The effectiveness and safety of dialectical behavior therapy for suicidal ideation and behavior in autistic adults: a pragmatic randomized controlled trial.

BACKGROUNDS: Many autistic people in mental health are suicidal. This study evaluated the effectiveness of dialectical behavior therapy (DBT) v. treatment as usual (TAU) in reducing suicidal ideation and suicide attempts. METHODS: At six Dutch mental health centers, 123 outpatients (18-65 years) with DSM-5 diagnosed autism spectrum disorder (ASD) and suicidal behavior were randomly assigned to the DBT intervention group (n = 63) or TAU control group (n = 60). Assessments were conducted at baseline, post-treatment at 6 months and 12-month follow-up. The primary outcomes were severity of suicidal ideation and frequency of suicide attempts. The severity of depression and social anxiety were secondary outcomes. RESULTS: At end-of-treatment, DBT significantly reduced both suicidal ideation (z = -2.24; p = 0.025; b = -4.41; s.e. = 197.0) and suicide attempts (z = -3.15; p = 0.002; IRR = 0.046; s.e. = 0.045) compared to TAU, but lost statistical significance at the 12-month follow-up. Depression severity significantly decreased with DBT (z = -1.99; p = 0.046: b = -2.74; s.e. = 1.37) remaining so at 12 months (z = -2.46; p = 0.014; b = -3.37; s.e. = 1.37). No effects were observed on social anxiety. Severe adverse events included two suicides in the TAU condition. CONCLUSIONS: DBT is an acceptable, safe, and short-term effective intervention to reduce suicidal ideation and suicide attempts in autistic adults with suicidal behavior.

Does outcome expectancy predict outcomes in online depression prevention? Secondary analysis of randomised-controlled trials.

BACKGROUND: Evidence shows that online interventions could prevent depression. However, to improve the effectiveness of preventive online interventions in individuals with subthreshold depression, it is worthwhile to study factors influencing intervention outcomes. Outcome expectancy has been shown to predict treatment outcomes in psychotherapy for depression. However, little is known about whether this also applies to depression prevention. The aim of this study was to investigate the role of participants' outcome expectancy in an online depression prevention intervention. METHODS: A secondary data analysis was conducted using data from two randomised-controlled trials (N = 304). Multilevel modelling was used to explore the effect of outcome expectancy on depressive symptoms and close-to-symptom-free status postintervention (6-7 weeks) and at follow-up (3-6 months). In a subsample (n = 102), Cox regression was applied to assess the effect on depression onset within 12 months. Explorative analyses included baseline characteristics as possible moderators. Outcome expectancy did not predict posttreatment outcomes or the onset of depression. RESULTS: Small effects were observed at follow-up for depressive symptoms (ß = -.39, 95% confidence interval [CI]: [-0.75, -0.03], p = .032, padjusted = .130) and close-to-symptom-free status (relative risk = 1.06, 95% CI: [1.01, 1.11], p = .013, padjusted = 0.064), but statistical significance was not maintained when controlling for multiple testing. Moderator analyses indicated that expectancy could be more influential for females and individuals with higher initial symptom severity. CONCLUSION: More thoroughly designed, predictive studies targeting outcome expectancy are necessary to assess the full impact of the construct for effective depression prevention. PATIENT OR PUBLIC CONTRIBUTION: This secondary analysis did not involve patients, service users, care-givers, people with lived experience or members of the public. However, the findings incorporate the expectations of participants using the preventive online intervention, and these exploratory findings may inform the future involvement of participants in the design of indicated depression prevention interventions for adults. CLINICAL TRIAL REGISTRATION: Original studies: DRKS00004709, DRKS00005973; secondary analysis: osf.io/9xj6a.

A Universal Digital Stress Management Intervention for Employees: Randomized Controlled Trial with Health-Economic Evaluation.

BACKGROUND: Stress is highly prevalent and known to be a risk factor for a wide range of physical and mental disorders. The effectiveness of digital stress management interventions has been confirmed; however, research on its economic merits is still limited. OBJECTIVE: This study aims to assess the cost-effectiveness, cost-utility, and cost-benefit of a universal digital stress management intervention for employees compared with a waitlist control condition within a time horizon of 6 months. METHODS: Recruitment was directed at the German working population. A sample of 396 employees was randomly assigned to the intervention group (n=198) or the waitlist control condition (WLC) group (n=198). The digital stress management intervention included 7 sessions plus 1 booster session, which was offered without therapeutic guidance. Health service use, patient and family expenditures, and productivity losses were self-assessed and used for costing from a societal and an employer's perspective. Costs were related to symptom-free status (PSS-10 [Perceived Stress Scale] score 2 SDs below the study population baseline mean) and quality-adjusted life years (QALYs) gained. The sampling error was handled using nonparametric bootstrapping. RESULTS: From a societal perspective, the digital intervention was likely to be dominant compared with WLC, with a 56% probability of being cost-effective at a willingness-to-pay (WTP) of €0 per symptom-free person gained. At the same WTP threshold, the digital intervention had a probability of 55% being cost-effective per QALY gained relative to the WLC. This probability increased to 80% at a societal WTP of €20,000 per QALY gained. Taking the employer's perspective, the digital intervention showed a probability of a positive return on investment of 78%. CONCLUSIONS: Digital preventive stress management for employees appears to be cost-effective societally and provides a favorable return on investment for employers. TRIAL REGISTRATION: German Clinical Trials Register DRKS00005699; https://drks.de/search/en/trial/DRKS00005699.

Longitudinal clinical and functional outcome in distinct cognitive subgroups of first-episode psychosis: a cluster analysis.

BACKGROUND: Cognitive deficits may be characteristic for only a subgroup of first-episode psychosis (FEP) and the link with clinical and functional outcomes is less profound than previously thought. This study aimed to identify cognitive subgroups in a large sample of FEP using a clustering approach with healthy controls as a reference group, subsequently linking cognitive subgroups to clinical and functional outcomes. METHODS: 204 FEP patients were included. Hierarchical cluster analysis was performed using baseline brief assessment of cognition in schizophrenia (BACS). Cognitive subgroups were compared to 40 controls and linked to longitudinal clinical and functional outcomes (PANSS, GAF, self-reported WHODAS 2.0) up to 12-month follow-up. RESULTS: Three distinct cognitive clusters emerged: relative to controls, we found one cluster with preserved cognition (n = 76), one moderately impaired cluster (n = 74) and one severely impaired cluster (n = 54). Patients with severely impaired cognition had more severe clinical symptoms at baseline, 6- and 12-month follow-up as compared to patients with preserved cognition. General functioning (GAF) in the severely impaired cluster was significantly lower than in those with preserved cognition at baseline and showed trend-level effects at 6- and 12-month follow-up. No significant differences in self-reported functional outcome (WHODAS 2.0) were present. CONCLUSIONS: Current results demonstrate the existence of three distinct cognitive subgroups, corresponding with clinical outcome at baseline, 6- and 12-month follow-up. Importantly, the cognitively preserved subgroup was larger than the severely impaired group. Early identification of discrete cognitive profiles can offer valuable information about the clinical outcome but may not be relevant in predicting self-reported functional outcomes.

Relative Effectiveness of CBT-Components and Sequencing in Indicated Depression Prevention for Adolescents: A Cluster-Randomized Microtrial.

OBJECTIVE: Cognitive Behavioral Therapy (CBT) was dismantled into four modules of three sessions each: cognitive restructuring (Think), behavioral activation (Act), problem solving (Solve) and relaxation (Relax). We investigated the modules' relative effectiveness in indicated depression prevention for adolescents and examined variations in sequencing of these modules. METHOD: We performed a pragmatic cluster-randomized microtrial with four parallel conditions: (1) Think-Act-Relax-Solve (n = 14 clusters, n = 81 participants); (2) Act-Think-Relax-Solve (n = 13, n = 69); (3) Solve-Act-Think-Relax (n = 13, n = 77); and (4) Relax-Solve-Act-Think (n = 12, n = 55). The sample consisted of 282 Dutch adolescents with elevated depressive symptoms (Mage = 13.8; 55.7% girls, 92.9% Dutch). In total 52 treatment groups were randomized as a cluster. Assessments were conducted at baseline, after each module and at 6-month follow-up with depressive symptoms as primary outcome. RESULTS: None of the modules (Think, Act, Solve, Relax) was associated with a significant decrease in depressive symptoms after three sessions and no significant differences in effectiveness were found between the modules. All sequences of modules were associated with a significant decrease in depressive symptoms at post-intervention, except the sequence Relax-Solve-Act-Think. At 6-month follow-up, all sequences showed a significant decrease in depressive symptoms. No significant differences in effectiveness were found between the sequences at post-intervention and 6-month follow-up. CONCLUSIONS: Regardless of the CBT technique provided, one module of three sessions may not be sufficient to reduce depressive symptoms. The sequence in which the CBT components cognitive restructuring, behavioral activation, problem solving and relaxation are offered, does not appear to significantly influence outcomes at post- intervention or 6-month follow-up. ABBREVIATIONS: CDI-2:F: Children's Depression Inventory-2 Full-length version; CDI-2:S: Children's Depression Inventory-2 Short version; STARr: Solve, Think, Act, Relax and repeat.

Evaluating Effect Moderators in Cognitive Versus Behavioral Based CBT-Modules and Sequences Towards Preventing Adolescent Depression.

OBJECTIVE: The aim of this study was to investigate age group, gender, and baseline depressive symptom severity as possible effect moderators in (1) cognitive versus behavioral based CBT-modules and (2) sequences of modules that started either with cognitive or behavioral modules in indicated depression prevention in adolescents. METHOD: We conducted a pragmatic cluster-randomized trial under four parallel conditions. Each condition consisted of four CBT-modules of three sessions (cognitive restructuring, problem solving, behavioral activation, relaxation), but the sequencing of modules differed. The CBT-modules and sequences were clustered into more cognitive versus more behavioral based approaches. The sample involved 282 Dutch adolescents with elevated depressive symptoms (Mage = 13.8; 55.7% girls, 92.9% Dutch). Assessments were conducted at baseline, after three sessions, at post-intervention and 6-month follow-up with self-reported depressive symptoms as the primary outcome. RESULTS: We found no evidence for substantial moderation effects. Age group, gender, and depressive symptom severity level at baseline did not moderate the effects of cognitive versus behavioral modules after three sessions. No evidence was also found that these characteristics moderated the effectiveness of sequences of modules that started either with cognitive or behavioral modules at post-intervention and 6-month follow-up. CONCLUSION: Cognitive and behavioral based modules and sequences in the prevention of depression in adolescents might apply to a relatively wide range of adolescents in terms of age group, gender, and severity levels of depressive symptoms.Abbreviation: CDI-2:F: Children's Depression Inventory-2 Full-length version; CDI-2:S: Children's Depression Inventory-2 Short version; STARr: Solve, Think, Act, Relax, and repeat.

Adolescent anxiety and depression: burden of disease study in 53,894 secondary school pupils in the Netherlands.

BACKGROUND: Prevalence rates of anxiety and depression in adolescence are rising markedly in early adolescence. It is important to quantify the non-fatal disease burden of anxiety and depression, such that early interventions can be well targeted, and resources can be allocated in a just and optimal way. This study aimed to estimate the non-fatal disease burden of anxiety and depression with and without suicidal ideation in girls and boys aged 13, 14, and 15 years. METHODS: Participants were 53,894 secondary school pupils who completed health questionnaires between September 2018 and July 2019. A design-based approach was used for complex survey data with post-stratification weights and taking clustering at school-level into account. At individual level, disability weights (DWs) were calculated for each disorder. At population level, DWs were multiplied by the point-prevalence per one thousand population of the respective disorders to compute years lived with disability (YLD). DWs and YLD of anxiety and depression were calculated with and without adjustment for comorbid eating disorders, substance use disorders and somatic illnesses. RESULTS: The unadjusted DW of depression with suicidal ideation (0.30) was greater than without suicidal ideation (0.26), and both were greater than the DW of anxiety (0.24). A similar ranking was obtained after adjusting for comorbidities. At population level, where the prevalence of the disorders come into play, the YLD disease burden was greatest for anxiety, followed by depression with suicidal ideation and depression without suicidal ideation with 17.40, 9.85, and 5.28 YLD per one thousand population, unadjusted for comorbidities. This pattern was the same after adjustment, but then the total YLD of depression with and without suicidal ideation was similar to the YLD of anxiety (12.47 and 12.46, respectively). Girls showed a significantly greater YLD burden of anxiety and depression than boys, but no differences were found between different age groups. CONCLUSIONS: From an individual clinical perspective, depression, especially when accompanied by suicidal ideation, was identified as a major health concern, especially in girls. From a public health perspective, both anxiety and depression, especially when accompanied by suicidal ideation, were identified as major drivers of disease burden, again most notably in girls.

rTMS combined with CBT as a next step in antidepressant non-responders: a study protocol for a randomized comparison with current antidepressant treatment approaches.

BACKGROUND: Major depressive disorder (MDD) is one of the most common psychiatric disorders, however, current treatment options are insufficiently effective for about 35% of patients, resulting in treatment-resistant depression (TRD). Repetitive transcranial magnetic stimulation (rTMS) is a form of non-invasive neuromodulation that is effective in treating TRD. Not much is known about the comparative efficacy of rTMS and other treatments and their timing within the treatment algorithm, making it difficult for the treating physician to establish when rTMS is best offered as a treatment option. This study aims to investigate the (cost-)effectiveness of rTMS (in combination with cognitive behavioral therapy (CBT) and continued antidepressant medication), compared to the next step in the treatment algorithm. This will be done in a sample of patients with treatment resistant non-psychotic unipolar depression. METHODS: In this pragmatic multicenter randomized controlled trial 132 patients with MDD are randomized to either rTMS or the next pharmacological step within the current treatment protocol (a switch to a tricyclic antidepressant or augmentation with lithium or a second-generation antipsychotic). Both groups also receive CBT. The trial consists of 8 weeks of unblinded treatment followed by follow-up of the cohort at four and 6 months. A subgroup of patients (n = 92) will have an extended follow-up at nine and 12 months to assess effect decay or retention. We expect that rTMS is more (cost-)effective than medication in reducing depressive symptoms in patients with TRD. We will also explore the effects of both treatments on symptoms associated with depression, e.g. anhedonia and rumination, as well as the effect of expectations regarding the treatments on its effectiveness. DISCUSSION: The present trial aims to inform clinical decision making about whether rTMS should be considered as a treatment option in patients with TRD. The results may improve treatment outcomes in patients with TRD and may facilitate adoption of rTMS in the treatment algorithm for depression and its implementation in clinical practice. TRIAL REGISTRATION: This trial is registered within the Netherlands Trial Register (code: NL7628 , date: March 29th 2019).

Effectiveness, Cost-effectiveness, and Cost-Utility of a Digital Smoking Cessation Intervention for Cancer Survivors: Health Economic Evaluation and Outcomes of a Pragmatic Randomized Controlled Trial.

BACKGROUND: Smoking cessation (SC) interventions may contribute to better treatment outcomes and the general well-being of cancer survivors. OBJECTIVE: This study aims to evaluate the effectiveness, cost-effectiveness, and cost-utility of a digital interactive SC intervention compared with a noninteractive web-based information brochure for cancer survivors. METHODS: A health economic evaluation alongside a pragmatic 2-arm parallel-group randomized controlled trial was conducted with follow-ups at 3, 6, and 12 months. The study was conducted in the Netherlands over the internet from November 2016 to September 2019. The participants were Dutch adult smoking cancer survivors with the intention to quit smoking. In total, 165 participants were included and analyzed: 83 (50.3%) in the MyCourse group and 82 (49.7%) in the control group. In the intervention group, participants had access to a newly developed, digital, minimally guided SC intervention (MyCourse-Quit Smoking). Control group participants received a noninteractive web-based information brochure on SC. Both groups received unrestricted access to usual care. The primary outcome was self-reported 7-day smoking abstinence at the 6-month follow-up. Secondary outcomes were quality-adjusted life years gained, number of cigarettes smoked, nicotine dependence, and treatment satisfaction. For the health economic evaluation, intervention costs, health care costs, and costs stemming from productivity losses were assessed over a 12-month horizon. RESULTS: At the 6-month follow-up, the quit rates were 28% (23/83) and 26% (21/82) in the MyCourse and control groups, respectively (odds ratio 0.47, 95% CI 0.03-7.86; P=.60). In both groups, nicotine dependence scores were reduced at 12 months, and the number of smoked cigarettes was reduced by approximately half. The number of cigarettes decreased more over time, and the MyCourse group demonstrated a significantly greater reduction at the 12-month follow-up (incidence rate ratio 0.87; 95% CI 0.76-1.00; P=.04). Intervention costs were estimated at US $193 per participant for the MyCourse group and US $74 for the control group. The mean per-participant societal costs were US $25,329 (SD US $29,137) and US $21,836 (SD US $25,792), respectively. In the cost-utility analysis, MyCourse was not preferred over the control group from a societal perspective. With smoking behavior as the outcome, the MyCourse group led to marginally better results per reduced pack-year against higher societal costs, with a mean incremental cost-effectiveness ratio of US $52,067 (95% CI US $32,515-US $81,346). CONCLUSIONS: At 6 months, there was no evidence of a differential effect on cessation rates; in both groups, approximately a quarter of the cancer survivors quit smoking and their number of cigarettes smoked was reduced by half. At 12 months, the MyCourse intervention led to a greater reduction in the number of smoked cigarettes, albeit at higher costs than for the control group. No evidence was found for a differential effect on quality-adjusted life years. TRIAL REGISTRATION: The Netherlands Trial Register NTR6011; https://www.trialregister.nl/trial/5434. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s12885-018-4206-z.

A randomized controlled trial of cognitive control training (CCT) as an add-on treatment for late-life depression: a study protocol.

BACKGROUND: Already a major health concern, late-life depression (LLD) is expected to form an increasing problem in the aging population. Moreover, despite current treatments, LLD is associated with a poor long-term prognosis and high rate of chronicity. Treatment provision and treatment accordingly warrant improvement, where add-on treatments might contribute to the efficacy of conventional therapies. Although it is known that impaired cognitive control contributes to LDD, it is not targeted sufficiently by current interventions. Research on cognitive control training (CCT) shows promising results on depressive symptoms, cognitive performance, and overall functioning. However, further research is needed to determine the long-term effects of CCT on LLD, its cost-effectiveness, and mechanisms of change. METHODS: In the current multicenter randomized controlled trial (RCT) with a between-subjects design participants aged 60 years and over with a current LLD receiving treatment as usual (TAU) are randomized to add-on CCT or placebo training. Randomization is stratified by depression severity. Participants will receive eight online CCT or placebo sessions spread across four consecutive weeks. They will complete a post-training assessment after 1 month and three follow-up assessments scheduled three, six and 12 months after completing the training. We expect CCT and TAU to be more (cost-)effective in reducing depressive symptoms than placebo training and TAU. Additionally, we will be looking at secondary clinical, cognitive and global functioning outcomes and likely mechanisms of change (e.g., improved cognitive functioning, reduced rumination, and improved inhibition of negative stimuli). DISCUSSION: The proposed RCT aims to contribute to the clinical and scientific knowledge on the long-term effects of CCT as an add-on treatment for LLD. Cost-effectiveness is particularly relevant considering the expected volume of the target demographic. The study will be a pragmatic trial with few inclusion restrictions, providing information on feasibility of web-based trainings in clinical settings. The outcomes are potentially generalizable to guidelines for treatment of LLD. TRIAL REGISTRATION: This trial is registered in the Netherlands Trial Register (code: NL7639 ). Registered 3 april 2019.

A systematic review of trial-based economic evaluations of internet- and mobile-based interventions for substance use disorders.

BACKGROUND: Substance use disorders (SUDs) contribute significantly to global rates of morbidity and mortality. Internet- and mobile-based interventions (IMIs) have been suggested as an adjunct to face-to-face health services. However, the evidence for the cost-effectiveness of IMIs for SUDs is scant. METHODS: A comprehensive literature search in PubMed, PsycINFO, the Cochrane Central Register of Controlled Trials, NHS Economic Evaluations Database, NHS Health Technology Assessment Database, Office of Health Economics Evaluations Database and EconLit was conducted. We included economic evaluations alongside randomized controlled trials of IMIs for SUDs compared with a control group. RESULTS: Of 1687 abstracts identified, 11 studies met the inclusion criteria. Targeted conditions were alcohol use disorder (four studies) and tobacco smoking (five studies) whereas two studies included any SUD. Cost-effectiveness results demonstrated that IMIs had a firm probability of being more cost-effective than TAU (e.g. less costs per additional abstinent person). Compared with (online) psycho-education, evidence towards an additional benefit of IMIs was less clear. Regarding cost-utility (e.g. costs per quality-adjusted life year gained), except for one study, results suggested that TAU and online psycho-education would probably be more preferable than IMIs. Quality of study reporting was at least adequate. CONCLUSIONS: The likelihood of IMIs being more cost-effective than TAU looks promising but more economic evaluations are needed in order to determine the economic merit of IMIs. With an increasing pressure on health care budgets, strategies to disseminate effective interventions at affordable costs are required. This review suggests that IMIs might carry that promise and have potential as a cost-effective strategy to scale-up existing evidence-based treatments for SUDs. SYSTEMATIC REVIEW REGISTRATION: The systematic review has been registered in the PROSPERO database (no. CRD42018099486).

Blended Acceptance and Commitment Therapy Versus Face-to-face Cognitive Behavioral Therapy for Older Adults With Anxiety Symptoms in Primary Care: Pragmatic Single-blind Cluster Randomized Trial.

BACKGROUND: Anxiety symptoms in older adults are prevalent and disabling but often go untreated. Most trials on psychological interventions for anxiety in later life have examined the effectiveness of face-to-face cognitive behavioral therapy (CBT). To bridge the current treatment gap, other treatment approaches and delivery formats should also be evaluated. OBJECTIVE: This study is the first to examine the effectiveness of a brief blended acceptance and commitment therapy (ACT) intervention for older adults with anxiety symptoms, compared with a face-to-face CBT intervention. METHODS: Adults aged between 55-75 years (n=314) with mild to moderately severe anxiety symptoms were recruited from general practices and cluster randomized to either blended ACT or face-to-face CBT. Assessments were performed at baseline (T0), posttreatment (T1), and at 6- and 12-month follow-ups (T2 and T3, respectively). The primary outcome was anxiety symptom severity (Generalized Anxiety Disorder-7). Secondary outcomes were positive mental health, depression symptom severity, functional impairment, presence of Diagnostic and Statistical Manual of Mental Disorders V anxiety disorders, and treatment satisfaction. RESULTS: Conditions did not differ significantly regarding changes in anxiety symptom severity during the study period (T0-T1: B=.18, P=.73; T1-T2: B=-.63, P=.26; T1-T3: B=-.33, P=.59). Large reductions in anxiety symptom severity (Cohen d≥0.96) were found in both conditions post treatment, and these were maintained at the 12-month follow-up. The rates of clinically significant changes in anxiety symptoms were also not different for the blended ACT group and CBT group (χ21=0.2, P=.68). Regarding secondary outcomes, long-term effects on positive mental health were significantly stronger in the blended ACT group (B=.27, P=.03, Cohen d=0.29), and treatment satisfaction was significantly higher for blended ACT than CBT (B=3.19, P<.001, Cohen d=0.78). No other differences between the conditions were observed in the secondary outcomes. CONCLUSIONS: The results show that blended ACT is a valuable treatment alternative to CBT for anxiety in later life. TRIAL REGISTRATION: Netherlands Trial Register TRIAL NL6131 (NTR6270); https://www.trialregister.nl/trial/6131.

Guided Internet-Based Cognitive Behavioral Therapy for Insomnia: Health-Economic Evaluation From the Societal and Public Health Care Perspective Alongside a Randomized Controlled Trial.

BACKGROUND: The evidence base for internet-based cognitive behavioral therapy for insomnia (iCBT-I) is firm; however, little is known about iCBT-I's health-economic effects. OBJECTIVE: This study aimed to evaluate the cost-effectiveness and cost-utility of iCBT-I in reducing insomnia among schoolteachers. METHODS: Schoolteachers (N=128) with clinically significant insomnia symptoms and work-related rumination were randomized to guided iCBT-I or a wait list control group, both with unrestricted access to treatment as usual. Health care use, patient and family expenditures, and productivity losses were self-assessed and used for costing from a societal and a public health care perspective. Costs were related to symptom-free status (score <8 on the insomnia severity index) and quality-adjusted life years (QALYs) gained. Sampling error was handled using nonparametric bootstrapping. RESULTS: Statistically significant differences favoring the intervention group were found for both health outcomes (symptom-free status yes or no: ß=.30; 95% CI 0.16-0.43; QALYs: ß=.019, 95% CI 0.01-0.03). From a societal perspective, iCBT-I had a 94% probability of dominating the wait list control for both health outcomes. From a public health care perspective, iCBT-I was more effective but also more expensive than the wait list control, resulting in an incremental cost-effectiveness ratio of €650 per symptom-free individual. In terms of QALYs, the incremental cost-effectiveness ratio was €11,285. At a willingness-to-pay threshold of €20,000 per QALY gained, the intervention's probability of being cost-effective was 89%. CONCLUSIONS: Our trial indicates that iCBT could be considered as a good value-for-money intervention for insomnia. TRIAL REGISTRATION: German Clinical Trial Registry: DRKS00004700; https://tinyurl.com/2nnk57jm. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/1745-6215-14-169.

Problem-solving intervention to prevent depression in non-professional caregivers: a randomized controlled trial with 8 years of follow-up.

BACKGROUND: Studies of psychological interventions for the prevention of depression have found significant effects in the short-term, but the long-term efficacy has yet to be determined. This study evaluated the 8-year effect of a randomized controlled trial for indicated prevention of depression in female caregivers. METHODS: A total of 173 non-professional female caregivers with subclinical depressive symptoms not meeting criteria for a major depressive episode (MDE) were randomized to either a brief problem-solving intervention (n = 89) or usual-care control group (n = 84). Blinded evaluators conducted an assessment at the 8-year follow-up. The primary outcome was Depression Status, defined by diagnoses of MDE since the 1-year follow-up using the Structured Clinical Interview for the Disorders of the DSM-5. The secondary outcome was current Depressive Symptom Severity. Regression analyses were conducted to evaluate the effect of the intervention on the outcomes. RESULTS: There were no significant differences in the Depression Status between the problem-solving (30.3%) and control groups (26.2%) (adjusted OR 1.25, 95% CI -0.58 to 2.69). Depressive Symptom Severity, however, was significantly lower in the problem-solving group compared to the control group at this follow-up, amounting to a small effect size of Cohen's d = 0.39 (adjusted B = -3.32, p = 0.018). CONCLUSIONS: This is the first study to assess such a long-term follow-up of intervention of indicated prevention of depression. Results seem to indicate that the protective effect of the intervention became smaller over time during follow-up. Future research should replicate these results.

Exercise enhances: study protocol of a randomized controlled trial on aerobic exercise as depression treatment augmentation.

BACKGROUND: Major depressive disorder (MDD) is a considerable public health concern. In spite of evidence-based treatments for MDD, many patients do not improve and relapse is common. Therefore, improving treatment outcomes is much needed and adjunct exercise treatment may have great potential. Exercise was shown to be effective as monotherapy for depression and as augmentation strategy, with evidence for increasing neuroplasticity. Data on the cost-effectiveness and the long-term effects of adjunct exercise treatment are missing. Similarly, the cognitive pathways toward remission are not well understood. METHODS: The present study is designed as a multicenter randomized superiority trial in two parallel groups with follow-up assessments up to 15 months. Currently depressed outpatients (N = 120) are randomized to guideline concordant Standard Care (gcSC) alone or gcSC with adjunct exercise treatment for 12 weeks. Randomization is stratified by gender and setting, using a four, six, and eight block design. Exercise treatment is offered in accordance with the NICE guidelines and empirical evidence, consisting of one supervised and two at-home exercise sessions per week at moderate intensity. We expect that gcSC with adjunct exercise treatment is more (cost-)effective in decreasing depressive symptoms compared to gcSC alone. Moreover, we will investigate the effect of adjunct exercise treatment on other health-related outcomes (i.e. functioning, fitness, physical activity, health-related quality of life, and motivation and energy). In addition, the mechanisms of change will be studied by exploring any change in rumination, self-esteem, and memory bias as possible mediators between exercise treatment and depression outcomes. DISCUSSION: The present trial aims to inform the scientific and clinical community about the (cost-)effectiveness and psychosocial mechanisms of change of adjunct exercise treatment when implemented in the mental health service setting. Results of the present study may improve treatment outcomes in MDD and facilitate implementation of prescriptive exercise treatment in outpatient settings. TRIAL REGISTRATION: This trial is registered within the Netherlands Trial Register (code: NL8432 , date: 6th March, 2020).

Implementing interventions to reduce work-related stress among health-care workers: an investment appraisal from the employer's perspective.

PURPOSE: The Stress-Prevention@Work implementation strategy has been demonstrated to be successful in reducing stress in employees. Now, we assess the economic return-on-investment to see if it would make for a favourable business case for employers. METHODS: Data were collected from 303 health-care workers assigned to either a waitlisted control condition (142 employees in 15 teams) or to Stress-Prevention@Work (161 employees in 15 teams). Main outcome was productivity losses measured using the Trimbos and iMTA Cost questionnaire in Psychiatry. Measurements were taken at baseline, 6, and 12 months post-baseline. RESULTS: The per-employee costs of the strategy were €50. Net monetary benefits were the benefits (i.e., improved productivity) minus the costs (i.e., intervention costs) and were the main outcome of this investment appraisal. Per-employee net benefits amounted to €2981 on average, which was an almost 60-fold payout of the initial investment of €50. There was a 96.7% likelihood for the modest investment of €50 to be offset by cost savings within 1 year. Moreover, a net benefit of at least €1000 still has a likelihood of 88.2%. CONCLUSIONS: In general, there was a high likelihood that Stress-Prevention@Work offers an appealing business case from the perspective of employers, but the employer should factor in the additional per-employee costs of the stress-reducing interventions. Still, if these additional costs were as high as €2981, then costs and benefits would break even. This study was registered in the Netherlands National Trial Register, trial code: NTR5527.

Cost-Effectiveness of Virtual Reality Cognitive Behavioral Therapy for Psychosis: Health-Economic Evaluation Within a Randomized Controlled Trial.

BACKGROUND: Evidence was found for the effectiveness of virtual reality-based cognitive behavioral therapy (VR-CBT) for treating paranoia in psychosis, but health-economic evaluations are lacking. OBJECTIVE: This study aimed to determine the short-term cost-effectiveness of VR-CBT. METHODS: The health-economic evaluation was embedded in a randomized controlled trial evaluating VR-CBT in 116 patients with a psychotic disorder suffering from paranoid ideation. The control group (n=58) received treatment as usual (TAU) for psychotic disorders in accordance with the clinical guidelines. The experimental group (n=58) received TAU complemented with add-on VR-CBT to reduce paranoid ideation and social avoidance. Data were collected at baseline and at 3 and 6 months postbaseline. Treatment response was defined as a pre-post improvement of symptoms of at least 20% in social participation measures. Change in quality-adjusted life years (QALYs) was estimated by using Sanderson et al's conversion factor to map a change in the standardized mean difference of Green's Paranoid Thoughts Scale score on a corresponding change in utility. The incremental cost-effectiveness ratios were calculated using 5000 bootstraps of seemingly unrelated regression equations of costs and effects. The cost-effectiveness acceptability curves were graphed for the costs per treatment responder gained and per QALY gained. RESULTS: The average mean incremental costs for a treatment responder on social participation ranged between €8079 and €19,525, with 90.74%-99.74% showing improvement. The average incremental cost per QALY was €48,868 over the 6 months of follow-up, with 99.98% showing improved QALYs. Sensitivity analyses show costs to be lower when relevant baseline differences were included in the analysis. Average costs per treatment responder now ranged between €6800 and €16,597, while the average cost per QALY gained was €42,030. CONCLUSIONS: This study demonstrates that offering VR-CBT to patients with paranoid delusions is an economically viable approach toward improving patients' health in a cost-effective manner. Long-term effects need further research. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number (ISRCTN) 12929657; http://www.isrctn.com/ISRCTN12929657.

Dismantling the relative effectiveness of core components of cognitive behavioural therapy in preventing depression in adolescents: protocol of a cluster randomized microtrial.

BACKGROUND: Both depressive disorder and subclinical depressive symptoms during adolescence are a major public health concern. Therefore, it is important that depression is detected at an early stage and is treated preventively. Prevention based on the principles of Cognitive Behavioural Therapy (CBT) has proven to be the most effective, however research has mainly focused on the effectiveness of "prevention packages" consisting of multiple CBT-components, rather than on the distinct CBT-components. This study will evaluate the relative effectiveness of four core components of CBT (cognitive restructuring (CR), behavioural activation (BA), problem solving (PS) and relaxation (RE)). In addition the relative (cost-)effectiveness of four different sequences of these components will be evaluated: (1) CR - BA - RE - PS, (2) BA - CR - RE - PS, (3) PS - GA - CR - RE and (4) RE - PS - BA - CR. METHODS: We will perform a non-blinded multisite cluster randomized prevention microtrial with four parallel conditions consisting of the four sequences. The four sequences of components will be offered in groups of high school students with elevated depressive symptoms. For each CBT-component a module of three sessions is developed. Assessments will be conducted at baseline, after each CBT-component, prior to each session, at post-intervention and at 6-month follow-up. Potential moderators and mediators will be evaluated exploratively to shed light on for whom the (sequences of) CBT-components are most effective and how effects are mediated. DISCUSSION: The potential value of the study is insight in the relative effectiveness of the four most commonly used CBT-components and four different sequences, and possible moderators and mediators in the prevention of depression among adolescents. This knowledge can be used to optimize and personalize CBT-programs. TRIAL REGISTRATION: The study is registered in the Dutch Trial Register (Trial NL5584 / NTR6176) on October 13, 2016.

Effectiveness of a self-management training for patients with chronic and treatment resistant anxiety or depressive disorders on quality of life, symptoms, and empowerment: results of a randomized controlled trial.

BACKGROUND: Anxiety and depressive disorders are common mental disorders. A substantial part of patients does not achieve symptomatic remission after treatment in specialized services. Current care as usual (CAU) for these patients consists of long-term supportive contacts. Termination of CAU is often not considered to be an option due to persistent symptoms, a low level of functioning, and the absence of further treatment options. A new intervention, ZemCAD, offers a program focused on rehabilitation and self-management, followed by referral back to primary care. METHODS: This multicenter randomized controlled trial was carried out in twelve specialized outpatient mental health care services in the Netherlands. Consenting and eligible patients were invited for the MINI interview and the baseline questionnaire. Assessments were done at 6 (T1), 12 (T2) and 18 (T3) months post baseline. We used linear mixed model analysis (LMM) to ascertain the effectiveness of the ZemCAD group relative to the CAU group on quality of life, symptom severity and empowerment. RESULTS: In total 141 patients were included. The results at 18-month follow-up regarding to quality of life and symptom severity, showed no significant differences between the ZemCAD group and the CAU group, except on the 'social relationships'-domain (d = 0.37). With regard to empowerment a significant difference between both groups was observed in the total empowerment score and one empowerment dimension (d = 0.45 and d = 0.39, respectively). After the ZemCAD intervention, more patients went from specialized outpatient mental health services back to a less specialized health care setting with less intensive treatment, such as primary care. CONCLUSION: The findings in this study suggest that patients with chronic and treatment-resistant anxiety and depression using the ZemCAD intervention improve on empowerment but not on symptom severity or quality of life. Since little is known about the effects of rehabilitation and self-management in patients with chronic and treatment resistant anxiety and depressive disorders, this is a first attempt to provide a proof-of-concept study in this under-researched but important field. TRIAL REGISTRATION: Netherlands Trial Register: NTR3335 , registered 7 March 2012.

Cost and Effectiveness of Blended Versus Standard Cognitive Behavioral Therapy for Outpatients With Depression in Routine Specialized Mental Health Care: Pilot Randomized Controlled Trial.

BACKGROUND: Cognitive behavioral therapy (CBT) is an effective treatment, but access is often restricted due to costs and limited availability of trained therapists. Blending online and face-to-face CBT for depression might improve cost-effectiveness and treatment availability. OBJECTIVE: This pilot study aimed to examine the costs and effectiveness of blended CBT compared with standard CBT for depressed patients in specialized mental health care to guide further research and development of blended CBT. METHODS: Patients were randomly allocated to blended CBT (n=53) or standard CBT (n=49). Blended CBT consisted of 10 weekly face-to-face sessions and 9 Web-based sessions. Standard CBT consisted of 15 to 20 weekly face-to-face sessions. At baseline and 10, 20, and 30 weeks after start of treatment, self-assessed depression severity, quality-adjusted life-years (QALYs), and costs were measured. Clinicians, blinded to treatment allocation, assessed psychopathology at all time points. Data were analyzed using linear mixed models. Uncertainty intervals around cost and effect estimates were estimated with 5000 Monte Carlo simulations. RESULTS: Blended CBT treatment duration was mean 19.0 (SD 12.6) weeks versus mean 33.2 (SD 23.0) weeks in standard CBT (P<.001). No significant differences were found between groups for depressive episodes (risk difference [RD] 0.06, 95% CI -0.05 to 0.19), response to treatment (RD 0.03, 95% CI -0.10 to 0.15), and QALYs (mean difference 0.01, 95% CI -0.03 to 0.04). Mean societal costs for blended CBT were €1183 higher than standard CBT. This difference was not significant (95% CI -399 to 2765). Blended CBT had a probability of being cost-effective compared with standard CBT of 0.02 per extra QALY and 0.37 for an additional treatment response, at a ceiling ratio of €25,000. For health care providers, mean costs for blended CBT were €176 lower than standard CBT. This difference was not significant (95% CI -659 to 343). At €0 per additional unit of effect, the probability of blended CBT being cost-effective compared with standard CBT was 0.75. The probability increased to 0.88 at a ceiling ratio of €5000 for an added treatment response, and to 0.85 at €10,000 per QALY gained. For avoiding new depressive episodes, blended CBT was deemed not cost-effective compared with standard CBT because the increase in costs was associated with negative effects. CONCLUSIONS: This pilot study shows that blended CBT might be a promising way to engage depressed patients in specialized mental health care. Compared with standard CBT, blended CBT was not considered cost-effective from a societal perspective but had an acceptable probability of being cost-effective from the health care provider perspective. Results should be carefully interpreted due to the small sample size. Further research in larger replication studies focused on optimizing the clinical effects of blended CBT and its budget impact is warranted. TRIAL REGISTRATION: Netherlands Trial Register NTR4650; https://www.trialregister.nl/trial/4408. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s12888-014-0290-z.