Internet-Delivered Exposure and Response Prevention for Pediatric Tourette Syndrome: 12-Month Follow-Up of a Randomized Clinical Trial.

Importance: Behavior therapy is a recommended intervention for Tourette syndrome (TS) and chronic tic disorder (CTD), but availability is limited and long-term effects are uncertain. Objective: To investigate the long-term efficacy and cost-effectiveness of therapist-supported, internet-delivered exposure and response prevention (ERP) vs psychoeducation for youths with TS or CTD. Design, Setting, And Participants: This 12-month controlled follow-up of a parallel group, superiority randomized clinical trial was conducted at a research clinic in Stockholm, Sweden, with nationwide recruitment. In total, 221 participants aged 9 to 17 years with TS or CTD were enrolled between April 26, 2019, and April 9, 2021, of whom 208 (94%) provided 12-month follow-up data. Final follow-up data were collected on June 29, 2022. Outcome assessors were masked to treatment allocation throughout the study. Interventions: A total of 111 participants were originally randomly allocated to 10 weeks of therapist-supported, internet-delivered ERP and 110 participants to therapist-supported, internet-delivered psychoeducation. Main Outcomes And Measures: The primary outcome was within-group change in tic severity, measured by the Total Tic Severity Score of the Yale Global Tic Severity Scale (YGTSS-TTSS), from the 3-month follow-up to the 12-month follow-up. Treatment response was defined as 1 (very much improved) or 2 (much improved) on the Clinical Global Impression-Improvement scale. Analyses were intention-to-treat and followed the plan prespecified in the published study protocol. A health economic evaluation was performed from 3 perspectives: health care organization (including direct costs for treatment provided in the study), health care sector (additionally including health care resource use outside of the study), and societal (additionally including costs beyond health care [eg, parent's absenteeism from work]). Results: In total, 221 participants were recruited (mean [SD] age, 12.1 [2.3] years; 152 [69%] male). According to the YGTSS-TTSS, there were no statistically significant changes in tic severity from the 3-month to the 12-month follow-up in either group (ERP coefficient, -0.52 [95% CI, -1.26 to 0.21]; P = .16; psychoeducation coefficient, 0.00 [95% CI, -0.78 to 0.78]; P > .99). A secondary analysis including all assessment points (baseline to 12-month follow-up) showed no statistically significant between-group difference in tic severity from baseline to the 12-month follow-up (coefficient, -0.38 [95% CI, -1.11 to 0.35]; P = .30). Treatment response rates were similar in both groups (55% in ERP and 50% in psychoeducation; odds ratio, 1.25 [95% CI, 0.73-2.16]; P = .42) at the 12-month follow-up. The health economic evaluation showed that, from a health care sector perspective, ERP produced more quality-adjusted life years (0.01 [95% CI, -0.01 to 0.03]) and lower costs (adjusted mean difference -$84.48 [95% CI, -$440.20 to $977.60]) than psychoeducation at the 12-month follow-up. From the health care organization and societal perspectives, ERP produced more quality-adjusted life years at higher costs, with 65% to 78% probability of ERP being cost-effective compared with psychoeducation when using a willingness-to-pay threshold of US $79 000. Conclusions And Relevance: There were no statistically significant changes in tic severity from the 3-month through to the 12-month follow-up in either group. The ERP intervention was not superior to psychoeducation at any time point. While ERP was not superior to psychoeducation alone in reducing tic severity at the end of the follow-up period, ERP is recommended for clinical implementation due to its likely cost-effectiveness and support from previous literature. Trial Registration: ClinicalTrials.gov Identifier: NCT03916055.

Effectiveness of internet-delivered cognitive behavioural therapy for anxiety and obsessive-compulsive disorders within routine clinical care in rural Sweden.

Few studies have evaluated the implementation of ICBT in regular child and adolescent mental health services (CAMHS). This study aimed to explore the acceptability, feasibility, and effectiveness of ICBT for children and adolescents with anxiety disorders and obsessive-compulsive disorder (OCD) within a rural CAMHS. The study also explored outcome predictors and long-term outcomes. Eighty-three participants were consecutively recruited from a non-specialized CAMHS in Region Jämtland Härjedalen in northern Sweden. Therapist-guided ICBT was offered during 12 weeks to children aged 8-17 with an anxiety disorder or OCD. Acceptability and feasibility measures included treatment adherence, treatment satisfaction, and adverse events. The primary outcome measure was the Clinical Global Impression-Severity. Secondary measures of effectiveness included clinician-, self-, and parent-ratings of symptom severity and functional impairment. Assessments were completed at baseline, post-treatment, and three-month follow-up (primary endpoint). A two-year follow up was conducted using medical records. Potential predictors included both patient characteristics and treatment variables. Results indicated that ICBT was both acceptable and feasible according to study measures. Statistically significant improvements were found from baseline to the three-month follow-up on clinician rated severity (B [SE] = -0.92 [0.09]; p < .001), as well as on all secondary measures. Forty-three percent of participants no longer fulfilled criteria for their principal disorder at the three-month follow-up. No serious adverse events were reported. Clinical improvement was highest among children with higher functioning at baseline (B [SE] = -0.05 [0.02]; p < .05). Forty-six percent of participants had been in contact with CAMHS during the two-year follow-up period, mainly for reasons other than their initial diagnosis. Findings suggest that ICBT could be an acceptable and feasible treatment option for young people with anxiety disorders and OCD in rural non-specialized CAMHS settings. Further studies are needed to confirm treatment effectiveness in this setting. Trial registration: NCT02926365.

Efficacy and acceptability of cognitive-behavioral therapy and serotonin reuptake inhibitors for pediatric obsessive-compulsive disorder: a network meta-analysis.

BACKGROUND: Cognitive-behavioral therapy (CBT) and serotonin reuptake inhibitors (SRIs) are recommended treatments for pediatric obsessive-compulsive disorder (OCD), but their relative efficacy and acceptability have not been comprehensively examined. Further, it remains unclear whether the efficacy of in-person CBT is conserved when delivered in other formats, such as over telephone/webcam or as Internet-delivered CBT (ICBT). METHODS: PubMed, PsycINFO, trial registries, and previous systematic reviews were searched for randomized controlled trials (RCTs) comparing CBT (in-person, webcam/telephone-delivered, or ICBT) or SRIs with control conditions or each other. Network meta-analyses were conducted to examine efficacy (post-treatment Children's Yale-Brown Obsessive Compulsive Scale) and acceptability (treatment discontinuation). Confidence in effect estimates was evaluated with CINeMA (Confidence in Network Meta-Analysis). RESULTS: Thirty eligible RCTs and 35 contrasts comprising 2,057 youth with OCD were identified. In-person CBT was significantly more efficacious than ICBT, waitlist, relaxation training, and pill placebo (MD range: 3.95-11.10; CINeMA estimate of confidence: moderate) but did not differ significantly from CBT delivered via webcam/telephone (MD: 0.85 [-2.51, 4.21]; moderate), SRIs (MD: 3.07 [-0.07, 6.20]; low), or the combination of in-person CBT and SRIs (MD: -1.20 [-5.29, 2.91]; low). SRIs were significantly more efficacious than pill placebo (MD: 4.59 [2.70, 6.48]; low) and waitlist (MD: 8.03 [4.24, 11.82]; moderate). No significant differences for acceptability emerged, but confidence in estimates was low. CONCLUSIONS: In-person CBT and SRIs produce clear benefits compared to waitlist and pill placebo and should be integral parts of the clinical management of pediatric OCD, with in-person CBT overall having a stronger evidence base. The combination of in-person CBT and SRIs may be most efficacious, but few studies hinder firm conclusions. The efficacy of CBT appears conserved when delivered via webcam/telephone, while more trials evaluating ICBT are needed.

The impact of reduced worry on general functioning: A mediation analysis from a randomized trial.

Previous lab findings have indicated that excessive worry may impair cognitive performance and problem solving capabilities but it is unclear if excessive worry also leads to broader impairments in general functioning. We report a secondary process data analysis of a large randomized waitlist-controlled trial (N = 670) of a self-guided online psychological intervention for dysfunctional worry related to the Covid-19 pandemic. Specific aims were to investigate (1) if improvements in general functioning were mediated by reductions in worry related to Covid-19 during the acute intervention phase, and (2) if reduced worry related to Covid-19 during acute intervention phase had a positive long-term impact on general functioning up to 1 year after the end of the intervention. To address aim 1, we used a mediation analysis framework where outcome (general functioning measured with an adapted version of the Work and Social Adjustment Scale) and the hypothesized mediator (worry measured with an adapted version of the Generalised Anxiety Disorder 7-Item Scale) were administered weekly during the controlled phase of the trial of 3 weeks. To address aim 2, we investigated if reductions in worry during the 3-week treatment period predicted improved general functioning at 1- and 12 months after treatment completion. Results showed that improvements in general functioning at week 3 were mediated by reductions in worry during the first 2 weeks of treatment (indirect effect estimate -0.08; 95% CI -0.15, -0.02). A sensitivity analysis indicated that the mediation effects dropped significantly when the residual correlation values between the mediator and the outcome exceeded r = 0. A reversed causation model was not significant. Additionally, reductions in worry during treatment predicted subsequent improvements in general functioning at both 1- and 12-month follow-ups (p < .05, -.001). Altogether, these results provide further support of the importance of targeting worry as a way to improve functioning among the large population of individuals with high levels of worry.

An online self-guided cognitive intervention for unwanted intrusive thoughts about harming infants in new parents: initial randomised controlled trial with mediation analysis.

Approximately one-fifth of new parents struggle with unwanted intrusive thoughts (UITs) about intentionally harming their child. This study evaluated the initial efficacy, feasibility and acceptability of a novel online self-guided cognitive intervention for new parents with distressing UITs. Self-recruited parents (N = 43, 93% female, age 23-43 years) of children 0-3 years reporting daily distressing and impairing UITs were randomized to the 8-week self-guided online cognitive intervention or to waiting-list. The primary outcome was change on the Parental Thoughts and Behaviour Checklist (PTBC) from baseline to week 8 (post-intervention). The PTBC and negative appraisals (mediator) were assessed at baseline, weekly, post-intervention and at the 1-month follow-up. Results showed that the intervention led to statistically significant reductions in distress and impairment associated with UITs at post-intervention (controlled between-group d = 0.99, 95% CI 0.56 to 1.43), which were maintained at the 1-month follow-up (controlled between-group d = 0.90, 95% CI 0.41 to 1.39). The intervention was deemed to be feasible and acceptable by the participants. Change in negative appraisals mediated reductions in UITs but the model was sensitive to mediator-outcome confounders. We conclude that this novel online self-guided cognitive intervention can potentially reduce the distress and impairment associated with UITs in new parents. Large-scale trials are warranted.Abbreviations: UITs: Unwanted Intrusive Thoughts PTBC: Parental Thoughts and Behaviour Checklist.

Condensed Internet-delivered prolonged exposure provided soon after trauma: a randomised trial.

BACKGROUND: Exposure to trauma is common and can have a profoundly negative impact on mental health. Interventions based on trauma-focused cognitive behavioural therapy have shown promising results to facilitate recovery. The current trial evaluated whether a novel, scalable and digital early version of the intervention, Condensed Internet-Delivered Prolonged Exposure (CIPE), is effective in reducing post-traumatic stress symptoms. METHOD: A single-site randomised controlled trial with self-referred adults (N = 102) exposed to trauma within the last 2 months. The participants were randomised to 3 weeks of CIPE or a waiting list (WL) for 7 weeks. Assessments were conducted at baseline, week 1-3 (primary endpoint), week 4-7 (secondary endpoint) and at 6-month follow-up. The primary outcome measure was PTSD Checklist for DSM-5 (PCL-5). RESULTS: The main analysis according to the intention-to-treat principle indicated statistically significant reductions in symptoms of post-traumatic stress in the CIPE group as compared to the WL group. The between-group effect size was moderate at week 3 (bootstrapped d = 0.70; 95% CI 0.33-1.06) and large at week 7 (bootstrapped d = 0.83; 95% CI 0.46-1.19). Results in the intervention group were maintained at the 6-month follow-up. No severe adverse events were found. CONCLUSIONS: CIPE is a scalable intervention that may confer early benefits on post-traumatic stress symptoms in survivors of trauma. The next step is to compare this intervention to an active control group and also investigate its effects when implemented in regular care.

Longitudinal study of gut microbiome in obsessive-compulsive disorder.

INTRODUCTION: Patients with obsessive-compulsive disorder (OCD) often have limited exposure to a diverse environment and perform repetitive compulsions such as excessive cleaning and washing, which could lead to altered gut microbiome. Therefore, longitudinal studies that investigate changes in gut microbiome before and after cognitive behavioral therapy based on exposure and response prevention (ERP) are warranted. METHODS: All study participants (N = 64) underwent a structured psychiatric diagnostic interview prior to inclusion. Nutritional intake was assessed with a comprehensive food frequency questionnaire. Stool samples were collected from OCD patients before ERP (n = 32) and 1 month after completion of ERP (n = 15), as well as from healthy controls (HCs; n = 32). Taxonomic and functional analyses were performed using data from microbiome whole genome sequencing. RESULTS: Patients with OCD at baseline reported consuming significantly less fiber than HCs (R2  = .12, F(2, 59) = 5.2, p ≤ .01). There were no significant differences in α- and ß-diversity indices, or taxonomic dissimilarities at the species level between patients with OCD and HCs, or within patients before and after ERP. Functional profiling based on gut microbial gene expression was grouped into 56 gut-brain modules with neuroactive potential. None of the gut-brain modules differed significantly in expression between patients with OCD at baseline and HCs or within patients before and after ERP. CONCLUSIONS: The diversity, composition, and functional profile of the gut microbiome in patients with OCD did not differ significantly from HCs and remained stable over time, despite behavioral changes.

Long-term effect of stepped-care vs in-person cognitive behavioral therapy for pediatric obsessive-compulsive disorder.

Long-term follow-up data from trials of digital mental health interventions are rare. This study reports 2-year follow-up data from a non-inferiority trial (N = 152) comparing stepped-care (internet-delivered cognitive behavioral therapy [CBT] followed by traditional in-person CBT if needed) vs in-person CBT for pediatric obsessive-compulsive disorder. Both treatment groups had comparable long-term effects, with the majority of participants being responders (stepped-care 66 %; in-person CBT 71 %) 2 years after the end of treatment.

The Cost of Obsessive-Compulsive Disorder in Swedish Youth.

The economic impact of pediatric obsessive-compulsive disorder (OCD) on society is unknown. We compared a wide range of individual-level cost data of children 7-17 years with OCD (n = 152) with a control group from the general population in Sweden (n = 768). The total annual cost in the OCD group was M = 11941€ (95%CI [9915-13966]), compared to the control group M = 6380 € (95%CI [5461-7299]), corresponding to an estimated marginal mean cost of OCD of 5560 € per person and year (z = 4.99, p < .001). OCD was associated with significantly higher healthcare costs, parental absence from work and school productivity loss. OCD symptom severity was positively associated with higher costs. The total societal burden of pediatric OCD in Sweden was estimated to be 94.3 € million per year (95%CI [56.9-131.8]). These results have important implications for policy makers and for the allocation of healthcare resources. Similar studies are needed in other countries in order to estimate the global cost of the disorder.