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BackgroundDue 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.MethodsThis 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-D17), with secondary depression indicators of treatment response and remission.ResultsWe 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-D17 (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.ConclusionsMBCT 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.

BackgroundMajor depressive disorder (MDD) is the leading cause of disability in the developed world, yet broadly effective treatments remain elusive. Up to 40% of patients with depression are unresponsive to at least two trials of antidepressant medication and thus have "treatment-resistant depression" (TRD). There is an urgent need for cost-effective, non-pharmacologic, evidence-based treatments for TRD. Mindfulness-Based Cognitive Therapy (MBCT) is an effective treatment for relapse prevention and residual depression in major depression, but has not been previously studied in patients with TRD in a large randomized trial.Methods/designThe purpose of this study was to evaluate whether MBCT is an effective augmentation of antidepressants for adults with MDD who failed to respond to standard pharmacotherapy. MBCT was compared to an active control condition, the Health-Enhancement Program (HEP), which incorporates physical activity, functional movement, music therapy and nutritional advice. HEP was designed as a comparator condition for mindfulness-based interventions to control for non-specific effects. Originally investigated in a non-clinical sample to promote stress reduction, HEP was adapted for a depressed population for this study. Individuals age 18 and older with moderate to severe TRD, who failed to respond to at least two trials of antidepressants in the current episode, were recruited to participate. All participants were taking antidepressants (Treatment as usual; TAU) at the time of enrollment. After signing an informed consent, participants were randomly assigned to either MBCT or HEP condition. Participants were followed for 1 year and assessed at weeks 1-7, 8, 24, 36, and 52. Change in depression severity, rate of treatment response and remission after 8 weeks were the primary outcomes measured by the clinician-rated Hamilton Depression Severity Rating (HAM-D) 17-item scale. The participant-rated Quick Inventory of Depression Symptomology (QIDS-SR) 16-item scale was the secondary outcome measure of depression severity, response, and remission.DiscussionTreatment-resistant depression entails significant morbidity and has few effective treatments. We studied the effect of augmenting antidepressant medication with MBCT, compared with a HEP control, for patients with TRD. Analyses will focus on clinician and patient assessment of depression, participants' clinical global impression change, employment and social functioning scores and quality of life and satisfaction ratings.Trial registrationClincalTrials.gov identifier: NCT01021254.

Objective: To examine whether metacognitive psychological skills, acquired in mindfulness-based cognitive therapy (MBCT), are also present in patients receiving medication treatments for prevention of depressive relapse and whether these skills mediate MBCT's effectiveness. Method: This study, embedded within a randomized efficacy trial of MBCT, was the first to examine changes in mindfulness and decentering during 6-8 months of antidepressant treatment and then during an 18-month maintenance phase in which patients discontinued medication and received MBCT, continued on antidepressants, or were switched to a placebo. In total, 84 patients (mean age = 44 years, 58% female) were randomized to 1 of these 3 prevention conditions. In addition to symptom variables, changes in mindfulness, rumination, and decentering were assessed during the phases of the study. Results: Pharmacological treatment of acute depression was associated with reductions in scores for rumination and increased wider experiences. During the maintenance phase, only patients receiving MBCT showed significant increases in the ability to monitor and observe thoughts and feelings as measured by the Wider Experiences (p less than 0.01) and Decentering (p less than 0.01) subscales of the Experiences Questionnaire and by the Toronto Mindfulness Scale. In addition, changes in Wider Experiences (p less than 0.05) and Curiosity (p less than 0.01) predicted lower Hamilton Rating Scale for Depression scores at 6-month follow-up. Conclusions: An increased capacity for decentering and curiosity may be fostered during MBCT and may underlie its effectiveness. With practice, patients can learn to counter habitual avoidance tendencies and to regulate dysphoric affect in ways that support recovery. (Contains 5 tables, 2 figures and 6 footnotes.)

Z. V. Segal et al. (2006) demonstrated that depressed patients treated to remission through either antidepressant medication (ADM) or cognitive-behavioral therapy (CBT), but who evidenced mood-linked increases in dysfunctional thinking, showed elevated rates of relapse over 18 months. The current study sought to evaluate whether treatment response was associated with gains in "decentering"--the ability to observe one's thoughts and feelings as temporary, objective events in the mind--and whether these gains moderated the relationship between mood-linked cognitive reactivity and relapse of major depression. Findings revealed that CBT responders exhibited significantly greater gains in decentering compared with ADM responders. In addition, high post acute treatment levels of decentering and low cognitive reactivity were associated with the lowest rates of relapse in the 18-month follow-up period. (Contains 2 figures, 1 table, and 1 footnote.)

Objective: Digital delivery of mindfulness-based cognitive therapy through the Mindful Mood Balance (MMB) program is clinically effective (Segal et al., 2020); however, the mechanisms through which this program delivers its benefits have not been established. Method: This study investigates the differential impact of the MMB program paired with usual depression care (UDC) compared to UDC alone on the putative targets of self-reported mindfulness, decentering, and rumination and the extent to which change in these targets mediates subsequent depressive relapse among a sample of predominantly White, female participants, with residual depressive symptoms. Results: The MMB program relative to UDC was associated with a significantly greater rate of change in decentering (t = 4.94, p <.0001, d = 0.46), mindfulness (t = 6.04, p <.0001, d = 0.56), and rumination (t = 3.82, p <.0001, d = 0.36). Subsequent depressive relapse also was mediated by prior change in these putative targets, with a significant natural indirect effect for decentering, χ2(1) = 7.25, p <.008, OR = 0.57; mindfulness, χ2(1) = 9.99, p <.002, OR = 0.50; and rumination, χ2(1) = 12.95, p <.001, OR = 0.35. Conclusions: These findings suggest the mechanisms of MMB are consistent with the conceptual model for mindfulness-based cognitive therapy and depressive relapse risk and that such processes can be modified through digital delivery. What is the public health significance of this article?: Evidence for putative target engagement and mediation is critical to identifying proximal markers of long-term benefit and guidance for the measurement and design of digital interventions for depression. [ABSTRACT FROM AUTHOR]

BackgroundMindful Mood Balance (MMB) is a Web-based intervention designed to treat residual depressive symptoms and prevent relapse. MMB was designed to deliver the core concepts of mindfulness-based cognitive therapy (MBCT), a group treatment, which, despite its strong evidence base, faces a number of dissemination challenges. ObjectiveThe present study is a qualitative investigation of participants’ experiences with MMB. MethodsQualitative content analysis was conducted via 38 exit interviews with MMB participants. Study inclusion required a current PHQ-9 (Patient Health Questionnaire) score ≤12 and lifetime history ≥1 major depressive episode. Feedback was obtained on specific website components, program content, and administration as well as skills learned. ResultsCodes were assigned to interview responses and organized into four main themes: MBCT Web content, MBCT Web-based group process, home practice, and evidence of concept comprehension. Within these four areas, participants highlighted the advantages and obstacles of translating and delivering MBCT in a Web-based format. Adding increased support was suggested for troubleshooting session content as well as managing time challenges for completing home mindfulness practice. Participants endorsed developing affect regulation skills and identified several advantages to Web-based delivery including flexibility, reduced cost, and time commitment. ConclusionsThese findings support the viability of providing MBCT online and are consistent with prior qualitative accounts derived from in-person MBCT groups. While there is certainly room for innovation in the domains of program support and engagement, the high levels of participant satisfaction indicated that MMB can significantly increase access to evidence-based psychological treatments for sub-threshold symptoms of unipolar affective disorder.

Introduction The 2 most established acute treatment modalities for major depressive disorder (MDD) are pharmacotherapy and evidence-based psychotherapy, particularly cognitive behavioural therapy (CBT). Both have roughly comparable outcomes. (1,2) Nevertheless, [...], Background: Longitudinal neuroimaging investigations of antidepressant treatment offer the opportunity to identify potential baseline biomarkers associated with poor outcome. Methods: To explore the neural correlates of nonresponse to cognitive behavioural therapy (CBT) or venlafaxine (VEN), we compared pretreatment (18)F-fluoro-2-deoxy-D-glucose positron emission tomography scans of participants with major depressive disorder responding to either 16 weeks of CBT (n = 7) or VEN treatment (n = 9) with treatment nonresponders (n = 8). Results: Nonresponders to CBT or VEN, in contrast to responders, exhibited pretreatment hypermetabolism at the interface of the pregenual and subgenual cingulate cortices. Limitations: Limitations of our study include the small sample sizes and the absence of both arterial sampling to determine absolute glucose metabolism and high-resolution structural magnetic resonance imaging coregistration for region-of-interest analyses. Conclusion: Our current findings are consistent with those reported in previous studies of relative hyperactivity in the ventral anterior cingulate cortex in treatment-resistant populations. Contexte: Les etudes de neuro-imagerie longitudinales pendant le traitement antidepresseur offrent la possibilite de reperer certains biomarqueurs de base susceptibles d'etre associes a une evolution moins favorable. Methodes: Pour explorer les correlats neuraux propres au phenomene de resistance a la therapie cognitivo-comportementale (TCC) ou au traitement par venlafaxine (VEN), nous avons compare les tomographies par emission de positrons au (18)F-fluoro-2-desoxy-D-glucose pretherapeutiques de participants atteints de troubles depressifs majeurs qui ont repondu soit a 16 semaines de TCC (n = 7), soit a un traitement par VEN (n = 9), a celles de participants n'ayant pas repondu au traitement (n = 8). Resultats: Comparativement aux participants ayant repondu au traitement, ceux qui n'ont repondu ni a la TCC ni a la VEN presentaient en pretraitement un hypermetabolisme au niveau de l'interface du cortex cingulaire ventro-anterieur du genou du corps calleux. Limites: Les limites de notre etude sont notamment la petite taille des echantillons et l'absence a la fois de prelevements arteriels pour determiner le metabolisme absolu du glucose et d'enregistrements simultanes d'imagerie par resonance magnetique structurelle de haute resolution a des fins d'analyse des regions concernees. Conclusion: Nos resultats actuels concordent avec ceux d'etudes anterieures sur l'hyperactivite relative du cortex cingulaire ventro-anterieur dans le traitement des populations refractaires au traitement.