The effects of psychotherapy for depression on anxiety symptoms: a meta-analysis

Background More than half of patients who present with depressive disorders also have elevated comorbid anxiety symptoms. Given the high comorbidity between these disorders, it is important to understand the extent that psychotherapies for depression additionally ameliorate symptoms of anxiety.Methods Systematic searches were conducted in PubMed, PSYCinfo, EMBASE, and the Cochrane Registry of Controlled Trials. Included studies were randomized controlled trials that compared psychotherapy compared with a control condition for the treatment of adults with a primary diagnosis or elevated symptoms of depression and that examined the effects of treatment on anxiety outcomes. Acute phase depression and anxiety (continuous measure) outcomes were extracted. Effect sizes were calculated by subtracting the average post-treatment scores of the psychotherapy group from the average post-treatment scores of the comparison group divided by the pooled standard deviation.Results Fifty-two studies of varying quality met the inclusion criteria. Pooled effect sizes showed that anxiety outcomes were significantly lower in the psychotherapy conditions than in control conditions at post-treatment [g = 0.52; 95% confidence interval (CI) 0.44-0.60; NNT (numbers-needed-to-treat) = 3.50]. Moderate heterogeneity was observed (I2 = 55%, 95% CI 40-66). Bivariate metaregression analysis revealed a significant association between depression and anxiety effect sizes at post-treatment Longer-term follow-ups of up to 14 months post-baseline showed indications for a small lasting effect of psychotherapy on anxiety outcomes (g = 0.27).Conclusions This meta-analysis provides evidence that psychotherapy aimed at depression can also reduce anxiety symptoms in relation to control conditions

Initial severity of depression and efficacy of cognitive-behavioural therapy: individual-participant data meta-analysis of pill-placebo-controlled trials

BACKGROUND: The influence of baseline severity has been examined for antidepressant medications but has not been studied properly for cognitive-behavioural therapy (CBT) in comparison with pill placebo. AIMS: To synthesise evidence regarding the influence of initial severity on efficacy of CBT from all randomised controlled trials (RCTs) in which CBT, in face-to-face individual or group format, was compared with pill-placebo control in adults with major depression. METHOD: A systematic review and an individual-participant data meta-analysis using mixed models that included trial effects as random effects. We used multiple imputation to handle missing data. RESULTS: We identified five RCTs, and we were given access to individual-level data (n = 509) for all five. The analyses revealed that the difference in changes in Hamilton Rating Scale for Depression between CBT and pill placebo was not influenced by baseline severity (interaction P = 0.43). Removing the non-significant interaction term from the model, the difference between CBT and pill placebo was a standardised mean difference of -0.22 (95% CI -0.42 to -0.02, P = 0.03, I2 = 0%). CONCLUSIONS: Patients suffering from major depression can expect as much benefit from CBT across the wide range of baseline severity. This finding can help inform individualised treatment decisions by patients and their clinicians.R01 MH060998 - NIMH NIH HHS; R34 MH086668 - NIMH NIH HHS; R01 AT007257 - NCCIH NIH HHS; R21 MH101567 - NIMH NIH HHS; K02 MH001697 - NIMH NIH HHS; R01 MH060713 - NIMH NIH HHS; R34 MH099311 - NIMH NIH HHS; R21 MH102646 - NIMH NIH HHS; K23 MH100259 - NIMH NIH HHS; R01 MH099021 - NIMH NIH HH

Cognitive-Behavioural Analysis System of Psychotherapy (CBASP), a drug, or their combination: differential therapeutics for persistent depressive disorder: a study protocol of an individual participant data network meta-analysis.

INTRODUCTION Despite important advances in psychological and pharmacological treatments of persistent depressive disorders in the past decades, their responses remain typically slow and poor, and differential responses among different modalities of treatments or their combinations are not well understood. Cognitive-Behavioural Analysis System of Psychotherapy (CBASP) is the only psychotherapy that has been specifically designed for chronic depression and has been examined in an increasing number of trials against medications, alone or in combination. When several treatment alternatives are available for a certain condition, network meta-analysis (NMA) provides a powerful tool to examine their relative efficacy by combining all direct and indirect comparisons. Individual participant data (IPD) meta-analysis enables exploration of impacts of individual characteristics that lead to a differentiated approach matching treatments to specific subgroups of patients. METHODS AND ANALYSIS We will search for all randomised controlled trials that compared CBASP, pharmacotherapy or their combination, in the treatment of patients with persistent depressive disorder, in Cochrane CENTRAL, PUBMED, SCOPUS and PsycINFO, supplemented by personal contacts. Individual participant data will be sought from the principal investigators of all the identified trials. Our primary outcomes are depression severity as measured on a continuous observer-rated scale for depression, and dropouts for any reason as a proxy measure of overall treatment acceptability. We will conduct a one-step IPD-NMA to compare CBASP, medications and their combinations, and also carry out a meta-regression to identify their prognostic factors and effect moderators. The model will be fitted in OpenBUGS, using vague priors for all location parameters. For the heterogeneity we will use a half-normal prior on the SD. ETHICS AND DISSEMINATION This study requires no ethical approval. We will publish the findings in a peer-reviewed journal. The study results will contribute to more finely differentiated therapeutics for patients suffering from this chronically disabling disorder. TRIAL REGISTRATION NUMBER CRD42016035886

Homogeneous low-molecular-weight heparins with reversible anticoagulant activity

Low-molecular-weight heparins (LMWHs) are carbohydrate-based anticoagulants clinically used to treat thrombotic disorders, but impurities, structural heterogeneity or functional irreversibility can limit treatment options. We report a series of synthetic LMWHs prepared by cost-effective chemoenzymatic methods. The high activity of one defined synthetic LMWH against human factor Xa (FXa) was reversible in vitro and in vivo using protamine, demonstrating that synthetically accessible constructs can have a critical role in the next generation of LMWHs

Strengthening mental health care systems for Syrian refugees in Europe and the Middle East: integrating scalable psychological interventions in 8 countries

The crisis in Syria has resulted in vast numbers of refugees seeking asylum in Syria’s neighbouring countries as well as in Europe. Refugees are at considerable risk of developing common mental disorders, including depression, anxiety, and posttraumatic stress disorder (PTSD). Most refugees do not have access to mental health services for these problems because of multiple barriers in national and refugee specific health systems, including limited availability of mental health professionals. To counter some of challenges arising from limited mental health system capacity the World Health Organization (WHO) has developed a range of scalable psychological interventions aimed at reducing psychological distress and improving functioning in people living in communities affected by adversity. These interventions, including Problem Management Plus (PM+) and its variants, are intended to be delivered through individual or group face to face or smartphone formats by lay, non-professional people who have not received specialized mental health training, We provide an evidence-based rationale for the use of the scalable PM+ oriented programmes being adapted for Syrian refugees and provide information on the newly launched STRENGTHS programme for adapting, testing and scaling up of PM+ in various modalities in both neighbouring and European countries hosting Syrian refugees

Cognitive-Behavioral Analysis System of Psychotherapy, Drug, or Their Combination for Persistent Depressive Disorder: Personalizing the Treatment Choice Using Individual Participant Data Network Metaregression.

BACKGROUND Persistent depressive disorder is prevalent, disabling, and often difficult to treat. The cognitive-behavioral analysis system of psychotherapy (CBASP) is the only psychotherapy specifically developed for its treatment. However, we do not know which of CBASP, antidepressant pharmacotherapy, or their combination is the most efficacious and for which types of patients. This study aims to present personalized prediction models to facilitate shared decision-making in treatment choices to match patients' characteristics and preferences based on individual participant data network metaregression. METHODS We conducted a comprehensive search for randomized controlled trials comparing any two of CBASP, pharmacotherapy, or their combination and sought individual participant data from identified trials. The primary outcomes were reduction in depressive symptom severity for efficacy and dropouts due to any reason for treatment acceptability. RESULTS All 3 identified studies (1,036 participants) were included in the present analyses. On average, the combination therapy showed significant superiority over both monotherapies in terms of efficacy and acceptability, while the latter 2 treatments showed essentially similar results. Baseline depression, anxiety, prior pharmacotherapy, age, and depression subtypes moderated their relative efficacy, which indicated that for certain subgroups of patients either drug therapy or CBASP alone was a recommendable treatment option that is less costly, may have fewer adverse effects and match an individual patient's preferences. An interactive web app (https://kokoro.med.kyoto-u.ac.jp/CBASP/prediction/) shows the predicted disease course for all possible combinations of patient characteristics. CONCLUSIONS Individual participant data network metaregression enables treatment recommendations based on individual patient characteristics

Which patients benefit specifically from short-term psychodynamic psychotherapy (STPP) for depression? Study protocol of a systematic review and meta-analysis of individual participant data

INTRODUCTION: Short-term psychodynamic psychotherapy (STPP) is an empirically supported treatment that is often used to treat depression. However, it is largely unclear if certain subgroups of depressed patients can benefit specifically from this treatment method. We describe the protocol for a systematic review and meta-analysis of individual participant data (IPD) aimed at identifying predictors and moderators of STPP for depression efficacy. METHOD AND ANALYSIS: We will conduct a systematic literature search in multiple bibliographic databases (PubMed, PsycINFO, Embase.com, Web of Science and Cochrane's Central Register of Controlled Trials), 'grey literature' databases (GLIN and UMI ProQuest) and a prospective trial register (http://www.controlled-trials.com). We will include studies reporting (a) outcomes on standardised measures of (b) depressed (c) adult patients (d) receiving STPP. We will next invite the authors of these studies to share the participant-level data of their trials and combine these data to conduct IPD meta-analyses. The primary outcome for this study is post-treatment efficacy as assessed by a continuous depression measure. Potential predictors and moderators include all sociodemographic variables, clinical variables and psychological patient characteristics that are measured before the start of treatment and are assessed consistently across studies. One-stage IPD meta-analyses will be conducted using mixed-effects models. ETHICS AND DISSEMINATION: Institutional review board approval is not required for this study. We intend to submit reports of the outcomes of this study for publication to international peer-reviewed journals in the fields of psychiatry or clinical psychology. We also intend to present the outcomes at international scientific conferences aimed at psychotherapy researchers and clinicians. The findings of this study can have important clinical implications, as they can inform expectations of STPP efficacy for individual patients, and help to make an informed choice concerning the best treatment option for a given patient. PROSPERO REGISTRATION NUMBER: CRD42017056029