Primary Care Behavioral Health in Sweden - a protocol of a cluster randomized trial evaluating outcomes related to implementation, organization, and patients (KAIROS).

BACKGROUND: Providing comprehensive and continuous care for patients whose conditions have mental or behavioral components is a central challenge in primary care and an important part of improving universal health coverage. There is a great need for high and routine availability of psychological interventions, but traditional methods for delivering psychotherapy often result in low reach and long wait times. Primary Care Behavioral Health (PCBH) is a method for organizing primary care in which behavioral health staff provide brief, flexible interventions to a large part of the population in active collaboration with other providers. While PCBH holds promise in addressing important challenges, it has not yet been thoroughly evaluated. METHODS: This cluster randomized trial will assess 17 primary care centers (PCCs) that are starting a PCBH implementation process. The PCCs will be divided into two groups, with one starting immediate implementation and the other acting as a control, implementing six months later. The purpose of the study is to strengthen the evidence base for PCBH regarding implementation-, organization-, and patient-level outcomes, taking into consideration that there is a partially dependent relationship between the three levels. Patient outcomes (such as increased daily functioning and reduction of symptoms) may be dependent on organizational changes (such as availability of treatment, waiting times and interprofessional teamwork), which in turn requires change in implementation outcomes (most notably, model fidelity). In addition to the main analysis, five secondary analyses will compare groups based on different combinations of randomization and time periods, specifically before and after each center achieves sufficient PCBH fidelity. DISCUSSION: A randomized comparison of PCBH and traditional primary care has, to our knowledge, not been made before. While the naturalistic setting and the intricacies of implementation pose certain challenges, we have designed this study in an effort to evaluate the causal effects of PCBH despite these complex aspects. The results of this project will be helpful in guiding decisions on how to organize the delivery of behavioral interventions and psychological treatment within the context of primary care in Sweden and elsewhere. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05335382. Retrospectively registered on March 13th, 2022.

Swedish multimodal cohort of patients with anxiety or depression treated with internet-delivered psychotherapy (MULTI-PSYCH).

PURPOSE: Depression and anxiety afflict millions worldwide causing considerable disability. MULTI-PSYCH is a longitudinal cohort of genotyped and phenotyped individuals with depression or anxiety disorders who have undergone highly structured internet-based cognitive-behaviour therapy (ICBT). The overarching purpose of MULTI-PSYCH is to improve risk stratification, outcome prediction and secondary preventive interventions. MULTI-PSYCH is a precision medicine initiative that combines clinical, genetic and nationwide register data. PARTICIPANTS: MULTI-PSYCH includes 2668 clinically well-characterised adults with major depressive disorder (MDD) (n=1300), social anxiety disorder (n=640) or panic disorder (n=728) assessed before, during and after 12 weeks of ICBT at the internet psychiatry clinic in Stockholm, Sweden. All patients have been blood sampled and genotyped. Clinical and genetic data have been linked to several Swedish registers containing a wide range of variables from patient birth up to 10 years after the end of ICBT. These variable types include perinatal complications, school grades, psychiatric and somatic comorbidity, dispensed medications, medical interventions and diagnoses, healthcare and social benefits, demographics, income and more. Long-term follow-up data will be collected through 2029. FINDINGS TO DATE: Initial uses of MULTI-PSYCH include the discovery of an association between PRS for autism spectrum disorder and response to ICBT, the development of a machine learning model for baseline prediction of remission status after ICBT in MDD and data contributions to genome wide association studies for ICBT outcome. Other projects have been launched or are in the planning phase. FUTURE PLANS: The MULTI-PSYCH cohort provides a unique infrastructure to study not only predictors or short-term treatment outcomes, but also longer term medical and socioeconomic outcomes in patients treated with ICBT for depression or anxiety. MULTI-PSYCH is well positioned for research collaboration.

Striatal dopamine D2 receptor availability as a predictor of subsequent alcohol use in social drinkers.

BACKGROUND AND AIMS: Whereas striatal dopamine D2 receptor (D2R) availability has shown to be altered in individuals with alcohol use disorder (AUD) and in healthy individuals with a family history of AUD, the role of D2R in the development of AUD is unknown. In this positron emission tomography (PET) study, we measured whether D2R availability is associated with subsequent alcohol use and alcohol-related factors, at a follow-up 8 to 16 years post-PET scan, in social drinkers. DESIGN: Longitudinal study investigating the association between PET data and later self-report measures in healthy individuals. SETTING: Academic research imaging centre in Stockholm, Sweden. PARTICIPANTS: There were 71 individuals (68 of whom had evaluable PET data, 5 females, 42.0 years mean age) from a series of previous PET studies. MEASUREMENTS: One PET examination with the D2R antagonist radioligand [11 C]raclopride at baseline and self-report measures assessing alcohol use, drug use, impulsivity, reward sensitivity and family history of alcohol or substance use disorder at follow-up. FINDINGS: We found no evidence for an association between D2R availability and later alcohol use (B = -0.019, B 95% CI = -0.043 to -0.006, P = 0.147) nor for the majority of the alcohol-related factors (B 95% CI = -0.034 to 0.004, P = 0.273-0.288). A negative association with a small effect size was found between D2R availability and later impulsivity (B = -0.017, B 95% CI = -0.034 to -0.001, P = 0.046). CONCLUSIONS: Low striatal dopamine D2 receptor availability may not be a strong predictor in the development of alcohol use disorder.

Predicting remission after internet-delivered psychotherapy in patients with depression using machine learning and multi-modal data.

This study applied supervised machine learning with multi-modal data to predict remission of major depressive disorder (MDD) after psychotherapy. Genotyped adult patients (n = 894, 65.5% women, age 18-75 years) diagnosed with mild-to-moderate MDD and treated with guided Internet-based Cognitive Behaviour Therapy (ICBT) at the Internet Psychiatry Clinic in Stockholm were included (2008-2016). Predictor types were demographic, clinical, process (e.g., time to complete online questionnaires), and genetic (polygenic risk scores). Outcome was remission status post ICBT (cut-off ≤10 on MADRS-S). Data were split into train (60%) and validation (40%) given ICBT start date. Predictor selection employed human expertise followed by recursive feature elimination. Model derivation was internally validated through cross-validation. The final random forest model was externally validated against a (i) null, (ii) logit, (iii) XGBoost, and (iv) blended meta-ensemble model on the hold-out validation set. Feature selection retained 45 predictors representing all four predictor types. With unseen validation data, the final random forest model proved reasonably accurate at classifying post ICBT remission (Accuracy 0.656 [0.604, 0.705], P vs null model = 0.004; AUC 0.687 [0.631, 0.743]), slightly better vs logit (bootstrap D = 1.730, P = 0.084) but not vs XGBoost (D = 0.463, P = 0.643). Transparency analysis showed model usage of all predictor types at both the group and individual patient level. A new, multi-modal classifier for predicting MDD remission status after ICBT treatment in routine psychiatric care was derived and empirically validated. The multi-modal approach to predicting remission may inform tailored treatment, and deserves further investigation to attain clinical usefulness.

Very long-term outcome of cognitive behavioral therapy for insomnia: one- and ten-year follow-up of a randomized controlled trial.

Insomnia is a common and chronic disorder, and cognitive behavioral therapy (CBT) is the recommended treatment. Very long-term follow-ups of CBT are very rare, and this study aimed to investigate if improvements were stable one and ten years after CBT for insomnia (CBT-i). Based on a three-armed randomized controlled trial of bibliotherapeutic CBT-i, participants received an insomnia-specific self-help book and were randomized to therapist guidance, no guidance, or a waitlist receiving unguided treatment after a delay. Six weeks of treatment was given to 133 participants diagnosed with insomnia disorder. After one and ten years, participants were assessed with self-reports and interviews. Improvements were statistically significant and well maintained at one- and ten-year follow-ups. Average Insomnia Severity Index score [95%CI] was 18.3 [17.7-18.8] at baseline, 10.1 [9.3-10.9] at post-treatment, 9.2 [8.4-10.0] at one- and 10.7 [9.6-11.8] at ten-year follow-up, and 64% and 66% of participants no longer fulfilled criteria for an insomnia diagnosis at one and ten years, respectively. Positive effects of CBT were still present after ten years. Insomnia severity remained low, and two-thirds of participants no longer fulfilled criteria for an insomnia diagnosis. This extends previous findings of CBT, further confirming it as the treatment of choice for insomnia.

Measures of emotion regulation: Convergence and psychometric properties of the difficulties in emotion regulation scale and emotion regulation questionnaire.

OBJECTIVE: Investigating unique and shared aspects of measures of emotion regulation (ER) advances our understanding of ER as a multidimensional construct. This study aimed to investigate psychometric properties of three ER-measures: Difficulties in Emotion Regulation Scale (DERS-36), the abbreviated version DERS-16, and Emotion Regulation Questionnaire (ERQ). METHODS: In a community sample (N = 843; 56% females) we investigated their internal consistency, factor structure, convergence, and association with symptoms of depression, anxiety, stress and substance abuse. RESULTS: The proposed factor structures of the DERS-16 and the ERQ demonstrated an adequate fit. There were moderate correlations between the two DERS versions (36 and 16) and ERQ subscales Reappraisal and Suppression. Total scores of DERS-36 and DERS-16 demonstrated preferential associations with depression and anxiety. Corresponding associations between ERQ subscales and psychiatric symptoms were weak. CONCLUSION: The results indicate that DERS-16 could be useful as an alternative, easily administered measure of ER difficulties.

An investigation and replication of sleep-related cognitions, acceptance and behaviours as predictors of short- and long-term outcome in cognitive behavioural therapy for insomnia.

The objectives were to investigate the potential for sleep-related behaviours, acceptance and cognitions to predict outcome (insomnia severity) of cognitive behavioural therapy for insomnia (CBT-I). Baseline and outcome data from four randomised controlled trials (n = 276) were used. Predictors were the Dysfunctional Beliefs and Attitudes about Sleep-10 (DBAS-10), Sleep-Related Behaviours Questionnaire (SRBQ), and Sleep Problems Acceptance Questionnaire (SPAQ), and empirically derived factors from a factor analysis combining all items at baseline (n = 835). Baseline values were used to predict post-treatment outcome, and pre-post changes in the predictors were used to predict follow-up outcomes after 3-6 months, 1 year, or 3-10 years, measured both as insomnia severity and as better or worse long-term sleep patterns. A majority (29 of 52) of predictions of insomnia severity were significant, but when controlling for insomnia severity, only two (DBAS-10 at short-term and SRBQ at mid-term follow-up) of the 12 predictions using established scales, and three of the 40 predictions using empirically derived factors, remained significant. The strongest predictor of a long-term, stable sleep pattern was insomnia severity reduction during treatment. Using all available predictors in an overfitted model, 21.2% of short- and 58.9% of long-term outcomes could be predicted. We conclude that although the explored constructs may have important roles in CBT-I, the present study does not support that the DBAS-10, SRBQ, SPAQ, or factors derived from them, would be unique predictors of outcome.

A very brief self-report scale for measuring insomnia severity using two items from the Insomnia Severity Index - development and validation in a clinical population.

OBJECTIVE: To develop a very brief scale with selected items from the Insomnia Severity Index (ISI), and to investigate the psychometric properties of the proposed scale in a psychiatric sample. METHODS: Patient data from seven Cognitive Behavioral Therapy (CBT) for insomnia trials and from regular care were used in psychometric analyses (N = 280-15 653). The samples included patients screening (N = 6936) or receiving treatment (N = 1725) for insomnia and other psychiatric conditions. Six criteria relating to component structure, sensitivity to change and clinical representativeness were used to select items. Psychometric analyses for the proposed very brief scale were performed. RESULTS: One item representing satisfaction/dissatisfaction with current sleep pattern and one item representing interferences with daily functioning, were selected to create the 2-item ISI version. Correlations with the full scale were high at screening, pre and post, and for change (0.82-0.94). Categorical omega was ⍵C = 0.86. With a cut-off of 6 points, the scale could detect Insomnia Disorder with a sensitivity of 84% and a specificity of 76%, which was close to the full ISI showing 86% and 80% respectively. CONCLUSIONS: The systematic psychometric evaluation based on a large sample from different contexts makes the proposed 2-item ISI version (ISI-2) a strong candidate for a very brief scale measuring insomnia, both for detecting cases and for measuring change during CBT with an overall high discriminative validity. ISI-2 is especially useful in clinical settings or population studies where there is a need to measure more than one condition at a time without overburdening patients. CLINICAL TRIALS: Trials used in this analysis: ClinicalTrials.gov identifier: NCT01105052 (https://www.clinicaltrials.gov/ct2/show/NCT01105052) (sample b), ClinicalTrials.gov identifier: NCT01256099 (https://clinicaltrials.gov/ct2/show/NCT01256099) (sample c and d), German clinical trial (DRKS), registration ID: DRKS00008745 (https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00008745) (sample e), ClinicalTrials.gov identifier: NCT01663844 (https://clinicaltrials.gov/ct2/show/NCT01663844) (sample f and g), ClinicalTrials.gov Identifier: NCT02743338 (https://clinicaltrials.gov/ct2/show/NCT02743338) (sample h).

Emotion dysregulation across levels of substance use.

Emotion dysregulation has shown to be of importance in the onset and maintenance of psychiatric disorders, including substance use disorders. How difficulties in emotion regulation differ across levels of substance use, and whether these relations are influenced by co-occurring psychiatric disorders, is less clear. This study aimed to identify difficulties in emotion regulation across the spectrum of substance use and evaluate the influence of co-occurring psychiatric symptoms. Self-reported emotion regulation difficulties, substance use, and other psychiatric symptoms were assessed in one community sample (n = 843) and two inpatient clinics, with substance use disorder populations (n = 415). Data were merged and analyzed with regression models and correlations. Emotion dysregulation was distributed across different levels of substance use, and significantly associated with substance use severity and frequency. High substance use severity and frequency was significantly associated with high scores on the emotion dysregulation facet specifically involving difficulties controlling impulsive behaviors. Psychiatric symptoms did not significantly influence the association between substance use and emotion dysregulation. Results indicate an association between emotion dysregulation and the frequency and severity of substance use, and also suggest that difficulties controlling impulsive behaviors may be a potentially useful treatment target for individuals with substance dependence.

Predicting treatment failure in regular care Internet-Delivered Cognitive Behavior Therapy for depression and anxiety using only weekly symptom measures.

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. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Development of a very brief scale for detecting and measuring panic disorder using two items from the Panic Disorder Severity Scale-Self Report.

OBJECTIVE: To minimize the burden in detecting and monitoring Panic Disorder and Agoraphobia by developing a very brief scale with selected items from the Panic Disorder Severity Scale-Self Report (PDSS-SR), and to investigate the proposed scale's psychometric properties in a comorbid sample. METHODS: A sample of 5103 patients from the Internet Psychiatry Clinic in Sweden, diagnosed and treated with Internet-based cognitive behavioral therapy for panic disorder (n = 1390), social anxiety disorder (n = 1313) or depression (n = 2400), responded to the PDSS-SR. Six criteria related to factor structure, sensitivity to change and clinical representativeness were used to select items. Psychometric analyses for the selected very brief scale were performed. RESULTS: Items 2 (distress during panic attacks) and 4 (agoraphobic avoidance), were selected to create the very brief PDSS-SR version. Correlations with the full scale were high at screening, pre and post, and for change (0.87-0.93). Categorical Omega was ⍵C = 0.74. With a cut-off of 3 points, the scale could detect panic disorder in a psychiatric sample with a sensitivity of 85% and a specificity of 66%. LIMITATIONS: Limitations include lack of healthy controls and lack of blinding on secondary outcome measures. CONCLUSION: The proposed 2-item PDSS-SR version is a good candidate for a very brief panic disorder questionnaire, both for detecting cases and for measuring change. This is especially useful in clinical settings when measuring more than one condition at a time.