cognitive–behavioural skills ‐ 5 groups were instructed by trained clinical psychologist or an occupational therapist (both therapists had undergone a training programme taught and supervised by one of the developers of MBCT (John D. Teasdale), had the experience of running at least 2 supervised pilot groups, and had an ongoing personal mindfulness practice). An independent check on therapist competency was established before therapists progressed to running trial groups: an experienced MBCT therapist independent of the trial rated at least 2 videotapes of MBCT therapy sessions and made an overall judgement as to whether the therapists were competent ‐ an adequate dose of MBCT was defined as participation in at least 4 of the 8 MBCT group sessions ‐ patients were supported in tapering and discontinuing their ADM by their primary care physician. Tapering/discontinuation regimens were determined by physicians and patients, although the research team asked that patients consider tapering/discontinuing their medication as soon following MBCT as they deemed appropriate and within 6 months of the MBCT group ending. This allowed (1) tapering to be conducted at a pace determined by physicians and patients and (2) a substantial window to the study’s end when patients had discontinued m‐ADM to monitor primary and secondary outcomes. The study team provided guideline information to physicians and patients about typical tapering/discontinuation regimens and possible withdrawal effects. If at any time the study team became aware of difficulties with medication tapering/ discontinuation, the MBCT therapist first contacted the patient to understand the difficulty, and then whenever appropriate encouraged the patient together with his or her physician to review the tapering/discontinuation regimen Compliance: all trial groups were videotaped with digital cameras for therapist supervision, checks on therapist competence, and checks on treatment adherence Control: maintenance antidepressant treatment ‐ changes in medication sometimes occurred during the maintenance treatment stage, but physicians and participants were asked to ensure the dose remained within therapeutic limits ‐ participants were monitored and treated by their physicians in primary care settings. During the maintenance phase, physicians were asked to manage antidepressant treatment in line with standard clinical practice ‐ primary care physicians were asked to meet with participants regularly to review their medication treatment ‐ protocol adherence was defined as continuing to take m‐ADM at a therapeutic maintenance dose for the duration of the trial ‐ compliance: medication adherence was monitored through patients’ self‐report at follow‐ups every 3 months, practice databases, and the Morisky Medication Adherence Scale (MMAS). If there were ongoing problems with adherence, these were addressed on a case‐by‐case basis with the goal of encouraging patients to continue taking a therapeutic dose of m‐ADM for the duration of the follow‐up period. Protocol adherence was defined as continuing to take antidepressants at a therapeutic maintenance dose for the duration of the trial
Outcomes	Primary outcomes ‐ relapse/recurrence; retrospectively assessed the 3‐month period between assessments every 3 months Definition of relapse/recurrence ‐ an episode meeting DSM–IV criteria for major depressive disorder using structured clinical interview for DSM‐IV Axis I disorders (SCID‐I) Secondary outcomes ‐ severity of relapse/recurrence: using DSM–IV specifiers: “mild,” “moderate,” “severe without psychotic features,” and “severe with psychotic features” (scale range 1 to 4) ‐ duration of relapse/recurrence: period of time in months that a person met SCID‐I criteria ‐ associated distress of relapse/recurrence, which was rated by patients on a 1 to 100‐point scale ranging from 0 (the least distressing episode of depression I have ever experienced) to 100 (the most distressing episode of depression I have ever experienced) ‐ residual depressive symptoms: observer‐rated interviewer‐administered 17‐item version of the HDRS and the 21‐item self‐report BDI ‐ psychiatric comorbidity; comorbid diagnoses identified at intake were reassessed at study end using relevant SCID‐I modules ‐ quality of life: the 26‐item, self‐report, short version of the WHO Quality of Life instrument (WHO QoL‐BREF) ‐ economic evaluation
Notes	Funding: study was supported by a grant from the UK Medical Research Council COI: no financial or other conflicts of interest Pilot trial of Kuyken 2015
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Comment: randomisation by using computer random number generator Quote: "block randomisation (block size 4) to the two groups was performed by an independent statistician using computer‐generated quasi‐random numbers"
Allocation concealment (selection bias)	Low risk	Comment: central allocation concealment Quote: "block randomisation to the two groups was performed by an independent statistician using computer‐generated quasi‐random numbers”
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 Quote: "if problems were identified at any assessment point, these were resolved through dialogue between a member of the research team not blind to treatment condition, the prescribing physician, and the patient, but we ensured that the research officer conducting follow‐ups remained blind to treatment condition"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Comment: outcome assessors are described as blinded to treatment allocation Quote: "patients were assessed by research staff blind to treatment allocation at intake and then again every 3 months up to 15 months post randomisation"
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Comment: low missing outcome data equal across groups (9/61 MBCT group and 10/62 antidepressant group) and reasons reported; inappropriate method used to impute missing data for secondary outcome (see discussion) Quote: "the analysis was performed according to the principle of intention to treat (ITT; i.e. all patients according to and included in random allocation)”; "for the primary survival outcome analyses, drop out/missing data were handled by censoring"; "for the small subset of cases with missing data on secondary outcomes, we used last variable carried forward to impute missing data“
Selective reporting (reporting bias)	High risk	Comment: study protocol available; majority of predefined primary and secondary outcomes reported. Study reported no adverse events but insufficient information about methods to judge. Other adverse events and withdrawal symptoms were not reported Quote: "no adverse events were recorded through the oversight of the Trial Steering Committee"
Other bias	Low risk	No other bias