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.

Working Alliance Inventory-Short Revised (WAI-SR): psychometric properties in outpatients and inpatients

The Working Alliance Inventory-Short Revised (WAI-SR) is a recently refined measure of the therapeutic alliance that assesses three key aspects of the therapeutic alliance: (a) agreement on the tasks of therapy, (b) agreement on the goals of therapy and (c) development of an affective bond. The WAI-SR demonstrated good psychometric properties in an initial validation in psychotherapy outpatients in the USA. The generalizability of these findings is limited because in some countries a substantial portion of individual psychotherapy is delivered in inpatient settings. This study investigated and compared the psychometric properties of the WAI-SR in German outpatients (N = 88) and inpatients (N = 243). In both samples reliability (alpha > 0.80) and convergent validity with the Helping Alliance Questionnaire were good (r > 0.64). Confirmatory factor analysis showed acceptable to good model fit for the proposed Bond-Task-Goal model in both samples. Multi-group analysis demonstrated that the same constructs were measured across settings. Alliance ratings of outpatients and inpatients differed regarding the overlap of alliance components and the magnitude of the alliance ratings: The differentiation of the alliance components was poorer in inpatients and they reported lower alliances. Unique aspects of the alliance in inpatient treatment are discussed and a need for further research on the alliance in inpatient settings is pointed out. Overall, the WAI-SR can be recommended for alliance assessment in both settings.

Testing the allegiance bias hypothesis: a meta-analysis

This meta-analysis investigated whether the association between researcher allegiance (RA) and the relative effect of two psychotherapies can be explained through the methodological weaknesses of the treatment comparisons. Seventy-nine comparisons of psychotherapies for depression or posttraumatic stress disorder (PTSD) were included. Methodological quality (MQ) was investigated as both a moderator and a mediator of the RA-outcome association. MQ included balanced nonspecific factors, balanced specific factors, conceptual quality, patients-per-therapist ratio, randomization to conditions and outcome assessment. The RA-outcome association was stronger when the MQ was low, suggesting a buffering effect of MQ. In addition, differences in the conceptual quality of treatments mediated the effect of RA on outcome. The results support the view that RA acts as a bias in treatment comparisons.

Identifying specific interpretations and use of safety behaviours in people with distressing visual hallucinations: an exploratory study

Visual hallucinations (VH) are a common experience and can be distressing and disabling, particularly for people suffering from psychotic illness. However, not everyone with visual hallucinations reports the experience to be distressing. Models of VH propose that appraisals of VH as a threat to wellbeing and the use of safety seeking behaviours help maintain the distress.

Diagnosis and treatment of an obsessive-compulsive disorder following traumatic brain injury: A single case and review of the literature

A 27-year-old patient with traumatic brain injury and neuropsychiatric symptoms fitting the obsessive-compulsive disorder was investigated. Brain CT-scan revealed left temporal and bilateral fronto-basal parenchymal contusions. Main Outcome Measure was the Yale-Brown Obsessive Compulsive Scale at pre- and post-treatment and at 6 months follow-up. The combination of pharmacotherapy and psychotherapy resulted in lower intensity and frequency of symptoms. Our case illustrates the importance of a detailed diagnostic procedure in order to provide appropriate therapeutic interventions. Further studies are needed to guide the clinician in determining which patients are likely to benefit from a psychotherapeutic intervention in combination with pharmacotherapy.

Is the allegiance effect an epiphenomenon of true efficacy differences between treatments? a meta-analysis

Many meta-analyses of comparative outcome studies found a substantial association of researcher allegiance (RA) and relative treatment effects. Therefore, RA is regarded as a biasing factor in comparative outcome research (RA bias hypothesis). However, the RA bias hypothesis has been criticized as causality might be reversed. That is, RA might be a reflection of true efficacy differences between treatments (true efficacy hypothesis). Consequently, the RA-outcome association would not be indicative of bias but an epiphenomenon of true efficacy differences. This meta-analysis tested the validity of the true efficacy hypothesis. This was done by controlling the RA-outcome association for true efficacy differences by restricting analysis to direct comparisons of treatments with equivalent efficacy. We included direct comparisons of different versions of trauma-focused therapy (TFT) in the treatment of posttraumatic stress disorder (PTSD). RA was measured from the research reports. Relative effect sizes for symptoms of PTSD were calculated. Random effects meta-regression was conducted. Twenty-nine comparisons of TFTs from 20 studies were identified. Initial heterogeneity among relative effect sizes was low. RA was a significant predictor of outcome and explained 12% of the variance in outcomes. The true efficacy hypothesis predicted the RA-outcome association to be zero; however, a substantial association was found. Thus, this study does not support the true efficacy hypothesis. Given findings from psychotherapy research and other fields that support a biasing influence of researcher preferences, RA should be regarded as a causal factor and conceptualized as a threat to the validity of conclusions from comparative outcome studies.

Tracking the implicit self using event-related potentials

Negative biases in implicit self-evaluation are thought to be detrimental to subjective well-being and have been linked to various psychological disorders, including depression. An understanding of the neural processes underlying implicit self-evaluation in healthy subjects could provide a basis for the investigation of negative biases in depressed patients, the development of differential psychotherapeutic interventions, and the estimation of relapse risk in remitted patients. We thus studied the brain processes linked to implicit self-evaluation in 25 healthy subjects using event-related potential (ERP) recording during a self-relevant Implicit Association Test (sIAT). Consistent with a positive implicit self-evaluation in healthy subjects, they responded significantly faster to the congruent (self-positive mapping) than to the incongruent sIAT condition (self-negative mapping). Our main finding was a topographical ERP difference in a time window between 600 and 700 ms, whereas no significant differences between congruent and incongruent conditions were observed in earlier time windows. This suggests that biases in implicit self-evaluation are reflected only indirectly, in the additional recruitment of control processes needed to override the positive implicit self-evaluation of healthy subjects in the incongruent sIAT condition. Brain activations linked to these control processes can thus serve as an indirect measure for estimating biases in implicit self-evaluation. The sIAT paradigm, combined with ERP, could therefore permit the tracking of the neural processes underlying implicit self-evaluation in depressed patients during psychotherapy.