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Antidepressant Monotherapy vs Sequential Pharmacotherapy and Mindfulness-Based Cognitive Therapy, or Placebo, for Relapse Prophylaxis in Recurrent Depression
Open accessAbstract
CONTEXT: Mindfulness-based cognitive therapy (MBCT) is a group-based psychosocial intervention designed to enhance self-management of prodromal symptoms associated with depressive relapse. OBJECTIVE: To compare rates of relapse in depressed patients in remission receiving MBCT against maintenance antidepressant pharmacotherapy, the current standard of care. DESIGN: Patients who met remission criteria after 8 months of algorithm-informed antidepressant treatment were randomized to receive maintenance antidepressant medication, MBCT, or placebo and were followed up for 18 months. SETTING: Outpatient clinics at the Centre for Addiction and Mental Health, Toronto, Ontario, Canada, and St Joseph's Healthcare, Hamilton, Ontario. PARTICIPANTS: One hundred sixty patients aged 18 to 65 years meeting DSM-IV criteria for major depressive disorder with a minimum of 2 past episodes. Of these, 84 achieved remission (52.5%) and were assigned to 1 of the 3 study conditions. INTERVENTIONS: Patients in remission discontinued their antidepressants and attended 8 weekly group sessions of MBCT, continued taking their therapeutic dose of antidepressant medication, or discontinued active medication and were switched to placebo. MAIN OUTCOME MEASURE: Relapse was defined as a return, for at least 2 weeks, of symptoms sufficient to meet the criteria for major depression on module A of the Structured Clinical Interview for DSM-IV. RESULTS: Intention-to-treat analyses showed a significant interaction between the quality of acute-phase remission and subsequent prevention of relapse in randomized patients (P = .03). Among unstable remitters (1 or more Hamilton Rating Scale for Depression score >7 during remission), patients in both MBCT and maintenance treatment showed a 73% decrease in hazard compared with placebo (P = .03), whereas for stable remitters (all Hamilton Rating Scale for Depression scores ≤7 during remission) there were no group differences in survival. CONCLUSIONS: For depressed patients achieving stable or unstable clinical remission, MBCT offers protection against relapse/recurrence on a par with that of maintenance antidepressant pharmacotherapy. Our data also highlight the importance of maintaining at least 1 long-term active treatment in unstable remitters.
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“For stable remitters (all HAM-D scores ≥ 7 during remission), there were no differences in relapse of absence of withdrawal symptoms measured a er antidepressants were tapered (relapse rates: 50% discontinuation group, 59% antidepressant group; HR not reported; P = 0.49).”
From Approaches for discontinuation versus continuation of long-term antidepressant use for depressive and anxiety disorders in adults (2021) · cites this paper as Segal 2010
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Among unstable remitters (one or more with HAM-D score ≥ 7 during remission), participants in the discontinuation group showed higher risk of relapse compared with those in the continuation group (relapse rates: discontinuation group 71%, 27% antidepressant; HR 4.16, 95% CI 1.12 to 14.3; P = 0.03).”
From Approaches for discontinuation versus continuation of long-term antidepressant use for depressive and anxiety disorders in adults (2021) · cites this paper as Segal 2010
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In the second study, 39 84 patients with recurrent depression who had remitted on antidepressants were randomly assigned to MBCT-TS, maintenance antidepressants, or pill placebo.Relapse or recurrence rates noted over 18 months of follow-up did not diff er for MBCT-TS (28%, n=5/18) and maintenance antidepressants (27%, n=3/11), but both were lower than with placebo (71%, n=10/14).39”
From 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 (2015) · cites this paper as [39]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Psychotherapy undertaken during a relapse prevention phase tends to focus on addressing any residual symptoms of depression, which have been shown to increase the chances of a relapse, on affect regulation and on self management skills needed to promote recovery (Segal 2010).”
From Interventions for preventing relapse and recurrence of a depressive disorder in children and adolescents (2012) · cites this paper as Segal 2010
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“and unstable remitters (28% for MBCT and discontinuation, 27% for continuation of antidepressant; HR 1.07, 95% CI 0.25 to 4.49; P = 0.93).”
From Approaches for discontinuation versus continuation of long-term antidepressant use for depressive and anxiety disorders in adults (2021) · cites this paper as Segal 2010
The cited source says what the claim attributes to it.
In the citing paper
“However, there was no difference between discontinuation with MBCT and continuation of antidepressants in stable remitters (62% for MBCT and discontinuation, 59% for continuation of antidepressant; P = 0.77)”
From Approaches for discontinuation versus continuation of long-term antidepressant use for depressive and anxiety disorders in adults (2021) · cites this paper as Segal 2010
The cited source says what the claim attributes to it.
In the citing paper
“In addition, MBCT appears to be at least as effective as mADM (Kuyken et al., 2008;Kuyken et al., 2015;Segal et al., 2010).”
From Adding mindfulness-based cognitive therapy to maintenance antidepressant medication for prevention of relapse/recurrence in major depressive disorder: Randomised controlled trial (2015) · cites this paper as Segal et al., 2010
The cited source says what the claim attributes to it.
In the citing paper
“Before this study, only two small studies 10,39 had compared MBCT-TS with maintenance antidepressants (panel).”
The cited source says what the claim attributes to it.
In the citing paper
“We pooled our trial data with the equivalent MBCT-TS and maintenance antidepressant medication groups of the previous two randomised controlled trials (n=123 10 and n=54 39 ), and used the equivalent 60-week follow-up point available across all three studies.The combined relative risk ratio of MBCT-TS versus maintenance antidepressants was 0•76 (95% CI 0•59-0•98), a risk reduction of 24%.There was”
The cited source says what the claim attributes to it.
In the citing paper
“The relapse prevention effect was not significant in the other two studies [87, 89].”
From Psychological interventions to prevent relapse in anxiety and depression: A systematic review and meta-analysis (2022) · cites this paper as [89]
The cited source says what the claim attributes to it.
In the citing paper
“Fava et al. [87] and Fava et al. [88] both had a follow-up period of 29 months and Segal et al. [89] had a follow up of 18 months.”
From Psychological interventions to prevent relapse in anxiety and depression: A systematic review and meta-analysis (2022) · cites this paper as [89]
The cited source says what the claim attributes to it.
In the citing paper
“However, one trial found it to be about as effective as long-term treatment with an antidepressant (Segal et al., 2010)”
From Prevention of Relapse and Recurrence in Adults with Major Depressive Disorder: Systematic Review and Meta-Analyses of Controlled Trials (2016) · cites this paper as Segal et al., 2010
The cited source says what the claim attributes to it.
In the citing paper
“evidence has accrued to suggest that MBCT may only be efficacious or advantageous over other forms of aftercare for those patients with greater vulnerability, in the form of recurrent depression, 97,98 unstable remission, 99,100 or a history of childhood trauma 98”
From Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder (2016) · cites this paper as [99]
In the citing paper
“MBIs also evidence unevenness in preventing relapse of MDD (e.g., 3+ versus >3 lifetime episodes) [30]”
From All together now: utilizing common functional change principles to unify cognitive behavioral and mindfulness-based therapies (2019) · cites this paper as [30]
In the citing paper
“In all those studies that compared MBCT to antidepressant medication, no overall significant advantage to MBCT was demonstrated 12,[20][21][22]35 and no advantage was observed by adding MBCT to antidepressant medication.20”
From Mindfulness-based cognitive therapy for prevention and time to depressive relapse: Systematic review and network meta-analysis (2021) · cites this paper as [12]
In the citing paper
“However, long-term follow-up studies also show that both MBCT and antidepressants can each confer enduring positive effects and thus MBCT may offer an alternative to medication in some cases.12,34,35”
From Mindfulness-based cognitive therapy for prevention and time to depressive relapse: Systematic review and network meta-analysis (2021) · cites this paper as [12]
In the citing paper
“Studies comparing MBCT with mADM (Kuyken et al., 2008;Segal et al., 2010;Kuyken et al., 2015) did not show any differences between the effectiveness of MBCT and that of mADM either.”
From Adding mindfulness-based cognitive therapy to maintenance antidepressant medication for prevention of relapse/recurrence in major depressive disorder: Randomised controlled trial (2015) · cites this paper as Segal et al., 2010
In the citing paper
“but the relapse/recurrence rate in our medication only condition of 37% was substantially lower than that of comparable studies (Kuyken et al., 2008;Kuyken et al., 2015;Segal et al., 2010).”
From Adding mindfulness-based cognitive therapy to maintenance antidepressant medication for prevention of relapse/recurrence in major depressive disorder: Randomised controlled trial (2015) · cites this paper as Segal et al., 2010
In the citing paper
“The overall teacher competency in our study was lower than in previous studies (Kuyken et al., 2008;Kuyken et al., 2015;Segal et al., 2010)”
From Adding mindfulness-based cognitive therapy to maintenance antidepressant medication for prevention of relapse/recurrence in major depressive disorder: Randomised controlled trial (2015) · cites this paper as Segal et al., 2010
In the citing paper
“residual symptoms (Segal et al., 2010)”
From Adding mindfulness-based cognitive therapy to maintenance antidepressant medication for prevention of relapse/recurrence in major depressive disorder: Randomised controlled trial (2015) · cites this paper as Segal et al., 2010
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When mindfulness is therapy: Ethical qualms, historical perspectives.
Harrington, A., & Dunne, J. D. (2015) · American Psychologist · doi:10.1037/a0039460 · Cited by 135
Farb, N. A. S., Anderson, A. K., Bloch, R. T., & Segal, Z. V. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.03.009 · Cited by 141
Self-citationA randomized controlled trial of mindfulness‐based cognitive therapy for bipolar disorder
Perich, T., Manicavasagar, V., Mitchell, P. B., Ball, J. R., & Hadzi‐Pavlovic, D. (2013) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.12033 · Cited by 136
Bockting, C. L. H., Klein, N. S., Elgersma, H. J., van Rijsbergen, G. D., Slofstra, C., Ormel, J., Buskens, E., Dekker, J., de Jong, P. J., Nolen, W. A., et al. (2018) · The Lancet Psychiatry · doi:10.1016/s2215-0366(18)30100-7 · Cited by 130
Kovács, M., Obrosky, D. S., & George, C. J. (2016) · Journal of Affective Disorders · doi:10.1016/j.jad.2016.05.042 · Cited by 140
Dimidjian, S., Goodman, S. H., Felder, J. N., Gallop, R., Brown, A. P., & Beck, A. (2015) · Archives of Women's Mental Health · doi:10.1007/s00737-014-0468-x · Cited by 118
Mindfulness-Based Cognitive Therapy With Older Adults: An Exploratory Study
Foulk, M. A., Ingersoll-Dayton, B., Kavanagh, J., Robinson, E., & Kales, H. C. (2014) · Journal of Gerontological Social Work · doi:10.1080/01634372.2013.869787 · Cited by 115
Wakefield, J. C. (2013) · Clinical Psychology Review · doi:10.1016/j.cpr.2013.03.007 · Cited by 115
Bédard, M., Felteau, M., Marshall, S., Cullen, N. K., Gibbons, C., Dubois, S. J., Maxwell, H., Mazmanian, D. S., Weaver, B., Rees, L. M., et al. (2013) · Journal of Head Trauma Rehabilitation · doi:10.1097/htr.0b013e3182a615a0 · Cited by 115
Clarke, K., Mayo-Wilson, E., Kenny, J., & Pilling, S. (2015) · Clinical Psychology Review · doi:10.1016/j.cpr.2015.04.002 · Cited by 113
Britton, W. B., Davis, J. H., Loucks, E. B., Peterson, B., Cullen, B. H., Reuter, L., Rando, A., Rahrig, H., Lipsky, J., & Lindahl, J. R. (2018) · Behaviour Research and Therapy · doi:10.1016/j.brat.2017.09.010 · Cited by 100
“Following the methods of other multi-arm MBCT and MBSR trials (Ong, Hedeker, Wyatt, & Manber, 2016; Segal et al., 2010) treatment allocation was performed at the group level.”
Ormel (2019) · doi:10.1097/yco.0000000000000505 · Cited by 102
Kechter, A., Amaro, H., & Black, D. S. (2019) · Mindfulness · doi:10.1007/s12671-018-0974-4 · Cited by 102
“For example, one article reported holding a 7-day intensive training for interventionists (Segal et al. 2010) while another reported assessing interventionists for competence and adherence and interventionists only progressed to delivering the intervention if all domains were clearly established (Kuyken et al.”
BackgroundCotton, S., Luberto, C. M., Sears, R. W., Strawn, J. R., Stahl, L., Wasson, R. S., Blom, T. J., & Delbello, M. P. (2016) · Early Intervention in Psychiatry · doi:10.1111/eip.12216 · Cited by 96
Van Leeuwen, E., van Driel, M. L., Horowitz, M. A., Kendrick, T., Donald, M., De Sutter, A. I., Robertson, L., & Christiaens, T. (2021) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd013495.pub2 · Cited by 90
Zhang, Z., Zhang, L., Zhang, G., Jin, J., & Zheng, Z. (2018) · BMC Psychiatry · doi:10.1186/s12888-018-1610-5 · Cited by 99
Don't Forget Your Body: Mindfulness, Embodiment, and the Treatment of Depression
Michalak, J., Burg, J. M., & Heidenreich, T. (2012) · Mindfulness · doi:10.1007/s12671-012-0107-4 · Cited by 117
Hawley, L. L., Padesky, C. A., Hollon, S. D., Mancuso, E., Laposa, J. M., Brozina, K., & Segal, Z. V. (2016) · Behavior Therapy · doi:10.1016/j.beth.2016.09.003 · Cited by 105
Self-citationVago, D. R., & Nakamura, Y. (2011) · Cognitive Therapy and Research · doi:10.1007/s10608-011-9391-x · Cited by 93
Relationship between dispositional mindfulness and substance use: Findings from a clinical sample
Bowen, S., & Enkema, M. C. (2014) · Addictive Behaviors · doi:10.1016/j.addbeh.2013.10.026 · Cited by 92
Complementary Therapies for Mental Health Disorders
Asher, G. N., Gerkin, J., & Gaynes, B. N. (2017) · Medical Clinics of North America · doi:10.1016/j.mcna.2017.04.004 · Cited by 93
McCartney, M., Nevitt, S., Lloyd, A., Hill, R., White, R., & Duarte, R. (2021) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.13242 · Cited by 93
Ribeiro, L., Atchley, R. M., & Oken, B. S. (2018) · Mindfulness · doi:10.1007/s12671-017-0781-3 · Cited by 91
Geschwind, N., Peeters, F., Huibers, M., van Os, J., & Wichers, M. (2012) · British Journal of Psychiatry · doi:10.1192/bjp.bp.111.104851 · Cited by 89
Chiesa, A., Castagner, V., Andrisano, C., Serretti, A., Mandelli, L., Porcelli, S., & Giommi, F. (2015) · Psychiatry Research · doi:10.1016/j.psychres.2015.02.003 · Cited by 89
de Abreu Costa, M., D’Alò de Oliveira, G. S., Tatton-Ramos, T., Manfro, G. G., & Salum, G. A. (2019) · Mindfulness · doi:10.1007/s12671-018-1058-1 · Cited by 85
Dimidjian, S., Beck, A., Felder, J. N., Boggs, J. M., Gallop, R., & Segal, Z. V. (2014) · Behaviour Research and Therapy · doi:10.1016/j.brat.2014.09.004 · Cited by 87
“…with evidence provided by secondary analyses reported in MBCT trials whose primary outcomes were differences in relapse rates (Kuyken et al., 2008; Segal et al., 2010) and randomized trials targeting RDS as a primary aim, with moderate to large effect sizes for MBCT in reducing RDS as compared to…”
ResultSelf-citationPreventing Depressive Relapse and Recurrence in Higher-Risk Cognitive Therapy Responders
Jarrett, R. B., Minhajuddin, A., Gershenfeld, H. K., Friedman, E. S., & Thase, M. E. (2013) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2013.1969 · Cited by 87
Michalak, J., Schultze, M., Heidenreich, T., & Schramm, E. (2015) · Journal of Consulting and Clinical Psychology · doi:10.1037/ccp0000042 · Cited by 86
Monshat, K., Khong, B. S. L., Hassed, C. S., Vella‐Brodrick, D., Norrish, J. M., Burns, J., & Herrman, H. (2012) · Journal of Adolescent Health · doi:10.1016/j.jadohealth.2012.09.008 · Cited by 100
Redei, E. E., Andrus, B. M., Kwasny, M. J., Seok, J., Cai, X., Ho, J., & Mohr, D. C. (2014) · Translational Psychiatry · doi:10.1038/tp.2014.66 · Cited by 83
Shallcross, A. J., Gross, J. J., Visvanathan, P. D., Kumar, N., Palfrey, A., Ford, B. Q., Dimidjian, S., Shirk, S., Holm-Denoma, J., Goode, K. M., et al. (2015) · Journal of Consulting and Clinical Psychology · doi:10.1037/ccp0000050 · Cited by 81
Kuyken, W., Hayes, R. A., Barrett, B. M., Byng, R., Dalgleish, T., Kessler, D. S., Lewis, G., Watkins, E. R., Morant, N. J., Taylor, R. S., et al. (2015) · Health Technology Assessment · doi:10.3310/hta19730 · Cited by 81
Grensman, A., Acharya, B. D., Wändell, P. E., Nilsson, G. H., Falkenberg, T., Sundin, Ö., & Werner, S. (2018) · BMC Complementary and Alternative Medicine · doi:10.1186/s12906-018-2141-9 · Cited by 95
Barnhofer, T., Crane, C., Brennan, K., Duggan, D. S., Crane, R. S., Eames, C., Radford, S., Silverton, S., Fennell, M. J. V., & Williams, J. M. G. (2015) · Journal of Consulting and Clinical Psychology · doi:10.1037/ccp0000027 · Cited by 80
“In fact, previous research has found that MBCT produced better effects in patients with unstable remissions as compared to those with stable remissions (Segal et al., 2010).”
ResultGalante, J., Iribarren, S. J., & Pearce, P. F. (2013) · Journal of Research in Nursing · doi:10.1177/1744987112466087 · Cited by 79
Khusid, M. A., & Vythilingam, M. (2016) · Military Medicine · doi:10.7205/milmed-d-14-00677 · Cited by 77
Effects of compassion meditation on a psychological model of charitable donation.
Ashar, Y. K., Andrews-Hanna, J. R., Yarkoni, T., Sills, J., Halifax, J., Dimidjian, S., & Wager, T. D. (2016) · Emotion · doi:10.1037/emo0000119 · Cited by 78
A two-factor model of relapse/recurrence vulnerability in unipolar depression
Farb, N. A. S., Irving, J. A., Anderson, A. K., & Segal, Z. V. (2015) · Journal of Abnormal Psychology · doi:10.1037/abn0000031 · Cited by 75
Self-citationMindfulness-based cognitive therapy for depression: trends and developments
Kocovski, N. L., & MacKenzie, M. B. (2016) · Psychology Research and Behavior Management · doi:10.2147/prbm.s63949 · Cited by 74
Should treatment for depression be based more on patient preference?
Winter, S., & Barber, J. (2013) · Patient Preference and Adherence · doi:10.2147/ppa.s52746 · Cited by 73
Brooker, J., Julian, J., Webber, L., Chan, J., Shawyer, F., & Meadows, G. (2013) · Mindfulness · doi:10.1007/s12671-012-0112-7 · Cited by 72
An Examination of Mindfulness-Based Programs in US Medical Schools
Barnes, N., Hattan, P., Black, D. S., & Schuman‐Olivier, Z. (2016) · Mindfulness · doi:10.1007/s12671-016-0623-8 · Cited by 78
Neurophysiological Mechanisms Supporting Mindfulness Meditation–Based Pain Relief: an Updated Review
Jinich-Diamant, A., Garland, E., Baumgartner, J., Gonzalez, N., Riegner, G., Birenbaum, J., Case, L., & Zeidan, F. (2020) · Current Pain and Headache Reports · doi:10.1007/s11916-020-00890-8 · Cited by 69
Metadata
- Authors
- Segal, Z. V., Bieling, P., Young, T., MacQueen, G., Cooke, R., Martin, L., Bloch, R., & Levitan, R. D.
- Affiliations
- Centre for Addiction and Mental Health (CA)
- University of British Columbia (CA)
- Corresponding author
- Segal, Zindel V.
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2010-12-06
- Volume
- 67
- Issue
- 12
- Pages
- 1256
- ISSN
- 0003-990X (ISSN-L)
- PMC
- PMC3311113
- OpenAlex
- W2153222062
- Cited by
- 429
- References
- 59
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 10 · 2023: 16 · 2022: 14 · 2021: 18 · 2020: 31 · 2019: 29 · 2018: 23 · 2017: 20 · 2016: 44 · 2015: 51 · 2014: 35 · 2013: 37 · 2012: 52
- FWCI
- 28.64
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01MH066992)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Social Sciences › Psychology › Clinical Psychology › Mindfulness and Compassion Interventions
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- recurrent depression, relapse prevention, mindfulness-based cognitive therapy, antidepressant monotherapy, major depressive disorder, prodromal symptoms
- MeSH terms
- Adolescent, Adult, Aged, Antidepressive Agents, Attention, Combined Modality Therapy, Major Depressive Disorder, Drug Administration Schedule, Female, Follow-Up Studies, Humans, Male, Middle Aged, Ontario, Outpatients, Psychiatric Status Rating Scales, Psychotherapy, Group, Cognitive Behavioral Therapy, Treatment Outcome, Diagnostic and Statistical Manual of Mental Disorders, Secondary Prevention, Young Adult
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