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Importance: Personalized treatment choices would increase the effectiveness of internet-based cognitive behavioral therapy (iCBT) for depression to the extent that patients differ in interventions that better suit them. Objective: To provide personalized estimates of short-term and long-term relative efficacy of guided and unguided iCBT for depression using patient-level information. Data Sources: We searched PubMed, Embase, PsycInfo, and Cochrane Library to identify randomized clinical trials (RCTs) published up to January 1, 2019. Study Selection: Eligible RCTs were those comparing guided or unguided iCBT against each other or against any control intervention in individuals with depression. Available individual patient data (IPD) was collected from all eligible studies. Depression symptom severity was assessed after treatment, 6 months, and 12 months after randomization. Data Extraction and Synthesis: We conducted a systematic review and IPD network meta-analysis and estimated relative treatment effect sizes across different patient characteristics through IPD network meta-regression. Main Outcomes and Measures: Patient Health Questionnaire-9 (PHQ-9) scores. Results: Of 42 eligible RCTs, 39 studies comprising 9751 participants with depression contributed IPD to the IPD network meta-analysis, of which 8107 IPD were synthesized. Overall, both guided and unguided iCBT were associated with more effectiveness as measured by PHQ-9 scores than control treatments over the short term and the long term. Guided iCBT was associated with more effectiveness than unguided iCBT (mean difference [MD] in posttreatment PHQ-9 scores, -0.8; 95% CI, -1.4 to -0.2), but we found no evidence of a difference at 6 or 12 months following randomization. Baseline depression was found to be the most important modifier of the relative association for efficacy of guided vs unguided iCBT. Differences between unguided and guided iCBT in people with baseline symptoms of subthreshold depression (P

Panic disorder (PD) has a lifetime prevalence of 2-4% and heritability estimates of 40%. The contributory genetic variants remain largely unknown, with few and inconsistent loci having been reported. The present report describes the largest genome-wide association study (GWAS) of PD to date comprising genome-wide genotype data of 2248 clinically well-characterized PD patients and 7992 ethnically matched controls. The samples originated from four European countries (Denmark, Estonia, Germany, and Sweden). Standard GWAS quality control procedures were conducted on each individual dataset, and imputation was performed using the 1000 Genomes Project reference panel. A meta-analysis was then performed using the Ricopili pipeline. No genome-wide significant locus was identified. Leave-one-out analyses generated highly significant polygenic risk scores (PRS) (explained variance of up to 2.6%). Linkage disequilibrium (LD) score regression analysis of the GWAS data showed that the estimated heritability for PD was 28.0-34.2%. After correction for multiple testing, a significant genetic correlation was found between PD and major depressive disorder, depressive symptoms, and neuroticism. A total of 255 single-nucleotide polymorphisms (SNPs) with p < 1 × 10-4 were followed up in an independent sample of 2408 PD patients and 228,470 controls from Denmark, Iceland and the Netherlands. In the combined analysis, SNP rs144783209 showed the strongest association with PD (pcomb = 3.10 × 10-7). Sign tests revealed a significant enrichment of SNPs with a discovery p-value of <0.0001 in the combined follow up cohort (p = 0.048). The present integrative analysis represents a major step towards the elucidation of the genetic susceptibility to PD.

Objective: Therapist guided Internet-Delivered Cognitive Behavior Therapy (ICBT) is effective, but as in traditional CBT, not all patients improve, and clinicians generally fail to identify them early enough. We predict treatment failure in 12-week regular care ICBT for Depression, Panic disorder and Social anxiety disorder, using only patients' weekly symptom ratings to identify when the accuracy of predictions exceed 2 benchmarks: (a) chance, and (b) empirically derived clinician preferences for actionable predictions. Method: Screening, pretreatment and weekly symptom ratings from 4310 regular care ICBT-patients from the Internet Psychiatry Clinic in Stockholm, Sweden was analyzed in a series of regression models each adding 1 more week of data. Final score was predicted in a holdout test sample, which was then categorized into Success or Failure (failure defined as the absence of both remitter and responder status). Classification analyses with Balanced Accuracy and 95% Confidence intervals was then compared to predefined benchmarks. Results: Benchmark 1 (better than chance) was reached 1 week into all treatments. Social anxiety disorder reached Benchmark 2 (>65%) at week 5, whereas Depression and Panic Disorder reached it at week 6. Conclusions: For depression, social anxiety and panic disorder, prediction with only patient-rated symptom scores can detect treatment failure 6 weeks into ICBT, with enough accuracy for a clinician to take action. Early identification of failing treatment attempts may be a viable way to increase the overall success rate of existing psychological treatments by providing extra clinical resources to at-risk patients, within a so-called Adaptive Treatment Strategy., QC 20200427

Objectives: To evaluate feasibility and preliminary effects of a new group treatment manual for adults with ADHD and to explore adherence to treatment and its relation to outcome. Method:Eighteen adults with ADHD recruited from neuropsychiatric units in Stockholm underwent a 14-week program including combined cognitive and dialectical behavior therapy. Assessments were made at baseline, posttreatment, and follow-up, at one and six months after treatment end. Primary outcome measure was the Adult ADHD Self Report Scale version 1.1. Results/Conclusion: ADHD symptoms significantly decreased (d = 1.29) and remained stable for 6 months. Measures of depression, perceived stress, and anxiety were also significantly reduced. Attendance and patient satisfaction was high. Use, comprehension, and perceived benefit of treatment components varied from medium to high. Total use of treatment components was, in general, positively correlated with favorable outcome. The current combination of treatment components may be a valuable addition to available treatments in psychiatric care.

The objective of this study was to explore the effects of treatment compliance in a guided individually tailored internet-based treatment (TAIL) in relation to depression and co-morbid symptoms. Compliance with the homework in the different treatment components in TAIL, each aimed at a specific condition, was rated for 207 participants by independent assessors. Six subgroups (n = 34-131) were constructed consisting of participants with co-occurring symptoms of worry, panic, social anxiety, stress, insomnia, or pain. For each group, hierarchical regression was used to investigate whether the total sum of compliance points, Overall Compliance, predicted reductions in depression and in condition-specific symptoms. Also, in each subgroup, it was tested whether working with specific treatment components, Specific Compliance, predicted reduction of the targeted symptoms. Overall Compliance predicted 15% of the reduction in depression symptoms. For participants with worry, panic, social anxiety, stress, or insomnia, Overall Compliance also predicted symptom reductions in that specific condition. Specific Compliance predicted reduction in the targeted symptoms for participants with social anxiety, stress, and insomnia. Specific Compliance with stress and insomnia components also predicted reductions in depression. Our results strengthen the importance of compliance in internet-based treatments. Because compliance with stress and insomnia components was particularly important for broad symptom reductions, these conditions should not be ignored when treating patients with co-morbid symptoms.

Internet-delivered cognitive behaviour therapy (ICBT) has existed for 20 years and there are now several controlled trials for a range of problems. In this paper, we focused on recent meta-analytic reviews of the literature and found moderate to large effects reported for panic disorder, social anxiety disorder, generalized anxiety disorder, posttraumatic stress disorder, and major depression. In total, we reviewed 9 recent meta-analytic reviews out of a total of 618 meta-analytic reviews identified using our search terms. In these selected reviews, 166 studies were included, including overlap in reviews on similar conditions. We also covered a recent review on transdiagnostic treatments and 2 reviews on face-to-face v. internet treatment. The growing number of meta-analytic reviews of studies now suggests that ICBT works and can be as effective as face-to-face therapy.

Objective: This study aimed to demonstrate proof of concept for an adaptive treatment strategy in Internet-delivered cognitive-behavioral therapy (ICBT), where risk of treatment failure is assessed early in treatment and treatment for at-risk patients is adapted to prevent treatment failure. Methods: A semiautomated algorithm assessed risk of treatment failure early in treatment in 251 patients undergoing ICBT for insomnia with therapist guidance. At-risk patients were randomly assigned to continue standard ICBT or to receive adapted ICBT. The primary outcome was self-rated insomnia symptoms using the Insomnia Severity Index in a linear mixed-effects model. The main secondary outcome was treatment failure (having neither responded nor remitted at the posttreatment assessment). Results: A total of 102 patients were classified as at risk and randomly assigned to receive adapted ICBT (N=51) or standard ICBT (N=51); 149 patients were classified as not at risk. Patients not at risk had significantly greater score reductions on the Insomnia Severity Index than at-risk patients given standard ICBT. Adapted ICBT for at-risk patients was significantly more successful in reducing symptoms compared with standard ICBT, and it decreased the risk of failing treatment (odds ratio= 0.33). At-risk patients receiving adapted ICBT were not more likely to experience treatment failure than those not at risk (odds ratio= 0.51), though they were less likely to experience remission. Adapted treatment required, on average, 14 more minutes of therapist-patient time per remaining week. Conclusions: An adaptive treatment strategy can increase treatment effects for at-risk patients and reduce the number of failed treatments. Future studies should improve accuracy in classification algorithms and identify key factors that boost the effect of adapted treatments.

The neurotransmitter serotonin has been widely implicated in the pathophysiology of major depressive disorder (MDD). In animal studies and human neuroimaging studies, involvement of the serotonin receptor 1B (5-HT1BR) in MDD and memory performance has been reported. However, the role of the 5-HT1BR in cognitive functions affected in MDD remains to be clarified. Ten patients with MDD diagnosis were examined with positron emission tomography (PET) and a battery of cognitive tests before and after Internet-based Cognitive Behavioral Therapy (ICBT). The results were compared to ten matched control subjects in order to investigate putative changes in 5-HT1BR availability and cognitive performance. Patients treated with ICBT showed statistically significant improvement relative to baseline in Verbal fluency, both letter and category production. Significant correlations were found between improvement in letter production and changes in 5-HT1BR availability in ventral striatum, between category production and amygdala, as well as between the improvement in Trailmaking test B and change in 5-HT1BR binding in dorsal brainstem, in amygdala and in hippocampus. The results suggest an association between 5-HT1BR binding and improvement in cognitive functioning. Replications in larger-scale studies are required to confirm these findings.

A Swedish example of integrated perinatal mental health care Mental disorders are common during the perinatal period and expose mother and child to major risks. Almost all women in Sweden attend maternal and child health care centers regularly before and after birth. This constitutes a unique opportunity to detect women with early signs of mental disorder or at risk of recurrence of prior illness. Identified women need fast access to diagnostic and treatment providers with specialized knowledge on perinatal mental disorders. As perinatal mental disorders can have severe consequences for mothers and their children a tight cooperation between caregivers is often needed.

Disorder-specific internet-based cognitive-behavioural therapy (ICBT) is effective for depression, panic disorder and social anxiety. In this benchmarking study, a new, individually tailored, ICBT programme (TAIL) showed effects on depression (n = 284, d = 1.33) that were non-inferior to disorder-specific ICBT for depression in routine care (n = 2358, d = 1.35). However, the hypotheses that TAIL for individuals with social anxiety or panic disorder is inferior to disorder-specific ICBT could not be rejected (social anxiety: TAIL d = 0.74 versus disorder-specific d = 0.81; panic: TAIL d = 1.11 versus disorder-specific d = 1.47). Our findings strengthen the empirical base for TAIL as an alternative to disorder-specific ICBT for depression.