Understanding emotion and emotional scarring in recurrent depression.

BACKGROUND: A single-item assessment of sad mood after remission from MDD is predictive of relapse, yet the mechanisms that play a role in depressive relapse remain poorly understood. METHODS: In 283 patients, remitted from recurrent depression (DSM-IV-TR criteria; HAM-D17 score ≤ 10), we examined emotional scarring, that is, whether the number of previous depressive episodes was associated with higher levels of sad mood as assessed with a 1-item Visual Analogue Mood Scale (VAMS). We then fitted a cross-sectional multivariate regression model to predict sad mood levels, including the Dysfunctional Attitude Scale Version-A, cognitive reactivity (Leiden Index of Depression Sensitivity), Ruminative Response Scale, and Everyday Problem Checklist. RESULTS: Patients with greater numbers of prior episodes experienced higher levels of sad mood after remission. In multivariate regression, intensity of daily stress and dysfunctional beliefs were associated with the VAMS (Adj. R(2)=.091) although not over and above depressive symptomatology (Adj. R(2)=.114). Cognitive reactivity was not associated with sadness. CONCLUSIONS: Our finding that patients with more previous MDEs reported higher levels of sad mood while remitted could be indicative of emotional scarring. Dysfunctional beliefs and intensity of daily stress were associated with sad mood but not over and above residual symptoms. Thus, illness related characteristics especially are associated with sad mood after remission. More negative affect after remission could result in lower stress tolerance or more stress intensity could result in negative affect. Future studies should examine premorbid sadness in a longitudinal cohort, and should study the exact pathway from stress, affect, and cognition to relapse.

Clinical effectiveness, cost-effectiveness and process evaluation of group schema therapy for eating disorders: study protocol for a multicenter randomized controlled trial.

BACKGROUND: Eating disorders (EDs), such as (atypical) Anorexia (AN) and Bulimia Nervosa (BN), are difficult to treat, causing socioeconomic impediments. Although enhanced cognitive behavioral therapy (CBT-E) is widely considered clinically effective, it may not be the most beneficial treatment for (atypical) AN and BN patients who do not show a rapid response after the first 4 weeks (8 sessions) of a CBT-E treatment. Alternatively, group schema therapy (GST) may be a valuable treatment for this ED population. Even though GST for EDs has yielded promising preliminary findings, the current body of evidence requires expansion. On top of that, data on cost-effectiveness is lacking. In light of these gaps, we aim to describe a protocol to examine whether GST is more (1) clinically effective and (2) cost-effective than CBT-E for (atypical) AN and BN patients, who do not show a rapid response after the first 4 weeks of treatment. Additionally, we will conduct (3) process evaluations for both treatments. METHODS: Using a multicenter RCT design, 232 Dutch (atypical) AN and BN patients with a CBT-E referral will be recruited from five treatment centers. Clinical effectiveness and cost-effectiveness will be measured before treatment, directly after treatment, at 6 and at 12 months follow-up. In order to rate process evaluation, patient experiences and the degree to which treatments are implemented according to protocol will be measured. In order to assess the quality of life and the achievement of personalized goals, interviews will be conducted at the end of treatment. Data will be analyzed, using a regression-based approach to mixed modelling, multivariate sensitivity analyses and coding trees for qualitative data. We hypothesize GST to be superior to CBT-E in terms of clinical effectiveness and cost-effectiveness for patients who do not show a rapid response to the first 4 weeks of a CBT-E treatment. DISCUSSION: To our knowledge, this is the first study protocol describing a multicenter RCT to explore the three aforementioned objectives. Related risks in performing the study protocol have been outlined. The expected findings may serve as a guide for healthcare stakeholders to optimize ED care trajectories. TRIAL REGISTRATION: clinicaltrials.gov (NCT05812950).

Disrupting the rhythm of depression: design and protocol of a randomized controlled trial on preventing relapse using brief cognitive therapy with or without antidepressants.

BACKGROUND: Maintenance treatment with antidepressants is the leading strategy to prevent relapse and recurrence in patients with recurrent major depressive disorder (MDD) who have responded to acute treatment with antidepressants (AD). However, in clinical practice most patients (up to 70-80%) are not willing to take this medication after remission or take too low dosages. Moreover, as patients need to take medication for several years, it may not be the most cost-effective strategy. The best established effective and available alternative is brief cognitive therapy (CT). However, it is unclear whether brief CT while tapering antidepressants (AD) is an effective alternative for long term use of AD in recurrent depression. In addition, it is unclear whether the combination of AD to brief CT is beneficial. METHODS/DESIGN: Therefore, we will compare the effectiveness and cost-effectiveness of brief CT while tapering AD to maintenance AD and the combination of CT with maintenance AD. In addition, we examine whether the prophylactic effect of CT was due to CT tackling illness related risk factors for recurrence such as residual symptoms or to its efficacy to modify presumed vulnerability factors of recurrence (e.g. rigid explicit and/or implicit dysfunctional attitudes). This is a multicenter RCT comparing the above treatment scenarios. Remitted patients on AD with at least two previous depressive episodes in the past five years (n = 276) will be recruited. The primary outcome is time related proportion of depression relapse/recurrence during minimal 15 months using DSM-IV-R criteria as assessed by the Structural Clinical Interview for Depression. Secondary outcome: economic evaluation (using a societal perspective) and number, duration and severity of relapses/recurrences. DISCUSSION: This will be the first trial to investigate whether CT is effective in preventing relapse to depression in recurrent depression while tapering antidepressant treatment compared to antidepressant treatment alone and the combination of both. In addition, we explore explicit and implicit mediators of CT. TRIAL REGISTRATION: Netherlands Trial Register (NTR): NTR1907.

Predictive value of attentional bias for the recurrence of depression: A 4-year prospective study in remitted depressed individuals.

Previous research showed that individuals who were remitted from a depressive disorder displayed heightened attention towards negative adjectives (e.g., worthless). We tested if this attentional bias (AB) is predictive of future recurrence of depressive episodes and/or having depressive symptoms at 2- and 4-year follow-up. We used a longitudinal approach within the Netherlands Study of Depression and Anxiety (NESDA) and selected participants who were remitted from Major Depressive Disorder (MDD) (n = 918). AB was measured with a verbal Exogenous Cueing Task; using 2 presentation times (500 and 1250 ms) and 3 stimulus types (negative, positive, neutral). Over 4 years, we prospectively assessed recurrence of depressive episodes and depressive symptomatology after participants completed the ECT. Diagnosis of depressive disorder was measured with clinical rating-scales and self-report questionnaires. A heightened probability of recurrence was neither associated with (heightened) AB for negative nor with (lowered) AB for positive adjectives. Thus, the findings do not support the view that an AB toward negative stimuli or away from positive stimuli plays a critical role in the recurrence of depression.

Cost-effectiveness, cost-utility and the budget impact of antidepressants versus preventive cognitive therapy with or without tapering of antidepressants.

BACKGROUND: As depression has a recurrent course, relapse and recurrence prevention is essential.AimsIn our randomised controlled trial (registered with the Nederlands trial register, identifier: NTR1907), we found that adding preventive cognitive therapy (PCT) to maintenance antidepressants (PCT+AD) yielded substantial protective effects versus antidepressants only in individuals with recurrent depression. Antidepressants were not superior to PCT while tapering antidepressants (PCT/-AD). To inform decision-makers on treatment allocation, we present the corresponding cost-effectiveness, cost-utility and budget impact. METHOD: Data were analysed (n = 289) using a societal perspective with 24-months of follow-up, with depression-free days and quality-adjusted life years (QALYs) as health outcomes. Incremental cost-effectiveness ratios were calculated and cost-effectiveness planes and cost-effectiveness acceptability curves were derived to provide information about cost-effectiveness. The budget impact was examined with a health economic simulation model. RESULTS: Mean total costs over 24 months were €6814, €10 264 and €13 282 for AD+PCT, antidepressants only and PCT/-AD, respectively. Compared with antidepressants only, PCT+AD resulted in significant improvements in depression-free days but not QALYs. Health gains did not significantly favour antidepressants only versus PCT/-AD. High probabilities were found that PCT+AD versus antidepressants only and antidepressants only versus PCT/-AD were dominant with low willingness-to-pay thresholds. The budget impact analysis showed decreased societal costs for PCT+AD versus antidepressants only and for antidepressants only versus PCT/-AD. CONCLUSIONS: Adding PCT to antidepressants is cost-effective over 24 months and PCT with guided tapering of antidepressants in long-term users might result in extra costs. Future studies examining costs and effects of antidepressants versus psychological interventions over a longer period may identify a break-even point where PCT/-AD will become cost-effective.Declaration of interestC.L.H.B. is co-editor of PLOS One and receives no honorarium for this role. She is also co-developer of the Dutch multidisciplinary clinical guideline for anxiety and depression, for which she receives no remuneration. She is a member of the scientific advisory board of the National Insure Institute, for which she receives an honorarium, although this role has no direct relation to this study. C.L.H.B. has presented keynote addresses at conferences, such as the European Psychiatry Association and the European Conference Association, for which she sometimes receives an honorarium. She has presented clinical training workshops, some including a fee. She receives royalties from her books and co-edited books and she developed preventive cognitive therapy on the basis of the cognitive model of A. T. Beck. W.A.N. has received grants from the Netherlands Organisation for Health Research and Development and the European Union and honoraria and speakers' fees from Lundbeck and Aristo Pharma, and has served as a consultant for Daleco Pharma.

Attentional bias for negative, positive, and threat words in current and remitted depression.

BACKGROUND: The aim of this study was to improve our understanding of the underlying mechanisms in the maintenance of depression. We examined attentional bias (AB) for negative and positive adjectives and general threat words in strictly-defined clinical groups of participants with pure Major Depressive Disorder (MDD) without a history of anxiety disorders (AD), mixed MDD and AD, and remitted participants. METHOD: We investigated both stimulus specificity and time course of AB in these groups, adopting a cross-sectional design. Data were drawn from the large scale Netherlands Study of Depression and Anxiety (NESDA), from which we selected all participants with pure current MDD without a history of AD (n = 29), all participants with current MDD and co-morbid AD(s) (n = 86), all remitted MDD participants (n = 294), and a comparison group without (a history of) MDD or ADs (n = 474). AB was measured with an Exogenous Cueing Task covering short and long presentation times (500 and 1250 ms) and 4 stimulus types (negative, positive, threat, neutral). RESULTS: Both traditional and trial level (dynamic) AB scores failed to show an AB for negative adjectives in participants with MDD or mixed MDD/AD. Specifically for long duration trials (1250 ms), remitted participants showed a larger AB traditional score (albeit the actual score still being negative) than the comparison group. The mixed MDD/AD group showed a higher trial-level AB score away from positive adjectives (1250 ms) than the comparisons. In addition, the mixed MDD/AD group showed higher and more variable trial-level AB scores away from short and towards longer presented general threat words together with a non-significant tendency to show less negative traditional AB scores for threat trials (500 ms) than the comparison group. CONCLUSIONS: All in all, the findings do not corroborate the view that an AB towards negative or away from positive adjectives is critically involved in currently depressed individuals. Yet, the relatively high (less negative) AB score for negative adjectives in remitted individuals points to the possibility that an AB for negative information may be involved as a risk factor in the recurrence of MDD.

Depression recurrence after recovery: Prognostic value of implicit and explicit self-depressed associations.

Identifying predictors of depression recurrence may highlight targets for relapse prevention. This study tested the hypothesis that strength of implicit and explicit self-depressed associations (SDA) following recovery would lower the threshold for the recurrence of depression. Two main analyses were conducted to test: (i) predictive validity of SDA for recurrence in individuals with a history of depression (at least six months depression free; n = 616, six-year follow-up); (ii) predictive validity of both post-depression SDA and the extent of change in SDA following recovery for recurrence in individuals who recovered in the first two years of the study (n = 220, four-year follow-up). Further exploratory analysis tested the scar model of SDA in participants without a history of depression at baseline. Recurrence rate was 49% in both the first and second analysis. In the first analysis, implicit SDA and explicit SDA were related to recurrence in the unadjusted models, but not when controlling for baseline symptoms. In the second analysis, post-depression explicit SDA predicted recurrence over and above baseline residual depressive symptomatology. There was no support that implicit SDA following depression related to recurrence. However, there was support that stronger explicit SDA following a recent depression increased risk for recurrence.

Effectiveness of preventive cognitive therapy while tapering antidepressants versus maintenance antidepressant treatment versus their combination in prevention of depressive relapse or recurrence (DRD study): a three-group, multicentre, randomised controlled trial.

BACKGROUND: Keeping individuals on antidepressants after remission or recovery of major depressive disorder is a common strategy to prevent relapse or recurrence. Preventive cognitive therapy (PCT) has been proposed as an alternative to maintenance antidepressant treatment, but whether its addition would allow tapering of antidepressants or enhance the efficacy of maintenance antidepressant treatment is unclear. We aimed to compare the effectiveness of antidepressants alone, with PCT while tapering off antidepressants, or PCT added to antidepressants in the prevention of relapse and recurrence. METHODS: In this single-blind, multicentre, parallel, three-group, randomised controlled trial, individuals recruited by general practitioners, pharmacists, secondary mental health care, or media were randomly assigned (10:10:8) to PCT and antidepressants, antidepressants alone, or PCT with tapering of antidepressants, using computer-generated randomised allocation stratified for number of previous depressive episodes and type of care. Eligible participants had previously experienced at least two depressive episodes and were in remission or recovery on antidepressants, which they had been receiving for at least the past 6 months. Exclusion criteria were current mania or hypomania, a history of bipolar disorder, any history of psychosis, current alcohol or drug abuse, an anxiety disorder that requires treatment, psychological treatment more than twice a month, and a diagnosis of organic brain damage. The primary outcome was time-related proportion of individuals with depressive relapse or recurrence in the intention-to-treat population, assessed four times in 24 months. Assessors were masked to treatment allocation, whereas physicians and participants could not be masked. This trial is registered with the Netherlands Trial Register, number NTR1907. FINDINGS: Between July 14, 2009, and April 30, 2015, 2486 participants were assessed for eligibility and 289 were randomly assigned to PCT and antidepressant (n=104), antidepressant alone (n=100), or PCT with tapering of antidepressant (n=85). The overall log-rank test was significant (p=0·014). Antidepressants alone were not superior to PCT while tapering off antidepressants in terms of the risk of relapse or recurrence (hazard ratio [HR] 0·86, 95% CI 0·56-1·32; p=0·502). Adding PCT to antidepressant treatment resulted in a 41% relative risk reduction compared with antidepressants alone (0·59, 0·38-0·94; p=0·026). There were two suicide attempts (one in the antidepressants alone group and one in the PCT with tapering of antidepressants group) and one death (in the PCT and antidepressants group) not related to the interventions during the 24 months' follow-up. INTERPRETATION: Maintenance antidepressant treatment is not superior to PCT after recovery, whereas adding PCT to antidepressant treatment after recovery is superior to antidepressants alone. PCT should be offered to recurrently depressed individuals on antidepressants and to individuals who wish to stop antidepressants after recovery. FUNDING: The Netherlands Organisation for Health Research and Development.

Personality and cognitive vulnerability in remitted recurrently depressed patients.

INTRODUCTION: Personality disorders (PDs) have been associated with a poor prognosis of Major Depressive Disorder (MDD). The aim of the current study was to examine cognitive vulnerability (i.e., dysfunctional beliefs, extremity of beliefs, cognitive reactivity, and rumination) that might contribute to this poor prognosis of patients with PD comorbidity. METHODS: 309 outpatients with remitted recurrent MDD (SCID-I; HAM-D17 ≤ 10) were included within two comparable RCTs and were assessed at baseline with the Personality Diagnostic Questionnaire-4(+) (PDQ-4(+)), the Dysfunctional Attitude Scale Version-A (DAS-A), the Leiden Index of Depression Sensitivity (LEIDS), the Ruminative Response Scale (RRS), and the Inventory of Depressive Symptomatology-Self Report (IDS-SR). RESULTS: We found an indication that the PD prevalence was 49.5% in this remitted recurrently depressed sample. Having a PD (and higher levels of personality pathology) was associated with dysfunctional beliefs, cognitive reactivity, and rumination. Extreme 'black and white thinking' on the DAS was not associated with personality pathology. Brooding was only associated with a Cluster C classification (t(308) = 4.03, p < .001) and with avoidant PD specifically (t(308) = 4.82, p < .001), while surprisingly not with obsessive-compulsive PD. LIMITATIONS: PDs were assessed by questionnaire and the analyses were cross-sectional in nature. CONCLUSION: Being the first study to examine cognitive reactivity and rumination in patients with PD and remitted MDD, we demonstrated that even after controlling for depressive symptomatology, dysfunctional beliefs, cognitive reactivity, and rumination were associated with personality pathology. Rumination might be a pathway to relapse for patients with avoidant PD. Replication of our findings concerning cognitive vulnerability and specific PDs is necessary.

Cognitive reactivity, self-depressed associations, and the recurrence of depression.

BACKGROUND: Mixed evidence exists regarding the role of cognitive reactivity (CR; cognitive responsivity to a negative mood) as a risk factor for recurrences of depression. One explanation for the mixed evidence may lie in the number of previous depressive episodes. Heightened CR may be especially relevant as a risk factor for the development of multiple depressive episodes and less so for a single depressive episode. In addition, it is theoretically plausible but not yet tested that the relationship between CR and number of episodes is moderated by the strength of automatic depression-related self-associations. AIM: To investigate (i) the strength of CR in remitted depressed individuals with a history of a single vs. multiple episodes, and (ii) the potentially moderating role of automatic negative self-associations in the relationship between the number of episodes and CR. METHOD: Cross-sectional analysis of data obtained in a cohort study (Study 1) and during baseline assessments in two clinical trials (Study 2). Study 1 used data from the Netherlands Study of Depression and Anxiety (NESDA) and compared never-depressed participants (n=901) with remitted participants with either a single (n=336) or at least 2 previous episodes (n=273). Study 2 included only remitted participants with at least two previous episodes (n=273). The Leiden Index of Depression Sensitivity Revised (LEIDS-R) was used to index CR and an Implicit Association Test (IAT) to measure implicit self-associations. RESULTS: In Study 1, remitted depressed participants with multiple episodes had significantly higher CR than those with a single or no previous episode. The remitted individuals with multiple episodes of Study 2 had even higher CR scores than those of Study 1. Within the group of individuals with multiple episodes, CR was not heightened as a function of the number of episodes, even if individual differences in automatic negative self-associations were taken into account. LIMITATIONS: The study employed a cross-sectional design, which precludes a firm conclusion with regard to the direction of this relationship. CONCLUSIONS: The findings are consistent with the view that high CR puts people at risk for recurrent depression and is less relevant for the development of an incidental depressive episode. This suggests that CR is an important target for interventions that aim to prevent the recurrence of depression.

How do you feel? Detection of recurrent Major Depressive Disorder using a single-item screening tool.

Mood is a key element of Major Depressive Disorder (MDD), and is perceived as a highly dynamic construct. The aim of the current study was to examine whether a single-item mood scale can be used for mood monitoring. One hundred thirty remitted out-patients were assessed using the Structured Clinical Interview for DSM-IV Axis-I Disorders (SCID-I), Visual Analogue Mood Scale (VAMS), 17-item Hamilton Depression Rating Scale (HAM-D17), and Inventory of Depressive Symptomatology-Self Report (IDS-SR). Of all patients, 13.8% relapsed during follow-up assessments. Area under the curves (AUCs) for the VAMS, HAM-D17 and IDS-SR were 0.94, 0.91, and, 0.86, respectively. The VAMS had the highest positive predictive value (PPV) without any false negatives at score 55 (PPV=0.53; NPV=1.0) and was the best predictor of current relapse status (variance explained for VAMS: 60%; for HAM-D17: 49%; for IDS-SR: 34%). Only the HAM-D17 added significant variance to the model (7%). Assessing sad mood with a single-item mood scale seems to be a straightforward and patient-friendly avenue for life-long mood monitoring. Using a diagnostic interview (e.g., the SCID) in case of a positive screen is warranted. Repeated assessment of the VAMS using Ecological Momentary Assessment (EMA) might reduce false positives.

Hidden scars in depression? Implicit and explicit self-associations following recurrent depressive episodes.

To help explain the recurrent nature of major depressive disorder, we tested the hypothesis that depressive episodes and/or the duration of depressive symptoms may give rise to persistent dysfunctional implicit and/or more explicit self-associations, which in turn may place people at risk for the recurrence of symptoms. We therefore examined, in the context of the Netherlands Study of Depression and Anxiety, whether the strength of self-depressed associations at baseline was related to the number of past episodes (retrospective analysis; n = 666), and whether the duration of symptoms between baseline and follow-up predicted self-depressed associations at 2-year follow-up (prospective analysis; n = 726). The lifetime Composite International Diagnostic Interviews and Life Chart Interview were used to index the number of depressive episodes; the Implicit Association Test and its explicit equivalent were used to index self-associations. Consistent with the hypothesis that self-depressed associations strengthen following prolonged activation of negative self-associations during depressive episodes, individuals' implicit and explicit self-depressed associations correlated positively both with the number of prior depressive episodes at baseline and with the duration of depressive symptoms between baseline and 2-year follow-up. There was evidence that these relationships held, particularly in the prospective study, even when controlling for neuroticism and current depressive symptoms, whereas the retrospective relationship between number of episodes and implicit self-associations fell just short of significance.

Adding cognitive therapy to dietetic treatment is associated with less relapse in obesity.

OBJECTIVE: The treatment of obesity is universally disappointing; although usually some weight loss is reported directly after treatment, eventual relapse to, or even above, former body weight is common. In this study it is tested whether the addition of cognitive therapy to a standard dietetic treatment for obesity might prevent relapse. It is argued that the addition of cognitive therapy might not only be effective in reducing weight and related concerns, depressed mood, and low self-esteem, but also has an enduring effect that lasts beyond the end of treatment. METHODS: Non-eating-disordered overweight and obese participants in a community health center (N=204) were randomly assigned to a group dietetic treatment+cognitive therapy or a group dietetic treatment+physical exercise. RESULTS: Both treatments were quite successful and led to significant decreases in BMI, specific eating psychopathology (binge eating, weight-, shape-, and eating concerns) and general psychopathology (depression, low self-esteem). In the long run, however, the cognitive dietetic treatment was significantly better than the exercise dietetic treatment; participants in the cognitive dietetic treatment maintained all their weight loss, whereas participants in the physical exercise dietetic treatment regained part (25%) of their lost weight. CONCLUSION: Cognitive therapy had enduring effects that lasted beyond the end of treatment. This potential prophylactic effect of cognitive therapy is promising; it might be a new strategy to combat the global epidemic of obesity.