| 1. |
- Andersson, Evelyn, et al.
(författare)
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Genetics of response to cognitive behavior therapy in adults with major depression : a preliminary report
- 2019
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Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 24:4, s. 484-490
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Boman, Magnus, et al.
(författare)
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Learning machines in Internet-delivered psychological treatment
- 2019
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Ingår i: Progress in Artificial Intelligence. - : Springer Verlag. - 2192-6352 .- 2192-6360. ; 8:4, s. 475-485
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 3. |
- Forsell, Erik, et al.
(författare)
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Development of a very brief scale for detecting and measuring panic disorder using two items from the Panic Disorder Severity Scale-Self Report
- 2019
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Ingår i: Journal of Affective Disorders. - : Elsevier. - 0165-0327 .- 1573-2517. ; 257, s. 615-622
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 4. |
- Forsell, Erik, et al.
(författare)
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Internet delivered cognitive behavior therapy for antenatal depression : A randomised controlled trial
- 2017
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Ingår i: Journal of Affective Disorders. - Amsterdam, Netherlands : Elsevier. - 0165-0327 .- 1573-2517. ; 221, s. 56-64
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 5. |
- Forsell, Erik, et al.
(författare)
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Proof of Concept for an Adaptive Treatment Strategy to Prevent Failures in Internet-Delivered CBT : A Single-Blind Randomized Clinical Trial With Insomnia Patients
- 2019
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Ingår i: American Journal of Psychiatry. - : American Psychiatric Association Publishing. - 0002-953X .- 1535-7228. ; 176:4, s. 315-323
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 6. |
- Heinonen, Essi, et al.
(författare)
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MAGDALENA : study protocol of a randomised, placebo-controlled trial on cognitive development at 2 years of age in children exposed to SSRI in utero
- 2018
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 8:8
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Ten per cent of all pregnant women are depressed. Standard therapy of pregnant women with moderate depression is selective serotonin reuptakeinhibitors (SSRI). Observational studies on neurodevelopment after fetal SSRI exposure show conflicting results. Our primary objective is to compare the cognitive development in children exposed to sertraline and maternal depression with those exposed to maternal depression and placebo in utero. We hypothesise that there is a significant neurodevelopmental difference between the groups. As a secondary objective, we study the add-on effect of sertraline to internet-based cognitive behavioural therapy (ICBT) to treat moderate depression during pregnancy. Methods and analysis MAGDALENA is a randomised, placebo-controlled, double-blinded trial in Stockholm Healthcare Region with 2.3 million inhabitants. The women are recruited in weeks 9-21 of pregnancy either through Antenatal Health Clinics or through social media. They are to be diagnosed with moderate depression without ongoing antidepressive therapy or any serious comorbidity. The women in the intervention arm receive sertraline combined with a 12-week period of ICBT; the control arm is treated with placebo and ICBT. We assess the cognitive development in the offspring at the age of 2 years using Bayley Scales of Infant and Toddler Development, third edition (BSID-III). We aim at recruiting 200 women, 100 women in each treatment arm, to ensure statistical power to detect a clinically relevant difference between the groups. Ethics and dissemination This randomised trial will provide long-sought evidence about the effects of SSRI and maternal depression during pregnancy on the neurodevelopment in the offspring. The study is approved by the Regional Ethical Review Board at Karolinska Institutet in Stockholm and the Swedish Medical Products Agency. It is registered with the European Clinical Trials Database (EudraCT), Number: 2013-004444-31. Results will be disseminated at scientific conferences, published in peer-reviewed journals and made available to the public.
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| 7. |
- Kraepelien, Martin, et al.
(författare)
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Comparing individually tailored to disorder-specific internet-based cognitive-behavioural therapy : benchmarking study
- 2018
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Ingår i: BJPsych Open. - Cambridge : Royal College of Psychiatrists. - 2056-4724. ; 4:4, s. 282-284
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Tidskriftsartikel (refereegranskat)abstract
- Disorder-specific internet-based cognitive-behavioural therapy (ICBT) is effective for depression, panic disorder and social anxiety. In this benchmarking study, a new, individually tailored, ICBT programme (TAIL) showed effects on depression (n = 284, d = 1.33) that were non-inferior to disorder-specific ICBT for depression in routine care (n = 2358, d = 1.35). However, the hypotheses that TAIL for individuals with social anxiety or panic disorder is inferior to disorder-specific ICBT could not be rejected (social anxiety: TAIL d = 0.74 versus disorder-specific d = 0.81; panic: TAIL d = 1.11 versus disorder-specific d = 1.47). Our findings strengthen the empirical base for TAIL as an alternative to disorder-specific ICBT for depression.
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| 8. |
- Kraepelien, Martin, et al.
(författare)
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Cost-effectiveness of internet-based cognitive-behavioural therapy and physical exercise for depression
- 2018
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Ingår i: BJPsych Open. - Cambridge : Cambridge University Press. - 2056-4724. ; 4:4, s. 265-273
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Tidskriftsartikel (refereegranskat)abstract
- Background Both internet-based cognitive-behavioural therapy (ICBT) and physical exercise are alternatives to treatment as usual (TAU) in managing mild to moderate depression in primary care. Aims To determine the cost-effectiveness of ICBT and physical exercise compared with TAU in primary care. Method Economic evaluation of a randomised controlled trial (N=945) in Sweden. Costs were estimated by a service use questionnaire and used together with the effects on quality-adjusted life-years (QALYs). The primary 3-month healthcare provider perspective in primary care was complemented by a 1-year societal perspective. Results The primary analysis showed that incremental cost per QALY gain was (sic)8817 for ICBT and (sic)14 571 for physical exercise compared with TAU. At the established willingness-to-pay threshold of (sic) 21 536 ( pound 20 000) per QALY, the probability of ICBT being cost-effective is 90%, and for physical exercise is 76%, compared with TAU. Conclusions From a primary care perspective, both ICBT and physical exercise for depression are likely to be cost-effective compared with TAU. (c) The Royal College of Psychiatrists 2018.
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| 9. |
- Pelcman, Benjamin, et al.
(författare)
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3-Substituted pyrazoles and 4-substituted triazoles as inhibitors of human 15-lipoxygenase-1
- 2015
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Ingår i: Bioorganic & Medicinal Chemistry Letters. - : Elsevier BV. - 0960-894X .- 1464-3405. ; 25:15, s. 3024-3029
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Tidskriftsartikel (refereegranskat)abstract
- Investigation of 1N-substituted pyrazole-3-carboxanilides as 15-lipoxygenase-1 (15-LOX-1) inhibitors demonstrated that the 1N-substituent was not essential for activity or selectivity. Additional halogen substituents on the pyrazole ring, however, increased activity. Further development led to triazole-4-carboxanilides and 2-(3-pyrazolyl) benzoxazoles, which are potent and selective 15-LOX-1 inhibitors.
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| 10. |
- Pelcman, Benjamin, et al.
(författare)
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N-Substituted pyrazole-3-carboxamides as inhibitors of human 15-lipoxygenase
- 2015
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Ingår i: Bioorganic & Medicinal Chemistry Letters. - : Elsevier BV. - 0960-894X .- 1464-3405. ; 25:15, s. 3017-3023
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Tidskriftsartikel (refereegranskat)abstract
- High-throughput screening was used to find selective inhibitors of human 15-lipoxygenase-1 (15-LOX-1). One hit, a 1-benzoyl substituted pyrazole-3-carboxanilide (1a), was used as a starting point in a program to develop potent and selective 15-LOX-1 inhibitors.
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