Internet-Based Cognitive Behavioral Therapy for Chronic Stress: A Randomized Controlled Trial

Objective: Patients with somatic conditions, such as psoriasis, frequently suffer from high burden of their disease in daily life and might benefit from internet-based cognitive behavioral therapy (ICBT) tailored to their adjustment problems. The aim of this multicenter randomized controlled trial was to examine the effects of therapist-guided, individually tailored ICBT in a clinical sample of patients with psoriasis. Methods: A total of 131 patients with psoriasis, who were screened for a psychological risk profile, were randomized to either care as usual (CAU, n = 66) or ICBT in addition to CAU (n = 65). Participants filled out standardized self-report questionnaires assessing physical and psychological functioning and impact on daily activities at baseline, posttreatment assessment, and 6-month follow-up. Results: In covariate-controlled linear mixed-model analyses, significantly larger improvements in ICBT compared to CAU were found in the primary outcomes physical functioning (p = 0.03, d = 0.36) and impact on daily activities (p = 0.04, d = 0.35), but not in psychological functioning (p = 0.32), up to 6 months after treatment compared to baseline. In explorative analyses, the working alliance measured at the beginning of ICBT treatment predicted improved physical (p = 0.02) and psychological (p < 0.001) outcomes. Conclusions: Results underline the promise of therapist-guided, individually tailored ICBT to improve physical functioning and reduce the impact of psoriasis on daily activities in patients with a psychological risk profile. Establishing a good therapeutic relationship early on may be an important factor that influences treatment outcomes in personalized ICBT interventions. Further research is needed to evaluate ICBT effectiveness in additional samples and to explore its underlying mechanisms.

BackgroundNoncardiac chest pain has a high prevalence and is associated with reduced quality of life, anxiety, avoidance of physical activity, and high societal costs. There is a lack of an effective, low-cost, easy to distribute intervention to assist patients with noncardiac chest pain.ObjectiveIn this study, we aimed to investigate the effectiveness of internet-based cognitive behavioral therapy with telephone support for noncardiac chest pain.MethodsWe conducted a randomized controlled trial, with a 12-month follow-up period, to compare internet-based cognitive behavioral therapy to a control condition (treatment as usual). A total of 162 participants aged 18 to 70 years with a diagnosis of noncardiac chest pain were randomized to either internet-based cognitive behavioral therapy (n=81) or treatment as usual (n=81). The participants in the experimental condition received 6 weekly sessions of internet-based cognitive behavioral therapy. The sessions covered different topics related to coping with noncardiac chest pain (education about the heart, physical activity, interpretations/attention, physical reactions to stress, optional panic treatment, and maintaining change). Between sessions, the participants also engaged in individually tailored physical exercises with increasing intensity. In addition to internet-based cognitive behavioral therapy sessions, participants received a brief weekly call from a clinician to provide support, encourage adherence, and provide access to the next session. Participants in the treatment-as-usual group received standard care for their noncardiac chest pain without any restrictions. Primary outcomes were cardiac anxiety, measured with the Cardiac Anxiety Questionnaire, and fear of bodily sensations, measured with the Body Sensations Questionnaire. Secondary outcomes were depression, measured using the Patient Health Questionnaire; health-related quality of life, measured using the EuroQol visual analog scale; and level of physical activity, assessed with self-report question. Additionally, a subgroup analysis of participants with depressive symptoms at baseline (PHQ-9 score ≥5) was conducted. Assessments were conducted at baseline, posttreatment, and at 3- and 12-month follow-ups. Linear mixed models were used to evaluate treatment effects. Cohen d was used to calculate effect sizes.ResultsIn the main intention-to-treat analysis at the 12-month follow-up time point, participants in the internet-based cognitive behavioral therapy group had significant improvements in cardiac anxiety (–3.4 points, 95% CI –5.7 to –1.1; P=.004, d=0.38) and a nonsignificant improvement in fear of bodily sensations (–2.7 points, 95% CI –5.6 to 0.3; P=.07) compared with the treatment-as-usual group. Health-related quality of life at the 12-month follow-up improved with statistical and clinical significance in the internet-based cognitive behavioral therapy group (8.8 points, 95% CI 2.8 to 14.8; P=.004, d=0.48) compared with the treatment-as-usual group. Physical activity had significantly (P<.001) increased during the 6-week intervention period for the internet-based cognitive behavioral therapy group. Depression significantly improved posttreatment (P=.003) and at the 3-month follow-up (P=.03), but not at the 12-month follow-up (P=.35). Participants with depressive symptoms at baseline seemed to have increased effect of the intervention on cardiac anxiety (d=0.55) and health-related quality of life (d=0.71) at the 12-month follow-up. In the internet-based cognitive behavioral therapy group, 84% of the participants (68/81) completed at least 5 of the 6 sessions.ConclusionsThis study provides evidence that internet-based cognitive behavioral therapy with minimal therapist contact and a focus on physical activity is effective in reducing cardiac anxiety and increasing health related quality of life in patients with noncardiac chest pain.Trial RegistrationClinicalTrials.gov NCT03096925; http://clinicaltrials.gov/ct2/show/NCT03096925

Social anxiety disorder (SAD) is one of the most common lifelong anxiety disorders. Although cognitive behavioural therapy (CBT) has proven to be effective in treating people with SAD, it may not be available for a considerable proportion of patients. Internet-based CBT (ICBT) is more accessible than face-to-face treatment. This meta-analysis evaluated the efficacy of ICBT in patients with SAD. We searched five databases, PubMed, Cochrane Central Register of Controlled Trials, Health Management Information Consortium, Ovid MEDLINE and EMBASE, and identified 20 eligible randomized controlled trials published from inception to 25 July 2020, with the outcome data from 1,743 participants. The results indicated that ICBT had a significant positive effect on patients with SAD compared with the control groups (g=-0.55). A subgroup analysis revealed that ICBT and CBT had an equal effect on treating patients with SAD (g=-0.18). There was also no difference between ICBT and ICBT plus other therapies in the treatment of patients with SAD (g=-0.07). The effect size of ICBT on patients with SAD was maintained at the 6-month follow-up (g=-0.08) and at the 12-month follow-up (g=-0.17). The findings of this review demonstrated that ICBT can significantly reduce SAD symptoms and that ICBT and face-to-face CBT produce equivalent effects. The results of this meta-analysis contributed to the literature on ICBT for the treatment of patients with SAD, although numerous aspects of ICBT were identified for future investigations.

Severe fatigue is a common and distressing symptom affecting approximately one in four survivors of breast cancer. The current study examined the efficacy of Internet-based cognitive behavioral therapy (ICBT) for severe fatigue in survivors of breast cancer compared with care as usual (CAU). The authors conducted a parallel-group randomized controlled trial. Severely fatigued, disease-free survivors of breast cancer who had completed cancer treatment at least 3 months previously were eligible. Participants were randomly allocated to ICBT or CAU using computer-generated stratified block randomization. The primary outcome of fatigue severity was assessed at baseline and after 6 months, as were the secondary outcomes of functional impairment, psychological distress, and quality of life. Statistical effects were tested with analyses of covariance (intention-to-treat analysis). Participants were recruited between January 2014 and March 2016 and assigned to ICBT (66 patients) or CAU (66 patients). Compared with the participants who had received CAU, those who had received ICBT reported lower fatigue scores at 6 months (mean difference [Δ], 11.5; 95% confidence interval [95% CI], 7.7-15.3) and a large effect size (Cohen d = 1.0), with the majority of patients (73%) demonstrating clinically significant improvement. ICBT also was found to lead to lower functional impairment (Δ, 297.8; 95% CI, 145.5-450.1) and psychological distress scores (Δ, 5.7; 95% CI, 3.4-7.9) and higher quality-of-life scores (Δ, 11.7; 95% CI, 5.8-17.7) compared with CAU, with medium to large effect sizes (Cohen d = 0.6-0.8). ICBT appears to be effective in reducing severe fatigue and related symptoms and meets the current need for easy accessible and more efficient evidence-based treatment options for severely fatigued survivors of breast cancer. Cancer 2017;123:3825-34. © 2017 American Cancer Society.

Subthreshold depression is a highly prevalent condition and a risk factor for developing a major depressive episode. Internet-based cognitive behaviour therapy may be a promising approach for the treatment of subthreshold depression. The current study had two aims: (1) to determine whether an internet-based cognitive behaviour therapy intervention and a group cognitive behaviour therapy intervention are more effective than a waiting-list control group; and (2) to determine whether the effect of the internet-based cognitive behaviour therapy differs from the group cognitive behaviour therapy intervention. A total of 191 women and 110 men with subthreshold depression were randomized into internet-based treatment, group cognitive behaviour therapy (Lewinsohn's Coping With Depression course), or a waiting-list control condition. The main outcome measure was treatment response after 10 weeks, defined as the difference in pre- and post-treatment scores on the Beck Depression Inventory (BDI). Missing data, a major limitation of this study, were imputed using the Multiple Imputation (MI) procedure Data Augmentation. In the waiting-list control group, we found a pre- to post-improvement effect size of 0.45, which was 0.65 in the group cognitive behaviour therapy condition and 1.00 within the internet-based treatment condition. Helmert contrasts showed a significant difference between the waiting-list condition and the two treatment conditions (p=0.04) and no significant difference between both treatment conditions (p=0.62). An internet-based intervention may be at least as effective as a commonly used group cognitive behaviour therapy intervention for subthreshold depression in people over 50 years of age.

In recent decades, stress-related disorders have received more attention, with an increasing prevalence, especially within the working population. The internet provides new options for broad dissemination, and a growing body of evidence suggests that web-based interventions for stress might be effective. However, few studies have examined the efficacy of interventions in clinical samples and work-related outcomes. The aim of this study was to evaluate the efficacy of an internet-based cognitive behavioral intervention for stress-related disorders integrating work-related aspects (work-focused and internet-based cognitive behavioral therapy [W-iCBT]), compared with a generic internet-based cognitive behavioral therapy (iCBT) group and a waitlist control (WLC) group. In this trial, 182 employees, mainly employed in the health care, IT, or educational sector, who fulfilled the criteria for a stress-related disorder, were randomized to a 10-week W-iCBT (n=61, 33.5%), generic iCBT (n=61, 33.5%), or WLC (n=60, 33%). Self-rated questionnaires on perceived stress, burnout, exhaustion, and other mental health- and work-related outcomes were administered before and after the treatment and at 6- and 12-month follow-ups. Compared with the WLC group, participants of the W-iCBT and iCBT groups showed an equal and significant reduction in the primary outcome (Shirom-Melamed Burnout Questionnaire [SMBQ]) from pretreatment to posttreatment assessment (Cohen d=1.00 and 0.83, respectively) and at the 6-month follow-up (Cohen d=0.74 and 0.74, respectively). Significant moderate-to-large effect sizes were also found in the secondary health- and work-related outcomes. The W-iCBT was the only group that exhibited significant effects on work ability and short-term sickness absence. Short-term sickness absence was 445 days lower than the WLC group and 324 days lower than the iCBT intervention group. However, no significant differences were found in terms of work experience or long-term sick leave. The work-focused and generic iCBT interventions proved to be superior compared with the control condition in reducing chronic stress and several other mental health-related symptoms. Interestingly, effects on work ability and short-term sickness absence were only seen between the W-iCBT intervention and the WLC groups. These preliminary results are promising, indicating that treatments that include work aspects may have the potential to accelerate recovery and reduce short-term sickness absence because of stress-related disorders. ClinicalTrials.gov NCT05240495; https://clinicaltrials.gov/ct2/show/NCT05240495 (retrospectively registered).

Although attentional bias modification training (ABM) and cognitive behavioural therapy (CBT) are two effective methods to decrease the symptoms of generalized anxiety disorders (GAD), to date, no randomized controlled trials have yet evaluated the effectiveness of an intervention combining internet-based cognitive behavioural therapy (ICBT) and ABM for adults with GAD. This study aimed to investigate the effectiveness of an intervention combining ICBT and ABM for adults with GAD. Sixty-three participants diagnosed with GAD were randomly assigned to the treatment group (ICBT with ABM; 31 participants) or the control group (ICBT with ABM placebo; 32 participants), and received 8 weeks of treatment and three evaluations. The CBT, ABM and ABM-placebo training were conducted via the internet. The evaluations were conducted at baseline, 8 weeks later, and 1 month later, respectively. Both the treatment and control groups reported significantly reduced anxiety symptoms and attentional bias, with no clear superiority of either intervention. However, the treatment group showed a greater reduction in negative automatic thoughts than the control group after treatment and at 1-month follow-up (η2 = 0.123). The results suggest that although not differing in therapeutic efficacy, the intervention combining ICBT and ABM is superior to the intervention combining ICBT and ABM-placebo in the reduction of negative automatic thoughts. ABM may be a useful augmentation of ICBT on reducing anxiety symptoms.

Cost-effectiveness of Internet-based cognitive behavior therapy vs. cognitive behavioral group therapy for social anxiety disorder: Results from a randomized controlled trial

• Despite the high prevalence of mental disorders, refugees underutilize mental health services. • Cultural adaptation of interventions is suggested as a way to narrow this treatment gap. • The Raha Arabic program was efficient in reducing symptoms of depression, anxiety, insomnia, and PTSD. • The Raha Arabic program was also efficient in improving resilience and well-being. • Treatment effects were sustained at the 6-month follow-up. Despite an elevated risk for developing mental health problems, evidence-based treatment options for this population remain scarce. The current study aimed to examine the efficacy of a culturally adapted internet-based cognitive behavioral therapy (iCBT) program for youth and young adults with mild to moderate mental health problems. Raha is a culturally adapted, guided, and tailored iCBT program for mild to moderate mental health problems. One hundred twenty-five Arabic-speaking refugee youth and young adults aged 15–29 years were randomly allocated to either a 10-week CA-iCBT condition or a wait-list control condition. The Hopkins Symptom Checklist (HSCL-25) served as the primary outcome measure and was assessed at pre-treatment, 4-week follow-up, post-treatment, and at 6-months post-treatment. Treatment effects were evaluated using a latent growth model. In the intention-to-treat analysis, anxiety and depressive symptoms on the HSCL-25 were significantly reduced in the treatment group compared with the wait-list control group, with a between-group effect size at post-treatment of Cohen’s d = 1.43 [0.97,1.89]. Treatment effects were sustained at the 6-month follow-up. Significant moderate-to-large effects were also observed across most secondary outcome measures. The findings of this study indicate that CA-iCBT is effective in reducing symptoms of common mental health problems in a population that generally underutilizes traditional mental health services.

While cognitive behavioral therapy has shown efficacy in treating stress-related disorders, such as adjustment disorder and exhaustion disorder, knowledge about factors contributing to treatment response is limited. Improved identification of such factors could enhance assessment procedures and treatment strategies. In addition, evaluating how traditional prediction methods and machine learning can complement each other may help bridge gaps in understanding and predicting treatment response. This study aims to (1) evaluate putative predictors of treatment response in patients with stress-related disorders using traditional prediction methods and (2) model treatment outcomes using a machine learning approach. This design combines the interpretability of traditional methods with the ability of machine learning to identify complex patterns. We will analyze data from a randomized controlled trial comparing 2 internet-delivered treatments, cognitive behavioral therapy versus an active control treatment, for patients diagnosed with adjustment disorder or exhaustion disorder (N=300). Prediction models will be based on pooled data from both treatment arms due to the limited sample size and lack of knowledge on predictors of treatment effects. Putative predictors include sociodemographic and clinical information, clinician-assessed data, self-rated symptoms, and cognitive test scores. The primary outcome of interest is responder status on the Perceived Stress Scale-10, evaluated based on the reliable change index posttreatment. For the traditional approach, univariate logistic regressions will be conducted for each predictor, followed by an ablation study for significant predictors. For the machine learning approach, 4 classifiers (logistic regression with elastic net, random forest, support vector machine, and AdaBoost) will be trained and evaluated. The dataset will be split into training (70%) and testing (30%) sets. Hyperparameter tuning will be conducted using 5-fold cross-validation with randomized search. Model performance will be assessed using balanced accuracy, precision, recall, and area under the curve. All data were collected between April 2021 and September 2022. We hypothesize that key predictors will include younger age, education level, baseline symptom severity, treatment credibility, and history of sickness absence. We anticipate that the machine learning models will outperform a dummy model predicting the majority class and achieve a balanced accuracy of ≥67%, thus indicating clinical usefulness. This study will contribute to the limited research on predictors of treatment outcome in stress-related disorders. The findings could support the development of more personalized and effective treatments for individuals diagnosed with adjustment disorder or exhaustion disorder, potentially improving clinical practice and patient outcomes. If successful, this dual approach may encourage future studies with larger datasets and the implementation of machine learning models in clinical settings, ultimately enhancing precision in mental health care. DERR1-10.2196/65790.

BackgroundNon-cardiac chest pain is common and associated with increased anxiety and reduced health-related quality of life. Randomized controlled trials on psychological interventions for patients with non-cardiac chest pain have reported mixed results. Patients with non-cardiac chest pain are a heterogeneous group. Identifying sub-groups that could potentially benefit more (or less) from an intervention would be valuable knowledge. We have conducted a randomized controlled trial where internet-based cognitive behavioural therapy (iCBT) had effect on reducing cardiac anxiety and increasing health-related quality of life at 12-month follow-up. The aim of the present study was to explore potential effect modifiers of iCBT in patients with non-cardiac chest pain on cardiac anxiety and/or health related quality of life at 12-month follow-up.MethodsWe analysed data from our randomized, controlled trial where 161 patients with non-cardiac chest pain were included and randomized to either iCBT or a treatment as usual (control). Cardiac anxiety measured by the Cardiac Anxiety Questionnaire and health-related quality of life measured by the EuroQol Visual Analog Scale at 12 month follow-up were the primary outcomes. Four potential baseline characteristics where identified as potential effect modifiers by a theory-based approach: (1) depression measured by the Patient Health Questionnaire; (2) anxiety measured by the Body Sensations Questionnaire; (3) prior healthcare contacts measured by a self-developed question; and (4) chest pain frequency measured by a self-developed question. Each potential effect modifier was analysed in a linear regression model where cardiac anxiety and EQ-VAS scores at 12-month follow-up, separately, were used as dependent variables. The potential differential treatment effect for each effect modifier was assessed by the interaction term: effect modifier x treatment group.ResultsDepression symptoms at baseline predicted a differential treatment effect at 12-month follow-up on health-related quality of life in favor of the iCBT group (regression coefficient of the interaction term: -1.85 (CI -3.28 to -0.41), p = 0.01), but not on cardiac anxiety at 12-month follow-up. Fear of bodily symptoms, chest pain frequency and prior health care contacts at baseline did not predict a treatment effect on either health-related quality of life or cardiac anxiety.ConclusionsDepression symptoms at baseline predicted a positive treatment effect of iCBT on health-related quality of life in patients suffering from non-cardiac chest pain. This indicates that it is important to identify patients with non-cardiac chest pain and co-occurring depression symptoms given that they are particularly likely to benefit from iCBT.Trial registrationClinicalTrials.gov NCT03096925.

BackgroundA major challenge of mental health care is to provide safe and effective treatment with limited resources. The main purpose of this study was to examine a value-based approach in clinical psychiatry when evaluating a process improvement initiative. This was accomplished by using the relatively new time driven activity based costing (TDABC) method within the more widely adopted cost-effectiveness analysis framework for economic evaluation of healthcare technologies. The objective was to evaluate the cost-effectiveness of allowing psychologists to perform post-treatment assessment previously performed by psychiatrists at an outpatient clinic treating depression using internet-based cognitive-behavioral therapy (ICBT).MethodsData was collected from 568 adult patients treated with ICBT for depression during 2013–2014. The TDABC methodology was used to estimate total healthcare costs, including development of process maps for the complete cycle of care and estimation of resource use and minute costs of staff, hospital space and materials based on their relative proportions used. Clinical outcomes were measured using the Patient Health Questionnaire depression scale (PHQ-9) before and after treatment and at 6-month follow-up. Cost-effectiveness analyses (CEA) was performed and the results presented as incremental net benefits (INB), cost-effectiveness acceptability curves (CEACs) and confidence ellipses to demonstrate uncertainty around the value of the organizational intervention.OutcomesTaking into account the complete healthcare process (from referral to follow-up assessment), treatment costs decreased from $709 (SD = $130) per patient in 2013 to $659 (SD = $134) in 2014 while treatment effectiveness was maintained; 27% had achieved full remission from depression after treatment (PHQ-9 < 5) during both 2013 and 2014 and an additional 35% and 33% had achieved partial remission in 2013 and 2014, respectively. At follow-up, 42% were in full remission after treatment during both 2013 and 2014; an additional 35% and 33% were in partial remission during 2013 and 2014, respectively. Confidence ellipses occupied the south-east (SE) and south-west (SW) quadrants of the incremental cost-effectiveness plane at both post-treatment and at follow-up, indicating that the ICBT treatment was less costly and equally effective after staff reallocation.ConclusionTreating patients to the target of full remission using psychologists instead of medical specialists for post-treatment assessment is cost-saving and consequently a more valuable use of limited resources. TDABC may be a useful tool for measuring resource costs, identifying quality improvement opportunities and evaluating the consequences of such initiatives. Combining TDABC with clinical outcome measures in CEA is potentially a useful approach in mental healthcare to estimate the value of process improvement initiatives.

BACKGROUND During the COVID-19 pandemic, health care professionals experienced high levels of depression. However, extant research has not highlighted effective internet-based psychological interventions to improve the mental health in this population during the pandemic. It remains unclear whether self-guided, internet-based cognitive behavioral therapy (iCBT) programs are effective in improving the mental health of health care workers during the COVID-19 pandemic. OBJECTIVE The aim of this study was to evaluate the effectiveness of a smartphone-based iCBT stress management program for reducing the depression experienced by nurses in Vietnam and Thailand. METHODS From March to April 2022, a 2-arm, parallel-group randomized controlled trial was implemented. One arm offered a 7-week self-guided iCBT program, and the other offered treatment as usual as a control arm. Full-time nurses were recruited from 6 hospitals: 2 hospitals in Vietnam and 4 hospitals in Thailand. The primary outcome of this program was the severity of depression measured by the Depression Anxiety Stress Scale-21 items. Follow-up surveys were conducted to measure the change in depression severity at 3 months (July-August 2022) and at 6 months (October-November 2022) after baseline. Mixed modeling for repeated measures was used to test the effects of the intervention compared with the control for the follow-up. RESULTS A total of 1203 nurses were included in this study: 602 in the intervention group and 601 in the control group. The follow-up rate at 3 and 6 months ranged from 85.7% (515/601) to 87.5% (527/602). The completion rate for the program was 68.1% (410/602). The group difference in depression was significant at the 3-month follow-up (coefficient=–0.92, 95% CI –1.66 to –0.18; &lt;i&gt;P&lt;/i&gt;=.02) and nonsignificant at the 6-month follow-up (coefficient=–0.33, 95% CI –1.11 to 0.45; &lt;i&gt;P&lt;/i&gt;=.41). The estimated effect sizes were –0.15 and –0.06 at the 3- and 6-month follow-ups, respectively. CONCLUSIONS Our study shows that the smartphone-based iCBT program was effective in reducing depression at the 3-month follow-up among hospital nurses in Vietnam and Thailand during the COVID-19 pandemic. However, the effect size was small, and therefore, these results may not be clinically meaningful. CLINICALTRIAL UMIN Clinical Trials Registry UMIN000044145; https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000050128 INTERNATIONAL REGISTERED REPORT RR2-10.20944/preprints202303.0450.v1

Kurdish immigrants in Sweden have a doubled risk of mental health problems, and refugee and immigrant populations underutilize mental health services. The present study investigated the efficacy of culturally adapted guided internet-based cognitive behavior therapy (ICBT) for depressive symptoms in a Kurdish population. We included 50 individuals who were randomized to either an 8-week treatment or a wait-list. The Beck Depression Inventory-II was the primary outcome measure, and measures of anxiety and insomnia were secondary outcomes. Depressive symptoms were significantly reduced (intention-to-treat analysis) in the treatment group, with a between-group effect size at posttreatment of Cohen's d = 1.27. Moderate to large between-group effects were also observed on all secondary outcome measures. Treatment effects were sustained at 11-month follow-up. The results provide preliminary support for culturally adapted ICBT as a complement to other treatment formats for treating symptoms of depression in a Kurdish population.

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.