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

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

The symptom-specific efficacy of antidepressant medication vs. cognitive behavioral therapy in the treatment of depression: results from an individual patient data meta-analysis

A recent individual patient data meta-analysis showed that antidepressant medication is slightly more efficacious than cognitive behavioral therapy (CBT) in reducing overall depression severity in patients with a DSM-defined depressive disorder. We used an update of that dataset, based on seventeen randomized clinical trials, to examine the comparative efficacy of antidepressant medication vs. CBT in more detail by focusing on individual depressive symptoms as assessed with the 17-item Hamilton Rating Scale for Depression. Five symptoms (i.e., “depressed mood”, “feelings of guilt”, “suicidal thoughts”, “psychic anxiety” and “general somatic symptoms”) showed larger improvements in the medication compared to the CBT condition (effect sizes ranging from.13 to.16), whereas no differences were found for the twelve other symptoms. In addition, network estimation techniques revealed that all effects, except that on “depressed mood”, were direct and could not be explained by any of the other direct or indirect treatment effects. Exploratory analyses showed that information about the symptom-specific efficacy could help in identifying those patients who, based on their pre-treatment symptomatology, are likely to benefit more from antidepressant medication than from CBT (effect size of.30) versus those for whom both treatments are likely to be equally efficacious. Overall, our symptom-oriented approach results in a more thorough evaluation of the efficacy of antidepressant medication over CBT and shows potential in “precision psychiatry”