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  • 1.
    Alimoradi, Zainab
    et al.
    Qazvin Univ Med Sci, Iran.
    Broström, Anders
    Jönköping University, Sweden;Linköping University Hospital, Sweden.
    Ohayon, Maurice M.
    Stanford Univ, USA.
    Lin, Chung-Ying
    Natl Cheng Kung Univ, Taiwan.
    Griffiths, Mark D.
    Nottingham Trent Univ, UK.
    Jernelov, Susanna
    Region Stockholm, Sweden;Karolinska Institutet, Sweden.
    Kaldo, Viktor
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology. Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Pakpour, Amir H.
    Jönköping University, Sweden.
    Reply to Liu et al.: "Effects of cognitive behavioral therapy for insomnia (CBT-I) on quality of life: A systematic review and meta-analysis"2022In: Sleep Medicine Reviews, ISSN 1087-0792, E-ISSN 1532-2955, Vol. 66, article id 101699Article in journal (Other academic)
  • 2.
    Alimoradi, Zainab
    et al.
    Qazvin Univ Med Sci, Iran.
    Jafari, Elahe
    Qazvin Univ Med Sci, Iran.
    Broström, Anders
    Jönköping University, Sweden;Linköping University Hospital, Sweden.
    Ohayon, Maurice M.
    Stanford Univ, USA.
    Lin, Chung-Ying
    Natl Cheng Kung Univ, Taiwan;Natl Cheng Kung Univ Hosp, Taiwan.
    Griffiths, Mark D.
    Nottingham Trent Univ, UK.
    Blom, Kerstin
    Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Jernelov, Susanna
    Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Kaldo, Viktor
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology. Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Pakpour, Amir H.
    Jönköping University, Sweden.
    Effects of cognitive behavioral therapy for insomnia (CBT-I) on quality of life: A systematic review and meta-analysis2022In: Sleep Medicine Reviews, ISSN 1087-0792, E-ISSN 1532-2955, Vol. 64, article id 101646Article, review/survey (Refereed)
    Abstract [en]

    The effects of cognitive behavioral therapy for insomnia (CBT-I) have consistently been shown to improve insomnia symptoms and other health-related outcomes, but the effects on QoL have been inconsistent. Many factors including the type CBT-I delivery and type of instrument used to assess QoL make the topic complex. The present systematic review and meta-analysis synthesized the evidence of CBT-I efficacy on QoL outcomes across different populations, delivery modes, and methodological aspects. Following the guidelines on preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), a literature search was conducted through PubMed, Web of Science, Scopus, and PsycINFO using keywords from relevant MeSH terms based on PICOS (Participants, Intervention, Comparison, Outcome and Study) criteria. Clinical trials investigating the effect of CBT-I as an intervention on QoL with any kind of control group were eligible if they reported mean scores and variation of QoL. Meta-analysis using a random-effect model was conducted to calculate the standardized mean differences (SMDs) in a set including all identified studies, as well as in three sub-sets: face-to-face CBT-I using randomized controlled trials (RCTs), online CBT-I using RCTs, and one-group pre- and post-treatment design. A total of 24 studies comprising 1977 participants (808 in an intervention group) from 12 countries were eligible for meta-analysis. The overall pooled estimate of SMD of QoL when all 24 studies were included was 0.47 (95% CI: 0.22; 0.72; I-2 = 84.5%; tau(2) = 0.31; p < 0.001). The overall pooled estimate of SMD of QoL was 0.46 (95% CI: 0.01-0.90; I-2 = 87.5%; tau(2) = 0.48, p < 0.001) for intervention groups with face-to-face CBT-I compared to controls; 0.47 (95% CI: 0.02-0.92; I-2 = 88.3%; tau(2) = 0.36; p = 0.04) for intervention groups with digital CBT-I compared to controls, and 0.46 (95% CI: 0.12-0.80; I-2 = 52.9%; tau(2) = 0.07; p = 0.08) for one-group pre- and post-comparison using CBT-I intervention compared to baseline. Moreover, effects of CBT-I on QoL were different across populations (pooled SMD = 0.59 for patients with insomnia; 0.29 for patients with insomnia comorbid with another major disorder; and 0.48 for other conditions) and types of QoL instruments (pooled SMD = 0.36 for disease-specific QoL instrument not on insomnia, 0.43 for generic QoL instrument, and 0.67 for a single-QoL-item instrument). The probability of publication bias was ruled out in overall and design specific sub-group analysis based on funnel plot and Egger's test. In conclusion, this meta-analysis confirmed a moderate, overall effect of CBT-I in improving QoL. However, due to small power and heterogeneity, future studies are needed to better explore the impact of moderating factors such as mode of delivery and type of QoL measure for assessment used. (C) 2022 The Author(s). Published by Elsevier Ltd.

  • 3.
    Andersson, Erik
    et al.
    Karolinska Institutet.
    Hedman, Erik
    Karolinska Institutet.
    Enander, Jesper
    Karolinska Institutet.
    Djurfeldt, Diana Radu
    Karolinska Institutet.
    Ljotsson, Brjann
    Karolinska Institutet.
    Cervenka, Simon
    Karolinska Institutet.
    Isung, Josef
    Karolinska Institutet.
    Svanborg, Cecilia
    Karolinska Institutet.
    Mataix-Cols, David
    Karolinska Institutet.
    Kaldo, Viktor
    Karolinska Institutet.
    Andersson, Gerhard
    Karolinska Institutet;Linköping University.
    Lindefors, Nils
    Karolinska Institutet.
    Rück, Christian
    Karolinska Institutet.
    d-Cycloserine vs Placebo as Adjunct to Cognitive Behavioral Therapy for Obsessive-Compulsive Disorder and Interaction With Antidepressants A Randomized Clinical Trial2015In: JAMA psychiatry, ISSN 2168-6238, E-ISSN 2168-622X, Vol. 72, no 7, p. 659-667Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE It is unclear whether D-cycloserine (DCS), a partial N-methyl-D-aspartate agonist that enhances fear extinction, can augment the effects of exposure-based cognitive behavioral therapy (CBT) for obsessive-compulsive disorder (OCD). OBJECTIVES To examine whether DCS augments the effects of CBT for OCD and to explore (post hoc) whether concomitant antidepressant medication moderates the effects of DCS. DESIGN, SETTING, AND PARTICIPANTS A 12-week, double-blind randomized clinical trial with 3-month follow-up conducted at an academic medical center between September 4, 2012, and September 26, 2013. Participants included 128 adult outpatients with a primary diagnosis of OCD and a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score of 16 or higher. Concurrent antidepressant medication was permitted if the dose had been stable for at least 2 months prior to enrollment and remained unchanged during the trial. The main analysis was by intention-to-treat population. INTERVENTIONS All participants received a previously validated Internet-based CBT protocol over 12 weeks and were randomized to receive either 50 mg of DCS or placebo, administered 1 hour before each of 5 exposure and response prevention tasks. MAIN OUTCOMES AND MEASURES Clinician-administered Y-BOCS score at week 12 and at 3-month follow-up. Remission was defined as a score of 12 or lower on the Y-BOCS. RESULTS In the primary intention-to-treat analyses, DCS did not augment the effects of CBT compared with placebo (mean [SD] clinician-rated Y-BOCS score, DCS: 13.86 [6.50] at week 12 and 12.35 [7.75] at 3-month follow-up; placebo: 11.77 [5.95] at week 12 and 12.37 [6.68] at 3-month follow-up) but showed a significant interaction with antidepressants (clinician-rated Y-BOCS, B = -1.08; Z = -2.79; P = .005). Post hoc analyses revealed that antidepressants significantly impaired treatment response in the DCS group but not the placebo group, at both posttreatment and follow-up (clinician-rated Y-BOCS: t(62) = -3.00; P = .004; and t(61) = -3.49; P < .001, respectively). In the DCS group, a significantly greater proportion of antidepressant-free patients achieved remission status at follow-up (60% [95% CI, 45%-74%]) than antidepressant-medicated patients (24% [95% CI, 9%-48%]) (P = .008). Antidepressants had no effect in the placebo group (50% [95% CI, 36%-64%] remission rate in both groups). CONCLUSIONS AND RELEVANCE The findings suggest that antidepressants may interact with DCS to block its facilitating effect on fear extinction. Use of DCS may be a promising CBT augmentation strategy but only in antidepressant-free patients with OCD.

  • 4.
    Andersson, Erik
    et al.
    Karolinska Institutet.
    Hedman, Erik
    Karolinska Institutet.
    Ljotsson, Brjann
    Karolinska Institutet.
    Wikström, Maja
    Karolinska Institutet.
    Elveling, Elin
    Karolinska Institutet.
    Lindefors, Nils
    Karolinska Institutet.
    Andersson, Gerhard
    Karolinska Institutet;Linköping University.
    Kaldo, Viktor
    Karolinska Institutet.
    Rück, Christian
    Karolinska Institutet.
    Cost-effectiveness of internet-based cognitive behavior therapy for obsessive-compulsive disorder: results from a randomized controlled trial2015In: Journal of Obsessive-Compulsive and Related Disorders, ISSN 2211-3649, E-ISSN 2211-3657, Vol. 4, p. 47-53Article in journal (Refereed)
    Abstract [en]

    Obsessive-compulsive disorder (OCD) is a common and disabling disorder. Although evidence-based psychological treatments exists, such as cognitive behavior therapy (CBT), the cost-effectiveness of CBT has not been properly investigated. In this trial, we used health economic data from a recently conducted randomized controlled trial, where 101 OCD patients were allocated to either internet-based CBT (ICBT) or control condition (online support therapy). We analyzed treatment effectiveness in relation to costs, using both a societal- (including all direct and indirect costs) and a health care unit perspective (including only the direct treatment costs). Bootstrapped net benefit regression analyses were also conducted, comparing the difference in costs and effects between ICBT and control condition, with different willingness-to-pay scenarios. Results showed that ICBT produced one additional remission for an average societal cost of $931 and this figure was even lower ($672) when narrowing the perspective to treatment costs only. The cost-utility analysis also showed that ICBT generated one additional QALY to an average price of $7186 from a societal perspective and $4800 when just analyzing the treatment costs. We conclude that ICBT is a cost-effective treatment and the next step in this line of research is to compare the cost-effectiveness of ICBT with face-to-face CBT. (C) 2014 Elsevier Inc. All rights reserved.

  • 5.
    Andersson, Erik
    et al.
    Karolinska Institutet.
    Ljotsson, Brjann
    Karolinska Institutet.
    Hedman, Erik
    Karolinska Institutet.
    Enander, Jesper
    Karolinska Institutet.
    Kaldo, Viktor
    Karolinska Institutet.
    Andersson, Gerhard
    Karolinska Institutet;Linköping University.
    Lindefors, Nils
    Karolinska Institutet.
    Rück, Christian
    Karolinska Institutet.
    Predictors and moderators of Internet-based cognitive behavior therapy for obsessive-compulsive disorder: Results from a randomized trial2015In: Journal of Obsessive-Compulsive and Related Disorders, ISSN 2211-3649, E-ISSN 2211-3657, Vol. 4, p. 1-7Article in journal (Refereed)
    Abstract [en]

    Internet-based cognitive behavior therapy (ICBT) for obsessive-compulsive disorder (OCD) has shown efficacy in randomized trials but many patients do not respond to the treatment, we therefore need to find predictors and moderators of treatment response. In this study, we analyzed predictors of ICBT response using both post-treatment as well as 24-month outcome data. As half of the participants were randomized to receive an Internet-based booster program as an adjunct to ICBT, we also investigated moderators of ICBT with or without booster. Results showed that more severe baseline OCD symptoms predicted worse end state outcome but also higher degree of change. Furthermore, high degree of working alliance predicted better outcome but patients with primary disgust emotions had worse treatment effects. The moderator analysis also indicated that scoring high on the obsessing subscale on the Obsessive-Compulsive Inventory-Revised predicted worse treatment outcome in the booster group. In conclusion, there are some possible predictors and moderators of ICBT for OCD but more research is needed with larger and clinically representative samples. (C) 2014 Elsevier Inc. All rights reserved.

  • 6.
    Andersson, Erik
    et al.
    Karolinska Institutet.
    Ljotsson, Brjann
    Karolinska Institutet.
    Hedman, Erik
    Karolinska Institutet.
    Hesser, Hugo
    Linköping University.
    Enander, Jesper
    Karolinska Institutet.
    Kaldo, Viktor
    Karolinska Institutet.
    Andersson, Gerhard
    Karolinska Institutet;Linköping University.
    Lindefors, Nils
    Karolinska Institutet.
    Ruck, Christian
    Karolinska Institutet.
    Testing the Mediating Effects of Obsessive Beliefs in Internet-Based Cognitive Behaviour Therapy for Obsessive-Compulsive Disorder: Results from a Randomized Controlled Trial2015In: Clinical Psychology and Psychotherapy, ISSN 1063-3995, E-ISSN 1099-0879, Vol. 22, no 6, p. 722-732Article in journal (Refereed)
    Abstract [en]

    Although cognitive interventions for obsessive-compulsive disorder (OCD) have been tested in randomized trials, there are few trials that have tested the specific mechanisms of cognitive interventions, i.e. how they achieve their effects. In this study, we aimed to investigate the mediating effects of a short cognitive intervention in the treatment of OCD and used data from a recently conducted randomized controlled trial where 101 participants were allocated to either Internet-based CBT (ICBT) or to a control condition. Obsessive beliefs were measured at pre-treatment, at the time they had received the cognitive intervention, and also at post-treatment. Weekly OCD symptoms were measured throughout the 10 weeks of treatment. We hypothesized that (1) the ICBT group would have greater reductions in obsessive beliefs (controlling for change in OCD symptoms) after completing the cognitive intervention, and that (2) this reduction would, in turn, predict greater OCD symptom reduction throughout the rest of the treatment period. Contrary to our expectations, the longitudinal mediation analysis indicated that (1) being randomized to ICBT actually increased the degree of obsessive beliefs after receiving the cognitive intervention at weeks 1-3, and (2) increase in obsessive beliefs predicted better outcome later in treatment. However, when repeating the analysis using cross-sectional data at post-treatment, the results were in line with the initial hypotheses. Results were replicated when the control condition received ICBT. We conclude that, although obsessive beliefs were significantly reduced at post-treatment for the ICBT group, early increase rather than decrease in obsessive beliefs predicted favourable outcome. Copyright (C) 2014 John Wiley & Sons, Ltd.

  • 7.
    Andersson, Erik
    et al.
    Karolinska Institutet.
    Ljotsson, Brjann
    Karolinska Institutet.
    Hedman, Erik
    Karolinska Institutet.
    Mattson, Simon
    Karolinska Institutet.
    Enander, Jesper
    Karolinska Institutet.
    Andersson, Gerhard
    Karolinska Institutet;Linköping University.
    Kaldo, Viktor
    Karolinska Institutet.
    Lindefors, Nils
    Karolinska Institutet.
    Rück, Christian
    Karolinska Institutet.
    Cost-effectiveness of an internet-based booster program for patients with obsessive-compulsive disorder: Results from a randomized controlled trial2015In: Journal of Obsessive-Compulsive and Related Disorders, ISSN 2211-3649, E-ISSN 2211-3657, Vol. 4, p. 14-19Article in journal (Refereed)
    Abstract [en]

    Cognitive behavior therapy (CBT) is an effective treatment for OCD when delivered face-to-face, in group-format and also via the internet. However, despite overall large effect sizes, a considerable amount of the patients relapse. One intervention that has the potential to reduce these relapse rates is booster programs, but if booster program is a cost-effective method of preventing relapse is still unknown. We used health economical data from a recent randomized controlled trial, where patients who had undergone an internet-based CBT were randomly allocated to receive an additional booster program. Assessment points were 4-, 7-, 12- and 24-month. Health economical data were primarily analyzed using a societal perspective. Results showed that the booster program was effective in preventing relapse, and the cost of one avoided relapse was estimated to $1066-1489. Cost-effectiveness acceptability curves showed that the booster program had a 90% probability of being cost-effective given a willingness to pay of $1000-1050 the first year, but this figure grew considerably after two years ($2500-5500). We conclude that internet-based booster programs are probably a cost-effective alternative within one-year time frame and that more treatment may be needed to maintain adequate cost-effectiveness up to two years. (C) 2014 Elsevier Inc. All rights reserved.

  • 8.
    Andersson, Erik
    et al.
    Karolinska Institutet.
    Steneby, S.
    Karolinska Institutet.
    Karlsson, K.
    Karolinska Institutet.
    Ljotsson, Brjann
    Karolinska Institutet.
    Hedman, Erik
    Karolinska Institutet.
    Enander, Jesper
    Karolinska Institutet.
    Kaldo, Viktor
    Karolinska Institutet.
    Andersson, Gerhard
    Karolinska Institutet;Linköping University.
    Lindefors, Nils
    Karolinska Institutet.
    Ruck, Christian
    Karolinska Institutet.
    Long-term efficacy of Internet-based cognitive behavior therapy for obsessive-compulsive disorder with or without booster: a randomized controlled trial2014In: Psychological Medicine, ISSN 0033-2917, E-ISSN 1469-8978, Vol. 44, no 13, p. 2877-2887Article in journal (Refereed)
    Abstract [en]

    Background. As relapse after completed cognitive behavior therapy (CBT) for obsessive-compulsive disorder (OCD) is common, many treatment protocols include booster programs to improve the long-term effects. However, the effects of booster programs are not well studied. In this study, we investigated the long-term efficacy of Internet-based CBT (ICBT) with therapist support for OCD with or without an Internet-based booster program. Method. A total of 101 participants were included in the long-term follow-up analysis of ICBT. Of these, 93 were randomized to a booster program or no booster program. Outcome assessments were collected at 4, 7, 12 and 24 months after receiving ICBT. Results. The entire sample had sustained long-term effects from pre-treatment to all follow-up assessments, with large within-group effect sizes (Cohen's d=1.58-2.09). The booster group had a significant mean reduction in OCD symptoms compared to the control condition from booster baseline (4 months) to 7 months, but not at 12 or 24 months. Participants in the booster group improved significantly in terms of general functioning at 7, 12 and 24 months, and had fewer relapses. Kaplan-Meier analysis also indicated a significantly slower relapse rate in the booster group. Conclusions. The results suggest that ICBT has sustained long-term effects and that adding an Internet-based booster program can further improve long-term outcome and prevent relapse for some OCD patients.

  • 9.
    Andersson, Evelyn
    et al.
    Karolinska Institutet, Sweden;Stockholm County Council, Sweden.
    Crowley, James J.
    Karolinska Institutet, Sweden;Univ N Carolina, USA;Univ N Carolina, USA.
    Lindefors, Nils
    Karolinska Institutet, Sweden;Stockholm County Council, Sweden.
    Ljotsson, Brjann
    Karolinska Institutet, Sweden.
    Hedman-Lagerlöf, Erik
    Karolinska Institutet, Sweden.
    Boberg, Julia
    Karolinska Institutet, Sweden;Stockholm County Council, Sweden.
    El Alaoui, Samir
    Karolinska Institutet, Sweden;Stockholm County Council, Sweden.
    Karlsson, Robert
    Karolinska Institutet, Sweden.
    Lu, Yi
    Karolinska Institutet, Sweden.
    Mattheisen, Manuel
    Karolinska Institutet, Sweden;Stockholm County Council, Sweden;Aarhus Univ, Denmark.
    Kahler, Anna K.
    Karolinska Institutet, Sweden.
    Svanborg, Cecilia
    Karolinska Institutet, Sweden;Stockholm County Council, Sweden.
    Mataix-Cols, David
    Karolinska Institutet, Sweden;Stockholm County Council, Sweden.
    Mattsson, Simon
    Karolinska Institutet, Sweden;Stockholm County Council, Sweden.
    Forsell, Erik
    Karolinska Institutet, Sweden;Stockholm County Council, Sweden.
    Kaldo, Viktor
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology. Karolinska Institutet, Sweden;Stockholm County Council, Sweden.
    Schalling, Martin
    Karolinska Institutet, Sweden;Karolinska University Hospital, Sweden.
    Lavebratt, Catharina
    Karolinska Institutet, Sweden;Karolinska University Hospital, Sweden.
    Sullivan, Patrick F.
    Univ N Carolina, USA;Karolinska Institutet, Sweden.
    Ruck, Christian
    Karolinska Institutet, Sweden;Stockholm County Council, Sweden.
    Genetics of response to cognitive behavior therapy in adults with major depression: a preliminary report2019In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 24, no 4, p. 484-490Article in journal (Refereed)
    Abstract [en]

    Major depressive disorder is heritable and a leading cause of disability. Cognitive behavior therapy is an effective treatment for major depression. By quantifying genetic risk scores based on common genetic variants, the aim of this report was to explore the utility of psychiatric and cognitive trait genetic risk scores, for predicting the response of 894 adults with major depressive disorder to cognitive behavior therapy. The participants were recruited in a psychiatric setting, and the primary outcome score was measured using the Montgomery Asberg Depression Rating Scale-Self Rated. Single-nucleotide polymorphism genotyping arrays were used to calculate the genomic risk scores based on large genetic studies of six phenotypes: major depressive disorder, bipolar disorder, attention-deficit/hyperactivity disorder, autism spectrum disorder, intelligence, and educational attainment. Linear mixed-effect models were used to test the relationships between the six genetic risk scores and cognitive behavior therapy outcome. Our analyses yielded one significant interaction effect (B = 0.09, p < 0.001): the autism spectrum disorder genetic risk score correlated with Montgomery Asberg Depression Rating Scale-Self Rated changes during treatment, and the higher the autism spectrum disorder genetic load, the less the depressive symptoms decreased over time. The genetic risk scores for the other psychiatric and cognitive traits were not related to depressive symptom severity or change over time. Our preliminary results indicated, as expected, that the genomics of the response of patients with major depression to cognitive behavior therapy were complex and that future efforts should aim to maximize sample size and limit subject heterogeneity in order to gain a better understanding of the use of genetic risk factors to predict treatment outcome.

  • 10.
    Bendix, Marie
    et al.
    Umeå University.
    Uvnäs-Moberg, Kerstin
    Swedish University of Agricultural Sciences.
    Petersson, Maria
    Karolinska Institutet.
    Kaldo, Viktor
    Karolinska Institutet.
    Åsberg, Marie
    Karolinska Institutet.
    Jokinen, Jussi
    Umeå University;Karolinska Institutet.
    Insulin and glucagon in plasma and cerebrospinal fluid in suicide attempters and healthy controls2017In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 81, p. 1-7Article in journal (Refereed)
    Abstract [en]

    Mental disorders and related behaviors such as suicidality and violence have been associated to dysregulation of e g carbohydrate metabolism. We hypothesized that patients after suicide attempt, compared to healthy controls, would have higher insulin and lower glucagon levels in plasma and cerebrospinal fluid and that these changes would be associated to violent behavior. Twenty-eight medication-free patients (10 women, 18 men), hospitalized after suicide attempt, and 19 healthy controls (7 women, 12 men) were recruited with the aim to study risk factors for suicidal behavior. Psychological/psychiatric assessment was performed with SCID I and II or the SCID interview for healthy volunteers respectively, the Karolinska Interpersonal Violence Scale (KIVS) for assessment of lifetime violence expression behavior, the Montgomery-Asberg-Depression-Scale (MADRS) and the Comprehensive Psychological Rating Scale (CPRS) for symptomatic assessment of depression and appetite. Fasting levels of insulin and glucagon were measured in plasma (P) and cerebrospinal fluid (CSF). Suicide attempters had higher insulin- and lower glucagon-levels in plasma- and CSF compared to controls. Except for P-glucagon these associations remained significant after adjusting for age and/or BMI. Patients reported significantly more expressed interpersonal violence compared to healthy volunteers. Expressed violence was significantly positively correlated with P- and CSF-insulin and showed a significant negative correlation with P-glucagon in study participants. These findings confirm and extend prior reports that higher insulin and lower glucagon levels in plasma and cerebrospinal fluid are associated with suicidal behavior pointing towards a potential autonomic dysregulation in the control of insulin and glucagon secretion in suicidal patients. (C) 2017 Elsevier Ltd. All rights reserved.

  • 11.
    Bergman Nordgren, Lise
    et al.
    Beteendeterapeutiska föreningen, Sweden.
    Wolf, Li
    Beteendeterapeutiska föreningen, Sweden.
    Gafvelin-Ramberg, Eva
    Svenska föreningen för kognitiva och beteendeterapeutiska terapier, Sweden.
    Kaldo, Viktor
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology.
    Katz, Dan
    Föreningen Vetenskap och folkbildning, Sweden.
    Melin, Lennart
    Uppsala University, Sweden.
    Linton, Steven J.
    Örebro University, Sweden.
    Sundin, Örjan
    Midsweden University, Sweden.
    Öst, Lars-Göran
    Stockholm university, Sweden.
    Polariserad debatt om riktlinjer skymmer viktiga frågor2018In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 115, no 37, p. 1372-1372Article in journal (Other (popular science, discussion, etc.))
    Abstract [sv]

    Debatten om Socialstyrelsens nya riktlinjer för ångest och depression har varit polariserad och inte konstruktiv. Diskussionen bör inte handla om PDT eller KBT utan om evidensbaserade metoder och kompetensbrist.

  • 12.
    Beukes, Eldre W.
    et al.
    Lamar Univ, USA;Anglia Ruskin Univ, UK.
    Baguley, David M.
    Nottingham Biomed Res Ctr, UK;Univ Nottingham, UK;Univ Nottingham Hosp, UK.
    Jacquemin, Laure
    Antwerp Univ Hosp, Belgium;Univ Antwerp, Belgium.
    Lourenco, Matheus P. C. G.
    Maastricht Univ, Netherlands;Catholic University of Leuven, Belgium.
    Allen, Peter M.
    Anglia Ruskin Univ, UK.
    Onozuka, Joy
    Amer Tinnitus Assoc, USA.
    Stockdale, David
    British Tinnitus Assoc, UK.
    Kaldo, Viktor
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology. Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Andersson, Gerhard
    Karolinska Institutet, Sweden;Region Stockholm, Sweden;Linköping University, Sweden.
    Manchaiah, Vinaya
    Lamar Univ, USA;Manipal Univ, India.
    Changes in Tinnitus Experiences During the COVID-19 Pandemic2020In: Frontiers In Public Health, ISSN 2296-2565, Vol. 8, p. 1-13, article id 592878Article in journal (Refereed)
    Abstract [en]

    Introduction: The COVID-19 pandemic has disrupted delivery of healthcare, economic activity, and affected social interactions. Identifying and supporting those most affected by the pandemic is required. The purpose of this study was to determine the impact of the pandemic on individuals with tinnitus and to identify mediating factors. Methods: This is a mixed-methods exploratory cross-sectional study, using data collected via an online survey from 3,103 individuals with tinnitus from 48 countries. The greatest representation was from North America (49%) and Europe (47%) and other countries were only marginally represented. Results: Although the study was aimed at those with pre-existing tinnitus, 7 individuals reported having COVID-19 initiated tinnitus. Having COVID-19 symptoms exacerbated tinnitus in 40% of respondents, made no change in 54%, and improved tinnitus in 6%. Other mediating factors such as the social and emotional consequences of the pandemic made pre-existing tinnitus more bothersome for 32% of the respondents, particularly for females and younger adults, better for 1%, and caused no change to tinnitus for 67%. Pre-existing tinnitus was significantly exacerbated for those self-isolating, experiencing loneliness, sleeping poorly, and with reduced levels of exercise. Increased depression, anxiety, irritability, and financial worries further significantly contributed to tinnitus being more bothersome during the pandemic period. Conclusions: These findings have implications for tinnitus management, because they highlight the diverse response both internal and external factors have on tinnitus levels. Clinical services should be mindful that tinnitus may be caused by contracting COVID-19 and pre-existing tinnitus may be exacerbated, although in the majority of respondents there was no change. Additional support should be offered where tinnitus severity has increased due to the health, social, and/or emotional effects of the COVID-19 pandemic. Tinnitus may be more bothersome for those experiencing loneliness, having fewer social interactions, and who are more anxious or worried.

  • 13.
    Beukes, Eldre W.
    et al.
    Lamar Univ, USA;Anglia Ruskin Univ, UK.
    Baguley, David M.
    Nottingham Biomed Res Ctr, UK;Univ Nottingham, UK;Nottingham Univ Hosp, UK.
    Manchaiah, Vinaya
    Lamar Univ, USA;Manipal Univ, India.
    Andersson, Gerhard
    Linköping University, Sweden;Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Allen, Peter M.
    Anglia Ruskin Univ, UK.
    Kaldo, Viktor
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology. Linköping University, Sweden.
    Jacquemin, Laure
    Antwerp Univ Hosp, Belgium;Univ Antwerp, Belgium.
    Lourenco, Matheus P. C. G.
    Maastricht Univ, Netherlands;Katholieke Univ Leuven, Belgium.
    Onozuka, Joy
    Amer Tinnitus Assoc, USA.
    Stockdale, David
    British Tinnitus Assoc, UK.
    Maidment, David W.
    Loughborough Univ, UK.
    Investigating tinnitus subgroups based on hearing-related difficulties2021In: International journal of clinical practice (Esher), ISSN 1368-5031, E-ISSN 1742-1241, Vol. 75, no 10, article id e14684Article in journal (Refereed)
    Abstract [en]

    Purpose Meaningfully grouping individuals with tinnitus who share a common characteristics (ie, subgrouping, phenotyping) may help tailor interventions to certain tinnitus subgroups and hence reduce outcome variability. The purpose of this study was to test if the presence of tinnitus subgroups are discernible based on hearing-related comorbidities, and to identify predictors of tinnitus severity for each subgroup identified. Methods An exploratory cross-sectional study was used. The study was nested within an online survey distributed worldwide to investigate tinnitus experiences during the COVID-19 pandemic. The main outcome measure was the tinnitus Handicap Inventory- Screening Version. Results From the 3400 respondents, 2980 were eligible adults with tinnitus with an average age of 58 years (SD = 14.7) and 49% (n = 1457) being female. A three-cluster solution identified distinct subgroups, namely, those with tinnitus-only (n = 1306; 44%), those presenting with tinnitus, hyperacusis, hearing loss and/or misophonia (n = 795; 27%), and those with tinnitus and hearing loss (n = 879; 29%). Those with tinnitus and hyperacusis reported the highest tinnitus severity (M = 20.3; SD = 10.5) and those with tinnitus and no hearing loss had the lowest tinnitus severity (M = 15.7; SD = 10.4). Younger age and the presence of mental health problems predicted greater tinnitus severity for all groups (beta <= -0.1, P <= .016). Conclusion Further exploration of these potential subtypes are needed in both further research and clinical practice by initially triaging tinnitus patients prior to their clinical appointments based on the presence of hearing-related comorbidities. Unique management pathways and interventions could be tailored for each tinnitus subgroup.

  • 14.
    Beukes, Eldre W.
    et al.
    Lamar Univ, USA;Anglia Ruskin Univ, UK.
    Lourenco, Matheus P. C. G.
    Maastricht Univ, Netherlands;Catholic University of Leuven, Belgium.
    Biot, Lana
    Univ Antwerp, Belgium.
    Andersson, Gerhard
    Linköping University, Sweden;Karolinska Institutet, Sweden.
    Kaldo, Viktor
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology. Karolinska Institutet, Sweden.
    Manchaiah, Vinaya
    Lamar Univ, USA;Manipal Univ, India.
    Jacquemin, Laure
    Univ Antwerp, Belgium;Antwerp Univ Hosp, Belgium.
    Suggestions for shaping tinnitus service provision in Western Europe: Lessons from the COVID-19 pandemic2021In: International journal of clinical practice (Esher), ISSN 1368-5031, E-ISSN 1742-1241, Vol. 75, no 7, article id e14196Article in journal (Refereed)
    Abstract [en]

    Background Tinnitus severity has been exacerbated because of the COVID-19 pandemic and those with tinnitus require additional support. Such support should be informed by patient preferences and needs. The objective of this study was to gather information from individuals with tinnitus living in Europe to inform stakeholders of the (a) support they needed in relation to changes associated with the COVID-19 pandemic and (b) suggestions regarding tinnitus care for the future. Methods A cross-sectional mixed method study design was used using closed and open-ended questions via an online survey. Data were gathered from 710 adults experiencing tinnitus in Western Europe, with the majority living in The Netherlands, Belgium and Sweden. Data were analysed using qualitative content analysis and descriptive statistics. Results Those with tinnitus indicated the following support needs during the pandemic (a) support for tinnitus, (b) support for hearing-related difficulties, (c) social support and (d) pandemic-related support. Five directions for future tinnitus care were provided, namely, (a) need for understanding professional support and access to multidisciplinary experts, (b) greater range of therapies and resources, (c) access to more information about tinnitus, (d) prioritising tinnitus research and (e) more support for hearing protection and hearing loss prevention. Conclusions The findings point to the need for accessible (remote), patient-centred, suitable and evidence-based tinnitus care. Insights from the current study can be used by various stakeholders including clinical practitioners and tinnitus support services to ensure those with tinnitus have access to the help and support required in order to reduce service provision insufficiencies.

  • 15.
    Beukes, Eldre W
    et al.
    Anglia Ruskin University, UK.
    Vlaescu, George
    Linköping University.
    Manchaiah, Vinaya
    Linköping University;Lamar University, USA;Audiology India, India.
    Baguley, David M
    Anglia Ruskin University, UK;Cambridge University Hospital NHS Foundation Trust, UK.
    Allen, Peter M
    Anglia Ruskin University, UK.
    Kaldo, Viktor
    Karolinska Institutet.
    Andersson, Gerhard
    Linköping University;Karolinska Institutet.
    Development and technical functionality of an Internet-based intervention for tinnitus in the UK2016In: Internet Interventions, ISSN 2214-7829, Vol. 6, p. 6-15Article in journal (Refereed)
    Abstract [en]

    Purpose

    Creative approaches to improve access to evidence-based tinnitus treatments are required. The purpose of this study was to develop an Internet-based cognitive behavioural therapy (iCBT) intervention, for those experiencing tinnitus in the United Kingdom (UK). Furthermore, it aimed, through technical functionality testing, to identify specific aspects of the iCBT that require improving.

    Method

    An innovative iCBT intervention for treating tinnitus in the UK has been developed using a cognitive-behavioural theoretical framework. This iCBT was evaluated by two user groups during this developmental phase. Initially, five expert reviews evaluated the intervention, prior to evaluation by a group of 29 adults experiencing significant levels of tinnitus distress. Both groups evaluated iCBT in an independent measures design, using a specifically designed satisfaction outcome measure.

    Results

    Overall, similar ratings were given by the expert reviewers and adults with tinnitus, showing a high level of satisfaction regarding the content, suitability, presentation, usability and exercises provided in the intervention. The iCBT intervention has been refined following technical functionality testing.

    Conclusions

    Rigorous testing of the developed iCBT intervention has been undertaken. These evaluations provide confidence that further clinical trials can commence in the UK, to assess the feasibility and effectiveness of this iCBT intervention for tinnitus.

  • 16.
    Blom, Kerstin
    et al.
    Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Forsell, Erik
    Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Hellberg, Monica
    Region Stockholm, Sweden.
    Svanborg, Cecilia
    Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Jernelov, Susanna
    Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Kaldo, Viktor
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology. Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Psychological Treatment of Comorbid Insomnia and Depression: A Double-Blind Randomized Placebo-Controlled Trial2024In: Psychotherapy and Psychosomatics, ISSN 0033-3190, E-ISSN 1423-0348Article in journal (Refereed)
    Abstract [en]

    Introduction: Insomnia and depression are highly prevalent disorders and commonly occur together. Cognitive behavioral therapy for insomnia, CBT-I, has been shown to be effective in treating insomnia and also comorbid depression. However, it is unclear whether effects of CBT-I on depression are specific or nonspecific. Also, depressive symptoms often remain too high after CBT-I, indicating a need for improved treatments. The objective was to determine whether combining CBT-I with CBT for depression, without increasing treatment length, reduces both insomnia and depression more than CBT for depression with a placebo insomnia intervention. Methods: A 12-week double-blind randomized controlled trial with a 6-month follow-up in a psychiatric setting using therapist-guided internet-delivered treatments was conducted. Patients (N = 126) were diagnosed with insomnia disorder and major depression by physicians. Primary outcome measures were as follows: self-rating scales Insomnia Severity Index (ISI) and Montgomery-angstrom sberg Depression Rating Scale (MADRS-S). Results: The combined treatment showed specific effects on insomnia severity over the control treatment (p = 0.007) but was not more effective in reducing depression severity. Within-group effects (Cohen's d) at post and at 6 months were as follows: ISI 1.40 and 1.42 (combined treatment), 0.95 and 1.00 (control); MADRS-S 0.97 and 1.12 (combined), 0.88 and 0.89 (control). Conclusions: CBT-I shows large specific effects on insomnia severity and is superior to control in this regard. Both treatments had similar effects on depression severity, i.e., combining CBT-I with CBT for depression did not enhance outcomes on depression compared to control. We suggest CBT-I should always be offered to patients with insomnia and depression comorbidity, possibly as the first-hand choice. Combining it with a psychological treatment for depression could be too burdening and may not be beneficial.

  • 17.
    Blom, Kerstin
    et al.
    Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Hentati Isacsson, Nils
    Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Forsell, Erik
    Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Rosen, Ann
    Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Kraepelien, Martin
    Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Jernelov, Susanna
    Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Kaldo, Viktor
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology. Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    An investigation and replication of sleep-related cognitions, acceptance and behaviours as predictors of short- and long-term outcome in cognitive behavioural therapy for insomnia2021In: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 30, no 5, article id e13376Article in journal (Refereed)
    Abstract [en]

    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.

  • 18.
    Blom, Kerstin
    et al.
    Karolinska Institutet.
    Jernelov, Susanna
    Karolinska Institutet.
    Ruck, Christian
    Karolinska Institutet.
    Lindefors, Nils
    Karolinska Institutet.
    Kaldo, Viktor
    Karolinska Institutet.
    Three-Year Follow-Up Comparing Cognitive Behavioral Therapy for Depression to Cognitive Behavioral Therapy for Insomnia, for Patients With Both Diagnoses2017In: Sleep, ISSN 0161-8105, E-ISSN 1550-9109, Vol. 40, no 8, article id UNSP zsx108Article in journal (Refereed)
    Abstract [en]

    This 3-year follow-up compared insomnia treatment to depression treatment for patients with both diagnoses. Forty-three participants were randomized to either treatment, in the form of Internet-delivered therapist-guided cognitive behavior therapy (CBT), and 37 (86%) participants provided primary outcome data at the 3-year follow-up. After 3 years, reductions on depression severity were similar in both groups (between-group effect size, d = 0.33, p =.45), while the insomnia treatment had superior effects on insomnia severity (d = 0.66, p <.05). Overall, insomnia treatment was thus more beneficial than depression treatment. The implication for practitioners, supported by previous research, is that patients with co-occurring depression and insomnia should be offered CBT for insomnia, in addition to medication or psychological treatment for depression.

  • 19.
    Blom, Kerstin
    et al.
    Karolinska Institutet.
    Jernelov, Susanna
    Karolinska Institutet.
    Ruck, Christian
    Karolinska Institutet.
    Lindefors, Nils
    Karolinska Institutet.
    Kaldo, Viktor
    Karolinska Institutet.
    Three-Year Follow-Up of Insomnia and Hypnotics after Controlled Internet Treatment for Insomnia2016In: Sleep, ISSN 0161-8105, E-ISSN 1550-9109, Vol. 39, no 6, p. 1267-1274, article id PII sp-00663-15Article in journal (Refereed)
    Abstract [en]

    Study Objectives: To investigate the long-term effects of therapist-guided Internet-based insomnia treatment on insomnia severity and sleep medication use, compared with active control. Methods: This study was an 8 week randomized controlled trial with follow-up posttreatment and at 6, 12, and 36 months, set at the Internet Psychiatry Clinic, Stockholm, Sweden. Participants were 148 media-recruited nondepressed adults with insomnia. Interventions were Guided Internet-based cognitive behavioral therapy for insomnia (ICBT-i) or active control treatment (ICBT-ctrl). Primary outcome was insomnia severity, measured with the Insomnia Severity Index. Secondary outcomes were sleep medication use and use of other treatments. Results: The large pretreatment to posttreatment improvements in insomnia severity of the ICBT-i group were maintained during follow-up. ICBT-ctrl exhibited significantly less improvement posttreatment (between-Cohen d = 0.85), but after 12 and 36 months, there was no longer a significant difference. The within-group effect sizes from pretreatment to the 36-months follow-up were 1.6 (ICBT-i) and 1.7 (ICBT-ctrl), and 74% of the interviewed participants no longer had insomnia diagnosis after 36 mo. ICBT-ctrl used significantly more sleep medication (P = 0.017) and underwent significantly more other insomnia treatments (P < 0.001) during the follow-up period. Conclusions: The large improvements in the ICBT-i group were maintained after 36 months, corroborating that CBT for insomnia has long-term effects. After 36 months, the groups did not differ in insomnia severity, but ICBT-ctrl had used more sleep medication and undergone more other additional insomnia treatments during the follow-up period.

  • 20.
    Blom, Kerstin
    et al.
    Karolinska Institutet.
    Jernelöv, Susanna
    Karolinska Institutet.
    Lindefors, Nils
    Karolinska Institutet.
    Kaldo, Viktor
    Karolinska Institutet.
    Facilitating and hindering factors in Internet-delivered treatment for insomnia and depression2016In: Internet Interventions, ISSN 2214-7829, Vol. 4, p. 51-60Article in journal (Refereed)
    Abstract [en]

    Insomnia and depression is a common and debilitating comorbidity, and treatment is usually given mainly for depression. Guided Internet-based cognitive behavioral therapy for insomnia (ICBT-i) was, in a recent study on which this report is based, found superior to a treatment for depression (ICBT-d) for this patient group, but many patients did not reach remission.

  • 21.
    Blom, Kerstin
    et al.
    Karolinska Institutet.
    Jerneov, Susanna
    Karolinska Institutet.
    Kraepelien, Martin
    Karolinska Institutet.
    Bergdahl, Malin Olseni
    Karolinska Institutet.
    Jungmarker, Kristina
    Karolinska Institutet.
    Ankartjärn, Linda
    Karolinska Institutet.
    Lindefors, Nils
    Karolinska Institutet.
    Kaldo, Viktor
    Karolinska Institutet.
    Internet Treatment Addressing either Insomnia or Depression, for Patients with both Diagnoses: A Randomized Trial2015In: Sleep, ISSN 0161-8105, E-ISSN 1550-9109, Vol. 38, no 2, p. 267-277Article in journal (Refereed)
    Abstract [en]

    Study Objectives: To compare treatment effects when patients with insomnia and depression receive treatment for either insomnia or depression. Design: A 9-w randomized controlled trial with 6- and 12-mo follow-up. Setting: Internet Psychiatry Clinic, Stockholm, Sweden. Participants: Forty-three adults in whom comorbid insomnia and depression were diagnosed, recruited via media and assessed by psychiatrists. Interventions: Guided Internet-delivered cognitive behavior therapy (ICBT) for either insomnia or depression. Measurements and Results: Primary outcome measures were symptom self-rating scales (Insomnia Severity Index [ISI] and the Montgomery Asberg Depression Rating Scale [MADRS-S]), assessed before and after treatment with follow-up after 6 and 12 mo. The participants' use of sleep medication and need for further treatment after completion of ICBT was also investigated. The insomnia treatment was more effective than the depression treatment in reducing insomnia severity during treatment (P = 0.05), and equally effective in reducing depression severity. Group differences in insomnia severity were maintained during the 12-mo follow-up period. Post treatment, participants receiving treatment for insomnia had significantly less self-rated need for further insomnia treatment (P < 0.001) and used less sleep medication (P < 0.05) than participants receiving treatment for depression. The need for depression treatment was similar in both groups. Conclusions: In this study, Internet-delivered treatment with cognitive behavior therapy (ICBT) for insomnia was more effective than ICBT for depression for patients with both diagnoses. This indicates, in line with previous research, that insomnia when comorbid with depression is not merely a symptom of depression, but needs specific treatment.

  • 22.
    Blom, Kerstin
    et al.
    Karolinska Institutet.
    Tillgren, Hanna Tarkian
    Linköping University.
    Wiklund, Tobias
    Dept PaLinköping University.
    Danlycke, Ewa
    Linköping University.
    Forssen, Mattias
    Linköping University.
    Söderström, Alexandra
    Linköping University.
    Johansson, Robert
    Linköping University.
    Hesser, Hugo
    Linköping University.
    Jernelov, Susanna
    Karolinska Institutet.
    Lindefors, Nils
    Karolinska Institutet.
    Andersson, Gerhard
    Karolinska Institutet;Linköping University.
    Kaldo, Viktor
    Karolinska Institutet.
    Internet-vs. group-delivered cognitive behavior therapy for insomnia: A randomized controlled non-inferiority trial2015In: Behaviour Research and Therapy, ISSN 0005-7967, E-ISSN 1873-622X, Vol. 70, p. 47-55Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to compare guided Internet-delivered to group-delivered cognitive behavioral therapy (CBT) for insomnia. We conducted an 8-week randomized controlled non-inferiority trial with 6-months follow-up. Participants were forty-eight adults with insomnia, recruited via media. Interventions were guided Internet-delivered CBT (ICBT) and group-delivered CBT (GCBT) for insomnia. Primary outcome measure was the Insomnia Severity Index (ISI), secondary outcome measures were sleep diary data, depressive symptoms, response- and remission rates. Both treatment groups showed significant improvements and large effect sizes for ISI (Within Cohen's d: ICBT post = 1.8, 6-months follow-up = 2.1; GCBT post = 2.1, 6-months follow-up = 2.2). Confidence interval of the difference between groups posttreatment and at FU6 indicated non-inferiority of ICBT compared to GCBT. At post-treatment, two thirds of patients in both groups were considered responders (ISI-reduction > 7p). Using diagnostic criteria, 63% (ICBT) and 75% (GCBT) were in remission. Sleep diary data showed moderate to large effect sizes. We conclude that both guided Internet-CBT and group-CBT in this study were efficacious with regard to insomnia severity, sleep parameters and depressive symptoms. The results are in line with previous research, and strengthen the evidence for guided Internet-CBT for insomnia. Trial registration: The study protocol was approved by, and registered with, the regional ethics review board in Linkoping, Sweden, registration number 2010/385-31. (C) 2015 The Authors. Published by Elsevier Ltd.

  • 23.
    Boberg, Julia
    et al.
    Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Kaldo, Viktor
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology. Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Mataix-Cols, David
    Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Crowley, James J.
    Karolinska Institutet, Sweden;Region Stockholm, Sweden;Univ N Carolina, USA.
    Roelstraete, Bjorn
    Karolinska Institutet, Sweden.
    Halvorsen, Matthew
    Univ N Carolina, USA.
    Forsell, Erik
    Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Isacsson, Nils H.
    Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Sullivan, Patrick F.
    Univ N Carolina, USA;Karolinska Institutet, Sweden.
    Svanborg, Cecilia
    Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Andersson, Evelyn H.
    Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Lindefors, Nils
    Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Kravchenko, Olly
    Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Mattheisen, Manuel
    Karolinska Institutet, Sweden;Region Stockholm, Sweden;Aarhus Univ, Denmark.
    Danielsdottir, Hilda B.
    Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Ivanova, Ekaterina
    Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Boman, Magnus
    Karolinska Institutet, Sweden;KTH Royal instute of technology, Sweden.
    de la Cruz, Lorena Fernandez
    Karolinska institutet, Sweden;Region Stockholm, Sweden.
    Wallert, John
    Karolinska institutet, Sweden;Region Stockholm, Sweden.
    Ruck, Christian
    Karolinska institutet, Sweden;Region Stockholm, Sweden.
    Swedish multimodal cohort of patients with anxiety or depression treated with internet-delivered psychotherapy (MULTI-PSYCH)2023In: BMJ Open, E-ISSN 2044-6055, Vol. 13, no 10, article id e069427Article in journal (Refereed)
    Abstract [en]

    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.

  • 24.
    Boman, Magnus
    et al.
    KTH Royal institute of Technology, Sweden.
    Ben Abdesslem, Fehmi
    RISE, Sweden.
    Forsell, Erik
    Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Gillblad, Daniel
    RISE, Sweden.
    Görnerup, Olof
    RISE, Sweden.
    Isacsson, Nils
    Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Sahlgren, Magnus
    RISE, Sweden.
    Kaldo, Viktor
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology. Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Learning machines in Internet-delivered psychological treatment2019In: Progress in Artificial Intelligence, ISSN 2192-6352, Vol. 8, no 4, p. 475-485Article in journal (Refereed)
    Abstract [en]

    A learning machine, in the form of a gating network that governs a finite number of different machine learning methods, is described at the conceptual level with examples of concrete prediction subtasks. A historical data set with data from over 5000 patients in Internet-based psychological treatment will be used to equip healthcare staff with decision support for questions pertaining to ongoing and future cases in clinical care for depression, social anxiety, and panic disorder. The organizational knowledge graph is used to inform the weight adjustment of the gating network and for routing subtasks to the different methods employed locally for prediction. The result is an operational model for assisting therapists in their clinical work, about to be subjected to validation in a clinical trial.

  • 25.
    Bondesson, Elisabeth
    et al.
    Lund University, Sweden;Skåne University Hospital, Sweden.
    Joud, Anna
    Lund University, Sweden;Skåne University Hospital, Sweden.
    Stigmar, Kjerstin
    Lund University, Sweden.
    Ringqvist, Asa
    Skåne University Hospital, Sweden.
    Kraepelien, Martin
    Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Kaldo, Viktor
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology. Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Wettermark, Björn
    Uppsala University, Sweden.
    Forsell, Yvonne
    Karolinska Institutet, Sweden.
    Petersson, Ingemar F.
    Lund University, Sweden;Skåne University Hospital, Sweden.
    Schelin, Maria E. C.
    Skåne University Hospital, Sweden;Lund University, Sweden.
    Utilization of healthcare and prescription medicines after non-pharmacological interventions for depression - A 3-year register follow-up of an RCT in primary care2022In: Preventive Medicine Reports, E-ISSN 2211-3355, Vol. 25, article id 101658Article in journal (Refereed)
    Abstract [en]

    Depression is a common, recurrent disorder. There is a need for readily available treatments with few negative side effects, that demands little resources and that are effective both in the short- and long term. Our aim was to investigate the long-term effectiveness of two different interventions; physical exercise and internet-based cognitive behavioural therapy (internet-CBT), compared to usual care in patients with mild to moderate depression in a Swedish primary care setting. We performed a register-based 3-year follow-up study of participants in the randomized controlled trial REGASSA (n = 940) using healthcare utilization and dispensed medicines as outcomes. We found no difference between the three groups regarding proportion of participants consulting healthcare due to mental illness or pain during follow-up. Regarding number of consultations, there was no difference between the groups, except for consultations related to pain. For this outcome both treatment arms had significantly fewer consultations compared to usual care, during year 2-3, the risk ratio (RR) for physical exercise and internet-CBT was 0.64 (95% CI = 0.43-0.95) and 0.61 (95% CI = 0.41-0.90), respectively. A significantly lower proportion of patients in both treatment arms were dispensed hypnotics and sedatives year 2-3 compared to the usual care arm, RR for both physical exercise and internet-CBT was 0.72 (95% CI = 0.53-0.98). No other differences between the groups were found. In conclusion, considering long-term effects, both physical exercise and internet-CBT, being resource-efficient treatments, could be considered as appropriate additions for patients with mild to moderate depression in primary care settings.

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  • 26.
    Bothelius, Kristoffer
    et al.
    Uppsala University.
    Jernelov, Susanna
    Karolinska Institutet.
    Fredrikson, Mats
    Uppsala University.
    McCracken, Lance M.
    Kings Coll London, UK.
    Kaldo, Viktor
    Karolinska Institutet.
    Measuring Acceptance of Sleep Difficulties: The Development of the Sleep Problem Acceptance Questionnaire2015In: Sleep, ISSN 0161-8105, E-ISSN 1550-9109, Vol. 38, no 11, p. 1815-1822Article in journal (Refereed)
    Abstract [en]

    Study Objectives: Acceptance may be an important therapeutic process in sleep medicine, but valid psychometric instruments measuring acceptance related to sleep difficulties are lacking. The purpose of this study was to develop a measure of acceptance in insomnia, and to examine its factor structure as well as construct validity. Design: In a cross-sectional design, a principal component analysis for item reduction was conducted on a first sample (A) and a confirmatory factor analysis on a second sample (B). Construct validity was tested on a combined sample (C). Setting: Questionnaire items were derived from a measure of acceptance in chronic pain, and data were gathered through screening or available from pretreatment assessments in four insomnia treatment trials, administered online, via bibliotherapy and in primary care. Participants: Adults with insomnia: 372 in sample A and 215 in sample B. Sample C (n = 820) included sample A and B with another 233 participants added. Measures: Construct validity was assessed through relations with established acceptance and sleep scales. Results: The principal component analysis presented a two-factor solution with eight items, explaining 65.9% of the total variance. The confirmatory factor analysis supported the solution. Acceptance of sleep problems was more closely related to subjective symptoms and consequences of insomnia than to diary description of sleep, or to acceptance of general private events. Conclusions: The Sleep Problem Acceptance Questionnaire (SPAQ), containing the subscales "Activity Engagement" and "Willingness", is a valid tool to assess acceptance of insomnia.

  • 27.
    Bratt, Anna S.
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology.
    Johansson, Maude
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology.
    Holmberg, Mats
    Linnaeus University, Faculty of Health and Life Sciences, Department of Health and Caring Sciences. Uppsala University, Sweden;Mälardalen University, Sweden.
    Fagerström, Cecilia
    Linnaeus University, Faculty of Health and Life Sciences, Department of Health and Caring Sciences. Linnaeus University, Linnaeus Knowledge Environments, Sustainable Health. Region Kalmar County, Sweden.
    Elmqvist, Carina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Health and Caring Sciences. Region Kronoberg, Sweden.
    Rusner, Marie
    Region Västra Götaland, Sweden;University of Gothenburg, Sweden.
    Kaldo, Viktor
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology. Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    An internet-based compassion course for healthcare professionals: Rationale and protocol for a randomised controlled trial2022In: Internet Interventions, ISSN 2214-7829, Vol. 28, article id 100463Article in journal (Refereed)
    Abstract [en]

    Background: Severe stress is one of the most common causes of sick leave in Sweden. Previous research hasshown that compassion interventions for healthcare professionals can decrease work-related stress through theintroduction of self-care, self-awareness, and emotion regulation abilities when experiencing difficult situations.Internet-based stress management interventions have hitherto shown promising results in reducing stress.However, further research is needed to examine the effectiveness of internet-based compassion interventions forhealthcare professionals.Objective: In the present study protocol, a randomised controlled trial is described, aiming to examine the effectsof an internet-based compassion course for healthcare professionals on work-related stress and stress ofconscience.Method: Healthcare professionals will be offered an internet-based stress management course of five modulesacross a period of five weeks. The design is a randomised controlled study consisting of three groups enrolled inone of the following: a compassion course (n = 120), a cognitive behavioural stress management course (n =120), or placed on a waitlist followed by either the compassion course or the cognitive behavioural stressmanagement course (n = 36). We hypothesise that the internet-based compassion course would reduce theparticipants’ stress of conscience to a greater degree compared to the other two groups. The secondary hypothesisis that the compassion course would increase the participants’ professional quality of life (i.e., higher jobsatisfaction and lower empathy fatigue) and self-compassion. In addition, the internet-based compassion courseis expected to reduce the participants’ work-related stress and sick leave rates to the same degree (non-inferiority)as the cognitive behavioural stress management course and to a higher degree when compared to thewaitlist condition. The primary outcome measure is the Stress of Conscience Questionnaire (SCQ) and the secondaryoutcome measures are the Professional Quality of Life Scale (PROQOL), the Work-related StressCopenhagen Psychosocial Questionnaire (COPSOQ), and the Self-compassion Scale (SCS). Assessments will beperformed at baseline, four weekly assessments during treatment, post-treatment (5 weeks), and follow-ups at 10weeks, 15 weeks, and 6 months. The repeated measures data will be analysed using a generalised estimatingequation for repeated measurements to examine whether changes over time differ between the groups andwhether the improvements persist over time.Discussion: The clinical trial is expected to provide novel data on the effects of compassion interventions and addto the existing knowledge of internet-based interventions for stress management in healthcare professionals.

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  • 28.
    Cassel, Maria
    et al.
    Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Blom, Kerstin
    Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Gatzacis, Jannis
    Region Stockholm, Sweden.
    Renblad, Peter
    Region Stockholm, Sweden.
    Kaldo, Viktor
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology. Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Jernelov, Susanna
    Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Clinical feasibility of cognitive behavioural therapy for insomnia in a real-world mixed sample at a specialized psychiatric outpatient clinic2022In: BMC Psychiatry, E-ISSN 1471-244X, Vol. 22, no 1, article id 600Article in journal (Refereed)
    Abstract [en]

    Background: A majority of psychiatric patients suffer from insomnia or insomnia-like problems. In addition to impairing quality of life, sleep problems can worsen psychiatric conditions, such as depression and anxiety, and can make treatment of various psychiatric conditions less successful. Several international guidelines recommend cognitive behavioural therapy for insomnia (CBT-I) as first line treatment. However, patients in psychiatric care are rarely offered this treatment, and there is a lack of studies evaluating the treatment in regular psychiatric settings. In this pilot study, we aimed to determine the clinical feasibility of a group-based CBT-I intervention in an outpatient clinical setting for patients with depression, bipolar disorder, anxiety disorders and PTSD. We also aimed to investigate if symptoms of insomnia, depression and anxiety changed after CBT-I. Methods: Seventeen patients at an out-patient psychiatric clinic for mixed psychiatric problems of anxiety, affective disorders and PTSD, were enrolled in a six-week long group-based CBT-I intervention. Primary outcomes were pre-defined aspects of treatment feasibility. Secondary outcomes were changes in self-reported symptoms of insomnia severity, depression, and anxiety between pre - and post intervention. Assessment of insomnia severity was also performed 3 months after treatment. Feasibility data is reported descriptively, changes in continuous data from preto post-treatment were analysed with dependent t-tests. Results: All feasibility criteria were met; there were enough patients to sustain at least one group per semester (e.g., minimum 8), 88% of included patients attended the first session, mean of attended sessions was 4.9 of 6, and dropout rate was 5.9%. Therapists, recruited from clinical staff, found the treatment manual credible, and possible to use at the clinic. Symptoms of insomnia decreased after treatment, as well as symptoms of depression and anxiety. Conclusion: CBT-I could prove as a clinically feasible treatment option for insomnia in a psychiatric outpatient setting.

  • 29.
    d'Onofrio, Paolo
    et al.
    Stockholm University, Sweden.
    Jernelov, Susanna
    Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Rosen, Ann
    Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Blom, Kerstin
    Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Kaldo, Viktor
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology. Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Schwarz, Johanna
    Stockholm University, Sweden;Karolinska Institutet, Sweden.
    Åkerstedt, Torbjörn
    Stockholm University, Sweden;Karolinska Institutet, Sweden.
    The Polysomnographical Meaning of Changed Sleep Quality - A Study of Treatment with Reduced Time in Bed2023In: Brain Sciences, ISSN 2076-3425, E-ISSN 2076-3425, Vol. 13, no 10, article id 1426Article in journal (Refereed)
    Abstract [en]

    Background: Reports of poor sleep are widespread, but their link with objective sleep (polysomnography-PSG) is weak in cross-sectional studies. In contrast, the purpose of this study was to investigate the association between changes in subjective and objective sleep variables using data from a study of the reduction in time in bed (TIB). Methods: One sleep recording was carried out at baseline and one at treatment week 5 (end of treatment) (N = 34). Results: The Karolinska Sleep Quality Index improved and was correlated with improvement in sleep efficiency (r = 0.41, p < 0.05) and reduction in TIB (r = -0.47, p < 0.01) and sleep latency (r = 0.36, p < 0.05). The restorative sleep index showed similar results. Improvements in the insomnia severity index (ISI) essentially lacked correlations with changes in the PSG variables. It was suggested that the latter may be due to the ISI representing a week of subjective sleep experience, of which a single PSG night may not be representative. Conclusions: It was concluded that changes in the subjective ratings of sleep are relatively well associated with changes in the PSG-based sleep continuity variables when both describe the same sleep.

  • 30.
    Eek, Niels
    et al.
    University of Gothenburg, Sweden.
    Sundström, Christopher
    Karolinska Institutet, Sweden;Region Stockholm, Sweden;Uppsala University, Sweden.
    Kraepelien, Martin
    Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Lundgren, Jesper
    University of Gothenburg, Sweden.
    Kaldo, Viktor
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology. Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Berman, Anne H.
    Uppsala University, Sweden.
    High- versus low-intensity internet interventions for alcohol use disorders (AUD): A two-year follow-up of a single-blind randomized controlled trial2023In: Internet Interventions, ISSN 2214-7829, Vol. 33, article id 100630Article in journal (Refereed)
    Abstract [en]

    Alcohol Use Disorders (AUD) are widespread and have serious consequences, but are among the most undertreated mental disorders. Internet interventions have been found effective in treating AUD, but we know little about long-term outcomes, two years or more after treatment. This study explored 12- and 24-month outcomes in alcohol consumption following initial 6-month improvements after a therapist-guided high-intensity internet intervention and an unguided low-intensity internet intervention among individuals with alcohol use disorder. Between-group comparisons were analyzed, as well as within-group comparisons with (1) pre-treatment measurements (2) post-treatment measurements. Participants consisted of a general population sample of internet help-seekers in Sweden. A total of 143 adults (47% men) with a score of 14 (women)/16 (men) or more on the Alcohol Use Disorders Identification Test, alcohol consumption of 11 (women)/14 (men) or more standard drinks the preceding week and & GE; 2 DSM-5 alcohol use disorder (AUD) criteria based on a diagnostic interview were included. The high- and low-intensity internet interventions (n = 72 and n = 71 respectively) consisted of modules based on relapse prevention and cognitive-behavioral therapy. The primary outcome was self-reported alcohol consumption in the preceding week measured as (1) number of standard drinks and (2) number of heavy drinking days. Attrition from self-reported questionnaires was 36% at the 12-month follow-up and 53% at the 24month follow-up. No significant between-group differences occurred in outcomes at either long-term follow-up. Regarding within-group differences, compared to pre-treatment, alcohol consumption was lower in both highand low-intensity interventions at both long-term follow-ups [within-group standard drinks effect sizes varied between g = 0.38-1.04 and heavy drinking days effect sizes varied between g = 0.65-0.94]. Compared to posttreatment, within-group alcohol consumption in the high intensity intervention increased at both follow-ups; for the low-intensity intervention, within-group consumption decreased at 12-month follow-up, but did not differ compared to post-treatment at 24 months. Both high- and low-intensity internet interventions for AUD were thus associated with overall reductions in alcohol consumption at long term follow-ups, with no significant differences between the two. However, conclusions are hampered by differential and non-differential attrition.

  • 31.
    El Alaoui, Samir
    et al.
    Karolinska Institutet.
    Hedman, Erik
    Karolinska Institutet.
    Kaldo, Viktor
    Karolinska Institutet.
    Hesser, Hugo
    Linköping University.
    Kraepelien, Martin
    Karolinska Institutet.
    Andersson, Evelyn
    Karolinska Institutet.
    Ruck, Christian
    Karolinska Institutet.
    Andersson, Gerhard
    Karolinska Institutet;Linköping University.
    Ljotsson, Brjann
    Karolinska Institutet.
    Lindefors, Nils
    Karolinska Institutet.
    Effectiveness of Internet-Based Cognitive-Behavior Therapy for Social Anxiety Disorder in Clinical Psychiatry2015In: Journal of Consulting and Clinical Psychology, ISSN 0022-006X, E-ISSN 1939-2117, Vol. 83, no 5, p. 902-914Article in journal (Refereed)
    Abstract [en]

    Objective: Internet-based cognitive-behavioral therapy (ICBT) has received increased attention as an innovative approach to improve access to evidence-based psychological treatments. Although the efficacy of ICBT for social anxiety disorder has been established in several studies, there is limited knowledge of its effectiveness and application in clinical psychiatric care. The purpose of this study was to evaluate the effectiveness of ICBT in the treatment of social anxiety disorder and to determine the significance of patient adherence and the clinic's years of experience in delivering ICBT. Method: A longitudinal cohort study was conducted using latent growth curve modeling of patients (N = 654) treated with ICBT at an outpatient psychiatric clinic between 2009 and 2013. The primary outcome measure was the Liebowitz Social Anxiety Scale-Self-Rated. Results: Significant reductions in symptoms of social anxiety were observed after treatment (effect size d = 0.86, 99% CI [0.74, 0.98]). Improvements were sustained at 6-month follow-up (d = 1.15, 99% CI [0.99, 1.32]). Patient adherence had a positive effect on the rate of improvement. A positive association between the clinic's years of experience with ICBT and treatment outcome was also observed. Conclusions: This study suggests that ICBT for social anxiety disorder is effective when delivered within the context of a unit specialized in Internet-based psychiatric care and may be considered as a treatment alternative for implementation within the mental health care system.

  • 32.
    El Alaoui, Samir
    et al.
    Karolinska Institutet.
    Ljotsson, Brjann
    Karolinska Institutet.
    Hedman, Erik
    Karolinska Institutet.
    Kaldo, Viktor
    Karolinska Institutet.
    Andersson, Evelyn
    Karolinska Institutet.
    Rück, Christian
    Karolinska Institutet.
    Andersson, Gerhard
    Karolinska Institutet;Linköping University.
    Lindefors, Nils
    Karolinska Institutet.
    Predictors of Symptomatic Change and Adherence in Internet-Based Cognitive Behaviour Therapy for Social Anxiety Disorder in Routine Psychiatric Care2015In: PLOS ONE, E-ISSN 1932-6203, Vol. 10, no 4, article id e0124258Article in journal (Refereed)
    Abstract [en]

    Objective A central goal of health care is to improve patient outcomes. Although several studies have demonstrated the effectiveness of therapist guided internet-based cognitive behaviour therapy (ICBT) for social anxiety disorder (SAD), a significant proportion of patients do not respond to treatment. Consequently, the aim of this study was to identify individual characteristics and treatment program related factors that could help clinicians predict treatment outcomes and adherence for individuals with SAD. Method The sample comprised longitudinal data collected during a 4-year period of adult individuals (N = 764) treated for SAD at a public service psychiatric clinic. Weekly self-rated Liebowitz Social Anxiety Scale (LSAS-SR) scores were provided. Rates of symptomatic change during treatment and adherence levels were analysed using multilevel modelling. The following domains of prognostic variables were examined: (a) socio-demographic variables; (b) clinical characteristics; (c) family history of mental illness; and (d) treatment-related factors. Results Higher treatment credibility and adherence predicted a faster rate of improvement during treatment, whereas higher overall functioning level evidenced a slower rate of improvement. Treatment credibility was the strongest predictor of greater adherence. Having a family history of SAD-like symptoms was also associated with greater adherence, whereas Attention-Deficit/Hyperactivity Disorder (ADHD)-like symptoms, male gender, and family history of minor depression predicted lower adherence. Also, the amount of therapist time spent per treatment module was negatively associated with adherence. Conclusions Results from a large clinical sample indicate that the credibility of ICBT is the strongest prognostic factor explaining individual differences in both adherence level and symptomatic improvement. Early screening of ADHD-like symptoms may help clinicians identify patients who might need extra support or an adjusted treatment. Therapist behaviours that promote adherence may be important for treatment response, although more research is needed in order to determine what type of support would be most beneficial.

  • 33.
    El Alaoui, Samir
    et al.
    Karolinska Institutet.
    Ljotsson, Brjann
    Karolinska Institutet.
    Hedman, Erik
    Karolinska Institutet.
    Svanborg, Cecilia
    Karolinska Institutet.
    Kaldo, Viktor
    Karolinska Institutet.
    Lindefors, Nils
    Karolinska Institutet.
    Predicting Outcome in Internet-Based Cognitive Behaviour Therapy for Major Depression: A Large Cohort Study of Adult Patients in Routine Psychiatric Care2016In: PLOS ONE, E-ISSN 1932-6203, Vol. 11, no 9, article id e0161191Article in journal (Refereed)
    Abstract [en]

    Background Although the effectiveness of therapist-guided internet-based cognitive behaviour therapy (ICBT) for treating depression has been well documented, knowledge of outcome predictors and risk factors associated with lower treatment response is limited, especially when the treatment has been conducted within a naturalistic clinical setting. Identification of such factors is important for clinicians when making treatment recommendations. Methods Data from a large cohort (N = 1738) of adult outpatients having been treated with ICBT for depression at an outpatient psychiatric clinic were analysed. A multilevel modelling approach was used to identify patient and treatment variables associated with the speed of recovery during treatment using weekly measurements of the Montgomery Asberg Depression Rating Scale Self-Rated (MADRS-S). Outcomes Adhering to the treatment, perceiving it as credible and working full-time emerged as predictors of a faster pace of recovery and were also associated with a lower level of depression at the end of treatment. Higher pre-treatment depression and sleep problems were associated with a greater improvement rate, but predicted higher depression after treatment. Having a history of psychotropic medication was associated with both slower improvement and higher post-treatment depression. Conclusion Perceived credibility of ICBT is a strong predictor of treatment response. Assessing patient beliefs and expectations may be a useful aid for clinicians when identifying those who are more or less likely to benefit from ICBT. Helping patients improve expectations prior to treatment may be an important goal for clinicians during the initial assessment phase.

  • 34.
    Farnsworth von Cederwald, Anneli
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology.
    Lilja, Josefine L.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology. University of Gothenburg, Sweden;Region Västra Götaland, Sweden.
    Isacsson, Nils Hentati
    Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Kaldo, Viktor
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology. Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Primary Care Behavioral Health in Sweden - a protocol of a cluster randomized trial evaluating outcomes related to implementation, organization, and patients (KAIROS)2023In: BMC Health Services Research, E-ISSN 1472-6963, Vol. 23, no 1, article id 1188Article in journal (Refereed)
    Abstract [en]

    BackgroundProviding 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.MethodsThis 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.DiscussionA 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 registrationClinicalTrials.gov: NCT05335382. Retrospectively registered on March 13th, 2022.

  • 35.
    Forsell, Erik
    et al.
    Karolinska Institutet.
    Bendix, Marie
    Umeå University.
    Holländare, Fredrik
    Örebro University.
    von Schultz, Barbara Szymanska
    Karolinska University Hospital.
    Nasiell, Josefine
    Karolinska Institutet.
    Blomdahl-Wetterholm, Margareta
    Stockholms Läns Sjuvårdsområde SLSO.
    Eriksson, Caroline
    Uppsala University.
    Kvarned, Sara
    Uppsala University.
    van der Linden, Johanna Lindau
    Uppsala University.
    Söderberg, Elin
    Uppsala University.
    Jokinen, Jussi
    Karolinska Institutet;Umeå University.
    Wide, Katarina
    Karolinska Institutet.
    Kaldo, Viktor
    Karolinska Institutet.
    Internet delivered cognitive behavior therapy for antenatal depression: A randomised controlled trial2017In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 221, p. 56-64Article in journal (Refereed)
    Abstract [en]

    Major depression occurs in 5-10% of pregnancies and is associated with many negative effects for mother and child, yet treatment options are scarce. To our knowledge, this is the first published randomised controlled trial on Internet delivered Cognitive Behavior Therapy (ICBT) for this group. Objective: To test the efficacy of a pregnancy adapted version of an existing 10-week ICBT-program for depression as well as assessing acceptability and adherence Design: Randomised controlled trial. Setting: Online and telephone. Population or sample: Self-referred pregnant women (gestational week 10-28 at intake) currently suffering from major depressive disorder. Methods: 42 pregnant women (gestational week 12-28) with major depression were randomised to either treatment as usual (TAU) provided at their antenatal clinic or to ICBT as an add-on to usual care. Main outcome measures: The primary outcome was depressive symptoms measured with the Montgomery-Asberg depression rating scale-self report (MADRS-S). The Edinburgh Postnatal Depression Scale and measures of anxiety and sleep were used. Credibility, satisfaction, adherence and utilization were also assessed. Results: The ICBT group had significantly lower levels of depressive symptoms post treatment (p < 0.001, Hedges g = 1.21) and were more likely to be responders (i.e. achieve a statistically reliable improvement) (RR = 0.36; p = 0.004). Measures of treatment credibility, satisfaction, utilization, and adherence were comparable to implemented ICBT for depression. Limitations: Small sample size and no long-term evaluation. Conclusion: Pregnancy adapted ICBT for antenatal depression is feasible, acceptable and efficacious. These results need to be replicated in larger trials to validate these promising findings.

  • 36.
    Forsell, Erik
    et al.
    Karolinska Institutet, Sweden;Stockholm County Council, Sweden.
    Isacsson, Nils
    Karolinska Institutet, Sweden;Stockholm County Council, Sweden.
    Blom, Kerstin
    Karolinska Institutet, Sweden;Stockholm County Council, Sweden.
    Jernelov, Susanna
    Karolinska Institutet, Sweden;Stockholm County Council, Sweden.
    Ben Abdesslem, Fehmi
    RISE, Sweden.
    Lindefors, Nils
    Karolinska Institutet, Sweden;Stockholm County Council, Sweden.
    Boman, Magnus
    KTH Royal institute of technology, Sweden.
    Kaldo, Viktor
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology. Karolinska Institutet, Sweden;Stockholm County Council, Sweden.
    Predicting Treatment Failure in Regular Care Internet-Delivered Cognitive Behavior Therapy for Depression and Anxiety Using Only Weekly Symptom Measures2020In: Journal of Consulting and Clinical Psychology, ISSN 0022-006X, E-ISSN 1939-2117, Vol. 88, no 4, p. 311-321Article in journal (Refereed)
    Abstract [en]

    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.

  • 37.
    Forsell, Erik
    et al.
    Karolinska Institutet, Sweden;Stockholm County Council, Sweden.
    Jernelov, Susanna
    Karolinska Institutet, Sweden;Stockholm County Council, Sweden.
    Blom, Kerstin
    Karolinska Institutet, Sweden;Stockholm County Council, Sweden.
    Kaldo, Viktor
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology. Karolinska Institutet, Sweden;Stockholm County Council, Sweden.
    Clinically sufficient classification accuracy and key predictors of treatment failure in a randomized controlled trial of Internet-delivered Cognitive Behavior Therapy for Insomnia2022In: Internet Interventions, ISSN 2214-7829, Vol. 29, article id 100554Article in journal (Refereed)
    Abstract [en]

    Background: In Adaptive Treatment Strategies, each patient's outcome is predicted early in treatment, and treatment is adapted for those at risk of failure. It is unclear what minimum accuracy is needed for a classifier to be clinically useful. This study aimed to establish a empirically supported benchmark accuracy for an Adaptive Treatment Strategy and explore the relative value of input predictors. Method: Predictions from 200 patients receiving Internet-delivered cognitive-behavioral therapy in an RCT was analyzed. Correlation and logistic regression was used to explore all included predictors and the predictive capacity of different models. Results: The classifier had a Balanced accuracy of 67 %. Eleven out of the 21 predictors correlated significantly with Failure. A model using all predictors explained 56 % of the outcome variance, and simpler models between 16 and 47 %. Important predictors were patient rated stress, treatment credibility, depression change, and insomnia symptoms at week 3 as well as clinician rated attitudes towards homework and sleep medication. Conclusions: The accuracy (67 %) found in this study sets a minimum benchmark for when prediction accuracy could be clinically useful. Key predictive factors were mainly related to insomnia, depression or treatment involvement. Simpler predictive models showed some promise and should be developed further, possibly using machine learning methods.

  • 38.
    Forsell, Erik
    et al.
    Karolinska Institutet, Sweden;Huddinge Hospital, Sweden.
    Jernelov, Susanna
    Karolinska Institutet, Sweden;Huddinge Hospital, Sweden;Karolinska Institutet, Sweden.
    Blom, Kerstin
    Karolinska Institutet, Sweden;Huddinge Hospital, Sweden.
    Kraepelien, Martin
    Karolinska Institutet, Sweden;Huddinge Hospital, Sweden.
    Svanborg, Cecilia
    Karolinska Institutet, Sweden;Huddinge Hospital, Sweden.
    Andersson, Gerhard
    Karolinska Institutet, Sweden;Huddinge Hospital, Sweden;Linköping University, Sweden.
    Lindefors, Nils
    Karolinska Institutet, Sweden;Huddinge Hospital, Sweden.
    Kaldo, Viktor
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology. Karolinska Institutet, Sweden;Huddinge Hospital, Sweden.
    Proof of Concept for an Adaptive Treatment Strategy to Prevent Failures in Internet-Delivered CBT: A Single-Blind Randomized Clinical Trial With Insomnia Patients2019In: American Journal of Psychiatry, ISSN 0002-953X, E-ISSN 1535-7228, Vol. 176, no 4, p. 315-323Article in journal (Refereed)
    Abstract [en]

    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.

  • 39.
    Forsell, Erik
    et al.
    Karolinska Institutet, Sweden;Stockholm County Council, Sweden.
    Kraepelien, Martin
    Karolinska Institutet, Sweden;Stockholm County Council, Sweden.
    Blom, Kerstin
    Karolinska Institutet, Sweden;Stockholm County Council, Sweden.
    Isacsson, Nils
    Karolinska Institutet, Sweden;Stockholm County Council, Sweden.
    Jernelov, Susanna
    Karolinska Institutet, Sweden;Stockholm County Council, Sweden.
    Svanborg, Cecilia
    Karolinska Institutet, Sweden;Stockholm County Council, Sweden.
    Rosen, Ann
    Karolinska Institutet, Sweden;Stockholm County Council, Sweden.
    Kaldo, Viktor
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology. Karolinska Institutet, Sweden;Stockholm County Council, Sweden.
    Development of a very brief scale for detecting and measuring panic disorder using two items from the Panic Disorder Severity Scale-Self Report2019In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 257, p. 615-622Article in journal (Refereed)
    Abstract [en]

    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 omega(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.

  • 40.
    Furukawa, Toshi A.
    et al.
    Kyoto Univ, Japan.
    Suganuma, Aya
    Kyoto Univ, Japan.
    Ostinelli, Edoardo G.
    Univ Oxford, UK.
    Andersson, Gerhard
    Karolinska Institutet, Sweden;Region Stockholm, Sweden;Linköping University, Sweden.
    Beevers, Christopher G.
    Univ Texas Austin, USA.
    Shumake, Jason
    Univ Texas Austin, USA.
    Berger, Thomas
    Univ Bern, Switzerland.
    Boele, Florien Willemijn
    Univ Leeds, UK.
    Buntrock, Claudia
    Friedrich Alexander Univ Erlangen Nurnberg, Germany.
    Carlbring, Per
    Stockholm University, Sweden.
    Choi, Isabella
    Univ Sydney, Australia.
    Christensen, Helen
    Black Dog Inst, Australia;Univ New South Wales, Australia.
    Mackinnon, Andrew
    Black Dog Inst, Australia;Univ New South Wales, Australia.
    Dahne, Jennifer
    Med Univ South Carolina, USA.
    Huibers, Marcus J. H.
    Vrije Univ Amsterdam, Netherlands.
    Ebert, David D.
    Tech Univ Munich, Germany.
    Farrer, Louise
    Australian Natl Univ, Australia.
    Forand, Nicholas R.
    Donald & Barbara Zucker Sch Med Hofstra Northwell, USA.
    Strunk, Daniel R.
    Ohio State Univ, USA.
    Ezawa, Iony D.
    Ohio State Univ, USA.
    Forsell, Erik
    Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Kaldo, Viktor
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology. Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Geraedts, Anna
    Soulve Innovat, Netherlands.
    Gilbody, Simon
    Univ York, UK.
    Littlewood, Elizabeth
    Univ York, UK.
    Brabyn, Sally
    Univ York, UK.
    Hadjistavropoulos, Heather D.
    Univ Regina, Canada.
    Schneider, Luke H.
    St Josephs Healthcare Hamilton, Canada.
    Johansson, Robert
    Stockholm University, Sweden.
    Kenter, Robin
    Univ Bergen, Norway.
    Kivi, Marie
    University of Gothenburg, Sweden.
    Bjorkelund, Cecilia
    University of Gothenburg, Sweden.
    Kleiboer, Annet
    Vrije Univ Amsterdam, Netherlands.
    Riper, Heleen
    Vrije Univ Amsterdam, Netherlands.
    Klein, Jan Philipp
    Luebeck Univ, Germany.
    Schroder, Johanna
    Univ Med Ctr Hamburg Eppendorf, Germany.
    Meyer, Bjorn
    GAIA AG, Germany.
    Moritz, Steffen
    Univ Med Ctr Hamburg Eppendorf, Germany.
    Bucker, Lara
    Univ Med Ctr Hamburg Eppendorf, Germany.
    Lintvedt, Ove
    Norwegian Ctr E-Hlth Res, Norway.
    Johansson, Peter
    Linköping University, Sweden.
    Lundgren, Johan
    Linköping University, Sweden.
    Milgrom, Jeannette
    Univ Melbourne, Australia.
    Gemmill, Alan W.
    Univ Melbourne, Australia.
    Mohr, David C.
    Northwestern Univ, USA.
    Montero-Marin, Jesus
    Univ Oxford, UK.
    Garcia-Campayo, Javier
    Miguel Servet Univ Hosp, Spain;RedIAPP, Spain.
    Nobis, Stephanie
    Klinikum Osnabruck, Germany.
    Zarski, Anna-Carlotta
    Friedrich Alexander Univ Erlangen Nurnberg, Germany.
    O'Moore, Kathleen
    Black Dog Inst, Australia;Univ New South Wales, Australia.
    Williams, Alishia D.
    Univ New South Wales, Australia.
    Newby, Jill M.
    Univ New South Wales, Australia.
    Perini, Sarah
    St Vincents Hosp, Australia.
    Phillips, Rachel
    Imperial Coll London, UK.
    Schneider, Justine
    Univ Nottingham, UK.
    Pots, Wendy
    Univ Twente, Netherlands.
    Pugh, Nicole E.
    Private practice, Canada.
    Richards, Derek
    Univ Dublin, Ireland;SilverCloud Hlth, Ireland.
    Rosso, Isabelle M.
    McLean Hosp, USA.
    Rauch, Scott L.
    McLean Hosp, USA.
    Sheeber, Lisa B.
    Oregon Res Inst, USA.
    Smith, Jessica
    Imperial Coll London, UK.
    Spek, Viola
    Fontys Univ Appl Sci, Netherlands.
    Pop, Victor J.
    Tilburg Univ, Netherlands.
    Unlu, Burcin
    PsyQ Online, Netherlands.
    van Bastelaar, Kim M. P.
    Amsterdam Univ Med Ctr, Netherlands.
    van Luenen, Sanne
    Leiden Univ, Netherlands.
    Garnefski, Nadia
    Leiden Univ, Netherlands.
    Kraaij, Vivian
    Leiden Univ, Netherlands.
    Vernmark, Kristofer
    Linköping University, Sweden.
    Warmerdam, Lisanne
    Natl Hlth Care Inst, Netherlands.
    van Straten, Annemieke
    Vrije Univ Amsterdam, Netherlands.
    Zagorscak, Pavle
    Free Univ Berlin, Germany.
    Knaevelsrud, Christine
    Free Univ Berlin, Germany.
    Heinrich, Manuel
    Free Univ Berlin, Germany.
    Miguel, Clara
    Vrije Univ Amsterdam, Netherlands.
    Cipriani, Andrea
    Univ Oxford, UK;Oxford Hlth NHS Fdn Trust, UK.
    Efthimiou, Orestis
    Univ Oxford, UK;Univ Bern, Switzerland.
    Karyotaki, Eirini
    Harvard Med Sch, USA.
    Cuijpers, Pim
    Vrije Univ Amsterdam, Netherlands.
    Dismantling, optimising, and personalising internet cognitive behavioural therapy for depression: a systematic review and component network meta-analysis using individual data2021In: Lancet psychiatry, ISSN 2215-0374, E-ISSN 2215-0366, Vol. 8, no 6, p. 500-511Article, review/survey (Refereed)
    Abstract [en]

    Findings We identified 76 RCTs, including 48 trials contributing individual participant data (11 704 participants) and 28 trials with aggregate data (6474 participants). The participants' weighted mean age was 42.0 years and 12 406 (71%) of 17 521 reported were women. There was suggestive evidence that behavioural activation might be beneficial (iMD -1.83 [95% credible interval (CrI) -2.90 to -0.80]) and that relaxation might be harmful (1.20 [95% CrI 0.17 to 2.27]). Baseline severity emerged as the strongest prognostic factor for endpoint depression. Combining human and automated encouragement reduced dropouts from treatment (incremental odds ratio, 0.32 [95% CrI 0.13 to 0.93]). The risk of bias was low for the randomisation process, missing outcome data, or selection of reported results in most of the included studies, uncertain for deviation from intended interventions, and high for measurement of outcomes. There was moderate to high heterogeneity among the studies and their components. 511

  • 41.
    Gervind, Elisabet
    et al.
    Västra Götalandsregionen, Sweden.
    Ben Salem, Mathilda
    Västra Götalandsregionen, Sweden.
    Svanborg, Cecilia
    Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Nyström, Monica E.
    Umeå University, Sweden;Karolinska Institutet, Sweden.
    Lilja, Josefine
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology. University of Gothenburg, Sweden.
    Kaldo, Viktor
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology. Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Weineland, Sandra
    Västra Götalandsregionen, Sweden;University of Gothenburg, Sweden.
    The influence of organizational models on the implementation of internet-based cognitive behavior therapy in primary care: A mixed methods study using the RE-AIM framework2024In: Internet Interventions, ISSN 2214-7829, Vol. 35, article id 100698Article in journal (Refereed)
    Abstract [en]

    Background: Internet-Based Cognitive Behavioral Therapy (iCBT) holds great potential in addressing mental health issues, yet its real-world implementation poses significant challenges. While prior research has predominantly focused on centralized care models, this study explores the implementation of iCBT in the context of decentralized organizational structures within the Swedish primary care setting, where all interventions traditionally are delivered at local Primary Care Centers (PCCs).Aim: This study aims to enhance our understanding of iCBT implementation in primary care and assess the impact of organizational models on the implementation's outcome using the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework.Method: A mixed-methods research design was employed to identify the factors influencing iCBT implementation across different levels, involving patients, therapists and managers. Data spanning two years was collected and analyzed through thematic analysis and statistical tests. The study encompassed 104 primary care centers, with patient data (n = 1979) sourced from the Swedish National Quality Register for Internet-Based Psychological Treatment (SibeR). Additionally, 53 iCBT therapists and 50 PCC managers completed the Normalization Measure Development Questionnaire, and 15 leaders participated in interviews.Results: Our investigation identified two implementation approaches, one concentrated and one decentralized. Implementation effectiveness was evident through adherence rates suggesting that iCBT is a promising approach for treating mental ill-health in primary care, although challenges were observed concerning patient assessment and therapist drift towards unstructured treatment. Mandatory implementation, along with managerial and organizational support, positively impacted adoption. Results vary in terms of adherence to established protocols, with therapists working in concentrated model showing a significantly higher percentage of registration in the quality register SibeR (X2 (1, N = 2973) = 430.5774, p = 0.001). They also showed significantly higher means in cognitive participation (Z = - 2.179, p = 0.029) and in reflective monitoring (Z = - 2.548, p = 0.011). Discussion: Overall, the study results demonstrate that iCBT, as a complex and qualitatively different intervention from traditional psychological treatment, can be widely implemented in primary care settings. The study's key finding highlights the substantial advantages of the concentrated organizational model. This model has strengths in sustainability, encourages reflective monitoring among therapists, the use of quality registers, and enforces established protocols.Conclusion: In conclusion, this study significantly contributes to the understanding of the practical aspects associated with the implementation of complex internet interventions, particularly in the context of internetbased cognitive-behavioral therapy (iCBT). The study highlights that effective iCBT integration into primary care requires a multifaceted approach, taking into account organizational models, robust support structures, and a commitment to maintaining quality standards. By emphasizing these factors, our research aims to provide actionable insights that can enhance the practicability and real-world applicability of implementing iCBT in primary care settings.

  • 42.
    Gogoulou, Evangelia
    et al.
    RISE, Sweden.
    Boman, Magnus
    KTH Royal instute of technology, Sweden.
    Abdesslem, Fehmi Ben
    RISE, Sweden.
    Isacsson, Nils
    Karolinska institutet, Sweden.
    Kaldo, Viktor
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology. Karolinska institutet, Sweden.
    Sahlgren, Magnus
    RISE, Sweden.
    Predicting treatment outcome from patient texts: The case of internet-based cognitive behavioural therapy2021In: EACL 2021 - 16th Conference of the European Chapter of the Association for Computational Linguistics, Proceedings of the Conference, Association for Computational Linguistics (ACL) , 2021, p. 575-580Conference paper (Refereed)
    Abstract [en]

    We investigate the feasibility of applying standard text categorisation methods to patient text in order to predict treatment outcome in Internet-based cognitive behavioural therapy. The data set is unique in its detail and size for regular care for depression, social anxiety, and panic disorder. Our results indicate that there is a signal in the depression data, albeit a weak one. We also perform terminological and sentiment analysis, which confirm those results. © 2021 Association for Computational Linguistics

  • 43.
    Görts Öberg, Katarina
    et al.
    Karolinska Institutet;Karolinska University Hospital.
    Hallberg, Jonas
    Karolinska Institutet;Karolinska University Hospital.
    Kaldo, Viktor
    Karolinska Institutet.
    Dhejne, Cecilia
    Karolinska University Hospital;Karolinska Institutet.
    Arver, Stefan
    Karolinska Institutet;Karolinska University Hospital.
    Hypersexual Disorder According to the Hypersexual Disorder Screening Inventory in Help-Seeking Swedish Men and Women With Self-Identified Hypersexual Behavior2017In: Sexual Medicine, E-ISSN 2050-1161, Vol. 5, no 4, p. E229-E236Article in journal (Refereed)
    Abstract [en]

    Introduction: The Hypersexual Disorder Screening Inventory (HDSI) was developed by the American Psychiatric Association for clinical screening of hypersexual disorder (HD). Aims: To examine the distribution of the proposed diagnostic entity HD according to the HDSI in a sample of men and women seeking help for problematic hypersexuality and evaluate some psychometric properties. Methods: Data on sociodemographics, the HDSI, the Sexual Compulsivity Scale (SCS), and the Cognitive and Behavioral Outcomes of Sexual Behavior were collected online from 16 women and 64 men who self-identified as hypersexual. Respondents were recruited by advertisements offering psychological treatment for hypersexual behavior. Main Outcome Measures: The HDSI, covering the proposed criteria for HD. Results: Of the entire sample, 50% fulfilled the criteria for HD. Compared with men, women scored higher on the HDSI, engaged more often in risky sexual behavior, and worried more about physical injuries and pain. Men primarily used pornography, whereas women had sexual encounters. The HD group reported a larger number of sexual specifiers, higher scores on the SCS, more negative effects of sexual behavior, and more concerns about consequences compared with the non-HD group. Sociodemographics had no influence on HD. The HDSI's core diagnostic criteria showed high internal reliability for men (a = 0.80) and women (a = 0.81). A moderate correlation between the HDSI and the SCS was found (0.51). The vast majority of the entire sample (76 of 80, 95%) fulfilled the criteria for sexual compulsivity according to the SCS. Conclusion: The HDSI could be used as a screening tool for HD, although further explorations of the empirical implications regarding criteria are needed, as are refinements of cutoff scores and specific sexual behaviors. Hypersexual problematic behavior causes distress and impairment and, although not included in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, HD should be endorsed as a diagnosis to develop evidence-based treatment and future studies on its etiology. Copyright (C) 2017, The Authors. Published by Elsevier Inc. on behalf of the International Society for Sexual Medicine. This is an open access article under the CC BY-NC-ND license.

  • 44.
    Hagström, David
    et al.
    Uppsala University.
    Kaldo, Viktor
    Karolinska Institutet.
    Escapism among players of MMORPGs: conceptual clarification, its relation to mental health factors, and development of a new measure2014In: CyberPsychology, Behavior and Social Networking, ISSN 2152-2715, E-ISSN 2152-2723, Vol. 17, no 1, p. 19-25Article in journal (Refereed)
    Abstract [en]

    Previous studies show that the concept of escapism needs to be clarified and that its relation to problematic online gaming and other factors needs further examination. This study uses well-established, basic learning theory to clarify the concept of escapism, and examines its relation to problematic gaming, psychological distress, and satisfaction with life among players of massively multiplayer online role-playing games (MMORPGs). MMORPG players (n=201) answered an online questionnaire where these factors were measured and correlated with a previously developed scale on motivation to play (MTPI), including extra items to cover positive and negative aspects of escapism. Factor analysis and construct validation show that positive aspects of escapism are theoretically and empirically unstable and that escapism is best clarified as purely "negative escapism," corresponding to playing being negatively reinforced as a way of avoiding everyday hassles and distress. Negative escapism had a stronger relationship to symptoms of Internet addiction, psychological distress, and life satisfaction than other variables and other more positive motivations to play. Future studies should use the revised subscale for escapism (in the MTPI-R) presented in the present study, for example when screening for Internet addiction.

  • 45.
    Hallberg, Jonas
    et al.
    Karolinska Institutet;Karolinska University Hospital.
    Kaldo, Viktor
    Karolinska Institutet.
    Arver, Stefan
    Karolinska Institutet;Karolinska University Hospital.
    Dhejne, Cecilia
    Karolinska University Hospital;Karolinska Institutet.
    Görts Öberg, Katarina
    Karolinska Institutet;Karolinska University Hospital.
    A Cognitive-Behavioral Therapy Group Intervention for Hypersexual Disorder: A Feasibility Study2017In: Journal of Sexual Medicine, ISSN 1743-6095, E-ISSN 1743-6109, Vol. 14, no 7, p. 950-958Article in journal (Refereed)
    Abstract [en]

    Background: The proposed criteria of the Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition for hypersexual disorder (HD) included symptoms reported by patients seeking help for excessive and out-of-control non-paraphilic sexual behavior, including sexual behaviors in response to dysphoric mood states, impulsivity, and risk taking. Although no prior studies of cognitive-behavioral therapy (CBT) for the treatment of HD have been performed, CBT has been found effective for dysphoric mood states and impulsivity. Aim: To investigate the feasibility of a CBT manual developed for HD explored through symptom decrease, treatment attendance, and clients' treatment satisfaction. Methods: Ten men with a diagnosis of HD took part in the CBT group program. Measurements were taken before, during, and at the end of treatment and 3 and 6 months after treatment. Outcomes: The primary outcome was the Hypersexual Disorder: Current Assessment Scale (HD: CAS) score that measured the severity of problematic hypersexual symptoms and secondary outcomes were the Hypersexual Disorder Screening Inventory (HDSI) score, the proportion of attended sessions, and the Client Satisfaction Questionnaire (CSQ-8) score. Results: Main results were significant decreases of HD symptoms from before to after treatment on HD: CAS and HDSI scores and a decrease in the number of problematic sexual behaviors during the course of therapy. A high attendance rate of 93% and a high treatment satisfaction score on CSQ-8 also were found. Clinical Implications: The CBT program seemed to ameliorate the symptoms of HD and therefore might be a feasible treatment option. Strengths and Limitations: This study provides data from a CBT program for the treatment of the specific proposed criteria of HD. Because of the small sample and lack of a control group, the results can be considered only preliminary. Conclusion: Although participants reported decreased HD symptoms after attending the CBT program, future studies should evaluate the treatment program with a larger sample and a randomized controlled procedure to ensure treatment effectiveness. Copyright (C) 2017, International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

  • 46.
    Hallberg, Jonas
    et al.
    Karolinska Institutet, Sweden;Karolinska University Hospital, Sweden.
    Kaldo, Viktor
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology. Karolinska Institutet, Sweden;Stockholm County Council, Sweden.
    Arver, Stefan
    Karolinska Institutet, Sweden;Karolinska University Hospital, Sweden.
    Dhejne, Cecilia
    Karolinska Institutet, Sweden;Stockholm County Council, Sweden.
    Jokinen, Jussi
    Karolinska Institutet, Sweden;Stockholm County Council, Sweden;Umeå University, Sweden.
    Oberg, Katarina Gorts
    Karolinska Institutet, Sweden;Karolinska University Hospital, Sweden.
    A Randomized Controlled Study of Group-Administered Cognitive Behavioral Therapy for Hypersexual Disorder in Men2019In: Journal of Sexual Medicine, ISSN 1743-6095, E-ISSN 1743-6109, Vol. 16, no 5, p. 733-745Article in journal (Refereed)
    Abstract [en]

    Background: Hypersexual disorder (HD) is defined as a condition in which the individual loses control over engagement in sexual behaviors, leading to distress and negative effects on key life areas. Cognitive behavioral therapy (CBT) has been proven to reduce symptoms of hypersexual behavior; however, no randomized controlled study of CBT interventions for HD has been reported previously. Aim: To investigate the efficacy of group-administered CBT for HD. Methods: Male participants (n = 137) diagnosed with HD, were randomized between 7 weeks of group-administered CBT (n = 70) and a waitlist control receiving the intervention after 8 weeks (n = 67). Measurements were administered at pre-, mid-, and posttreatment, with follow-up after 3 and 6 months. Outcomes: The primary outcome was the Hypersexual Disorder: Current Assessment Scale (HD: CAS), and secondary outcomes were the Sexual Compulsivity Scale (SCS) and measures of depression (Montgomery-Asberg Depression Rating Scale (MADRS-S), psychological distress (Clinical Outcomes in Routine Evaluation Outcome Measure (CORE-OM), and treatment satisfaction (CSQ-8). Results: A significantly greater decrease in HD symptoms and sexual compulsivity, as well as significantly greater improvements in psychiatric well-being, were found for the treatment condition compared with the waitlist. These effects remained stable at 3 and 6 months after treatment. Clinical Implications: CBT can ameliorate HD symptoms and psychiatric distress, suggesting that the CBT program may serve as a first-line treatment in clinical settings. Strengths & Limitations: This is the first randomized controlled study evaluating the efficacy of a CBT programin a rather large sample of HD-specific diagnosed men. The long-termtreatment effects are vague due to the low response rate on follow-up measurements, and the efficacy of this program for hypersexual women remains unknown. Conclusion: This study supports the efficacy of a group-administered CBT program as a treatment option for HD; however, future studies should include women, comprise dismantling analysis of the constituting interventions, and evaluate other treatment formats, for example, administration via the Internet. Copyright (C) 2019, International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

  • 47.
    Hallberg, Jonas
    et al.
    Karolinska Institutet, Sweden;Karolinska University Hospital, Sweden.
    Kaldo, Viktor
    Linnaeus University, Faculty of Health and Life Sciences, Department of Psychology. Karolinska Institutet, Sweden;Region Stockholm, Sweden.
    Arver, Stefan
    Karolinska Institutet, Sweden;Karolinska University Hospital, Sweden.
    Dhejne, Cecilia
    Karolinska Institutet, Sweden;Karolinska University Hospital, Sweden.
    Piwowar, Marta
    Karolinska University Hospital, Sweden.
    Jokinen, Jussi
    Karolinska Institutet, Sweden;Region Stockholm, Sweden;Umeå University, Sweden.
    Oberg, Katarina Gorts
    Karolinska Institutet, Sweden;Karolinska University Hospital, Sweden.
    Internet-Administered Cognitive Behavioral Therapy for Hypersexual Disorder, With or Without Paraphilia(s) or Paraphilic Disorder(s) in Men: A Pilot Study2020In: Journal of Sexual Medicine, ISSN 1743-6095, E-ISSN 1743-6109, Vol. 17, no 10, p. 2039-2054Article, review/survey (Refereed)
    Abstract [en]

    Background: Hypersexual disorder (HD) is a condition in which the individual experiences loss of control over engagement in sexual behaviors, leading to negative effects on various areas of life. Paraphilias often present concomitantly with HD, and although cognitive behavioral therapy (CBT) has been proven to reduce engagement in hypersexual behavior, no studies have investigated the effects of Internet-administered CBT (ICBT) on HD, with or without paraphilia(s) or paraphilic disorder(s). Aim: To investigate the effects of Internet-administered CBT on HD, with or without paraphilia(s) or paraphilic disorder(s). Methods: Male participants (n = 36) evaluated positive according to the proposed diagnostic HD criteria, with or without paraphilia(s) or paraphilic disorder(s), received 12 weeks of ICBT. Measures were administered weekly over the treatment period, with an additional follow-up measurement 3 months after completion of treatment. An assessment interview was performed 2 weeks after treatment. Outcomes: The primary outcome was the Hypersexual Behavior Inventory (HBI-19), and secondary outcomes were the Hypersexual Disorder: Current Assessment Scale (HD:CAS), the Sexual Compulsivity Scale (SCS), as well as a tentative composite of 6 Severity Self-rating Measures, for Paraphilic Disorders and depression (Montgomery-Asberg Depression Rating Scale [MADRS-S]), psychological distress (Clinical Outcomes in Routine Evaluation Outcome Measure [CORE-OM]), and treatment satisfaction (CSQ-8). Results: Large, significant decreases in HD symptoms and sexual compulsivity were found, as well as moderate improvements in psychiatric well-being and paraphilic symptoms. These effects remained stable 3 months after treatment. Clinical Implications: ICBT can ameliorate HD symptoms, psychiatric distress, and paraphilic symptoms, which suggests that the ICBT for HD, with or without paraphilia(s) or paraphilic disorder(s), may constitute a valuable addition of treatment options in clinical settings. Strengths and Limitations: This is the first study evaluating the efficacy ofICBT on a sample of men suffering from HD. In addition, a proportion of the sample reported concomitant paraphilic interests and disorders, thus mirroring an everyday clinical practice in the field of sexual medicine. No control group was assigned, and some of the outcome measures are still to be validated. The long-term effects of ICBT and its efficacy in hypersexual women are unknown. Conclusions: This study gives support for ICBT as an effective treatment option for HD. Future evaluations of the treatment program should include women and larger samples in randomized controlled procedures and investigate the long-term effects. Copyright (C) 2020, International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

  • 48.
    Hallgren, Mats
    et al.
    Karolinska Institutet.
    Helgadottir, Björg
    Karolinska Institutet.
    Herring, Matthew P.
    Univ Limerick, Ireland.
    Zeebari, Zangin
    Karolinska Institutet.
    Lindefors, Nils
    Karolinska Institutet.
    Kaldo, Viktor
    Karolinska Institutet.
    Öjehagen, Agneta
    Lund University.
    Forsell, Yvonne
    Karolinska Institutet.
    Exercise and internet-based cognitive-behavioural therapy for depression: multicentre randomised controlled trial with 12-month follow-up2016In: British Journal of Psychiatry, ISSN 0007-1250, E-ISSN 1472-1465, Vol. 209, no 5, p. 416-422Article in journal (Refereed)
    Abstract [en]

    Background Evidence-based treatment of depression continues to grow, but successful treatment and maintenance of treatment response remains limited. Aims To compare the effectiveness of exercise, internet-based cognitive behavioural therapy (ICBT) and usual care for depression. Method A multicentre, three-group parallel, randomised controlled trial was conducted with assessment at 3 months (post-treatment) and 12 months (primary end-point). Outcome assessors were masked to group allocation. Computer generated allocation was performed externally in blocks of 36 and the ratio of participants per group was 1:1:1. In total, 945 adults with mild to moderate depression aged 18-71 years were recruited from primary healthcare centres located throughout Sweden. Participants were randomly assigned to one of three 12-week interventions: supervised group exercise, clinician-supported ICBT or usual care by a physician. The primary outcome was depression severity assessed by the Montgomery-angstrom sberg Depression Rating Scale (MADRS). Results The response rate at 12-month follow-up was 84%. Depression severity reduced significantly in all three treatment groups in a quadratic trend over time. Mean differences in MADRS score at 12 months were 12.1 (ICBT), 11.4 (exercise) and 9.7 (usual care). At the primary end-point the group x time interaction was significant for both exercise and ICBT. Effect sizes for both interventions were small to moderate. Conclusions The long-term treatment effects reported here suggest that prescribed exercise and clinician-supported ICBT should be considered for the treatment of mild to moderate depression in adults. (C) The Royal College of Psychiatrists 2016.

  • 49.
    Hallgren, Mats
    et al.
    Karolinska Institutet.
    Kraepelien, Martin
    Karolinska Institutet.
    Öjehagen, Agneta
    Lund University.
    Lindefors, Nils
    Karolinska Institutet.
    Zeebari, Zangin
    Karolinska Institutet.
    Kaldo, Viktor
    Karolinska Institutet.
    Forsell, Yvonne
    Karolinska Institutet.
    Physical exercise and internet-based cognitive-behavioural therapy in the treatment of depression: randomised controlled trial2015In: British Journal of Psychiatry, ISSN 0007-1250, E-ISSN 1472-1465, Vol. 207, no 3, p. 227-234Article in journal (Refereed)
    Abstract [en]

    Background Depression is common and tends to be recurrent. Alternative treatments are needed that are non-stigmatising, accessible and can be prescribed by general medical practitioners. Aims To compare the effectiveness of three interventions for depression: physical exercise, internet-based cognitive behavioural therapy (ICBT) and treatment as usual (TAU). A secondary aim was to assess changes in self-rated work capacity. Method A total of 946 patients diagnosed with mild to moderate depression were recruited through primary healthcare centres across Sweden and randomly assigned to one of three 12-week interventions (trail registry: KCTR study ID: KT20110063). Patients were reassessed at 3 months (response rate 78%). Results Patients in the exercise and ICBT groups reported larger improvements in depressive symptoms compared with TAU. Work capacity improved over time in all three groups (no significant differences). Conclusions Exercise and ICBT were more effective than TAU by a general medical practitioner, and both represent promising non-stigmatising treatment alternatives for patients with mild to moderate depression. Copyright and usage (C) The Royal College of Psychiatrists 2015.

  • 50.
    Hedman, E.
    et al.
    Karolinska Institutet.
    Ljótsson, B.
    Karolinska Institutet.
    Rück, C.
    Karolinska Institutet.
    Bergström, J.
    Stockholm University.
    Andersson, G.
    Karolinska Institutet;Linköping University.
    Kaldo, Viktor
    Karolinska Institutet.
    Jansson, L.
    Karolinska Institutet.
    Andersson, E.
    Karolinska Institutet.
    Andersson, E.
    Karolinska Institutet.
    Blom, K.
    Karolinska Institutet.
    El Alaoui, S.
    Karolinska Institutet.
    Falk, L.
    Karolinska Institutet.
    Ivarsson, J.
    Karolinska Institutet.
    Nasri, B.
    Karolinska Institutet.
    Rydh, S.
    Karolinska Institutet.
    Lindefors, N.
    Karolinska Institutet.
    Effectiveness of Internet-based cognitive behaviour therapy for panic disorder in routine psychiatric care2013In: Acta Psychiatrica Scandinavica, ISSN 0001-690X, E-ISSN 1600-0447, Vol. 128, no 6, p. 457-467Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    Guided Internet-based cognitive behaviour therapy (ICBT) for panic disorder has been shown to be efficacious in several randomized controlled trials. However, the effectiveness of the treatment when delivered within routine psychiatric care has not been studied. The aim of this study was to investigate the effectiveness of ICBT for panic disorder within the context of routine psychiatric care.

    METHOD:

    We conducted a cohort study investigating all patients (n = 570) who had received guided ICBT for panic disorder between 2007 and 2012 in a routine care setting at an out-patient psychiatric clinic providing Internet-based treatment. The primary outcome measure was the Panic Disorder Severity Scale-Self-report (PDSS-SR).

    RESULTS:

    Participants made large improvements from screening and pretreatment assessments to posttreatment (Cohen's d range on the PDSS-SR = 1.07-1.55). Improvements were sustained at 6-month follow-up.

    CONCLUSION:

    This study suggests that ICBT for panic disorder is as effective when delivered in a routine care context as in the previously published randomized controlled trials.

123 1 - 50 of 110
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