A Randomized Controlled Trial of Mindfulness-Based Cognitive Therapy for Treatment-Resistant Depression
Open accessAbstract
Background: Due to the clinical challenges of treatment-resistant depression (TRD), we evaluated the efficacy of mindfulness-based cognitive therapy (MBCT) relative to a structurally equivalent active comparison condition as adjuncts to treatment-as-usual (TAU) pharmacotherapy in TRD. Methods: This single-site, randomized controlled trial compared 8-week courses of MBCT and the Health Enhancement Program (HEP), comprising physical fitness, music therapy and nutritional education, as adjuncts to TAU pharmacotherapy for outpatient adults with TRD. The primary outcome was change in depression severity, measured by percent reduction in the total score on the 17-item Hamilton Depression Rating Scale (HAM-D 17), with secondary depression indicators of treatment response and remission. Results: We enrolled 173 adults; mean length of a current depressive episode was 6.8 years (SD = 8.9). At the end of 8 weeks of treatment, a multivariate analysis showed that relative to the HEP condition, the MBCT condition was associated with a significantly greater mean percent reduction in the HAM-D 17 (36.6 vs. 25.3%; p = 0.01) and a significantly higher rate of treatment responders (30.3 vs. 15.3%; p = 0.03). Although numerically superior for MBCT than for HEP, the rates of remission did not significantly differ between treatments (22.4 vs. 13.9%; p = 0.15). In these models, state anxiety, perceived stress and the presence of personality disorder had adverse effects on outcomes. Conclusions: MBCT significantly decreased depression severity and improved treatment response rates at 8 weeks but not remission rates. MBCT appears to be a viable adjunct in the management of TRD.
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Mindfulness-based cognitive therapy combines mindfulness practice with cognitive therapy elements and has been shown to prevent depression relapse and improve anxiety symptoms.
“Mindfulness-based cognitive therapy (MBCT) is a newer MBI that combines mindfulness practice with cognitive therapy elements and has been shown to prevent depression relapse and improve anxiety symptoms (Eisendrath et al., 2016; Evans et al., 2008; Kuyken et al., 2015; Segal et al., 2013; Tickell et al., 2020).”
From Online Mindfulness-Based Cognitive Therapy for People with Parkinson’s Disease and Their Caregivers: a Pilot Study (2022) · cites this paper as Eisendrath et al., 2016
The Methods (Study Treatment Interventions; page unavailable) describe MBCT as using meditation and cognitive-behavioral exercises. The Introduction (page unavailable) reports evidence that MBCT prevents depressive relapse in patients who had achieved remission. The Results discuss anxiety as a predictor of poorer depression-treatment response, not as a symptom shown to improve with MBCT. (LLM, conf=0.88)
Experimental — accuracy not yet measuredChildhood trauma predicts poorer outcomes in MBCT treatment for active depression yet better outcomes when MBCT is used as a relapse prevention program in remitted individuals who are not currently depressed.
“Such findings indicate that childhood trauma predicts poorer outcomes in MBCT treatment for active depression [13, 14] yet better outcomes when MBCT is used as a relapse prevention program in remitted individuals who are not currently depressed [11, 12].”
From Childhood trauma and subclinical PTSD symptoms predict adverse effects and worse outcomes across two mindfulness-based programs for active depression (2025) · cites this paper as [14]
The Results report that higher childhood emotional-abuse scores were associated with poorer response and remission in this active-depression trial. However, emotional abuse was the only childhood-trauma subscale with a significant association, and it did not predict outcomes differently for MBCT versus the control treatment. The relapse-prevention clause is attributed to other citations, not this paper. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIn a randomized controlled trial, MBCT was significantly more efficacious than treatment-as-usual in reducing depression severity in treatment-resistant depression, but not in the number of cases who remitted.
“MBCT was significantly more efficacious than TAU in reducing depression severity, but not the number of cases who remitted.”
From The pursuit of euthymia (2020) · cites this paper as [92]
The Results report a significantly greater reduction in depression severity with MBCT and no statistically significant difference in remission rates. But the Abstract Methods and Introduction identify the comparator as the Health-Enhancement Program (HEP), with treatment-as-usual pharmacotherapy given in both arms—not TAU alone. Page numbers are unavailable in our copy. (LLM, conf=0.91)
Experimental — accuracy not yet measuredIn that trial, MBCT and control groups did not differ significantly in depression remission rates.
“Despite these promising findings, the MBCT and control groups did not differ significantly on rates of depression remission, suggesting that the effects of MBCT were not strong enough to impact full disorder remission.”
From Mindfulness-Based Interventions for Anxiety and Depression (2017) · cites this paper as [55]
In a trial of modified MBCT for treatment-resistant depression, MBCT reduced posttreatment depressive symptoms compared with an active control (Health Enhancement Program).
“In one of these trials, Eisendrath and colleagues55 tested the efficacy of a modified MBCT program for individuals with current treatment-resistant depression. Results showed that MBCT reduced depressive symptoms posttreatment compared to a well-matched active control program (Health Enhancement Program, or HEP).”
From Mindfulness-Based Interventions for Anxiety and Depression (2017) · cites this paper as [55]
Mindfulness meditation is effective for sleep problems, anxiety, and depression, which often co-occur with pain in Veterans.
“MM has also been shown to be effective for treating conditions frequently co-occurring with pain in Veterans, including sleep problems[32, 33], anxiety,[31, 34] and depression.[35, 36]”
From The chronic pain skills study: Protocol for a randomized controlled trial comparing hypnosis, mindfulness meditation and pain education in Veterans (2020) · cites this paper as [36]
Of the five studies assessing self-compassion as a mediator, only Eisendrath et al. (2016) did not find an effect of change in self-compassion on their primary outcome.
“Of the five studies assessing self-compassion as a mediator, only Eisendrath et al. (2016) did not find an effect of change in self-compassion on their primary outcome.”
From Effectiveness of Self-Compassion Related Therapies: a Systematic Review and Meta-analysis (2019) · cites this paper as Eisendrath et al. (2016)
An RCT investigating MBCT for active treatment-resistant depression showed reduced likelihood of treatment response and remission in individuals with a history of childhood emotional abuse.
“Moreover, an RCT investigating MBCT for active treatment-resistant depression showed reduced likelihood of treatment response and remission in individuals with a history of childhood emotional abuse [14].”
From Childhood trauma and subclinical PTSD symptoms predict adverse effects and worse outcomes across two mindfulness-based programs for active depression (2025) · cites this paper as [14]
Research is beginning to identify practitioner-level factors, such as trauma history or psychiatric conditions, that may influence meditation-related outcomes or require modifications in teacher training, program structure, or inclusion and exclusion criteria.
“For example, research is beginning to identify practitioner-level factors, such as trauma history [61, 164] or psychiatric conditions [165], that may influence meditation-related outcomes or require modifications in teacher training, program structure, or inclusion and exclusion criteria [166].”
From The varieties of contemplative experience: A mixed-methods study of meditation-related challenges in Western Buddhists (2017) · cites this paper as [164]
The protocol was adapted from an earlier MBCT protocol for people with PD by shortening sessions, removing mindful eating, and substituting chair yoga for full-body yoga.
“Modifications included shortening sessions from 2.5 h to 90 min in order to accommodate motor or non-motor (anxiety, attention, and mood changes) fluctuations; eliminating the mindful eating exercise (which could be perceived as insensitive by people with PD, who often have anosmia); and performing chair yoga instead of full body yoga.”
From Online Mindfulness-Based Cognitive Therapy for People with Parkinson’s Disease and Their Caregivers: a Pilot Study (2022) · cites this paper as Eisendrath et al., 2016
The Methods (Study Treatment Interventions; page unavailable) describe adapting MBCT for treatment-resistant depression, not Parkinson’s disease. They mention shorter meditations but do not describe 90-minute sessions, removal of mindful eating, or chair yoga. Searches for those modifications and PD found no supporting passage in our copy. (LLM, conf=0.78)
Experimental — accuracy not yet measuredMindfulness-based cognitive therapy is as effective as medication in preventing depression relapse among adults with a history of recurrent depression.
“Studies suggest that mindfulness-based cognitive therapy is as effective as medication in preventing depression relapse among adults with a history of recurrent depression and in reducing depressive symptoms among those with active depression [39,40].”
From The Impact of an Online Mindfulness-Based Practice Program on the Mental Health of Brazilian Nurses during the COVID-19 Pandemic (2023) · cites this paper as [40]
Mindfulness-based cognitive therapy reduces depressive symptoms among those with active depression.
“Studies suggest that mindfulness-based cognitive therapy is as effective as medication in preventing depression relapse among adults with a history of recurrent depression and in reducing depressive symptoms among those with active depression [39,40].”
From The Impact of an Online Mindfulness-Based Practice Program on the Mental Health of Brazilian Nurses during the COVID-19 Pandemic (2023) · cites this paper as [40]
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BackgroundMethodInfluentialClosed-loop digital meditation improves sustained attention in young adults
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ter Avest, M. J., Dusseldorp, E., Huijbers, M., van Aalderen, J. V., Cladder-Micus, M. B., Spinhoven, P., Greven, C., & Speckens, A. (2019) · Behaviour Research and Therapy · doi:10.1016/j.brat.2019.103467 · Cited by 13 · see citing works
Lubbers, J., Geurts, D. E. M., Spinhoven, P., Cladder-Micus, M. B., Ennen, D., Speckens, A. E. M., & Spijker, J. (2024) · Depression and Anxiety · doi:10.1155/da/3511703 · Cited by 10 · see citing works
An App-Based Workplace Mindfulness Intervention, and Its Effects Over Time
Lu, Y., Remond, J., Bunting, M., Ilieș, R., Tripathi, N., & Narayanan, J. (2021) · Frontiers in Psychology · doi:10.3389/fpsyg.2021.615137 · Cited by 10 · see citing works
Garcia-Toro, M., Aguilar-Latorre, A., Garcia, A., Navarro-Guzmán, C., Gervilla, E., Seguí, A., Gazquez, F., Marino, J. A., Gomez-Juanes, R., Serrano-Ripoll, M. J., et al. (2023) · Frontiers in Psychology · doi:10.3389/fpsyg.2023.1008891 · Cited by 10 · see citing works
Mindfulness for academic performance in health professions students: a systematic review
Lekamge, R. B., Gasevic, D., Karim, M. N., & Ilic, D. (2022) · BMJ evidence-based medicine · doi:10.1136/bmjebm-2021-111853 · Cited by 7 · see citing works
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- Authors
- Eisendrath, S. J., Gillung, E., Delucchi, K. L., Segal, Z. V., Nelson, J. C., McInnes, L. A., Mathalon, D. H., & Feldman, M. D.
- Affiliations
- University of California, San Francisco (US)
- ORCID
- Venue
- Psychotherapy and Psychosomatics
- Publisher
- S. Karger AG
- Published
- 2016
- Volume
- 85
- Issue
- 2
- Pages
- 99-110
- ISSN
- 0033-3190 (ISSN-L)
- 1423-0348
- PMC
- PMC4756643
- OpenAlex
- W2252873284
- Cited by
- 187
- References
- 82
- Citations by year
- 2026: 12 · 2025: 15 · 2024: 23 · 2023: 14 · 2022: 21 · 2021: 17 · 2020: 23 · 2019: 19 · 2018: 25 · 2017: 13 · 2016: 5
- FWCI
- 27.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Psychotherapy and Psychosomatics (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (5r01at004572-04)
- National Center for Complementary and Alternative Medicine
- National Center for Complementary and Integrative Health (R01AT004572.)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Mindfulness and Compassion Interventions
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- mindfulness-based cognitive therapy, treatment-resistant depression, adjunctive psychotherapy, pharmacotherapy, music therapy, nutrition education, physical fitness, depression severity, treatment response, remission, state anxiety, perceived stress, personality disorders
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Depressive Disorder, Major, Major Depressive Disorder, Female, Humans, Male, Middle Aged, Cognitive Behavioral Therapy, Young Adult, Depressive Disorder, Treatment-Resistant, Mindfulness
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