Does employer involvement in primary health care enhance return to work for patients with stress-related mental disorders? a cluster randomized controlled trial.

BACKGROUND: Stress-related disorders have become a major challenge for society and are associated with rising levels of sick leave. The provision of support to facilitate the return to work (RTW) for this patient group is of great importance. The aim of the present study was to evaluate whether a new systematic procedure with collaboration between general practitioners (GPs), rehabilitation coordinators (RCs) and employers could reduce sick leave days for this patient group. METHOD: Employed patients with stress-related diagnoses seeking care at primary health care centres (PHCCs) were included in either the intervention group (n = 54), following the systematic intervention procedure, or the control group (n = 58), receiving treatment as usual (TAU). The intervention included a) a training day for participant GPs and RCs, b) a standardised procedure for GPs and RCs to follow after training, c) the opportunity to receive clinical advice from specialist physicians in the research group. Outcome measures for RTW were sick leave days. RESULTS: The median number of registered gross sick leave days was lower for the control group at six, 12 and 24 months after inclusion, but the difference was not statistically significant. The control group had significantly fewer net sick leave days at three months (p = 0.03) at six months (p = 0.00) and at 12-months follow-up (p = 0.01). At 24 months, this difference was no longer significant. CONCLUSIONS: The PRIMA intervention, which applied a standardized procedure for employer involvement in the rehabilitation process for patients with stress-related disorders, actually increased time to RTW compared to TAU. However, at 24 months, the benefit of TAU could no longer be confirmed. The study was registered on 16/01/2017 (ClinicalTrials.gov, NCT03022760).

Effects of Additional Individually Tailored Interventions on Sick-Leave and Symptoms in Patients with Exhaustion Disorder: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effects of adding individually tailored interventions to a standard treatment in patients with stress-related exhaustion disorder, with regard to sick-leave days and symptoms of burnout. The study design was a 2-armed randomized controlled intervention, with follow-up after 15 months. Data were obtained from patients referred to the Institute of Stress Medicine, and were collected between 2011 and 2014 in western Sweden. METHODS: Inclusion criteria were scoring above cut-off in at least 1 of 4 dimensions; mental and physical exhaustion, disturbed sleep, reduced cognitive function and perceived poor self-esteem. The total study population comprised 142 patients (112 females, 30 males) allocated through block randomization to either the intervention group (n = 71) or the control group (n = 71). The intervention group received 1-4 individually tailored interventions (physical activity, cognitive behaviour therapy for insomnia, computerized memory training, cognitive behavioural therapy for self-esteem), based on the results of screening assessments. The interventions were additional to a standard treatment. The control group received solely the standard treatment. The primary outcome measure was the proportion of participants not sicklisted at the 15-month follow-up. RESULTS: At the 15-month follow-up, 30% of subjects in the intervention group and 34% in the control group had 0% sick-listed (p = 0.58). No change between baseline and follow-up was seen in 42% of the intervention group and 39% of the control group, while an increased sick-leave rate was seen in 1% of the intervention group and 4% of the control group. However, no statistically significant difference was seen between groups. CONCLUSION: Adding individually tailored interventions to a standard treatment in patients with stress-related exhaustion did not reduce sick-leave days or burnout symptoms.

Effects of a Person-Centered eHealth Intervention for Patients on Sick Leave Due to Common Mental Disorders (PROMISE Study): Open Randomized Controlled Trial.

BACKGROUND: Sick leave due to common mental disorders (CMDs) is a public health problem in several countries, including Sweden. Given that symptom relief does not necessarily correspond to return to work, health care interventions focusing on factors that have proven important to influence the return to work process, such as self-efficacy, are warranted. Self-efficacy is also a central concept in person-centered care. OBJECTIVE: The aim of this study is to evaluate the effects of a person-centered eHealth intervention for patients on sick leave due to CMDs. METHODS: A randomized controlled trial of 209 patients allocated to either a control group (107/209, 51.2%) or an intervention group (102/209, 48.8%) was conducted. The control group received usual care, whereas the intervention group received usual care with the addition of a person-centered eHealth intervention. The intervention was built on person-centered care principles and consisted of telephone support and a web-based platform. The primary outcome was a composite score of changes in general self-efficacy (GSE) and level of sick leave at the 6-month follow-up. An intention-to-treat analysis included all participants, and a per-protocol analysis consisted of those using both the telephone support and the web-based platform. RESULTS: At the 3-month follow-up, in the intention-to-treat analysis, more patients in the intervention group improved on the composite score than those in the control group (20/102, 19.6%, vs 10/107, 9.3%; odds ratio [OR] 2.37, 95% CI 1.05-5.34; P=.04). At the 6-month follow-up, the difference was no longer significant between the groups (31/100, 31%, vs 25/107, 23.4%; OR 1.47, 95% CI 0.80-2.73; P=.22). In the per-protocol analysis, a significant difference was observed between the intervention and control groups at the 3-month follow-up (18/85, 21.2%, vs 10/107, 9.3%; OR 2.6, 95% CI 1.13-6.00; P=.02) but not at 6 months (30/84, 35.7%, vs 25/107, 23.4%; OR 1.8, 95% CI 0.97-3.43; P=.06). Changes in GSE drove the effects in the composite score, but the intervention did not affect the level of sick leave. CONCLUSIONS: A person-centered eHealth intervention for patients on sick leave due to CMDs improved GSE but did not affect the level of sick leave. TRIAL REGISTRATION: ClinicalTrials.gov NCT03404583; https://clinicaltrials.gov/ct2/show/NCT03404583.

Person-centred eHealth intervention for patients on sick leave due to common mental disorders: study protocol of a randomised controlled trial and process evaluation (PROMISE).

INTRODUCTION: The number of people dealing with common mental disorders (CMDs) is a major concern in many countries, including Sweden. Sickness absence resulting from CMDs is often long-lasting and advancing return to work is a complex process impacted by several factors, among which self-efficacy appears to be an important personal resource. Person-centred care (PCC) has previously shown positive effects on self-efficacy however this needs to be further investigated in relation to patients with CMDs and in an eHealth context. METHODS AND ANALYSIS: This study is an open randomised controlled trial comparing a control group receiving standard care with an intervention group receiving standard care plus PCC by telephone and a digital platform. The primary outcome measure is a composite score of changes in sick leave and self-efficacy. Participants will include 220 primary care patients on sick leave due to CMDs and data will mainly be collected through questionnaires at baseline and 3, 6, 12 and 24 months from the inclusion date. Inclusion is ongoing and expected to be completed during the fall of 2020. A process and health economic evaluation will also be conducted. ETHICS AND DISSEMINATION: This study was approved by the Regional Ethical Review Board in Gothenburg, Sweden. Results will be published in peer-reviewed scientific journals and presented at national and international scientific conferences. This project is part of a broader research programme conducted at the Gothenburg Centre for Person-Centred Care (GPCC), where extensive work is undertaken to disseminate knowledge on and implementation of PCC. TRIAL REGISTRATION NUMBER: NCT03404583.

Long-term follow-up of residual symptoms in patients treated for stress-related exhaustion.

BACKGROUND: Many patients with stress-related exhaustion seem to struggle with long-term recovery. The primary aim of this study was to explore residual symptoms and perceived recovery in patients previously treated for stress-related exhaustion, 7 years after seeking care. METHODS: A total of 217 former patients (74% women) previously treated for exhaustion disorder were asked to participate in follow-ups 2, 3, 5, and 7 years post treatment. Symptoms of depression, and anxiety were measured with questionnaires. Remaining symptoms of extreme fatigue, sleep disturbances, problems with concentration, problems with memory and reduced stress tolerance, were rated with single item questions. A subgroup of patients (n = 163) participated in a clinical assessment to confirm residual stress-related exhaustion not caused by other diseases. RESULTS: Almost half of the patients previously treated for stress-related exhaustion perceive fatigue 7 years after initially seeking care, and as many as 73% reported decreased stress tolerance. The clinical assessment confirmed that a third of the patients were clinically judged as still suffering from stress-related exhaustion. Male and female patients showed similar patterns regarding residual symptoms. CONCLUSIONS: One third of patients with exhaustion disorder are clinically judged to have exhaustion, 7 years after seeking care. Further studies are needed to elucidate the reason for such a long-term recovery and ultimately to identify methods for prevention.

Growth factors and neurotrophins in patients with stress-related exhaustion disorder.

Growth factors, such as vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF), and neurotrophic factors, including brain-derived neurotophic factor (BDNF), have attracted attention in studies of the biological effects of long-term stress exposure due to their neuroprotective roles. This study investigated whether circulating levels of EGF, VEGF and BDNF were altered in individuals with stress-related exhaustion disorder. Forty patients diagnosed with exhaustion disorder and 40 healthy subjects (50% women) provided fasting blood samples for analysis of EGF, VEGF, and BDNF in plasma. We found significantly lower levels of EGF, VEGF, and BDNF in patients with ED compared to healthy controls. This pattern was seen in both male and female patients. Given the important roles of BDNF and VEGF for brain plasticity and neurogenesis, decreased levels after long-term stress exposure could indicate increased risk of neuronal damage and cognitive impairments in this patient group.

Involving the employer to enhance return to work among patients with stress-related mental disorders - study protocol of a cluster randomized controlled trial in Swedish primary health care.

BACKGROUND: Work-related stress has become a major challenge for social security and health care systems, employers and employees across Europe. In Sweden, sickness absence particularly due to stress-related disorders has increased excessively in recent years, and the issue of how to improve sustainable return to work in affected employees is high up on the political agenda. The literature on interventions for return to work in patients with common mental disorders is still inconclusive. This randomized controlled trial (RCT) aims to contribute with knowledge about how physicians and rehabilitation coordinators in primary health care can involve the employer in the rehabilitation of patients with stress-related disorders. The objective is to evaluate whether the early involvement of the patient's employer can reduce the time for return to work compared to treatment as usual. A process study will complete the RCT with information about what prerequisites primary health caregivers need to succeed with this endeavor. METHODS: Twenty-two primary care centers were randomized to either intervention or control group. At the intervention centers, physicians and rehabilitation coordinators underwent training, providing them with both knowledge and practical tools to involve the employer in rehabilitation. At the patient level, employed patients with an ICD-10 F43 diagnosis were eligible for participation (n=132). Difference in proportion of patients on full- or part-time sick leave at three, six and 12 months after inclusion will be investigated. Register data, logbooks and interviews with coordinators and physicians at both intervention and control centers will be used for process evaluation. DISCUSSION: Although the issue of how to tackle work-related stress can be recognized all across Europe, Sweden face an urgent need to curb the disproportional increase of stress-related disorders in the sick-leave statistics. Since physicians are limited by time constraints, the rehabilitation coordinator may be a helpful resource to take this contact. The current study will contribute to knowledge about how this collaboration can be organized to facilitate employer involvement and reduce time to return to work among patients suffering from work related stress. TRIAL REGISTRATION: Registered on 1 November 2016, ClinicalTrials.gov, NCT03022760 .

Working memory and attention are still impaired after three years in patients with stress-related exhaustion.

Cognitive impairment is one of the most pronounced symptoms reported by patients with stress-related mental health problems. Impairments related to executive function and to some extent speed and attention are therefore common in patients with stress-related burnout/exhaustion. In this paper we present a follow-up of cognitive performance in patients with stress-related exhaustion several years after they initially sought medical care. Thirty patients and 27 healthy controls, mean age 49 years (SD 6.5) and 55 years (SD 6.7) respectively, were included, all of whom had undergone baseline measurements of neuropsychological functioning. The mean follow-up time was three years. Half of the patients still reported mental health problems at follow-up and over time no major changes in cognitive performance were noted. The patients still performed significantly poorer than controls with regard to cognitive functions, mainly related to speed, attention and memory function. Long-lasting impairment of cognitive functions related to speed, attention and memory function noted in patients with stress-related exhaustion should be acknowledged and taken into consideration during treatment and when discussing a return to work. Follow-up periods longer than three years are needed to explore the persistence of the cognitive impairment.

Prevalence and course of somatic symptoms in patients with stress-related exhaustion: does sex or age matter.

BACKGROUND: Both mental and somatic symptoms are commonly reported in patients with stress-related problems. We have explored the prevalence of somatic symptoms in patients seeking medical care for stress-related mental health problems and followed the course of illness alongside with that the patients receive multimodal treatment. METHOD: This study comprises data from 228 patients (69% women, mean age 43 years) who fulfilled the criteria for Exhaustion Disorder (ED). Somatic symptoms were assessed at baseline and after 3, 6, 12 and 18 months using the one-page questionnaire Primary Care Evaluation of Mental Disorders. Prevalence of different symptoms was compared between men and women and patients, over and below 40 years of age, and possible predictors of recovery were explored. RESULTS: Tiredness and low energy are the core symptom reported by the patients. Almost all (98%) reported at least one somatic symptom and 45% reported six symptoms or more, which was similar for men and women. Nausea, gas or indigestion are the most common symptoms (67%) followed by headaches (65%) and dizziness (57%). The number of symptoms reported was significantly related to the severity of mental health problems. The only difference between the sexes was that "chest pain" and "pain or problems during sexual intercourse" were more common among males. Patients over forty more often reported "pain in arms, legs or joints, knees, hips" and this was also the only symptom that did not significantly decline during treatment. Neither sex, age, symptom duration before seeking medical care, education or any other predictor tested was shown to predict recovery in patients reporting six symptoms or more. CONCLUSION: A heavy burden of somatic symptoms was generally seen in most patients with stress-related exhaustion. Somatic symptoms are equally common in males and females and in younger and older patients. The somatic symptoms seem to be mostly stress-related since all symptoms, except musculoskeletal pain, reduce with individualised treatment designed for stress-related mental problems. This study brings to attention the complicated burden of both somatic and mental symptoms in patients with stress-related exhaustion, raising several clinical implications of interest to discuss.

Course of mental symptoms in patients with stress-related exhaustion: does sex or age make a difference?

BACKGROUND: Long-term sick leave due to mental health problems, especially among women, is a substantial problem in many countries, and a major reason for this is thought to be psychosocial stress. The recovery period of different patient groups with stress-related mental health problems can differ considerably. We have studied the course of mental health symptoms during 18 months of multimodal treatment in relation to sex and age in a group of patients with stress-related exhaustion. METHODS: The study group includes 232 patients (68% women) referred to a stress clinic and who fulfilled the criteria for Exhaustion Disorder (ED). The majority also fulfilled diagnostic criteria for depression and/or anxiety; this was similar among women and men. Symptoms were assessed at baseline, three, six, 12 and 18 months by the Shirom-Melamed Burnout Questionnaire (SMBQ) and the Hospital Anxiety and Depression scale (HAD). A total SMBQ mean score of ≥ 4 was used to indicate clinical burnout, which correlates well with the clinical diagnosis of ED. RESULTS: There were no statistically significant differences between women and men or between young and old patients in the self-reported symptoms at baseline. The proportion that had high burnout scores decreased over time, but one-third still had symptoms of clinical burnout after 18 months. Symptoms indicating probable depression or anxiety (present in 34% and 65% of the patients at baseline, respectively) declined more rapidly, in most cases within the first three months, and were present only in one out of 10 after 18 months. The course of illness was not related to sex or age. The duration of symptoms before seeking health care, but not the level of education or co-morbid depression, was a predictor of recovery from symptoms of burnout after 18 months. CONCLUSIONS: The course of mental illness in patients seeking specialist care for stress-related exhaustion was not related to sex or age. The burden of mental symptoms is high and similar for men and women, and at the 18 month follow-up, one-third of the study group still showed symptoms of burnout. A long duration of symptoms before consultation was associated with a prolonged time of recovery, which underlines the importance of early detection of stress-related symptoms.

Monocyte chemotactic protein-1 (MCP-1) and growth factors called into question as markers of prolonged psychosocial stress.

BACKGROUND: Psychosocial stress is becoming a major contributor to increased mental ill-health and sick leave in many countries. Valid markers of chronic stress would be valuable for diagnostic and prognostic purposes. A recent study suggested monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) as markers of chronic stress. We aimed to confirm these potential biomarkers of prolonged psychosocial stress in female patients. METHODOLOGY/PRINCIPAL FINDINGS: Circulating levels of MCP-1, EGF and VEGF, along with several other cytokines, were measured in plasma from 42 female patients suffering from exhaustion due to prolonged psychosocial stress and 42 control subjects, using a protein biochip immunoassay. There were no significant differences between patients and controls in any of the cytokines or growth factors analyzed. Furthermore, when using a different protein bioassay and reanalyzing MCP-1 and VEGF in the same samples, markedly different levels were obtained. To further explore if inflammation is present in patients with exhaustion, the classical inflammatory marker C-reactive protein (CRP) was measured in another group of patients (n=89) and controls (n=88) showing a small but significant increase of CRP levels in the patients. CONCLUSIONS/SIGNIFICANCE: MCP-1, EGF and VEGF may not be suitable markers of prolonged psychosocial stress as previously suggested. Furthermore, significant differences were obtained when using two different protein assays measuring the same samples, indicating that comparing studies where different analytic techniques have been used might be difficult. Increased levels of CRP indicate that low-grade inflammation might be present in patients with exhaustion due to prolonged stress exposure but this inflammation does not seem to be reflected by increase in circulating MCP-1 or other cytokines measured.