A network analysis of exhaustion disorder symptoms throughout treatment.

BACKGROUND: Stress-induced Exhaustion Disorder (ED) is associated with work absenteeism and adverse health outcomes. Currently, little is known regarding how the symptoms of ED are interrelated and whether the patterns of symptoms influence treatment outcomes. To this end, the current study applied network analyses on ED patients participating in a multimodal intervention. METHODS: The first aim of the study was to explore the internal relationships between exhaustion symptoms and identify symptoms that were more closely related than others. A second aim was to examine whether the baseline symptom network of non-responders to treatment was more closely connected than the baseline symptom networks of responders, by comparing the sum of all absolute partial correlations in the respective groups' symptom network. This comparison was made based on the hypothesis that a more closely connected symptom network before treatment could indicate poorer treatment outcomes. Network models were constructed based on self-rated ED symptoms in a large sample of patients (n = 915) participating in a 24-week multimodal treatment program with a 12-month follow-up. RESULTS: The internal relations between self-rated exhaustion symptoms were stable over time despite markedly decreased symptom levels throughout participation in treatment. Symptoms of limited mental stamina and negative emotional reactions to demands were consistently found to be the most closely related to other ED symptoms. Meanwhile, sleep quality and irritability were weakly related to other exhaustion symptoms. The symptom network for the full sample became significantly more closely connected from baseline to the end of treatment and 12-month follow-up. The symptom network of non-responders to treatment was not found to be more closely connected than the symptom network of responders at baseline. CONCLUSIONS: The results of the current study suggest symptoms of limited mental stamina and negative emotional reactions to demands are central ED symptoms throughout treatment, while symptoms of irritability and sleep quality seem to have a weak relation to other symptoms of ED. The implications of these findings are discussed in relation to the conceptualization, assessment, and treatment of ED. TRIAL REGISTRATION: The clinical trial was registered on Clinicaltrials.gov 2017-12-02 (Identifier: NCT03360136).

Symptoms, work situation and work functioning 10 years after rehabilitation of stress-induced exhaustion disorder.

BACKGROUND: Stress-induced exhaustion disorder (SED) is the most common reason for long-term sick leave in Sweden and the recovery process may be long and troublesome. This study explores the symptoms of burnout, depression and anxiety among patients with SED 10 years after termination of a multimodal rehabilitation program. Another aim of the study was to investigate work situation, work functioning, and any remaining exhaustion and sleeping disorders among those who were gainfully employed at the 10-year follow-up. METHODS: This longitudinal study included 107 patients (91 women and 16 men), who had been diagnosed with SED 10 years prior to the study. After establishing the diagnosis they all underwent and completed an multimodal rehabilitation program. Data on symptoms of burnout, anxiety and depression were collected before and after the multimodal rehabilitation program, and at follow-ups after additional 1 year and an additional 10 years. At the 10-year follow-up, work situation, work functioning, and symptoms of exhaustion and sleep disorders were assessed in those who were gainfully employed (89 patients). RESULTS: Symptoms of burnout, anxiety, and depression remained stable from the 1- to the 10-year follow-up after completed rehabilitation. Among participants who were gainfully employed, 73% had changed workplaces, and 31.5% had reduced their working hours. Common reasons for these changes were lack of energy or because they had chosen to prioritise their lives differently. Work functioning was rated as moderate, one third self-reported SED to some extent, and one fifth reported moderate-to-severe insomnia. CONCLUSION: A relatively large proportion of former patients with SED have residual health problems 10 years after rehabilitation and some have not been able to return to full-time work. Preventive and early rehabilitative interventions with adjustments and measures at the organisational level are probably needed to achieve a more sustainable working life.

Psychological Treatment of Exhaustion Due to Persistent Non-Traumatic Stress: A Scoping Review.

BACKGROUND: Exhaustion due to persistent non-traumatic stress (ENTS) is a significant health problem with substantial personal, social, and economic impact. While there are increasing studies of ENTS, there is no international agreement on how it should be diagnosed and treated. This scoping review aimed to map definitions, diagnoses, treatments, outcome measures, and outcomes in psychological treatment studies of ENTS. A further aim was to assess the quality of the treatments and map what change processes are described within ENTS interventions. METHODS: A PRISMA-guided scoping review of psychological treatment studies delivered in a clinical setting for ENTS was conducted using the databases of PubMed, PsycINFO, and CINAHL. RESULTS: Of the 60 studies included, the majority (87%) stemmed from Europe. The most recurrent term for ENTS was burnout, and the diagnosis most often utilized was exhaustion disorder. Several treatments were reported, the most frequent being cognitive behavioral therapy (CBT) (68%). Statistically significant outcomes relevant to ENTS were reported in 65% (n = 39) of the studies, with effect sizes between 0.13 and 1.80. In addition, 28% of the treatments were rated as high quality. The most frequent change processes described were dysfunctional sleep, avoidance, behavioral activation, irrational thoughts and beliefs, worry, perceived competence/positive management, psychological flexibility, and recuperation. CONCLUSIONS: While several treatments based on CBT show promising results for ENTS, there do not seem to be any uniformly established methods, theoretical models, or change processes. Instead of adopting a monocausal, syndromal, and potentially bio-reductionist perspective on ENTS, a process-based approach to treatment is encouraged.

Effects of adding early cooperation and a work-place dialogue meeting to primary care management for sick-listed patients with stress-related disorders: CO-WORK-CARE-Stress - a pragmatic cluster randomised controlled trial.

OBJECTIVES: To investigate whether intensified cooperation between general practitioner (GP), care manager and rehabilitation coordinator (RC) for patients sick-listed for stress-related mental disorder, combined with a person-centred dialogue meeting with employer, could reduce sick-leave days compared with usual care manager contact. DESIGN: Pragmatic cluster-randomised controlled trial, randomisation at primary care centre (PCC) level. SETTING: PCCs in Region Västra Götaland, Sweden, with care manager organisation. PARTICIPANTS: Of 30 invited PCCs, 28 (93%) accepted the invitation and recruited 258 patients newly sick-listed due to stress-related mental disorder (n = 142 intervention, n = 116 control PCCs). INTERVENTION: Cooperation between GP, care manager and rehabilitation coordinator from start of illness notification plus a person-centred dialogue meeting between patient and employer within 3 months. Regular contact with care manager was continued at the control PCCs. MAIN OUTCOME MEASURES: 12-months net and gross number of sick-leave days. Secondary outcomes: Symptoms of stress, depression, anxiety; work ability and health related quality of life (EQ-5D) over 12 months. RESULTS: There were no significant differences between intervention and control groups after 12 months: days on sick-leave (12-months net sick-leave days, intervention, mean = 110.7 days (95% confidence interval (CI) 82.6 - 138.8); control, mean = 99.1 days (95% CI 73.9 - 124.3)), stress, depression, or anxiety symptoms, work ability or EQ-5D. There were no significant differences between intervention and control groups concerning proportion on sick-leave after 3, 6, 12 months. At 3 months 64.8% were on sick-leave in intervention group vs 54.3% in control group; 6 months 38% vs 32.8%, and12 months 16.9% vs 15.5%. CONCLUSION: Increased cooperation at the PCC between GP, care manager and RC for stress-related mental disorder coupled with an early workplace contact in the form of a person-centred dialogue meeting does not reduce days of sick-leave or speed up rehabilitation.Trial registration: ClinicalTrials.gov Identifier: NCT03250026 https://clinicaltrials.gov/study/NCT03250026?tab=results#publicationsCO-WORK-CAREFirst Posted: August 15, 2017. Recruitment of PCCs: September 2017. Inclusion of patients from December 2017.

Mediators during a Multimodal intervention for stress-induced exhaustion disorder.

Our understanding of the underlying psychological processes of development, maintenance, and treatments for stress-induced exhaustion disorder (ED) remains limited. Therefore, the current study aimed to explore whether sleep concerns, pathological worry, perfectionistic concerns, and psychological flexibility mediate change in exhaustion symptoms during a Multimodal intervention for ED based on Cognitive behavioral therapy principles. Participants (N = 913) were assessed at three time points, and mediation was explored using a two-criteria analytical model with linear mixed-effects models (criterion one) and random intercepts cross-lagged panel modeling (criterion 2). Criterion one for mediation was successfully met, as the findings indicated significant associations between time in treatment, with all suggested mediators, and exhaustion symptoms (significant ab-products). However, criterion two was not satisfied as changes in the mediators did not precede changes in exhaustion symptoms. Therefore, mediation could not be established. Instead, changes in the suggested mediators appeared to result from changes in exhaustion symptoms. Consequently, sleep concerns, pathological worry, perfectionistic concerns, and psychological flexibility appear to improve in conjunction with exhaustion symptoms during treatment, where improvement in exhaustion is indicated as the main driving factor, based on this exploratory analysis. The implications of these findings are contextualized within a broader framework of process-based therapy.

Is the road to burnout paved with perfectionism? The prevalence of obsessive-compulsive personality disorder in a clinical longitudinal sample of female patients with stress-related exhaustion.

OBJECTIVES: Few studies have investigated the relationship between stress-related mental health problems and obsessive-compulsive personality disorder (OCPD). Similarly, little research has focused on the moderating effect of OCPD on recovery in clinical patients with stress-related mental health problems. The general aim of this study was to investigate the prevalence of OCPD and the associations between OCPD and level of burnout, anxiety, and depression symptoms, during a 7-years follow-up in a clinical longitudinal sample of female patients with stress-related exhaustion. METHOD: The included patients (n = 84) were referred to a specialist outpatient clinic for patients with stress-related exhaustion between 2006 and 2011. Data was collected at the initial examination and during a 7-year treatment follow-up. RESULTS: OCPD was the most common personality disorder in the present clinical sample, with 40% of patients fulfilling the criteria. There was a significant association between OCPD and the degree of burnout symptoms as well as the degree of depression, both at baseline and during the 7-year follow-up. No significant association between OCPD and levels of anxiety was observed. CONCLUSION: The results support the hypothesis that there might be an association between OCPD and stress-related exhaustion, including preservation of symptoms over time. OCPD and its related traits, such as perfectionism, may be important factors to consider when constructing effective treatment and rehabilitation plans for these patients.

Associations between improvements in psychological variables and subsequent sick leave among persons receiving a multimodal intervention for exhaustion disorder.

BACKGROUND: The incidence of sick leave due to stress-related disorders such as exhaustion disorder (ED) is high in many economically developed countries. Meanwhile, knowledge about facilitating return to work during clinical interventions for ED patients is still limited. The current study aimed to investigate if improvements in exhaustion symptoms, insomnia, perfectionistic behaviors, psychological flexibility, and perceived work ability during treatment of ED were associated with subsequent sick leave in the year following treatment. METHODS: Using a cohort of 880 ED patients who had participated in a multimodal intervention based on Cognitive Behavior Therapy, we estimated the association between one standard deviation (SD) improvement in treatment-related variables and the rate of net days of sick leave one-year following treatment. RESULTS: Our results showed that improvements in all treatment-related variables were associated with lower sick leave rates one year following treatment. Improvements in exhaustion symptoms (rate ratio (RR): 0.70 [95% CI 0.66; 0.75]) and self-perceived work ability (RR 0.56 [95% CI 0.50; 0.63]) showed the strongest associations to subsequent sick leave. CONCLUSIONS: These findings suggest that interventions focusing on exhaustion symptoms, insomnia, perfectionistic behaviors, psychological flexibility, and perceived work ability can have a meaningful impact on ED patients' subsequent sick leave. TRIAL REGISTRATION: Clinicaltrials.gov (Identifier: NCT03360136).

Predictors and sub-groups in the treatment of stress-induced exhaustion disorder.

Little is known about psychological interventions for stress-induced Exhaustion disorder (ED), and there is a need for more research to improve the outcomes obtained in treatments. The present study examines predictors of improvement, including sub-group responses, in a large sample of ED patients receiving a Multimodal intervention (MMI) based on Cognitive Behavior Therapy (N = 915). In step one, available variables were explored separately as predictors of improvement in ED symptoms. In step two, sub-groups were explored through Latent Class Analysis to reduce the heterogeneity observed in the larger group and to investigate whether combining the variables from step one predicted symptom improvement. Younger age, no previous sick leave due to ED, and scoring high on anxiety, depression, insomnia, perfectionism, and treatment credibility emerged as separate predictors of improvement. In the sub-group analyses, a sub-group including participants who were single and had a lower income showed less improvement. Overall, people with ED participating in MMI report symptom improvement regardless of characteristics before treatment. However, the present findings do have the potential to inform future treatments for ED, as they highlight perfectionism as a predictor of improvement and the importance of assessing treatment credibility during treatment.

Exhaustion disorder and altered brain activity in frontal cortex detected with fNIRS.

Patients with stress-related Exhaustion Disorder (ED) have problems with memory and executive function. These problems have been associated with deviant activity in prefrontal cortex (PFC). We investigated cognitive performance and functional activity in the PFC during prolonged mental activity in patients with ED (n = 20, 16 women) with a mean duration since diagnosis of 46 ± 23 months in comparison to healthy individuals (n = 20, 12 women). A block of six neuropsychological tests was performed in a sequence that was repeated once. The brain imaging technique, functional near infrared spectroscopy (fNIRS) was used for all tests. There were no differences between the groups in terms of changes over time, i.e. difference between first and second test block. In the Stroop-Simon test, the controls showedhigher functional activity in the frontal cortex. In the left ventrolateral PFC, we observed an increased activity in controls in the incongruent compared to the congruent trials, whereas no changes were detected in the ED patient group. During processing speed tasks, only ED patients showed higher functional activity in right dorsolateral PFC. The ED patients reported lower subjective energy level and they also performed less well on a mental control task compared to healthy individuals. In conclusion, ED patients showed altered functional activity compared to controls, indicating that ED patients process information differently in the prefrontal cortex, but the functional activity did not change during the 2½ hr procedure, as revealed by the test-retest design. Lay summary In this paper we show that patient with exhaustion disorder have a reduced functional activity in the prefrontal cortex. This functional activity was not affected by 2.5 hours mental activity.

Impaired cognitive functioning in stress-induced exhaustion disorder: a new tablet-based assessment.

BACKGROUND: The adverse health effects of stress induced exhaustion disorder (SED) cause increasing concern in Western societies. This disorder is characterized by severe fatigue, decreased tolerance to further stress, and attention and memory lapses. Despite subjective complaints, individual cognitive deficits are not always detected in a clinical setting, which calls for the validation of more sensitive instruments. AIM: The objective of this study was to investigate if a short, tablet-based serial naming task, MapCog Spectra (MCS) could be used as a marker for cognitive problems in SED. PARTICIPANTS: The study comprised of 39 subjects (35 females, four males) with SED. Their mean age was 46,8 years (SD 10.1; range 30-60 yrs.). All participants were healthcare professionals, with a college or university degree, doctors, registered nurses, and psychologists. METHODS: The MCS was used to assess the number of aberrant pauses during serial naming of coloured geometrical shapes. The Coding, Matrix Reasoning, Digit Span, Symbol Search of the WAIS-IV, and RUFF 2&7 tests, were administered together with a short interview. RESULTS: Mean values were within normal reference limits for all tests, except for the MCS, which showed a significantly higher number of aberrant pauses (p < 0,001) in the SED group, compared to normal reference values. Although subjects performed within normal limits on the RUFF 2&7, a significant difference between individuals was found in the performance strategy of the participants. CONCLUSION: Here we report that subjects with SED have performance deficits on the MCS, in terms of aberrant pause times, despite average performance on WAIS-IV tests measuring inductive reasoning, processing speed, working memory, and attention. We also demonstrate that subjects use different strategies to overcome their problems. These findings add to the growing evidence of cognitive deficits in SED and that the MCS might aid neuropsychologists in disentangling cognitive markers, important to substantiate the subjective complaints of affected individuals.

Self-reported changes in work situation - a cross-sectional study of patients 7 years after treatment for stress-related exhaustion.

BACKGROUND: Exhaustion disorder (ED) is a common cause of sick leave in Sweden, and patients often have long-lasting symptoms and reduced work capacity. The aim of this study was to explore whether patients with ED had made any changes in their work situation from the period of treatment and up to 7 years later. METHODS: In this cross-sectional study, patients diagnosed with ED at a specialist outpatient clinic were followed up after 7 years (n = 217). They received questionnaires at baseline covering sex, age, marital status, level of education, and symptoms of burnout, depression, and anxiety measured with the Shirom-Melamed Burnout Questionnaire and the Hospital Anxiety and Depression Scale. After 7 years, they were sent a follow-up questionnaire asking about their work situation and work-related stressors both before they fell sick and at the 7-year follow-up. There were three questions on work situation (change of workplace, change of work tasks, and change of working hours), and 155 patients responded to all three. RESULTS: After 7 years, the majority of the patients (63%; n = 98/155) reported that they had made some kind of change at work. Women were more likely than men to report decreased working hours (p = 0.001), and work-related stressors such as conflicts at work, reorganization, deficient leadership, and general discontent with the work situation were significantly more common at baseline in the group who had made changes at work. Patients who made no changes at work experienced more work-related stress due to quantitative demands in the 7-year follow-up. CONCLUSION: The majority of the patients with ED made some kind of change in their work situation, and gender differences were found for changes of work tasks and working hours. Work-related stressors might be decisive for making changes at work.

Self-rated exhaustion disorder and associated health-related factors among municipal employees in rural areas of northern Sweden.

OBJECTIVE: The aims of this study among municipal employees in rural areas of northern Sweden were to assess the prevalence of self-rated exhaustion disorder (s-ED), describe plausible between-group differences in self-reported health-related factors among employees with or without s-ED, and identify health-related factors associated with s-ED. METHODS: In a cross-sectional study, data were collected from 1093 municipal employees (76.1% women) in two rural areas using an instrument measuring s-ED and health variables drawn from the Modern Worklife Questionnaire (MWQ), the Perceived Stress Scale (PSS), and the National Board of Health and Welfare's questions about physical activity. Comparisons were made between an s-ED and a non-s-ED group. Health-related factors associated with s-ED were identified through a logistic regression. RESULTS: Self-rated exhaustion disorder was reported by 21.5% of the participants. Health-related factors associated with s-ED were cognitive problems, sleep problems, depressive symptoms, high stress, poor self-rated health, and stomach problems. There was no statistically significant difference in the prevalence of participants who met the criteria of physical activity among s-ED and non-s-ED group. CONCLUSION: Findings from this study suggest that s-ED is more common among municipal employees in rural areas than in other working populations in Sweden. Several health-related factors were associated with s-ED. Regular use of a self-rated instrument in evaluating the organizational and social work environment can identify people at risk of developing exhaustion disorder and requiring long-term sick leave.

Self-reported cognitive impairment and daily life functioning 7-12 years after seeking care for stress-related exhaustion.

The overall aim of this study was to investigate self-reported cognitive difficulties, daily life activities, and health/sleep factors in former patients with exhaustion disorder (ED) who still fulfill the clinical criteria for exhaustion 7-12 years after seeking care. The Sahlgrenska Self-reported Cognitive Impairment Questionnaire (SASCI-Q) was used to measure cognitive difficulties, daily life activities, and health/sleep factors. Three groups were compared: previous patients still judged to be clinically exhausted seven years or more after seeking care (n = 51); previous patients considered clinically recovered (n = 98); and healthy controls (n = 50). Patients who still fulfilled the diagnostic criteria for ED reported widespread problems related to cognition, fatigue, and daily life functioning compared to the clinically recovered group. Furthermore, despite no longer fulfilling the clinical criteria, the recovered patients still reported more problems related to cognitive functioning and fatigue compared to healthy controls. Thus, this group appeared intermediary between the non-recovered group and healthy controls regarding self-reported cognitive functioning. To conclude, ED may have considerable negative long-term effects, and it is possible that some of these residual symptoms, particularly the cognitive problems and persistent fatigue, are permanent in some patients. Preventive measures should be the primary focus for all stakeholders, since the consequences of stress-related mental health problems seem to be extensive and long-lasting.

Standardized multimodal intervention for stress-induced exhaustion disorder: an open trial in a clinical setting.

BACKGROUND: Long-term sick-leave due to stress-related ill-health is increasing in several economically developed countries. Even though different forms of interventions are administered in regular care for stress-related disorders, such as Stress-induced Exhaustion disorder (SED), the scientific evidence for the effectiveness of such treatments is sparse. The objective of this study was to explore changes in SED-symptoms and return-to-work-rates in a large group of SED-patients participating in a standardized Multimodal intervention (MMI) in a clinical setting. METHOD: This open clinical trial tracked 390 patients who fulfilled the criteria for SED undergoing a 24-week MMI, including return-to-work-strategies. Before inclusion, all patients underwent a multi-professional assessment by a team of licensed physicians, licensed psychologists, and licensed physiotherapists. Self-rated questionnaires were administered before treatment, at treatment-start, mid-treatment, post-treatment, and at 12-month follow-up. Within-group change was evaluated over time with mixed-effects models. Beyond different symptoms, working time, sick-leave compensation, and adverse effects were also measured. RESULTS: There were significant improvements in symptoms of SED, burnout, anxiety, depression, and insomnia, with large within-group effect sizes (d = 0.91-1.76), improvements that were maintained at 12-month follow-up. Furthermore, there was a significant increase in quality of life and large improvements in average working time and sick-leave compensation. Some adverse effects were reported, mainly concerning an increase in stress, anxiety, and worry. CONCLUSION: SED-patients participating in this standardized MMI reported large symptom alleviation, increased working time and reduced sick-leave compensation, indicating a beneficial treatment. There were some adverse effects, but no more so than other psychological treatments. This study confirms previous findings that high levels of depression and anxiety decrease to sub-clinical levels during treatment, while symptoms of SED also decline, yet still persists above sub-clinical levels at 12-month follow-up. On the whole, this open clinical trial suggests that a standardized MMI, administered in a clinical setting, improves symptoms and return-to-work rates in a clinically representative SED-population. TRIAL REGISTRATION: This study was registered on Clinicaltrials.gov 2017.12.02 (Identifier: NCT03360136 ).

Hopeful struggling for health: Experiences of participating in computerized cognitive training and aerobic training for persons with stress-related exhaustion disorder.

It is important to understand how people with exhaustion disorder (ED) perceive interventions aiming to facilitate cognitive functioning. Therefore, the overall aim of this study was to explore experiences from persons with ED after participating in a 12-week intervention of either computerized cognitive training or aerobic training. Both interventions were performed in addition to a multimodal rehabilitation programme. Thirteen participants, 11 women and 2 men, were interviewed about pros and cons with participating in the training. The interviews were analysed with Qualitative Content Analysis. The analyses resulted in the theme hopeful struggling for health and the categories support, motivation and sensations. It was hard work recovering from ED. Support from others who are in the same situation, family members, and technology and routines for the training were strongly emphasized as beneficial for recovery. Timing, i.e., matching activities to the rehabilitation programme, getting feedback and perceiving joy in the training were important for motivation. Participants in both interventions experienced positive sensations with improved memory performance, everyday life functioning and increased faith in the prospect of recovery. However, it is important to consider various aspects of support and motivation in both computerized cognitive training and aerobic training to enable participants to pursue their participation.

Effects of cognitive behavioural therapy and return-to-work intervention for patients on sick leave due to stress-related disorders: Results from a randomized trial.

The aim of this study was to evaluate specific effects for patients with adjustment or exhaustion disorder, the Stress subgroup (n = 152), regarding symptom severity and sick leave after CBT, a return-to-work intervention (RTW-I), and a combination of them (COMBO), using data from a randomized trial. In the original study, primary care patients on sick leave (N = 211) were randomized to CBT (n = 64), RTW-I (n = 67), or COMBO (n = 80). Blinded Clinician Severity Rating (CSR) of symptoms and sick leave registry data were primary outcomes. Subgroup analyses showed that for the Stress subgroup, CBT led to greater reduction of symptoms than RTW-I posttreatment, but COMBO did not differ from CBT or RTW-I. Regarding sick leave, there was no difference between treatments in the Stress subgroup. An exploratory analysis of the treatment effects in a subgroup of patients with depression, anxiety or insomnia indicates that RTW-I reduced sick leave faster than CBT. We conclude that CBT may be promising as an effective treatment of stress and exhaustion disorder.

Plasma metabolomic patterns in patients with exhaustion disorder.

Exhaustion disorder (ED) is a stress-related disorder that often implies a great burden on the individual patient as well as on society. Previous studies have shown that ED is associated with metabolic deviations, such as lowered fasting glucose. Several mechanisms have been discussed as a plausible explanation of the lack of energy described by these patients. Metabolic processes and reduced ability to mobilize energy have been suggested as important factors. This study investigated metabolomics in 20 patients diagnosed with ED and compared them with 21 healthy controls. Plasma metabolic profiles were examined in both fasting and nonfasting (postprandial) conditions. Blood plasma samples were analyzed for metabolite content using gas chromatography mass spectrometry. A total of 62 different metabolites were simultaneously detected in each of the samples. Multivariate models indicated systematic differences between patients with ED and healthy controls in both their fasting and nonfasting plasma metabolite levels. Lysine and octadecenoic acid were more abundant and glutamine, glycine, serine and gluconic acid were less abundant in the patients across both conditions. In the present study, we comprehensively and simultaneously screen for changes in a large number of metabolites. Our results show a difference in systemic metabolites between patients with exhaustion disorder and healthy controls both in the fasting and in the postprandial states. Here, we present new potential biomarkers mirroring exhaustion disorder metabolism. Lay summary Exhaustion disorder (ED) patients suffer from stress-related symptoms including a reduced energy level. This study investigates the body's metabolism in patients with ED, both fasting and after a meal. New potential markers that may help future investigations on ED were identified.

Longitudinal associations between cardiorespiratory fitness and stress-related exhaustion, depression, anxiety and sleep disturbances.

BACKGROUND: In the last few years, so-called "common mental disorders", including adjustment disorder and stress-related exhaustion, have outrivalled musculoskeletal disorders as being the leading cause of long-term sick leave in Sweden. Cardiorespiratory fitness level defined as "the maximal amount of physiological work that an individual can do as measured by oxygen consumption" has in many studies shown to reduce the risk of several life-style related diseases and moreover to improve mood, well-being and physical performance. The aim of the present study was to investigate, longitudinal associations between cardiorespiratory fitness and self-reported physical activity levels and the severity of symptoms connected to stress-related exhaustion, depression, anxiety, and sleep disturbances among women clinically diagnosed with stress-related exhaustion disorder (ED). METHODS: The study was that of a longitudinal cohort study consisting of women (n = 88) diagnosed with stress-related ED in a specialist clinic in Gothenburg, Sweden. Cardiorespiratory fitness was measured with the Åstrand indirect test of maximal oxygen uptake (VO2max) and subjective measures of physical activity levels were rated on 4-graded physical activity scale. To measure and follow symptoms of ED over time the SMBQ-questionnaire (Shirom Melamed Burnout Questionnaire) was used. The Hospital Anxiety and Depression Scale (HADS) was used to measure depression and anxiety. A proxy variable for capturing overall disturbed sleep used to measure sleep. Longitudinal associations for continuous outcome variables and the dichotomous variable sleep were analysed using mixed- effects regression models with random intercepts. Regression coefficients along with the 95% confidence interval (CI) are presented as measures of association. Both exposures and the outcome were measured simultaneously over six waves (T1-T6). RESULTS: The results showed statistically significant associations between level of fitness and reduced symptoms of stress-related exhaustion over time. Best improvements over time were seen in patients having a medium cardiorespiratory fitness level. No associations could be found between cardiorespiratory fitness level over time and anxiety, depression or sleep disturbances. CONCLUSION: Having medium cardiorespiratory fitness was positivity associated with a more sustained reduction in symptoms of ED overtime compared to those having low or high cardiorespiratory fitness levels. The clinical implication following this result is that an individual recommendation based on a medium level of physical activity in line with the recommendations from ACSM (American College of Sports Medicine) is preferable compared to recommendations including more vigorous physical activity in order to restore and sustainably reduce symptoms of exhaustion disorder over time.

Cost-Effectiveness of Therapist-Guided Internet-Based Cognitive Behavioral Therapy for Stress-Related Disorders: Secondary Analysis of a Randomized Controlled Trial.

BACKGROUND: Stress-related disorders are associated with significant suffering, functional impairment, and high societal costs. Internet-based cognitive behavioral therapy (ICBT) is a promising treatment for stress-related disorders but has so far not been subjected to health economic evaluation. OBJECTIVE: The objective of this study was to evaluate the cost-effectiveness and cost-utility of ICBT for patients with stress-related disorders in the form of adjustment disorder (AD) or exhaustion disorder (ED). We hypothesized that ICBT, compared with a waitlist control (WLC) group, would generate improvements at low net costs, thereby making it cost-effective. METHODS: Health economic data were obtained in tandem with a randomized controlled trial of a 12-week ICBT in which patients (N=100) were randomized to an ICBT (n=50) or a WLC (n=50) group. Health outcomes and costs were surveyed pre- and posttreatment. We calculated incremental cost-effectiveness ratios (ICERs) based on remission rates and incremental cost-utility ratios (ICURs) based on health-related quality of life. Bootstrap sampling was used to assess the uncertainty of our results. RESULTS: The ICER indicated that the most likely scenario was that ICBT led to higher remission rates compared with the WLC and was associated with slightly larger reductions in costs from pre- to posttreatment. ICBT had a 60% probability of being cost-effective at a willingness to pay (WTP) of US $0 and a 96% probability of being cost-effective at a WTP of US $1000. The ICUR indicated that ICBT also led to improvements in quality of life at no net societal cost. Sensitivity analyses supported the robustness of our results. CONCLUSIONS: The results suggest that ICBT is a cost-effective treatment for patients suffering from AD or ED. Compared with no treatment, ICBT for these patients yields large effects at no or minimal societal net costs. TRIAL REGISTRATION: ClinicalTrials.gov NCT02540317; https://clinicaltrials.gov/ct2/show/NCT02540317.

Stepped care in primary care - guided self-help and face-to-face cognitive behavioural therapy for common mental disorders: a randomized controlled trial.

BACKGROUND: Common mental disorders (CMD) cause large suffering and high societal costs. Cognitive behavioural therapy (CBT) can effectively treat CMD, but access to treatment is insufficient. Guided self-help (GSH) CBT, has shown effects comparable with face-to-face CBT. However, not all patients respond to GSH, and stepping up non-responders to face-to-face CBT, could yield larger response rates. The aim was to test a stepped care model for CMD in primary care by first evaluating the effects of GSH-CBT and secondly, for non-responders, evaluating the additional effect of face-to-face CBT. METHODS: Consecutive patients (N = 396) with a principal disorder of depression, anxiety, insomnia, adjustment or exhaustion disorder were included. In Step I, all patients received GSH-CBT. In Step II, non-responders were randomized to face-to-face CBT or continued GSH. The primary outcome was remission status, defined as a score below a pre-established cutoff on a validated disorder-specific scale. RESULTS: After GSH-CBT in Step I, 40% of patients were in remission. After Step II, 39% of patients following face-to-face CBT were in remission compared with 19% of patients after continued GSH (p = 0.004). Using this stepped care model required less than six therapy sessions per patient and led to an overall remission rate of 63%. CONCLUSIONS: Stepped care can be effective and resource-efficient to treat CMD in primary care, leading to high remission rates with limited therapist resources. Face-to-face CBT speeded up recovery compared with continued GSH. At follow-ups after 6 and 12 months, remission rates were similar in the two groups.