Antidepressant Monotherapy vs Sequential Pharmacotherapy and Mindfulness-Based Cognitive Therapy, or Placebo, for Relapse Prophylaxis in Recurrent Depression
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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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In Segal 2010, among stable remitters, there was no difference in relapse between discontinuation and continuation groups (50% vs 59%; P=0.49).
“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
The Relapse section reports 50% relapse with placebo after antidepressant taper versus 59% with maintenance antidepressants among stable remitters, with P=.49 for that comparison. However, the Study Phases section defines stable remission as HRSD scores ≤7, not ≥7 as the citing sentence states. The cited passages also do not establish the sentence’s suggestion about withdrawal symptoms. (LLM, conf=0.90)
Experimental — accuracy not yet measuredIn Segal 2010, among unstable remitters, the discontinuation group had a higher risk of relapse than the continuation group (71% vs 27%; HR 4.16, 95% CI 1.12 to 14.3; P=0.03).
“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
The Relapse section reports adjusted relapse rates of 71% for placebo (antidepressant discontinuation) and 27% for maintenance antidepressants among unstable remitters, with P=.03. Its hazard ratio is expressed in the opposite direction: 0.24 (95% CI 0.07–0.89) for maintenance antidepressants versus placebo, approximately 4.16 (1.12–14.3) when inverted. The Study Phases section defines unstable remission by occasional elevated HRSD scores of 8–14, not by a score of ≥7, as the citing sentence states. Page numbers are unavailable in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn the second study, 84 patients with recurrent depression who had remitted on antidepressants were randomly assigned to MBCT-TS, maintenance antidepressants, or pill placebo; over 18 months of follow-up, relapse or recurrence rates did not differ 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).
“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]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredResidual symptoms of depression have been shown to increase the chances of a relapse.
“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
The Study Phases section (page unavailable) defines unstable remission by intermittent depressive symptoms, and the Relapse section reports substantial relapse among unstable remitters receiving placebo. The paper links residual symptoms with relapse prevention, but these treatment comparisons do not establish that residual symptoms themselves increase the chance of relapse. (LLM, conf=0.76)
Experimental — accuracy not yet measuredIn Segal 2010, there was no difference between discontinuation with MBCT and continuation of antidepressants in unstable remitters (28% vs 27%; HR 1.07, 95% CI 0.25 to 4.49; P = 0.93).
“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
In Segal 2010, there was no difference between discontinuation with MBCT and continuation of antidepressants in stable remitters (62% vs 59%; P = 0.77).
“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
Before this study, only two small studies had compared MBCT-TS with maintenance antidepressants.
“Before this study, only two small studies 10,39 had compared MBCT-TS with maintenance antidepressants (panel).”
Pooling this trial's data with the equivalent MBCT-TS and maintenance antidepressant groups of the previous two randomised controlled trials (n=123 and n=54) at the equivalent 60-week follow-up gave a combined relative risk ratio of 0.76 (95% CI 0.59-0.98), a risk reduction of 24%, with no evidence of statistical heterogeneity.
“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”
In two studies, the relapse prevention effect of psychological intervention plus discontinuation of ADM was not significant.
“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]
Fava et al. [87] and Fava et al. [88] had a follow-up period of 29 months, and Segal et al. [89] had a follow-up of 18 months.
“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]
Mindfulness-based cognitive psychotherapy was about as effective as long-term treatment with an antidepressant in one trial.
“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
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, unstable remission, or a history of childhood trauma.
“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]
MBIs show unevenness in preventing relapse of MDD depending on lifetime episodes.
“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 studies comparing MBCT to antidepressant medication, no overall significant advantage to MBCT was demonstrated, and no advantage was observed by adding MBCT to antidepressant medication.
“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]
Long-term follow-up studies show that both MBCT and antidepressants can each confer enduring positive effects and thus MBCT may offer an alternative to medication in some cases.
“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]
MBCT appears to be at least as effective as mADM.
“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
Studies comparing MBCT with mADM did not show any differences between the effectiveness of MBCT and that of mADM.
“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
The relapse/recurrence rate in our medication only condition of 37% was substantially lower than that of comparable studies.
“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
The overall teacher competency in our study was lower than in previous studies.
“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
Residual symptoms are associated with better treatment response to MBCT.
“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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“, 2000), unstable remission (Segal et al., 2010), and childhood trauma (Kuyken et al.”
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“However, one trial found it to be about as effective as long-term treatment with an antidepressant (Segal et al., 2010), and others found beneficial effects among patients with at least three previous depressive episodes (Teasdale et al.”
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“Psychotherapists and clinicians use both to treat similar types of conditions, such as major depression (Lynn et al. 2010; Segal et al. 2010; Alladin 2014), acute or chronic pain (Patterson and Jensen 2003; Chiesa and Serretti 2011), and substance abuse (Barnes et al. 2010; Brewer et al. 2010).”
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“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.”
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“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.”
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- 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 › 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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