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Criteria for treatment-resistant depression (TRD) and partially responsive depression (PRD) as subtypes of major depressive disorder (MDD) are not unequivocally defined. In the present document we used a Delphi-method-based consensus approach to define TRD and PRD and to serve as operational criteria for future clinical studies, especially if conducted for regulatory purposes. We reviewed the literature and brought together a group of international experts (including clinicians, academics, researchers, employees of pharmaceutical companies, regulatory bodies representatives, and one person with lived experience) to evaluate the state-of-the-art and main controversies regarding the current classification. We then provided recommendations on how to design clinical trials, and on how to guide research in unmet needs and knowledge gaps. This report will feed into one of the main objectives of the EUropean Patient-cEntric clinicAl tRial pLatforms, Innovative Medicines Initiative (EU-PEARL, IMI) MDD project, to design a protocol for platform trials of new medications for TRD/PRD.

Criteria for treatment-resistant depression (TRD) and partially responsive depression (PRD) as subtypes of major depressive disorder (MDD) are not unequivocally defined. In the present document we used a Delphi-method-based consensus approach to define TRD and PRD and to serve as operational criteria for future clinical studies, especially if conducted for regulatory purposes. We reviewed the literature and brought together a group of international experts (including clinicians, academics, researchers, employees of pharmaceutical companies, regulatory bodies representatives, and one person with lived experience) to evaluate the state-of-the-art and main controversies regarding the current classification. We then provided recommendations on how to design clinical trials, and on how to guide research in unmet needs and knowledge gaps. This report will feed into one of the main objectives of the EUropean Patient-cEntric clinicAl tRial pLatforms, Innovative Medicines Initiative (EU-PEARL, IMI) MDD project, to design a protocol for platform trials of new medications for TRD/PRD.

Background: Although highly prevalent among inflammatory bowel disease (IBD) patients, fatigue remains an unmet clinical need. The aim was to describe the prevalence of fatigue in an IBD population in remission and identify factors associated with fatigue. Methods: IBD patients in clinical and biochemical remission under treatment with immunomodulators or biologicals were included. Fatigue, physical tiredness and depression were assessed using the fatigue Visual Analogue Scale (fVAS), the Shortened Fatigue Questionnaire (SFQ) and the Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR), respectively. Relevant clinical and biochemical parameters were included in regression analyses to identify factors associated with physical fatigue. Results: In total, 157 IBD patients were included. Up to 45.9% of patients reported fatigue, physical tiredness was observed in 51% and depression in 10.8%. The majority of patients with subclinical depression were fatigued. Female sex (OR = 4.17 [1.55–6.78], p = 0.002) was independently associated with physical fatigue. Transferrin saturation (OR = −0.11 [−0.22–−0.007], p = 0.037) and treatment with adalimumab (compared to infliximab, OR = −3.65 [−7.21–−0.08], p = 0.045) entailed a lower risk of fatigue. Conclusion: Fatigue is observed in about half of IBD patients in remission and can be a symptom of underlying undetected depression. Sex, transferrin saturation and medication were identified as independent risk factors.

Previous research suggests that a stronger focus on positive emotions and positive mental health may improve efficacy of Cognitive Behavior Therapy (CBT). Objectives were to compare differential improvement of depressive symptoms (primary outcome), positive affect, and positive mental health indices during positive CBT (P-CBT; CBT in a solution-focused framework, amplified with optional positive psychology exercises) versus traditional, problem-focused CBT (T-CBT). Forty-nine patients with major depressive disorder (recruited in an outpatient mental health care facility specialized in mood disorders) received two treatment blocks of eight sessions each (cross-over design, order randomized). Intention-To-Treat mixed regression modelling indicated that depressive symptoms improved similarly during the first, but significantly more in P-CBT compared to T-CBT during the second treatment block. Rate of improvement on the less-frequently measured secondary outcomes was not significantly different. However, P-CBT was associated with significantly higher rates of clinically significant or reliable change for depression, negative affect, and happiness. Effect sizes for the combined treatment were large (pre-post Cohen's d = 2.71 for participants ending with P-CBT, and 1.85 for participants ending with T-CBT). Positive affect, optimism, subjective happiness and mental health reached normative population averages after treatment. Overall, findings suggest that explicitly focusing on positive emotions efficiently counters depressive symptoms.

Purpose: The majority of people with schizophrenia has impaired insight, which is related to a poorer outcome. In this study, we evaluate a new psychosocial intervention 'REFLEX' aimed at improving insight in people with schizophrenia. REFLEX focuses on targeting stigma-sensitivity, perspective taking and self-reflection in people with schizophrenia and low insight. Primary objective is to improve insight and subsequently to improve functional outcome and symptoms.Method: A total of 121 people diagnosed with schizophrenia according to DSM IV criteria with impaired insight was included in 2012-2015 from seven sites in a multicenter randomized controlled trial. REFLEX was compared to an active control condition consisting of group-wise simplified cognitive remediation training. Primary outcome of the study were the preconditions of insight: internalized stigma, self-reflection, mental flexibility and perspective taking. Clinical insight and cognitive insight were secondary outcomes.Results: Although perspective taking, self-reflection, mental flexibility and stigma sensitivity remained unchanged after the intervention, results showed a significant improvement of clinical insight in both conditions directly after treatment (SAI-E Rater, p Conclusion: Though insight improved in both conditions, REFLEX was not superior to simplified drill-and-practice cognitive remediation training. Nevertheless, this study indicates that structured interventions can significantly improve insight. Further research on the underlying mechanisms of both conditions is needed, as insight is unlikely to improve spontaneously in chronic patients. (C) 2018 Published by Elsevier B.V.

Background Light therapy has been used to treat winter depression in bipolar disorder, although the dose, duration, and timing of treatment have differed. The present study is an open trial of light therapy for depressive episodes in autumn/winter using a Dutch protocol specific for patients with a bipolar disorder. Methods Data were collected for the seasons September–April 2017–2018 and September–April 2018–2019. In total, 58 patients received light therapy for a minimum of 7 days and a maximum of 21 days; there was a follow-up measurement after two weeks. Outcomes were quick inventory of depressive symptomatology (QIDS) scores and side effects. Results QIDS scores were significantly lower at the last day of therapy (B = − 6.00, p Conclusions The Dutch light therapy protocol for patients with a bipolar disorder may be effective in treating a seasonal depression and side effects are mild. Light therapy deserves a prominent place in the treatment because effects may be large and quick.

Research has shown that the amount of media exposure is associated with post-event mental health problems. Whether bereaved individuals have negative experiences with media reports and whether they are associated with post-event mental health is unclear. This study evaluated these experiences and associations following the MH17-disaster. How media reports were experienced (nine topics, modified MAS), depression symptoms (QIDS-SR), functional problems (WSAS) and event-related coping self-efficacy (CSE) were assessed about one year post-disaster (May-August 2015) among Dutch bereaved (N = 152). A substantial minority reported negative experiences such as reports made me angry (30%) and made me sad (48%). Latent profile analysis with symptoms, problems and coping self-efficacy as indicators, identified four classes of post-disaster mental health: a Well-Functioning Class (1), 35.1%; a Mild-Problems Class (2), 30.4%; a Sub-Clinical Class (3), 27.0%; and a Clinical Class (4), 7.4%. Differences in symptoms, problems and coping self-efficacy levels between classes were large according to Cohen’s d’s. Multivariate logistic regression (MLR) showed that the Clinical Class (4) compared to the Well-Functioning Class (1), more often that felt that reports strongly ‘embarrassed me’, ‘made me feel sad’, ‘filled me with fear’ and ‘served as a magnifying glass’. Future research should assess opportunities and effects of limiting media consumption.

Mood and behaviour are thought to be under considerable influence of the seasons, but evidence is not unequivocal. The purpose of this study was to investigate whether mood and affect are related to the seasons, and what is the role of neuroticism in this association. In a national internet-based crowdsourcing project in the Dutch general population, individuals were invited to assess themselves on several domains of mental health. ANCOVA was used to test for differences between the seasons in mean scores on the Positive and Negative Affect Schedule (PANAS) and Quick Inventory of Depressive Symptomatology (QIDS). Within-subject seasonal differences were tested as well, in a subgroup that completed the PANAS twice. The role of neuroticism as a potential moderator of seasonality was examined. Participants (n = 5,282) scored significantly higher on positive affect (PANAS) and lower on depressive symptoms (QIDS) in spring compared to summer, autumn and winter. They also scored significantly lower on negative affect in spring compared to autumn. Effect sizes were small or very small. Neuroticism moderated the effect of the seasons, with only participants higher on neuroticism showing seasonality. There was no within-subject seasonal effect for participants who completed the questionnaires twice (n = 503), nor was neuroticism a significant moderator of this within-subjects effect. The findings of this study in a general population sample participating in an online crowdsourcing study do not support the widespread belief that seasons influence mood to a great extent. For, as far as the seasons did influence mood, this only applied to highly neurotic participants and not to low-neurotic participants. The underlying mechanism of cognitive attribution may explain the perceived relation between seasonality and neuroticism.

With the development of the Behavioral Activation for Depression Scale (BADS) by Kanter, et al. [1], different behavioral aspects of depression like activation, rumination or avoidance, and functional impairment can be measured. The long and the short versions of the BADS, however, show differences in the quality of psychometric properties. We wanted to validate the short and long forms of the BADS. We therefore evaluated the factor structure, the psychometric properties, and the construct validity of the long version and the subscales in a clinically depressed German sample (n=258) in study 1. In study 2, we explored the factor structure and the psychometric properties of the short version of the BADS in a subsyndromal sample with elevated depressive symptoms (n=406). In study 1, our results replicated the four factor solution of the BADS-25 original version and showed good psychometric properties. However, with regard to the BADS-9 only the French factor solution of the short BADS-9 demonstrated acceptable fit with low internal consistency of the subscale Avoidance. Thus, only the total score of the short form can be recommended.

Objective: To investigate the multifactorial relationship between illness insight, cognitive and emotional processes, and illness characteristics in bipolar disorder patients. Methods: Data from 85 euthymic or mildly to moderately depressed bipolar disorder patients were evaluated. Insight was measured using the Mood Disorder Insight Scale (total score and subscale scores: awareness of illness, symptom attribution, and need for treatment). Cognitive and emotional functioning was measured in four domains (processing speed, memory, executive functioning, and emotional learning) in addition to premorbid IQ. Illness characteristics were assessed using the Mini-International Neuropsychiatric Interview, the Questionnaire for Bipolar Disorder, and the Inventory of Depressive Symptomatology-self rating scale. Regression analyses were performed for the whole sample. Post-hoc, interactions with lifetime psychotic features (LPF) were statistically tested and if significant, analyses were repeated for patients with (n = 36) and without (n = 49) LPF separately. Results: In the whole group, better insight was associated with lower processing speed, better memory performance, increased emotional learning, higher level of depressive symptoms, and longer duration of illness. Patients with LPF had worse awareness of illness, but better symptom attribution than patients without LPF. No group differences for need for treatment and overall insight were found. Finally, processing speed significantly predicted subscores for symptom attribution in patients with LPF only. Conclusions: Cognitive functioning as well as impairments in emotional learning and psychotic features independently contributes to impaired insight in bipolar disorder. Processing speed seems to be a key variable in the prediction of insight in patients with LPF and not in patients without LPF.

Objective: The authors assessed gender differences in the proportion of clinical visits spent depressed, manic, or euthymic in patients with bipolar disorder. Method: Data were analyzed from 711 patients with bipolar I or II disorder who were followed prospectively over 7 years (13,191 visits). The main outcome measures were the presence of symptoms of depression or of hypomania or mania, measured by the Inventory of Depressive Symptomatology and the Young Mania Rating Scale. Data were analyzed using three separate repeated-measures regressions with a logistic link function to model the probability that an individual was depressed, manic, or euthymic. The models controlled for bipolar I or bipolar II diagnosis, rapid cycling, age, time in the study, comorbid anxiety disorders, and comorbid substance use disorders. Results: In approximately half of visits, patients had depressive, manic, or hypomanic symptoms. The likelihood of having depressive symptoms was significantly greater for women than for men. This was accounted for by higher rates in women of rapid cycling and anxiety disorders, each of which was associated with increased rates of depression. All patient groups showed an increase in number of euthymic visits and a decrease in number of visits with depressive and manic symptoms with increased time in study. Conclusions: Bipolar patients spend a substantial proportion of their time ill. Significant gender differences exist, with women spending a greater proportion of their visits in the depressive pole. This finding appears to be related to the corresponding differences in rates of rapid cycling and anxiety disorders. (Am J Psychiatry 2010; 167:708-715)

Objectives: Via an international panel of experts, this paper attempts to document, review, interpret, and propose operational definitions used to describe the course of bipolar disorders for worldwide use, and to disseminate consensus opinion, supported by the existing literature, in order to better predict course and treatment outcomes. Methods: Under the auspices of the International Society for Bipolar Disorders, a task force was convened to examine, report, discuss, and integrate findings from the scientific literature related to observational and clinical trial studies in order to reach consensus and propose terminology describing course and outcome in bipolar disorders. Results: Consensus opinion was reached regarding the definition of nine terms (response, remission, recovery, relapse, recurrence, subsyndromal states, predominant polarity, switch, and functional outcome) commonly used to describe course and outcomes in bipolar disorders. Further studies are needed to validate the proposed definitions. Conclusion: Determination and dissemination of a consensus nomenclature serve as the first step toward producing a validated and standardized system to define course and outcome in bipolar disorders in order to identify predictors of outcome and effects of treatment. The task force acknowledges that there is limited validity to the proposed terms, as for the most part they represent a consensus opinion. These definitions need to be validated in existing databases and in future studies, and the primary goals of the task force are to stimulate research on the validity of proposed concepts and further standardize the technical nomenclature.

In depression research, symptoms are routinely assessed via rating scales and added to construct sum-scores. These scores are used as a proxy for depression severity in cross-sectional research, and differences in sum-scores over time are taken to reflect changes in an underlying depression construct. To allow for such interpretations, rating scales must (a) measure a single construct, and (b) measure that construct in the same way across time. These requirements are referred to as unidimensionality and measurement invariance. We investigated these 2 requirements in 2 large prospective studies (combined n = 3,509) in which overall depression levels decrease, examining 4 common depression rating scales (1 self-report, 3 clinician-report) with different time intervals between assessments (between 6 weeks and 2 years). A consistent pattern of results emerged. For all instruments, neither unidimensionality nor measurement invariance appeared remotely tenable. At least 3 factors were required to describe each scale, and the factor structure changed over time. Typically, the structure became less multifactorial as depression severity decreased (without however reaching unidimensionality). The decrease in the sum-scores was accompanied by an increase in the variances of the sum-scores, and increases in internal consistency. These findings challenge the common interpretation of sum-scores and their changes as reflecting 1 underlying construct. The violations of common measurement requirements are sufficiently severe to suggest alternative interpretations of depression sum-scores as formative instead of reflective measures. We discuss the possible causes of these violations such as response shift bias, restriction of range, and regression to the mean. (PsycINFO Database Record

Background Self-report instruments for the assessment of depressive symptoms in patients with psychotic disorders are scarce. The Quick Inventory of Depressive Symptoms (QIDS-SR16) may be a useful self-report instrument, but has received little attention in this field. This paper aimed to test the psychometric properties of the QIDS-SR16 questionnaire in patients with a psychotic disorder. Methods Patients diagnosed with a psychotic disorder from health care institutions in The Netherlands were included in the study. Depressive symptoms were assessed with the QIDS-SR16 and the Calgary Depression Scale for Schizophrenia (CDSS). Psychotic symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS) and extrapyramidal symptoms (EPS) with three EPS rating scales. Spearman’s correlation coefficients were used to compare the total score of the QIDS-SR16 with the total scores of the CDSS, PANSS-subscales and EPS rating scales. Results In a sample of 621 patients with psychotic disorders, the QIDS-SR16 showed good internal consistency (α = 0.87). The QIDS-SR16 correlated moderately with the CDSS (r = 0.44) and the PANSS subscale for emotional distress (r = 0.47). The QIDS-SR16 showed weak correlation with the PANSS subscale for negative symptoms (r = 0.28) and minimal correlation with EPS rating scales (r = 0.09-0.16). Conclusions The QIDS-SR16 may reliably assess depressive symptoms in patients with psychotic disorders, but its concurrent validity with the CDSS was rather poor in this population. We would recommend developing a new self-report questionnaire for the assessment of depressive symptoms in patients with psychotic disorders. Electronic supplementary material The online version of this article (doi:10.1186/s12888-014-0247-2) contains supplementary material, which is available to authorized users.

Background: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is thought to be associated with more mood symptoms and worse cognitive functioning. This study examined whether variation in HPA axis activity underlies the association between mood symptoms and cognitive functioning.Methodology/Principal Findings: In 65 bipolar patients cognitive functioning was measured in domains of psychomotor speed, speed of information processing, attentional switching, verbal memory, visual memory, executive functioning and an overall mean score. Severity of depression was assessed by the Inventory of Depressive Symptomatology-self rating version. Saliva cortisol measurements were performed to calculate HPA axis indicators: cortisol awakening response, diurnal slope, the evening cortisol level and the cortisol suppression on the dexamethasone suppression test. Regression analyses of depressive symptoms and cognitive functioning on each HPA axis indicator were performed. In addition we calculated percentages explanation of the association between depressive symptoms and cognition by HPA axis indicators. Depressive symptoms were associated with dysfunction in psychomotor speed, attentional switching and the mean score, as well as with attenuation in diurnal slope value. No association was found between HPA axis activity and cognitive functioning and HPA axis activity did not explain the associations between depressive symptoms and cognition.Conclusions/Significance: As our study is the first one in this field specific for bipolar patients and changes in HPA-axis activity did not seem to explain the association between severity of depressive symptoms and cognitive functioning in bipolar patients, future studies are needed to evaluate other factors that might explain this relationship.

Objective: To investigate the multifactorial relationship between illness insight, cognitive and emotional processes, and illness characteristics in bipolar disorder patients. Methods: Data from 85 euthymic or mildly to moderately depressed bipolar disorder patients were evaluated. Insight was measured using the Mood Disorder Insight Scale (total score and subscale scores: awareness of illness, symptom attribution, and need for treatment). Cognitive and emotional functioning was measured in four domains (processing speed, memory, executive functioning, and emotional learning) in addition to premorbid IQ. Illness characteristics were assessed using the Mini-International Neuropsychiatric Interview, the Questionnaire for Bipolar Disorder, and the Inventory of Depressive Symptomatology-self rating scale. Regression analyses were performed for the whole sample. Post-hoc, interactions with lifetime psychotic features (LPF) were statistically tested and if significant, analyses were repeated for patients with (n = 36) and without (n = 49) LPF separately. Results: In the whole group, better insight was associated with lower processing speed, better memory performance, increased emotional learning, higher level of depressive symptoms, and longer duration of illness. Patients with LPF had worse awareness of illness, but better symptom attribution than patients without LPF. No group differences for need for treatment and overall insight were found. Finally, processing speed significantly predicted subscores for symptom attribution in patients with LPF only. Conclusions: Cognitive functioning as well as impairments in emotional learning and psychotic features independently contributes to impaired insight in bipolar disorder. Processing speed seems to be a key variable in the prediction of insight in patients with LPF and not in patients without LPF.

The aim of this study was to simultaneously examine a wide range of risk factors and clinical characteristics in their predictive value for the 1-year severity of depressive symptoms. Data from 789 participants in the Netherlands Study of Depression and Anxiety (NESDA), a large psychiatric cohort study, with a major depressive disorder (MDD) at baseline were used. Depression severity at 1-year follow-up was studied using linear and multinomial logistic regression models. Results of the analyses showed that high neuroticism, no partner and older age were found predictive of a poorer outcome independent of baseline clinical characteristics. Further, comorbid anxiety disorder, first episode, having a moderate subtype (vs. melancholic), and higher baseline depression severity predicted poorer outcome. To conclude, both risk factors and clinical characteristics independently predicted 1-year severity of depressive symptoms. The findings indicate that the prediction of prognosis and identification of persons at risk of a poor outcome should not only be based on clinical characteristics, but on risk factors as well.

Objective: The authors assessed gender differences in the proportion of clinical visits spent depressed, manic, or euthymic in patients with bipolar disorder. Method: Data were analyzed from 711 patients with bipolar I or II disorder who were followed prospectively over 7 years (13,191 visits). The main outcome measures were the presence of symptoms of depression or of hypomania or mania, measured by the Inventory of Depressive Symptomatology and the Young Mania Rating Scale. Data were analyzed using three separate repeated-measures regressions with a logistic link function to model the probability that an individual was depressed, manic, or euthymic. The models controlled for bipolar I or bipolar II diagnosis, rapid cycling, age, time in the study, comorbid anxiety disorders, and comorbid substance use disorders. Results: In approximately half of visits, patients had depressive, manic, or hypomanic symptoms. The likelihood of having depressive symptoms was significantly greater for women than for men. This was accounted for by higher rates in women of rapid cycling and anxiety disorders, each of which was associated with increased rates of depression. All patient groups showed an increase in number of euthymic visits and a decrease in number of visits with depressive and manic symptoms with increased time in study. Conclusions: Bipolar patients spend a substantial proportion of their time ill. Significant gender differences exist, with women spending a greater proportion of their visits in the depressive pole. This finding appears to be related to the corresponding differences in rates of rapid cycling and anxiety disorders. (Am J Psychiatry 2010; 167:708-715)

Background: The Inventory of Depressive Symptomatology Self Report (IDS-SR) is a widely used but heterogeneous measure of depression severity. Insight in its factor structure and dimensionality could help to develop more homogeneous IDS-SR subscales. However previous factoranalytical studies have found mixed results, Therefore. the present study tested which factor structure underlies the IDS-SR and, in addition, if the factors can be used as unidimensional subscales.Methods: Confirmatory factor analysis (CFA) was done to identify the best-fitting factor structure. The study sample consisted of 2600 individuals (mean age 40.5 +/- 12.1). We assessed model fit in 4 groups: 957 Major Depressive Disorder (MDD) patients, 450 remitted MOD patients, 570 patients with an anxiety disorder and 623 healthy controls to test the consistency of model fit. Rasch analyses in the full sample were used to evaluate and optimize the unidimensionality and psychometric quality of the factors.Results: CFA indicated that a 3-factor model fits the IDS-SR data best and is consistent across groups, with a 'mood/cognition' factor, an 'anxiety/arousal' factor and a 'sleep' factor. In addition, Rasch analyses indicated that the 'mood/cognition' and 'anxiety/arousal' factors could be optimized to be used as unidimensional subscales.Limitations: The fit of only 4 models was tested, ranging from a 1- to 4-factor model.Conclusions: The IDS-SR is a heterogeneous instrument with a multifactorial underlying structure. It is possible to measure more homogeneous symptomatology with IDS-SR subscales, which could be useful in clinical practice and scientific research. (C) 2010 Elsevier B.V. All rights reserved.

Background: Cognitive dysfunction is clearly recognized in bipolar patients, but the degree of impairment varies due to methodological factors as well as heterogeneity in patient populations. The goal of this study was to evaluate cognitive functioning in bipolar patients and to assess its association with depressive symptoms. Post hoc the relationship with lifetime alcohol use disorder was explored.Methodology/Principal Findings: The study included 110 bipolar patients and 75 healthy controls. Patients with severe depressive symptoms, (hypo) manic symptoms and current severe alcohol use disorder were excluded. Diagnoses were evaluated via the Mini-International Neuropsychiatric Interview. Cognitive functioning was measured in domains of psychomotor speed, speed of information processing, attentional switching, verbal memory, visual memory, executive functioning and an overall mean score. Severity of depression was assessed by the Inventory of Depressive Symptomatology-self rating. Patients were euthymic (n=46) or with current mild (n=38) or moderate (n=26) depressive symptoms. Cognitive impairment was found in 26% (z-score 2 or more above reference control group for at least one domain) of patients, most prominent in executive functioning (effect size; ES 0.49) and speed of information processing (ES 0.47). Depressive symptoms were associated with dysfunction in psychomotor speed (adjusted beta 0.43; R(2) 7%), speed of information processing (adjusted beta 0.36; R(2) 20%), attentional switching (adjusted beta 0.24; R(2) 16%) and the mean score (adjusted beta 0.23; R(2) 24%), but not with verbal and visual memory and executive functioning. Depressive symptoms explained 24% of the variance in the mean z-score of all 6 cognitive domains. Comorbid lifetime alcohol use (n=21) was not associated with cognitive dysfunction.Conclusions/Significance: Cognitive dysfunction in bipolar disorder is more severe in patients with depressive symptoms, especially regarding speed and attention. Therefore, interpretation of cognitive functioning in patients with depressive symptoms should be cautious. No association was found between cognitive functioning and lifetime comorbid alcohol use disorder.

Background: Depression is a common psychiatric disorder characterized by a high rate of relapse and recurrence. The most commonly used strategy to prevent relapse/recurrence is maintenance treatment with antidepressant medication (mADM). Recently, it has been shown that Mindfulness-Based Cognitive Therapy (MBCT) is at least as effective as mADM in reducing the relapse/recurrence risk. However, it is not yet known whether combination treatment of MBCT and mADM is more effective than either of these treatments alone. Given the fact that most patients have a preference for either mADM or for MBCT, the aim of the present study is to answer the following questions. First, what is the effectiveness of MBCT in addition to mADM? Second, how large is the risk of relapse/recurrence in patients withdrawing from mADM after participating in MBCT, compared to those who continue to use mADM after MBCT? Methods/design: Two parallel-group, multi-center randomized controlled trials are conducted. Adult patients with a history of depression (3 or more episodes), currently either in full or partial remission and currently treated with mADM (6 months or longer) are recruited. In the first trial, we compare mADM on its own with mADM plus MBCT. In the second trial, we compare MBCT on its own, including tapering of mADM, with mADM plus MBCT. Follow-up assessments are administered at 3-month intervals for 15 months. Primary outcome is relapse/recurrence. Secondary outcomes are time to, duration and severity of relapse/recurrence, quality of life, personality, several process variables, and incremental cost-effectiveness ratio. Discussion: Taking into account patient preferences, this study will provide information about a) the clinical and cost-effectiveness of mADM only compared with mADM plus MBCT, in patients with a preference for mADM, and b) the clinical and cost-effectiveness of withdrawing from mADM after MBCT, compared with mADM plus MBCT, in patients with a preference for MBCT. Trial registration: ClinicalTrials.gov: NCT00928980