publications

Preprints

2023

1. Empirically Defining Treatment Response and Remission in Obsessive-Compulsive Disorder Using the Obsessive-Compulsive Inventory–Revised

   Flygare, Oskar, Wallert, John, Chen, Long-Long, Fernández de la Cruz, Lorena, Lundström, Lina, Mataix-Cols, David, Rück, Christian, and Andersson, Erik

   Behavior Therapy Jan 2023

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   In clinical trials of obsessive-compulsive disorder (OCD), clinical outcomes are generally measured using lengthy clinician-administered interviews. However, in routine clinical practice, many clinicians lack the time to administer such instruments. This study evaluated cutoffs for treatment response and remission in OCD using the self-rated Obsessive-Compulsive Inventory—Revised (OCI-R). Data from 349 patients in three clinical trials of cognitive-behavioral therapy for OCD were pooled for analysis. The OCI-R was compared to gold-standard criteria for response and remission based on the clinician-administered Yale–Brown Obsessive Compulsive Scale and the Clinical Global Impression Scale. The results showed that a ≥40% reduction on the OCI-R was the optimal cutoff for treatment response, with a sensitivity of 0.72 and a specificity of 0.79. For remission status, the optimal cutoff was ≤8 points on the OCI-R, with a sensitivity of 0.57 and specificity of 0.83. Results from additional analyses using the 12-item version of the OCI were similar. These cutoffs provide a simple and time-efficient way to help determine treatment response and remission in OCD when the administration of clinician-administered instruments is unfeasible.

2. Cost-Effectiveness of Internet-Delivered Cognitive Behaviour Therapy for Body Dysmorphic Disorder: Results from a Randomised Controlled Trial

   Flygare, Oskar, Andersson, Erik, Glimsdal, Gjermund, Mataix-Cols, David, Pascal, Diana, Rück, Christian, and Enander, Jesper

   Internet Interventions Jan 2023

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   Objectives To evaluate the cost-effectiveness of internet-delivered cognitive behaviour therapy for body dysmorphic disorder (BDD-NET). Design Secondary cost-effectiveness analysis from a randomised controlled trial on BDD-NET versus online supportive psychotherapy. Setting Academic medical center. Participants Self-referred adult participants with a primary diagnosis of body dysmorphic disorder and a score of 20 or higher on the modified Yale-Brown Obsessive Compulsive Scale for BDD (n\,= 94). Patients receiving concurrent psychotropic drug treatment were included if the dose had been stable for at least two months. Interventions Participants received either BDD-NET (n\,= 47) or online supportive psychotherapy (n\,= 47) for 12 weeks. Primary and secondary outcome measures The primary outcome measures were cost-effectiveness and cost-utility from a societal perspective, using remission status from a diagnostic interview and quality-adjusted life years (QALY), respectively. Secondary outcome measures were cost-effectiveness and cost-utility from a health care perspective and the clinic’s perspective. Results Compared to supportive psychotherapy, BDD-NET produced one additional remission for an average societal cost of \4132. The cost-utility analysis showed that BDD-NET generated one QALY to an average cost of \14,319 from a societal perspective. Conclusions BDD-NET is a cost-effective treatment for body dysmorphic disorder, compared to online supportive psychotherapy. The efficacy and cost-effectiveness of BDD-NET should next be directly compared to in-person cognitive behaviour therapy. Trial registration NCT02010619.

3. Association of Anxiety or Depression with Risk of Recurrent Cardiovascular Events and Death after Myocardial Infarction: A Nationwide Registry Study

   Flygare, Oskar, Boberg, Julia, Rück, Christian, Hofmann, Robin, Leosdottir, Margret, Mataix-Cols, David, de la Cruz, Lorena Fernández, Richman, Peter, and Wallert, John

   International Journal of Cardiology Apr 2023

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   Background Depression and anxiety are risk factors for patients with myocardial infarction (MI). However, the association of a previous psychiatric diagnosis of anxiety or depression, or only such self-reported symptoms, with cardiovascular outcomes and mortality post-MI has not been previously examined in the same nationwide cohort. Methods We linked demographic, socioeconomic and clinical data from four nationwide Swedish registries for patients enrolled in cardiac rehabilitation (CR) after first-time MI (2006–2015, N\,= 45,096). After multiple imputation, we applied Cox regression to estimate the post-MI outcome risk for patients with a previous psychiatric diagnosis of anxiety/depression (Diagnosis), patients with no formal diagnosis but self-reported symptoms of anxiety/depression (Symptoms), versus patients with neither Diagnosis nor Symptoms (Reference). Results During one-year follow-up, fully adjusted models showed that patients with Diagnosis had a higher risk (hazard ratio [95%CI]) of all-cause mortality (1.86 [1.36, 2.53]), reinfarction (1.14 [1.06, 1.22]), their composite (1.15 [1.07, 1.23]), and an extended cardiovascular composite (1.19 [1.12, 1.26]), versus Reference, even though 77% reported no symptoms at the time of MI. In patients with Symptoms, estimates were also elevated yet somewhat attenuated compared to Reference. Findings were fairly robust across multiple sensitivity analyses. Conclusions Both a previous diagnosis, and present self-reported symptoms of anxiety or depression are associated with an increased risk of death and recurrent cardiovascular events in adults with first-time MI. Only screening for present symptoms is inadequate for assessing this excessive risk. Assessment of both psychiatric history and self-reported symptoms seems warranted for these patients.

4. Effectiveness of Internet-based Cognitive-Behavioural Therapy for Obsessive-Compulsive Disorder (OCD-NET) and Body Dysmorphic Disorder (BDD-NET) in the Swedish Public Health System Using the RE-AIM Implementation Framework

   Lundström, Lina,  Flygare, Oskar, Ivanova, Ekaterina, Mataix-Cols, David, Enander, Jesper, Pascal, Diana, Chen, Long-Long, Andersson, Erik, and Rück, Christian

   Internet Interventions Mar 2023

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   Objectives Therapist-guided internet-delivered cognitive behaviour therapy (ICBT) is an efficacious treatment for obsessive-compulsive disorder (OCD) and body dysmorphic disorder (BDD), but it is unclear if the results obtained in controlled trials can be reproduced in clinical settings. We evaluated the implementation of ICBT for OCD (OCD-NET) and BDD (BDD-NET) in the Swedish public health system. Methods Consecutive referrals to an outpatient psychiatric clinic providing ICBT, with a primary diagnosis of OCD or BDD, were included in the study. Four hundred and thirty-four participants started OCD-NET and 163 started BDD-NET. The primary outcome measures were the Yale Brown Obsessive Compulsive Scale (Y-BOCS) and the Y-BOCS for BDD (BDD-YBOCS), respectively. Participants were assessed before treatment, weekly during treatment, and after treatment. The study used the RE-AIM implementation framework, and the elements of reach, effectiveness, adoption, and implementation for the evaluation. Results Intention to treat analysis of the OCD-NET sample (n = 434) showed a significant decrease in OCD symptoms from pre-treatment to post-treatment (mean reduction = -8.77 [95 % CI -9.48 to -8.05] p < .001, d = 1.94 [95 % CI 1.75 to 2.13]). Forty-nine percent (95 % CI 43 % to 56 %) of the participants in OCD-NET were classified as treatment responders and 21 % (95 % CI 16 % to 27 %) were in remission. Participants in BDD-NET (n = 163) also showed a significant decrease in BDD symptoms from pre-post treatment (mean reduction = -11.37 [95 % CI -12.9 to -9.87] p < .001, d = 2.07 [95 % CI 1.74 to 2.40]) and 69 % (95 % CI 58 % to 79 %) of the participants were classified as treatment responders and 48 % (95 % CI 38 % to 58 %) were in full or partial remission. Eighty-seven percent of the participants in OCD-NET and 78 % in BDD-NET were treatment completers and participants in both treatment groups reported a high treatment satisfaction at post treatment (OCD-NET = 87 %, BDD-NET = 79 %). The most reported negative effects attributed to the treatments were transient experiences of unpleasant feelings (52 %) and anxiety (50 %). The implementation also influenced treatment delivery and dramatically decreased the mean number of patients waiting to receive face-to-face treatment at the clinic. Conclusions Our results indicate that OCD-NET and BDD-NET are suitable treatments for implementation in a Swedish public health service.

2022

1. Implementing Therapist-Guided Internet-Delivered Cognitive Behaviour Therapy for Obsessive–Compulsive Disorder in the UK’s IAPT Programme: A Pilot Trial

   Flygare, Oskar, Lundström, Lina, Andersson, Erik, Mataix-Cols, David, and Rück, Christian

   British Journal of Clinical Psychology Mar 2022

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   Objectives Digital therapies such as internet-delivered cognitive behaviour therapy (ICBT) can improve treatment access for patients with common mental disorders, but are rarely used in the Improving Access to Psychological Therapies (IAPT) programme in the United Kingdom. The objective of this study was to evaluate an evidence-based ICBT intervention for obsessive-compulsive disorder (OCD-NET) in three IAPT services in an open trial. Methods Consecutively referred patients with a primary diagnosis of OCD (n = 474) were offered OCD-NET. Symptoms of OCD, depression, anxiety, and level of functioning were measured weekly throughout treatment. Results In the full intention to treat sample (n = 474), the intervention was associated with large reductions in self-reported OCD symptoms (d = 1.77), anxiety (d = 1.55) and depression (d = 0.8), as well as improvements in functional impairment (d = 0.51 to 0.72). Further, 35% of participants were in recovery at their last assessment, 25% achieved reliable improvement and 15% met criteria for both recovery and improvement. Among participants completing at least 4 modules (n = 261), corresponding to an adequate ‘dose’ of treatment, the rates of recovery (44%), reliable improvement (34%) and reliable recovery (21%) were higher. A majority of participants were satisfied with the online treatment and found the online materials helpful. Conclusions OCD-NET is an effective treatment when delivered in regular care within the IAPT system. Challenges associated with implementing ICBT in regular health care are discussed.

2. Effect of Internet-Based vs Face-to-Face Cognitive Behavioral Therapy for Adults With Obsessive-Compulsive Disorder: A Randomized Clinical Trial

   Lundström, Lina,  Flygare, Oskar, Andersson, Erik, Enander, Jesper, Bottai, Matteo, Ivanov, Volen Z., Boberg, Julia, Pascal, Diana, Mataix-Cols, David, and Rück, Christian

   JAMA Network Open Mar 2022

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   Cognitive behavioral therapy (CBT) for obsessive-compulsive disorder (OCD) is a highly specialized treatment that is in short supply worldwide.To investigate whether both therapist-guided and unguided internet-based CBT (ICBT) are noninferior to face-to-face CBT for adults with OCD, to conduct a health economic evaluation, and to determine whether treatment effects were moderated by source of participant referral.This study is a single-blinded, noninferiority, randomized clinical trial, with a full health economic evaluation, conducted between September 2015 and January 2020, comparing therapist-guided ICBT, unguided ICBT, and individual face-to-face CBT for adults with OCD. Follow-up data were collected up to 12 months after treatment. The study was conducted at 2 specialist outpatient OCD clinics in Stockholm, Sweden. Participants included a consecutive sample of adults with a primary diagnosis of OCD, either self-referred or referred by a clinician. Data analysis was performed from June 2019 to January 2022.Guided ICBT, unguided ICBT, and face-to-face CBT delivered over 14 weeks.The primary end point was the change in OCD symptom severity from baseline to 3-month follow-up. The noninferiority margin was 3 points on the masked assessor-rated Yale-Brown Obsessive Compulsive Scale.A total of 120 participants were enrolled (80 women [67%]; mean [SD] age, 32.24 [9.64] years); 38 were randomized to the face-to-face CBT group, 42 were randomized to the guided ICBT group, and 40 were randomized to the unguided ICBT group. The mean difference between therapist-guided ICBT and face-to-face CBT at the primary end point was 2.10 points on the Yale-Brown Obsessive Compulsive Scale (90% CI, -0.41 to 4.61 points; P\,=\,.17), favoring face-to-face CBT, meaning that the primary noninferiority results were inconclusive. The difference between unguided ICBT and face-to-face CBT was 5.35 points (90% CI, 2.76 to 7.94 points; P\,<\,.001), favoring face-to-face CBT. The health economic analysis showed that both guided and unguided ICBT were cost-effective compared with face-to-face CBT. Source of referral did not moderate treatment outcome. The most common adverse events were anxiety (30 participants [25%]), depressive symptoms (20 participants [17%]), and stress (11 participants [9%]).The findings of this randomized clinical trial of ICBT vs face-to-face CBT for adults with OCD do not conclusively demonstrate noninferiority. Therapist-guided ICBT could be a cost-effective alternative to in-clinic CBT for adults with OCD in scenarios where traditional CBT is not readily available; unguided ICBT is probably less efficacious but could be an alternative when providing remote clinician support is not feasible.ClinicalTrials.gov Identifier: NCT02541968

3. Operational Definitions of Treatment Response and Remission in Obsessive-Compulsive Disorder Capture Meaningful Improvements in Everyday Life

   Mataix-Cols, David, Andersson, Erik, Aspvall, Kristina, Boberg, Julia, Crowley, James J., Schipper, Elles, Cruz, Lorena Fernández,  Flygare, Oskar, Ivanova, Ekaterina, Lenhard, Fabian, Lundström, Lina, Rück, Christian, Serlachius, Eva, and Cervin, Matti

   Psychotherapy and Psychosomatics Oct 2022

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   Introduction: The operational definitions of treatment response, partial response, and remission in obsessive-compulsive disorder (OCD) are widely used in clinical trials and regular practice. However, the clinimetric sensitivity of these definitions, that is, whether they identify patients that experience meaningful changes in their everyday life, remains unexplored. Objective: The objective was to examine the clinimetric sensitivity of the operational definitions of treatment response, partial response, and remission in children and adults with OCD. Methods: Pre- and post-treatment data from five clinical trials and three cohort studies of children and adults with OCD (n = 1,528; 55.3% children, 61.1% female) were pooled. We compared (1) responders, partial responders, and non-responders and (2) remitters and non-remitters on self-reported OCD symptoms, clinician-rated general functioning, and self-reported quality of life. Remission was also evaluated against post-treatment diagnostic interviews. Results: Responders and remitters experienced large improvements across validators. Responders had greater improvements than partial responders and non-responders on self-reported OCD symptoms (Cohen’s d 0.65–1.13), clinician-rated functioning (Cohen’s d 0.53–1.03), and self-reported quality of life (Cohen’s d 0.63–0.73). Few meaningful differences emerged between partial responders and non-responders. Remitters had better outcomes across most validators than non-remitters. Remission criteria corresponded well with absence of post-treatment diagnosis (sensitivity/specificity: 93%/83%). Using both the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the Clinical Global Impression Scale yielded more conservative results and more robust changes across validators, compared to only using the Y-BOCS. Conclusions: The current definitions of treatment response and remission capture meaningful improvements in the everyday life of individuals with OCD, whereas the concept of partial response has dubious clinimetric sensitivity.

4. Effectiveness of Multimodal Treatment for Young People with Body Dysmorphic Disorder in Two Specialist Clinics

   Rautio, Daniel, Gumpert, Martina, Jassi, Amita, Krebs, Georgina,  Flygare, Oskar, Andrén, Per, Monzani, Benedetta, Peile, Lauren, Jansson-Fröjmark, Markus, Lundgren, Tobias, Hillborg, Maria, Silverberg-Mörse, Maria, Clark, Bruce, Fernández de la Cruz, Lorena, and Mataix-Cols, David

   Behavior Therapy Sep 2022

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   Body dysmorphic disorder (BDD) typically originates in adolescence and is associated with considerable adversity. Evidence-based treatments exist but research on clinical outcomes in naturalistic settings is extremely scarce. We evaluated the short- and long-term outcomes of a large cohort of adolescents with BDD receiving specialist multimodal treatment and examined predictors of symptom improvement. We followed 140 young people (age range 10-18) with a diagnosis of BDD treated at two national and specialist outpatient clinics in Stockholm, Sweden (n=96) and London, England (n=44), between January 2015 and April 2021. Participants received multimodal treatment consisting of cognitive behaviour therapy and, in 72% of cases, medication (primarily selective serotonin reuptake inhibitors). Data were collected at baseline, post-treatment, and 3, 6, and 12 months after treatment.The primary outcome measure was the clinician-rated Yale-Brown Obsessive-Compulsive Scale Modified for BDD, Adolescent version (BDD-YBOCS-A). Secondary outcomes included self-reported measures of BDD symptoms, depressive symptoms, and global functioning. Mixed-effects regression models showed that BDD-YBOCS-A scores decreased significantly from baseline to post-treatment (coefficient [95% confidence interval]=-16.33 [-17.90 to -14.76], p<0.001; within-group effect size (Cohen’s d)=2.08 (95% confidence interval, 1.81 to 2.35). At the end of the treatment, 79% of the participants were classified as responders and 59% as full or partial remitters. BDD symptoms continued to improve throughout the follow-up. Improvement was also seen on all secondary outcome measures. Linear regression models identified baseline BDD symptom severity as a predictor of treatment outcome at post-treatment, but no consistent predictors were found at the 12-month follow-up. To conclude, multimodal treatment for adolescent BDD is effective in both the short- and long-term when provided flexibly within a specialist setting. Considering the high personal and societal costs of BDD, specialist care should be made more widely available.

5. Predicting Remission after Internet-Delivered Psychotherapy in Patients with Depression Using Machine Learning and Multi-Modal Data

   Wallert, John, Boberg, Julia, Kaldo, Viktor, Mataix-Cols, David,  Flygare, Oskar, Crowley, James J., Halvorsen, Matthew, Ben Abdesslem, Fehmi, Boman, Magnus, Andersson, Evelyn, Hentati Isacsson, Nils, Ivanova, Ekaterina, and Rück, Christian

   Translational Psychiatry Sep 2022

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

2021

1. Executive Functioning in Body Dysmorphic Disorder and Obsessive–Compulsive Disorder

   Chen, Long Long,  Flygare, Oskar, Wallert, John, Enander, Jesper, Ivanov, Volen Z., Rück, Christian, and Djurfeldt, Diana

   CNS Spectrums Jul 2021

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   Abstract Objective To assess executive functions (EFs) in patients with body dysmorphic disorder (BDD) and obsessive–compulsive disorder (OCD) compared with healthy controls. Methods Adults diagnosed with BDD (n = 26) or OCD (n = 29) according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and healthy controls (n = 28) underwent validated and computerized neuropsychological tests, spatial working memory (SWM), intra–extra-dimensional set shifting (IED), and stop signal task (SST), from the Cambridge Neuropsychological Test Automated Battery (CANTAB). Test performance was compared between groups, and correlated with standardized symptom severity of BDD and OCD. Significance level was set to P  < .05. Results There were no statistically significant between-group differences on key outcome measures in SWM, IED, or SST. There was a weak positive correlation between symptom severity and test errors on SWM and IED in both OCD and BDD groups; increased clinical severity was associated with more errors in these tests. Furthermore, there was a negative correlation between symptom severity and SST in the BDD group. Conclusions Patients with BDD or OCD did not differ from healthy control subjects in terms of test performance; however, there were several statistically significant correlations between symptom severity and performance in those with BDD or OCD. More studies on EFs in BDD and OCD are required to elucidate if there are differences in EFs between these two disorders.

2. Subjective Mental Health and Need for Care among Psychiatric Outpatients during the COVID-19 Pandemic: Results from an Outreach Initiative in Sweden

   Flygare, Oskar, Ivanov, Volen Z., Säll, Roland, Malaise, Henrik, Ivanova, Ekaterina, Rück, Christian, Jayaram-Lindström, Nitya, and Martinsson, Lina

   Psychiatry Research Oct 2021
3. Empirically Defining Treatment Response and Remission in Body Dysmorphic Disorder Using a Short Self-Report Instrument

   Flygare, Oskar, Chen, Long-Long, Fernández de la Cruz, Lorena, Enander, Jesper, Mataix-Cols, David, Rück, Christian, and Andersson, Erik

   Behavior Therapy Jul 2021
4. Validity and Reliability of the Diagnostic Codes for Hypochondriasis and Dysmorphophobia in the Swedish National Patient Register: A Retrospective Chart Review

   Rautio, Daniel, Vilaplana-Pérez, Alba, Gumpert, Martina, Ivanov, Volen Z., Linde, Johanna, Österman, Susanna,  Flygare, Oskar, Isung, Josef, Isomura, Kayoko, Krig, Sonja, Serlachius, Eva, Högström, Jens, Rück, Christian, Mataix-Cols, David, and Cruz, Lorena Fernández

   BMJ Open Dec 2021

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   Objectives In the International Classification of Diseases, Tenth Edition (ICD-10), hypochondriasis (illness anxiety disorder) and dysmorphophobia (body dysmorphic disorder) share the same diagnostic code (F45.2). However, the Swedish ICD-10 allows for these disorders to be coded separately (F45.2 and F45.2A, respectively), potentially offering unique opportunities for register-based research on these conditions. We assessed the validity and reliability of their ICD-10 codes in the Swedish National Patient Register (NPR). Design Retrospective chart review. Methods Six hundred individuals with a diagnosis of hypochondriasis or dysmorphophobia (300 each) were randomly selected from the NPR. Their medical files were requested from the corresponding clinics, located anywhere in Sweden. Two independent raters assessed each file according to ICD-10 definitions and Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision and Fifth Edition criteria. Raters also completed the Clinical Global Impression–Severity (CGI-S) and the Global Assessment of Functioning (GAF). Primary outcome measure Per cent between-rater agreement and positive predictive value (PPV). Intraclass correlation coefficients for the CGI-S and the GAF. Results Eighty-four hypochondriasis and 122 dysmorphophobia files were received and analysed. The inter-rater agreement rate regarding the presence or absence of a diagnosis was 95.2% for hypochondriasis and 92.6% for dysmorphophobia. Sixty-seven hypochondriasis files (79.8%) and 111 dysmorphophobia files (91.0%) were considered ‘true positive’ cases (PPV=0.80 and PPV=0.91, respectively). CGI-S scores indicated that symptoms were moderately to markedly severe, while GAF scores suggested moderate impairment for hypochondriasis cases and moderate to serious impairment for dysmorphophobia cases. CGI-S and GAF inter-rater agreement were good for hypochondriasis and moderate for dysmorphophobia. Conclusions The Swedish ICD-10 codes for hypochondriasis and dysmorphophobia are sufficiently valid and reliable for register-based studies. The results of such studies should be interpreted in the context of a possible over-representation of severe and highly impaired cases in the register, particularly for dysmorphophobia.

5. Swedish Nationwide Time Series Analysis of Influenza and Suicide Deaths from 1910 to 1978

   Rück, Christian, Mataix-Cols, David, Malki, Kinda, Adler, Mats,  Flygare, Oskar, Runeson, Bo, and Sidorchuk, Anna

   BMJ Open Jul 2021

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   Objectives There is concern that the COVID-19 pandemic will be associated with an increase in suicides, but evidence supporting a link between pandemics and suicide is limited. Using data from the three influenza pandemics of the 20th century, we aimed to investigate whether an association exists between influenza deaths and suicide deaths. Design Time series analysis. Setting Sweden. Participants Deaths from influenza and suicides extracted from the Statistical Yearbook of Sweden for 1910–1978, covering three pandemics (the Spanish influenza, the Asian influenza and the Hong Kong influenza). Main outcome measures Annual suicide rates in Sweden among the whole population, men and women. Non-linear autoregressive distributed lag models was implemented to explore if there is a short-term and/or long-term relationship of increases and decreases in influenza death rates with suicide rates during 1910–1978. Results Between 1910 and 1978, there was no evidence of either short-term or long-term significant associations between influenza death rates and changes in suicides (β coefficients of 0.00002, p=0.931 and β=0.00103, p=0.764 for short-term relationship of increases and decreases in influenza death rates, respectively, with suicide rates, and β=-0.0002, p=0.998 and β=0.00211, p=0.962 for long-term relationship of increases and decreases in influenza death rates, respectively, with suicide rates). The same pattern emerged in separate analyses for men and women. Conclusions We found no evidence of short-term or long-term association between influenza death rates and suicide death rates across three 20th century pandemics.

2020

1. Predictors of Remission from Body Dysmorphic Disorder after Internet-Delivered Cognitive Behavior Therapy: A Machine Learning Approach

   Flygare, Oskar, Enander, Jesper, Andersson, Erik, Ljótsson, Brjánn, Ivanov, Volen Z., Mataix-Cols, David, and Rück, Christian

   BMC Psychiatry Dec 2020
2. Adapted Cognitive Behavior Therapy for Obsessive–Compulsive Disorder with Co-Occurring Autism Spectrum Disorder: A Clinical Effectiveness Study

   Flygare, Oskar, Andersson, Erik, Ringberg, Helene, Hellstadius, Anna-Clara, Edbacken, Johan, Enander, Jesper, Dahl, Matti, Aspvall, Kristina, Windh, Indra, Russell, Ailsa, Mataix-Cols, David, and Rück, Christian

   Autism Jan 2020

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   Obsessive–compulsive disorder and autism spectrum disorder commonly co-occur. Adapted cognitive behavior therapy for obsessive–compulsive disorder in adults with autism spectrum disorder has not previously been evaluated outside the United Kingdom. In this study, 19 adults with obsessive–compulsive disorder and autism spectrum disorder were treated using an adapted cognitive behavior therapy protocol that consisted of 20 sessions focused on exposure with response prevention. The primary outcome was the clinician-rated Yale–Brown Obsessive–Compulsive Scale. Participants were assessed up to 3 months after treatment. There were significant reductions on the Yale–Brown Obsessive–Compulsive Scale at post-treatment (d\,= 1.5), and improvements were sustained at follow-up (d\,= 1.2). Self-rated obsessive–compulsive disorder and depressive symptoms showed statistically significant reductions. Improvements in general functioning and quality of life were statistically non-significant. Three participants (16%) were responders at post-treatment and four (21%) were in remission from obsessive–compulsive disorder. At follow-up, three participants (16%) were responders and one (5%) was in full remission. Adapted cognitive behavior therapy for obsessive–compulsive disorder in adults with co-occurring autism spectrum disorder is associated with reductions in obsessive–compulsive symptoms and depressive symptoms. However, outcomes are modest; few patients were completely symptom free, and treatment engagement was low with few completed exposures and low adherence to homework assignments. We identify and discuss the need for further treatment refinement for this vulnerable group.

2019

1. Long-Term Outcome of Therapist-Guided Internet-Based Cognitive Behavioural Therapy for Body Dysmorphic Disorder (BDD-NET): A Naturalistic 2-Year Follow-up after a Randomised Controlled Trial

   Enander, Jesper, Ljótsson, Brjánn, Anderhell, Lina, Runeborg, Martin,  Flygare, Oskar, Cottman, Oskar, Andersson, Erik, Dahlén, Sofia, Lichtenstein, Linn, Ivanov, Volen Z., Mataix-Cols, David, and Rück, Christian

   BMJ Open Jan 2019

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   Objectives Most patients with body dysmorphic disorder (BDD) do not receive evidence-based treatment. A randomised controlled trial (RCT) has found that a therapist-guided internet-based cognitive–behavioural therapy (CBT) programme for BDD (BDD-NET) can be delivered safely via the internet with significant improvements in BDD symptom severity in the short term. The purpose of this study was to evaluate if the therapeutic gains of BDD-NET are maintained 2 years after treatment. Setting Academic medical centre. Participants A naturalistic 2-year follow-up study of the 88 self-referred adult outpatients with a diagnosis of BDD that had received BDD-NET within the context of the RCT. Primary and secondary outcomes The primary outcome was the BDD-Yale-Brown Obsessive-Compulsive Scale (YBOCS). Responder status was defined as a ≥30% reduction in symptoms. Remission was defined as no longer meeting Diagnostic and Statistical Manual of Mental Disorders 5th edition criteria for BDD. Secondary outcomes included measures of depression, global functioning and quality of life. Results The efficacy of BDD-NET was sustained long- term, with further improvements observed on the BDD-YBOCS during the follow-up period. At follow-up, 69% (95% CI 57% to 80%) were classified as responders and 56% (95% CI 43% to 69%) were in remission. Gains on depressive symptoms and global functioning were also sustained but not quality of life. A majority of participants reported that the main reason for seeking help for their BDD was the possibility to access the treatment from home. Conclusion BDD-NET is an effective treatment for BDD, and the patients’ gains are maintained in the long term. BDD-NET has the potential to increase access to CBT and may lower the threshold for BDD sufferers to seek help in the first place. Trial registration number NCT02010619.

2. Internet-Based, Therapist-Guided, Cognitive–Behavioural Therapy for Body Dysmorphic Disorder with Global Eligibility for Inclusion: An Uncontrolled Pilot Study

   Gentile, Andrew J, La Lima, Christopher,  Flygare, Oskar, Enander, Jesper, Wilhelm, Sabine, Mataix-Cols, David, and Rück, Christian

   BMJ Open Mar 2019
3. Sudden Gains in Internet-Based Cognitive Behavior Therapy for Obsessive-Compulsive Disorder

   Hamdeh, Adel Abu, Bjureberg, Johan, Lenhard, Fabian, Hedman-Lagerlöf, Erik,  Flygare, Oskar, Lundström, Lina, Ljótsson, Brjánn, Mataix-Cols, David, Rück, Christian, and Andersson, Erik

   Journal of Obsessive-Compulsive and Related Disorders Apr 2019

2018

1. Enhancing Group Cognitive-Behavioral Therapy for Hoarding Disorder with between-Session Internet-based Clinician Support: A Feasibility Study

   Ivanov, Volen Z., Enander, Jesper, Mataix-Cols, David, Serlachius, Eva, Månsson, Kristoffer N.T., Andersson, Gerhard,  Flygare, Oskar, Tolin, David, and Rück, Christian

   Journal of Clinical Psychology Feb 2018

   Abs

   Objective Hoarding disorder (HD) is difficult to treat. In an effort to increase efficacy and engagement in cognitive-behavioral therapy (CBT), we developed and evaluated a novel intervention comprising group CBT combined with between-session Internet-based clinician support for people with HD. Method Twenty participants with HD received group CBT combined with an Internet-support system enabling therapist–participant communication between group sessions. Results The treatment was associated with a significant reduction on the Saving Inventory—Revised (SI-R) and a large effect size (Cohen’s d = 1.57) was found at posttreatment. Treatment gains were maintained at the 3-month follow-up. Group attendance was high and no participants dropped out from treatment prematurely. Between-session motivational support from the therapist was most frequently mentioned as the main strength of the system. Conclusion The results of this study support adding Internet-based clinician support to group CBT for HD to increase treatment adherence and, potentially, improve the overall efficacy of CBT.

2. Long-Term Social Skills Group Training for Children and Adolescents with Autism Spectrum Disorder: A Randomized Controlled Trial

   Jonsson, Ulf, Olsson, Nora Choque, Coco, Christina, Görling, Anders,  Flygare, Oskar, Råde, Anna, Chen, Qi, Berggren, Steve, Tammimies, Kristiina, and Bölte, Sven

   European Child & Adolescent Psychiatry May 2018

   Abs

   Social skills group training (SSGT) is widely used for intellectually able children and adolescents with autism spectrum disorder (ASD). Previous studies indicate small to moderate effects on social communication capacities. The duration of most available programs is relatively short, and extended training might lead to further improvement. This randomized controlled trial compared an extended 24-week version of the SSGT program KONTAKT with standard care. The weekly sessions gradually shifted in content from acquisition of new skills to real-world application of the acquired skills. A total of 50 participants with ASD (15 females; 35 males) aged 8–17 years were included. The study was conducted at two child and adolescent psychiatry outpatient units in Sweden. The primary outcome was the Social Responsiveness Scale–Second Edition (SRS-2) rated by parents and blinded teachers. Secondary outcomes included parent- and teacher-rated adaptive behaviors, trainer-rated global functioning and clinical severity, and self-reported child and caregiver stress. Assessments were made at baseline, posttreatment, and at 3-months follow-up. Parent-rated SRS-2 scores indicated large effects posttreatment [- 19.2; 95% CI - 29.9 to - 8.5; p < .001, effect size (ES) = 0.76], which were maintained at follow-up (- 20.7; 95% CI - 31.7 to - 9.7; p < .0001, ES = 0.82). These estimates indicate substantially larger improvement than previously reported for shorter SSGT. However, the effects on teacher-rated SRS-2 and most secondary outcomes did not reach statistical significance. Our results suggest added benefits of extended SSGT training, implying that service providers might reach better results by optimizing the delivery of SSGT.

3. Study Protocol for a Single-Blind, Randomised Controlled, Non-Inferiority Trial of Internet-Based versus Face-to-Face Cognitive Behaviour Therapy for Obsessive–Compulsive Disorder

   Rück, Christian, Lundström, Lina,  Flygare, Oskar, Enander, Jesper, Bottai, Matteo, Mataix-Cols, David, and Andersson, Erik

   BMJ Open Sep 2018

   Abs

   Introduction Expert guidelines recommend cognitive–behavioural therapy (CBT) as a first-line treatment for obsessive–compulsive disorder (OCD), but the majority of patients with OCD do not have access to CBT. Internet-delivered CBT (ICBT) has the potential to make this evidence-based treatment more accessible while requiring less therapist time than traditional face-to-face (f2f) CBT. Data from six clinical trials suggest that ICBT for OCD is both efficacious and cost-effective, but whether ICBT is non-inferior to traditional f2f CBT for OCD is yet unknown. Methods and analysis A single-blind, randomised, controlled, non-inferiority trial comparing therapist-guided ICBT, unguided ICBT and individual (f2f) CBT for adult OCD patients. The primary objective is to investigate whether ICBT is non-inferior to gold standard f2f CBT. Secondary objectives are to investigate if ICBT is equally effective when delivered unguided, to establish the cost-effectiveness of ICBT and to investigate if the treatment outcome differs between self-referred and clinically referred patients. Participants will be recruited at two specialist OCD clinics in Stockholm and also through online self-referral. Participants will be randomised to one of three treatment conditions: F2f CBT, ICBT with therapist support or unguided ICBT. The total number of participants will be 120, and masked assessments will be administered at baseline, biweekly during treatment, at post-treatment and at 3-month and 12-month follow-ups. The main outcome measure is the clinician-rated Yale-Brown Obsessive Compulsive Scale (Y-BOCS) at 3-month follow-up. The margin of non-inferiority is set to 3 points on the Y-BOCS using a 90% CI. Ethics and dissemination The study has been approved by the Regional Ethics Board of Stockholm (REPN 2015/1099-31/2) and registered at Clinicaltrials.gov (NCT02541968). The study will be reported in accordance with the Consolidated Standards of Reporting Trials statement for non-pharmacological trials. The results will be published in peer-reviewed academic journals and disseminated to patient organisations and media. Trial registration number NCT02541968; Pre-results.

2017

1. Social Skills Training for Children and Adolescents With Autism Spectrum Disorder: A Randomized Controlled Trial

   Olsson, Nora Choque,  Flygare, Oskar, Coco, Christina, Görling, Anders, Råde, Anna, Chen, Qi, Lindstedt, Katarina, Berggren, Steve, Serlachius, Eva, Jonsson, Ulf, Tammimies, Kristiina, Kjellin, Lars, and Bölte, Sven

   J. Am. Acad. Child Adolesc. Psychiatry May 2017

2013

1. Other People as Means to a Safe End

   Golkar, Armita, Selbing, Ida,  Flygare, Oskar, Ohman, Arne, and Olsson, Andreas

   Psychol. Sci. Jan 2013