The Impact of Treatments for Depression on the Dynamic Network Structure of Mental States: Two Randomized Controlled Trials.

Evidence is growing that vulnerability to depression may be characterized by strong negative feedback loops between mental states. It is unknown whether such dynamics between mental states can be altered by treatment. This study examined whether treatment with imipramine or treatment with Mindfulness-Based Cognitive Therapy (MBCT) reduces the connectivity within dynamic networks of mental states in individuals with depressive symptoms. In the Imipramine trial, individuals diagnosed with major depression were randomized to imipramine treatment or placebo-pill treatment (n = 50). In the Mind-Maastricht trial, individuals with residual depressive symptoms were randomized to Mindfulness-Based Cognitive Therapy (MBCT) or to a waiting-list control condition (n = 119). Lagged associations among mental states, as assessed with the Experience Sampling Method (ESM), were estimated at baseline and post-intervention. The results show that few of the dynamic network connections changed significantly over time and few of the changes after MBCT and imipramine treatment differed significantly from the control groups. The decrease in average node connectivity after MBCT did not differ from the decrease observed in the waiting-list control group. Our findings suggest that imipramine treatment and MBCT do not greatly change the dynamic network structure of mental states, even though they do reduce depressive symptomatology.

Assessing psychosocial vulnerability and care needs of pretransplant patients by means of the INTERMED.

OBJECTIVE: We investigated whether the INTERMED, a generic instrument for assessing biopsychosocial case complexity and direct care, identifies organ transplant patients at risk of unfavourable post-transplant development by comparing it to the Transplant Evaluation Rating Scale (TERS), the established measure for pretransplant psychosocial evaluation. METHOD: One hundred nineteen kidney, liver, and heart transplant candidates were evaluated using the INTERMED, TERS, SF-36, EuroQol, Montgomery-Åsberg Depression Rating Scale (MADRS), and Hospital Anxiety & Depression Scale (HADS). RESULTS: We found significant relationships between the INTERMED and the TERS scores. The INTERMED highly correlated with the HADS,MADRS, and mental and physical health scores of the SF-36 Health Survey. CONCLUSIONS: The results demonstrate the validity and usefulness of the INTERMED instrument for pretransplant evaluation. Furthermore, our findings demonstrate the different qualities of INTERMED and TERS in clinical practice. The advantages of the psychiatric focus of the TERS and the biopsychosocial perspective of the INTERMED are discussed in the context of current literature on integrated care.

Pitfalls in the assessment, analysis, and interpretation of routine outcome monitoring (ROM) Data: results from an outpatient clinic for integrative mental health.

There is considerable debate about routine outcome monitoring (ROM) for scientific or benchmarking purposes. We discuss pitfalls associated with the assessment, analysis, and interpretation of ROM data, using data of 376 patients. 206 patients (55 %) completed one or more follow-up measurements. Mixed-model analysis showed significant improvement in symptomatology, quality of life, and autonomy, and differential improvement for different subgroups. Effect sizes were small to large, depending on the outcome measure and subgroup. Subtle variations in analytic strategies influenced effect sizes substantially. We illustrate how problems inherent to design and analysis of ROM data prevent drawing conclusions about (comparative) treatment effectiveness.

Comorbidity of common mental disorders with cancer and their treatment gap: findings from the World Mental Health Surveys.

OBJECTIVE: This study aimed to study the comorbidity of common mental disorders (CMDs) and cancer, and the mental health treatment gap among community residents with active cancer, cancer survivors and cancer-free respondents in 13 high-income and 11 low-middle-income countries. METHODS: Data were derived from the World Mental Health Surveys (N = 66,387; n = 357 active cancer, n = 1373 cancer survivors, n = 64,657 cancer-free respondents). The World Health Organization/Composite International Diagnostic Interview was used in all surveys to estimate CMDs prevalence rates. Respondents were also asked about mental health service utilization in the preceding 12 months. Cancer status was ascertained by self-report of physician's diagnosis. RESULTS: Twelve-month prevalence rates of CMDs were higher among active cancer (18.4%, SE = 2.1) than cancer-free respondents (13.3%, SE = 0.2) adjusted for sociodemographic confounders and other lifetime chronic conditions (adjusted odds ratio (AOR) = 1.44, 95% CI 1.05-1.97). CMD rates among cancer survivors (14.6%, SE = 0.9) compared with cancer-free respondents did not differ significantly (AOR = 0.95, 95% CI 0.82-1.11). Similar patterns characterized high-income and low-middle-income countries. Of respondents with active cancer who had CMD in the preceding 12 months, 59% sought services for mental health problems (SE = 5.3). The pattern of service utilization among people with CMDs by cancer status (highest among persons with active cancer, lower among survivors and lowest among cancer-free respondents) was similar in high-income (64.0%, SE = 6.0; 41.2%, SE = 3.0; 35.6%, SE = 0.6) and low-middle-income countries (46.4%, SE = 11.0; 22.5%, SE = 9.1; 17.4%, SE = 0.7). CONCLUSIONS: Community respondents with active cancer have higher CMD rates and high treatment gap. Comprehensive cancer care should consider both factors.

Positive affect and survival in patients with stable coronary heart disease: findings from the Heart and Soul Study.

OBJECTIVE: Positive affect can improve survival, but the mechanisms responsible for this association are unknown. We sought to evaluate the association between positive affect and mortality in patients with stable coronary heart disease and to determine biological and behavioral factors that might explain this association. METHOD: The Heart and Soul Study is a prospective cohort study of 1,018 outpatients with stable coronary heart disease. Participants were recruited between September 11, 2000, and December 20, 2002, and were followed up to June 2011. Baseline positive affect was assessed by using the 10-item positive affect subscale of the Positive and Negative Affect Schedule. Cox proportional hazards regression was used to estimate the risk of mortality (primary outcome measure) and cardiovascular events (heart failure, myocardial infarction, stroke, transient ischemic attack) associated with positive affect, adjusting for baseline cardiac disease severity and depression. We also evaluated the extent to which these associations were explained by potential biological and behavioral mediators. RESULTS: A total of 369 patients (36%) died during a mean ± SD follow-up period of 7.1 ± 2.5 years. Positive affect was not significantly associated with cardiovascular events (hazard ratio [HR]: 0.89; 95% CI, 0.79-1.00; P = .06). However, each standard deviation (8.8-point) increase in positive affect score was associated with a 16% decreased risk of all-cause mortality (HR: 0.84; 95% CI, 0.76-0.92; P = .001). After adjustment for cardiac disease severity and depressive symptoms, positive affect remained significantly associated with improved survival (HR: 0.87; 95% CI, 0.78-0.97; P = .01). The association was no longer significant after adjustment for behavioral factors, and particularly physical activity (HR: 0.92; 95% CI, 0.82-1.03; P = .16). Further adjustment for C-reactive protein and omega-3 fatty acids did not result in any meaningful changes (HR: 0.94; 95% CI, 0.84-1.06; P = .31). CONCLUSIONS: In this sample of outpatients with coronary heart disease, positive affect was associated with improved survival. This association was largely explained by physical activity.

Revealing causal heterogeneity using time series analysis of ambulatory assessments: application to the association between depression and physical activity after myocardial infarction.

OBJECTIVE: Studies in psychosomatic medicine are characterized by analyses that typically compare groups. This nomothetic approach leads to conclusions that apply to the average group member but not necessarily to individual patients. Idiographic studies start at the individual patient and are suitable to study associations that differ between time points or between individuals. We illustrate the advantages of the idiographic approach in analyzing ambulatory assessments, taking the association between depression and physical activity after myocardial infarction as an example. METHODS: Five middle-aged men who had myocardial infarction with mild to moderate symptoms of depression were included in this study. Four of these participants monitored their physical activity and depressive symptoms during a period of 2 to 3 months using a daily self-registration form. The time series of each individual participant were investigated using vector autoregressive modeling, which enables the analysis of temporal dynamics between physical activity and depression. RESULTS: We found causal heterogeneity in the association between depression and physical activity. Participants differed in the predominant direction of effect, which was either from physical activity to depression (n = 1, 85 observations, unstandardized effect size = -0.183, p = .03) or from depression to physical activity (n = 2, 65 and 59 observations, unstandardized effect sizes = -0.038 and -0.381, p < .001 and p = .04). Also, the persistency of effects differed among individuals. CONCLUSIONS: Vector autoregressive models are suitable in revealing causal heterogeneity and can be easily used to analyze ambulatory assessments. We suggest that these models might bridge the gap between science and clinical practice by translating epidemiological results to individual patients.

Obstructive sleep apnea/hypopnea syndrome and poor response to sertraline in patients with coronary heart disease.

OBJECTIVE: Evidence from several clinical trials in patients with coronary heart disease suggests that depression that does not respond to treatment is associated with a particularly high risk of adverse cardiac outcomes. The purpose of this study was to determine whether obstructive sleep apnea/hypopnea syndrome (OSAHS) is associated with a poor response to antidepressant medication in patients with coronary heart disease. METHOD: This was a secondary analysis of data from a randomized, double-blind, placebo-controlled clinical trial of omega-3 fatty-acid augmentation of sertraline for depression in patients with coronary heart disease. Patients with documented coronary heart disease were recruited between May 2005 and December 2008 from cardiology practices in St Louis, Missouri, and through cardiac diagnostic laboratories affiliated with Washington University School of Medicine, St Louis, Missouri. One hundred five patients (mean age = 58 years) with coronary heart disease and current major depressive disorder (DSM-IV) were randomized to receive sertraline plus either omega-3 or placebo for 10 weeks. Cyclical heart-rate patterns associated with OSAHS were detected via ambulatory electrocardiography prior to treatment. Symptoms of depression were measured at baseline and follow-up with the Beck Depression Inventory-II (BDI-II) and the 17-item Hamilton Depression Rating Scale (HDRS-17). The primary endpoint was the BDI-II score at 10 weeks. RESULTS: Thirty of the 105 patients (29%) were classified as having probable moderate to severe OSAHS on the basis of nighttime heart-rate patterns. These OSAHS patients had significantly higher scores on both the BDI-II (t = -2.78, P = .01) and the HDRS-17 (t = -2.33, P = .02) at follow-up as compared to the reference group. Adjustment for baseline depression score, treatment arm (omega-3 vs placebo), body mass index, and inflammatory markers did not change the results. Patients with OSAHS reported higher item scores at follow-up on all depressive symptoms measured with the BDI-II compared to those without OSAHS. CONCLUSIONS: Obstructive sleep apnea/hypopnea syndrome is associated with a relatively poor response to sertraline treatment for depression. Future research should determine the contribution of OSAHS to the increased risk of adverse cardiac outcome associated with treatment-resistant depression.

Supplementation with eicosapentaenoic omega-3 fatty acid does not influence serum brain-derived neurotrophic factor in diabetes mellitus patients with major depression: a randomized controlled pilot study.

BACKGROUND: Low brain-derived neurotrophic factor (BDNF) levels are observed in both depressed and diabetes patients. Animal research has shown that omega-3 polyunsaturated fatty acids increase BDNF levels. In this exploratory randomized double-blind placebo-controlled study in diabetes patients with major depression, we tested whether (a) omega- 3 ethyl-eicosapentaenoic acid (E-EPA) leads to increased serum BDNF levels and (b) whether changes in BDNF levels are associated with corresponding changes in depression. METHODS: Patients received 1 g/day E-EPA (n = 13) or placebo (n = 12) for 12 weeks, in addition to ongoing antidepressant therapy. At baseline and 12-week follow-up, we determined serum BDNF levels and depression severity, using the Montgomery-Åsberg Depression Rating Scale. RESULTS: We found no effect of E-EPA on BDNF levels (t = -0.144, p = 0.887), and changes in BDNF levels and depression severity were not significantly associated (Spearman's ρ = -0.115, p = 0.593). CONCLUSION: Our study does not provide evidence that supplementation with E-EPA improves BDNF levels in depressed diabetes patients already using antidepressants.

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.

More than the sum of its parts: meta-analysis and its potential to discover sources of heterogeneity in psychosomatic medicine.

Meta-analyses may contribute to more reliable knowledge about the existence of certain relations in the area of psychosomatic research. Surprisingly, the increasing popularity of meta-analysis is not reflected in the number of meta-analyses of observational studies published in Psychosomatic Medicine. This may be due to the specific difficulties that apply to meta-analyses of observational research. The aim of this paper is to provide a nontechnical overview of the principles of meta-analysis applied to observational research. We will highlight general principles of meta-analysis and discuss the major threats to its validity, with an emphasis on its specific merits and pitfalls for psychosomatic research, using several examples. We conclude that meta-analysis is a relatively simple technique, leaving little reason for not routinely applying it when performing a systematic review. An adequately conducted meta-analysis may not only provide a summary estimate of a certain association, but it has additional value in discovering relevant confounders, mediators, and moderators, as well as identifying areas of research that require more attention.

Case and care complexity in the medically ill.

The authors have argued that complexity in general health care is increasingly prevalent because of the increase in patients who have multimorbid conditions, and the increased professional and technical possibilities of medicine. In the increasingly complex care systems, it is necessary-specifically when treating patients in need of integrated care by several providers-that an optimal match between case and care complexity be found in order to prevent poor outcomes in this vulnerable group. The authors discussed several approaches to case complexity that can be identified in the literature. Most of them seem unsuitable for adjusting case and care complexity, and inadequate for designing multidisciplinary care. Theoretic approaches to case complexity may be of interest, but did not result in clinically meaningful information. The INTERMED, which can be considered the first empirically based instrument to link case and care complexity, is an attempt to improve care delivery and outcomes for the complex medically ill.

Identifiers, or "red flags," of complexity and need for integrated care.

Because complex medical patients are a subgroup of the medical population and because complexity assessment involves extra effort, preselection of these patients through identifiers is necessary. There is no best identifier for complexity, and the one most suitable for the population served should be selected. This article provides a table with potential identifiers and discusses the difference between disease-oriented screening and treatment and a more generic approach such as complexity screening and complexity management.

Operationalizing integrated care on a clinical level: the INTERMED project.

During the last 10 years the INTERMED method has been developed as a generic method for the assessment of bio-psychosocial health risks and health needs and for planning of integrated treatment. The INTERMED has been conceptualized to counteract divisions and fragmentation of medical care. Designed to enhance the communication between patients and the health providers as well as between different professions and disciplines, the INTERMED is a visualized, action-oriented decision-support tool. This article presents various aspects of the INTERMED, such as its relevance, description, scoring, the related patient interview and treatment planning, scientific evaluation, implementation, and support for the method.