Cognitive behavioral therapy for stress-related disorders

Background: Stress-related disorders in the form of adjustment disorder (AD) and exhaustion disorder (ED) are prevalent and associated with significant suffering, functional impairment and high societal costs. Cognitive behavioral therapy (CBT) may be effective in reducing stress, but studies using clinical samples diagnosed with stress-related disorders are few, and evidence is lacking to support treatment guidelines. Because accessibility to CBT is limited, it is important to investigate treatment delivery formats that enable high scalability. Health economic evaluations of treatments are needed to guide decision makers in how to use limited healthcare resources efficiently. Further, the study of potential mediators of treatment effect is important to inform treatment development for patients diagnosed with AD or ED. Aims: The overall aim of Study I was to evaluate the effect of CBT, a return-to-work intervention (RTW-I), and a combination of the two (COMBO) for patients on sick leave due to a common mental disorder (CMD; AD, ED, anxiety disorders, depression, and insomnia). Of particular interest to the present thesis was to evaluate the effect of a new CBT protocol used to treat patients with stress-related disorders in Study I. In Study II, the aim was to evaluate the efficacy of that same CBT protocol when delivered as a therapist-guided internet-based treatment (ICBT) for individuals with AD or ED. In Study III, we aimed to investigate cost-effectiveness of the ICBT. In Study IV, we aimed to investigate sleep impairment as a putative mediator of the effect of ICBT on symptoms of stress and exhaustion. Methods: In Study I, consecutively recruited primary care patients (N = 211) who were on sick leave due to a CMD were randomized to disorder specific CBT, a RTW-I, or to COMBO. Main outcomes were symptom severity and net days on sick leave. Of the total sample, a majority (72%) of patients met diagnostic criteria for AD or ED and were treated with the new CBT protocol for stress-related disorders. In Study II, nationally recruited participants (N = 100) diagnosed with AD or ED were randomized to ICBT for stress-related disorders or to a waitlist control condition (WLC). Level of perceived stress was the main outcome. Studies III and IV were based on data collected in Study II. In Study III, cost- effectiveness and cost-utility of the ICBT were evaluated from a societal and a healthcare perspective, using remission rates and health-related quality of life to calculate incremental cost-effectiveness and cost-utility ratios respectively. In Study IV, weekly measurements of sleep impairment (the putative mediator) and outcomes (perceived stress and exhaustion) throughout the course of ICBT were analyzed using latent growth models within a structural equation framework. Results: Results of Studies I and II indicated that the CBT for stress-related disorders was effective in reducing symptoms compared with the RTW-I and the WLC respectively. Subgroup analyses of AD and ED in Study II indicated that the treatment was equally effective for both diagnostic groups. Treatment effect on sick leave (Study I) and work ability (Study II) was, however, small and non-significant compared with control conditions. Results from Study III suggested that, compared with the WLC, ICBT was a cost effective treatment, yielding large effects at no or minimal societal net costs in only 12 weeks. In Study IV, reduced sleep impairment was found to statistically mediate the effect of ICBT on symptoms of perceived stress and exhaustion. Conclusions: A relatively short CBT protocol designed to meet the presumed needs of patients diagnosed with AD or ED was indicated to be effective in reducing symptoms both when delivered as a face-to-face treatment and when delivered via the internet. If implemented in routine care, ICBT has the potential to increase access to efficacious treatment for many suffering individuals at no additional societal net costs. Reduced sleep impairment may be of importance to achieve successful treatment outcomes. The results motivate further investigation of the treatment using different control groups, longer follow- up periods, and more fine-grained evaluations of treatment mechanisms. Further investigation into interventions that may have an effect on work-related outcomes is warranted

Chronic fatigue syndromes: real illnesses that people can recover from

The ‘Oslo Chronic Fatigue Consortium’ consists of researchers and clinicians who question the current narrative that chronic fatigue syndromes, including post-covid conditions, are incurable diseases. Instead, we propose an alternative view, based on research, which offers more hope to patients. Whilst we regard the symptoms of these conditions as real, we propose that they are more likely to reflect the brain's response to a range of biological, psychological, and social factors, rather than a specific disease process. Possible causes include persistent activation of the neurobiological stress response, accompanied by associated changes in immunological, hormonal, cognitive and behavioural domains. We further propose that the symptoms are more likely to persist if they are perceived as threatening, and all activities that are perceived to worsen them are avoided. We also question the idea that the best way to cope with the illness is by prolonged rest, social isolation, and sensory deprivation. Instead, we propose that recovery is often possible if patients are helped to adopt a less threatening understanding of their symptoms and are supported in a gradual return to normal activities. Finally, we call for a much more open and constructive dialogue about these conditions. This dialogue should include a wider range of views, including those of patients who have recovered from them

Psychometric and structural properties of the Karolinska Exhaustion Disorder Scale : a 1,072-patient study

Objective: Exhaustion disorder is a stress-related diagnosis that was introduced in 2005 to the Swedish version of the International Statistical Classification of Diseases and Related Health Problems, 10th edition (ICD-10). The Karolinska Exhaustion Disorder Scale (KEDS) was developed to assess exhaustion disorder symptomatology. While the KEDS is intended to reflect a single construct and be used based on its total score, the instrument's characteristics have received limited attention. This study investigated the KEDS's psychometric and structural properties in a large clinical sample. Methods: The study relied on data from 1,072 patients diagnosed with exhaustion disorder that were included in two clinical trials in Sweden. We investigated the dimensionality, homogeneity, and reliability of the KEDS using advanced statistical techniques, including exploratory structural equation modeling (ESEM) bifactor analysis. Results: A one-factor confirmatory analytic model exhibited a poor fit, suggesting at least a degree of multidimensionality. The ESEM bifactor analysis found the general factor to explain about 72% of the common variance extracted, with an omega hierarchical coefficient of 0.680. Thus, the ESEM bifactor analysis did not clearly support the scale's essential unidimensionality. A homogeneity analysis revealed a scale-level H of only 0.296, suggesting that KEDS's total scores do not accurately rank individuals on the latent continuum assumed to underlie the measure. The KEDS's reliability was modest, signaling considerable measurement error. Conclusion: Findings reveal important limitations to the KEDS with possible implications for the status of exhaustion disorder as a nosological category

Characterization of exhaustion disorder and identification of outcomes that matter to patients : Qualitative content analysis of a Swedish national online survey

Fatigue is a common presenting problem in healthcare settings, often attributed to chronic psychosocial stress. Understanding of fatigue and development of evidence-based treatments is hampered by a lack of consensus regarding diagnostic definitions and outcomes to be measured in clinical trials. This study aimed to map outcome domains of importance to the Swedish diagnosis stress-induced exhaustion disorder (ED; ICD-10, code F43.8 A). An online survey was distributed nationwide in Sweden to individuals who reported to have been diagnosed with ED and to healthcare professionals working with ED patients. To identify outcome domains, participants replied anonymously to four open-ended questions about symptoms and expectations for ED-treatment. Qualitative content analysis was conducted of a randomized subsample of respondents, using a mathematical model to determine data saturation. Six hundred seventy participants (573 with reported ED, 97 healthcare professionals) completed the survey. Qualitative content analysis of answers supplied by 105 randomized participants identified 87 outcomes of importance to ED encompassing physical, cognitive, and emotional symptoms as well as functional disability. Self-rating scales indicated that many ED participants, beyond reporting fatigue, also reported symptoms of moderate to severe depression, anxiety, insomnia, poor self-rated health, and sickness behavior. This study presents a map of outcome domains of importance for ED. Results shed light on the panorama of issues that individuals with ED deal with and can be used as a step to further understand the condition and to reach consensus regarding outcome domains to measure in clinical trials of chronic stress and fatigue. Preregistration: Open Science Framework (osf.io) with DOI https://doi.org/10.17605/OSF.IO/4VUAG

Inflammatory cytokines in patients with common mental disorders treated with cognitive behavior therapy

Peripheral inflammation has been found associated with psychiatric disorders. However, results are inconclusive as to its role in common mental disorders (CMDs), i.e., depression, anxiety, insomnia and stress-related disorders. Further, some research suggests that cognitive behavior therapy (CBT) could reduce inflammatory markers in CMDs. In the present study, we measured pro-inflammatory cytokines (tumor necrosis factor alpha [TNF-α], interleukin-6 [IL-6] and IL-8) pre- and post-treatment in two clinical trials (N ​= ​367) investigating CBT for patients with CMDs in primary care. We hypothesized that higher levels of these cytokines would be associated with more severe psychiatric symptoms (i.e., symptoms of depression, stress and anxiety). We also hypothesized that level of cytokines would decrease after CBT and that the reduced levels would correlate with a reduction in symptoms. Results showed that in men, higher levels of TNF-α were associated with more severe psychiatric symptoms. Further, age moderated the association between TNF-α, as well as IL-6, and stress, and exploratory stratified analyses revealed significant associations in subgroups. No other significant associations between cytokines and psychiatric symptoms were found. None of the cytokines were reduced following CBT, and the marked improvements in psychiatric symptoms after treatment were not associated with changes in cytokines. In conclusion, although inflammation might be of relevance in subgroups, it seems to be of limited importance for clinical improvements across mild to moderate CMDs

Exhaustion disorder : Scoping review of research on a recently introduced stress-related diagnosis

Background: Symptoms related to chronic stress are prevalent and entail high societal costs, yet there is a lack of international consensus regarding diagnostics and treatment. A new stress-related diagnosis, exhaustion disorder, was introduced into the Swedish version of ICD-10 in 2005. Since then, use of the diagnosis has increased rapidly. Aims: To create the first comprehensive synthesis of research on exhaustion disorder to report on the current state of knowledge. Preregistration: Open Science Framework (osf.io), doi 10.17605/OSF.IO/VFDKW. Method: A PRISMA-guided scoping review of all empirical studies of exhaustion disorder was conducted. Searches were run in the MEDLINE, PsycInfo and Web of Science databases. Data were systematically charted and thematically categorised based on primary area of investigation. Results: Eighty-nine included studies were sorted into six themes relating to lived experience of exhaustion disorder (n = 9), symptom presentation and course (n = 13), cognitive functioning (n = 10), biological measures (n = 24), symptom measurement scales (n = 4) and treatment (n = 29). Several studies indicated that individuals with exhaustion disorder experience a range of psychiatric and somatic symptoms beyond fatigue, but robust findings within most thematic categories were scarce. The limited number of studies, lack of replication of findings and methodological limitations (e.g. small samples and scarcity of specified primary outcomes) preclude firm conclusions about the diagnostic construct. Conclusions: More research is needed to build a solid knowledge base for exhaustion disorder. International collaboration regarding the conceptualisation of chronic stress and fatigue is warranted to accelerate the growth of evidence