Huijbers 2016.

Study characteristics
Methods	Design: parallel 2‐group non‐inferiority randomised trial Prerandomisation phases: no Duration post randomisation: 65 weeks (15 months) Aim: to investigate whether mindfulness‐based cognitive therapy (MBCT) with discontinuation of long‐term antidepressant treatment is non‐inferior to MBCT + long‐term antidepressant treatment
Participants	Country: Netherlands Setting: community adults (outpatients from 12 secondary and tertiary psychiatric outpatient clinics, referred by mental healthcare professionals or recruited by advertisements in the media (television, magazines, and newspapers)) Type of AD: SSRI, TCA, other Duration of antidepressant treatment prerandomisation: at least 24 weeks (mean duration not reported) Duration of antidepressant treatment post stabilisation: not reported Primary diagnosis: recurrent depression Number of previous episodes (SD): 5.9 (5.3) discontinuation, 5.6 (4.1) antidepressant Total number of randomised participants: 249 (128 discontinuation, 121 antidepressant) Severity of depressive symptoms at randomisation (IDS‐C), mean (SD): 12.6 (9.6) discontinuation, 12.6 (10.5) antidepressant Number of participants in full remission (IDS‐C ≤ 11), n: 70/128 (55%) discontinuation, 63/121 (52%) antidepressant Number of participants in partial remission (IDS‐C > 11), n: 58/128 (45%) discontinuation, 58/121 (48%) antidepressant Gender distribution (F): 72% intervention, 63% control Mean age, year (SD): 50.7 (10.6) discontinuation, 49.9 (10.5) antidepressant Inclusion criteria ‐ history ≥ 3 depressive episodes (DSM‐IV criteria) ‐ in full or partial remission ‐ currently treated with antidepressants for at least 6 months ‐ 18 years of age or older ‐ Dutch speaking Definition of response/remission: not currently meeting DSM‐IV criteria for major depressive disorder ‐ full remission (IDS‐C ≤ 11) ‐ partial remission (IDS‐C > 11) Exclusion criteria ‐ bipolar disorder ‐ any primary psychotic disorder ‐ clinically relevant neurological/somatic illness ‐ current alcohol or drug dependency ‐ high dosage of benzodiazepines (42 mg lorazepam equivalents daily) ‐ recent electroconvulsive therapy ‐ previous MBCT and/or extensive meditation experience ‐ current psychological treatment with frequency more than once per 3 weeks ‐ inability to complete interviews and self‐report questionnaires
Interventions	Intervention 1: MBCT followed by guided discontinuation of antidepressants (without placebo) Description: MBCT was largely based on the protocol by Segal, Williams, & Teasdale with some adaptations. The intervention consisted of 8 weekly sessions of 2.5 hours and 1 day of silent practice between the sixth and seventh sessions. MBCT included formal meditation exercises such as the body scan, sitting meditation, walking meditation, and mindful movement, as well as informal exercises such as bringing present‐moment awareness to everyday activities. Cognitive–behavioural techniques included education, monitoring and scheduling of activities, identification of negative automatic thoughts, and devising a relapse prevention plan. Participants were encouraged to practice meditation at home for about an hour a day using CDs Delivery: treatment was delivered in groups of 8 to 12 participants at 12 different centres, with a total of 19 teachers and 111 MBCT courses. Groups were mixed, comprising patients from both treatment groups, as well as patients not included in the trial Treatment duration: 8 consecutive weeks Tapering scheme: recommendation to withdraw over a period of 5 weeks, starting after the seventh session of MBCT. A protocol for medication tapering was developed for this study by 2 experts in pharmacological treatment of major depressive disorder. For discontinuation, we recommended a minimum of 3 and a maximum of 12 consultations during the follow‐up period Providers: withdrawal of AD supervised by psychiatrists Adherence to the study protocol was defined as attending 4 or more MBCT sessions, as in previous studies, and having fully discontinued antidepressant before the 6‐month follow‐up assessment (i.e. within 6 months after baseline and within approximately 3 to 4 months after the last MBCT session) Integrity of delivery: videotapes of MBCT sessions were available for 15 teachers. Two tapes per teacher were randomly selected. Teacher competency was examined by 2 independent expert raters, using Mindfulness‐Based Interventions: Teaching Assessment Criteria Intervention 2: MBCT and continuation of antidepressants Description: MBCT as in Intervention 1 For continuation of antidepressant, a minimum of 1 consultation with a psychiatrist was recommended. Psychiatrists were instructed to maintain or reinstate an adequate dose of antidepressants, and recommendations to manage side effects were provided Compliance: adherence to the study protocol was defined as attending 4 or more MBCT sessions and using a therapeutic dose of antidepressant at each follow‐up contact during the observed time period (using last observation carried forward for participants who did not complete all assessments)
Outcomes	Primary outcomes ‐ relapse/recurrence, assessed with SCID‐I every 3 months ‐ definition of relapse, measured with SCID‐I Secondary outcomes ‐ time to relapse/recurrence, calculated in weeks from the start of the study until the start of the first relapse/recurrence ‐ severity of (residual) depressive symptoms, measured with the Dutch version of the IDS‐C at every assessment during 15 months ‐ quality of life, assessed at baseline and at 3 and 15 months using the 26‐item self‐report WHO QoL short version
Notes	Participants with strong treatment preference for MBCT A parallel RCT was comparing MBCT + continuation of antidepressant versus antidepressant alone for patients wanting to hold on to their medication Funding: study was an independent study supported by ZonMW, The Netherlands Organization for Health Research and Development (ZonMW) grant COI: none reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Comments: randomisation was done by using a computer random number generator Quote: "randomisation was performed using a website‐based application, developed specifically for this study by an independent statistician, with a minimisation procedure ... stratified for..."
Allocation concealment (selection bias)	Low risk	Comments: central allocation Quote: “one to one allocation performed online”
Blinding of participants and personnel (performance bias) All outcomes	High risk	Comments: not double‐blinded; results likely to be affected Quote: "unblinding of patients and research assistants could not be avoided"
Blinding of outcome assessment (detection bias) All outcomes	High risk	Comments: no blinding of outcome assessment; results likely to be affected. Quote: "the research assistants conducting the assessments could not be masked to treatment group since they were also involved in the practical organisation of the trial"; "it was impossible to keep the research assistants at the different sites masked to group..."
Incomplete outcome data (attrition bias) All outcomes	High risk	Comment: lost to follow‐up 28% in intervention and 31% in control Quote: "patients whose follow‐up data were unavailable or who did not experience a relapse/recurrence before the end of the follow‐up period were treated as censored observations ..."
Selective reporting (reporting bias)	High risk	Comment: study protocol is available. Depressive symptoms reported only at 3 months ‐ not at other pre‐specified time points. Adverse events and withdrawal symptoms should be reported as this is fundamental in a drug discontinuation trial
Other bias	Low risk	None