Repetitive transcranial magnetic stimulation (r-TMS) and selective serotonin reuptake inhibitor-resistance in obsessive-compulsive disorder: A meta-analysis and clinical implications.

INTRODUCTION: Despite promising results from several randomized controlled trials (RCTs) and meta-analyses, the efficacy of r-TMS as a treatment for OCD remains controversial, at least in part owing to inconsistency in the trial methodologies and heterogeneity in the trial outcomes. This meta-analysis attempts to explain some of this heterogeneity by comparing the efficacy of r-TMS in patients with or without resistance to treatment with selective serotonin reuptake inhibitors (SSRI), defined using standardized criteria. METHODS: We conducted a pre-registered (PROSPERO ID: 241381) systematic review and meta-analysis. English language articles reporting blinded RCTs were retrieved from searches using MEDLINE, PsycINFO, and Cochrane Library databases. Studies were subjected to subgroup analysis based on four stages of treatment resistance, defined using an adaptation of published criteria (1 = not treatment resistant, 2 = one SSRI trial failed, 3 = two SSRI trials failed, 4 = two SSRI trials failed plus one or more CBT trial failed). Meta-regression analyses investigated patient and methodological factors (age, duration of OCD, illness severity, stage of treatment-resistance, or researcher allegiance) as possible moderators of effect size. RESULTS: Twenty-five independent comparisons (23 studies) were included. Overall, r-TMS showed a medium-sized reduction of Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores (Hedge's g: -0.47; 95%CI: - 0.67 to -0.27) with moderate heterogeneity (I2 = 39.8%). Assessment of publication bias using Trim and Fill analysis suggested a reduced effect size that remained significant (g: -0.29; 95%CI: -0.51 to -0.07). Subgroup analysis found that those studies including patients non-resistant to SSRI (stage 1) (g: -0.65; 95%CI: -1.05 to -0.25, k = 7) or with low SSRI-resistance (stage 2) (g:-0.47; 95%CI: -0.86 to -0.09, k = 6) produced statistically significant results with low heterogeneity, while studies including more highly resistant patients at stage 3 (g: -0.39; 95%CI: -0.90 to 0.11, k = 4) and stage 4 (g: -0.36; 95%CI: -0.75 to 0.03, k = 8) did not. Intriguingly, the only significant moderator of the effect size found by meta-regression was the severity of baseline depressive symptoms. All trials showed evidence of researcher allegiance in favour of the intervention and therefore caution is required in interpreting the reported effect sizes. CONCLUSION: This meta-analysis shows that r-TMS is an effective treatment for OCD, but largely for those not resistant to SSRI or failing to respond to only one SSRI trial. As a consequence, r-TMS may be best implemented earlier in the care pathway. These findings would have major implications for clinical service development, but further well-powered RCTs, which eliminate bias from researcher allegiance, are needed before definitive conclusions can be drawn.

Efficacy of group psychotherapy for anxiety disorders: A systematic review and meta-analysis.

Objective: This meta-analysis evaluates the efficacy of group psychotherapy in the treatment of anxiety disorders. Method: A comprehensive literature search using PubMed, PsychInfo, Web of Science, CENTRAL, and manual searches was conducted to locate randomized controlled trials. We found 57 eligible studies (k = 76 comparisons) including 3656 participants receiving group psychotherapy or an alternative treatment for generalized anxiety disorder, social anxiety disorder, and panic disorder. Results: Effect size estimates show that group psychotherapy reduces specific symptoms of anxiety disorders more effectively than no-treatment control groups (g = 0.92, [0.81; 1.03], k = 43) and treatments providing common unspecific treatment factors (g = 0.29 [0.10; 0.48], k = 12). No significant differences were found compared to individual psychotherapy (g = 0.24 [-0.09; 0.57], k = 7) or pharmacotherapy (g = -0.05 [-0.33; 0.23], k = 6). The effects were unrelated to factors of the group treatment. Within head-to-head studies, a significant moderating effect emerged for researcher allegiance. Conclusions: Our results support the efficacy of group psychotherapy for anxiety disorders. They indicate that mixed-diagnoses groups are equally effective as diagnosis-specific groups, although further evidence is required. Future primary studies should address differential effectiveness, include a wider range of therapeutic approaches as well as active comparison groups.

Allegiance effects in mindfulness-based interventions for psychiatric disorders: A meta-re-analysis.

Objectives: A recent meta-analysis reported that mindfulness-based interventions (MBIs) outperform specific active control conditions but not evidence-based treatments (EBTs) across various psychiatric conditions. Given both comparison conditions represent bona fide treatments, the superiority of MBIs over other bona fide treatments is unexpected. The current study examined researcher allegiance (RA) as a potential source of bias that may explain this result. Method: All studies from the original meta-analysis that compared MBIs with bona fide psychological treatments were included. RA was independently coded using established methods. A series of meta-analyses examined the RA-outcome association and the degree to which RA may account for the effect of EBT status. Results: Sixty independent comparisons (n = 5,627) were included. MBIs outperformed bona fide treatment comparisons overall (g = 0.13), but effects were smaller with EBT comparisons. RA towards MBIs was associated with larger effects. No evidence for superiority of MBIs was found when RA was absent or balanced. Further, EBT status no longer predicted effects when controlling for RA. Conclusions: RA appears to be a potential source of bias in MBI research that should be considered when interpreting existing studies (clinical trials, meta-analyses) and planning future studies. RA may account for smaller effects when using EBT comparisons.

A Systematic Appraisal of Conflicts of Interest and Researcher Allegiance in Clinical Studies of Dry Needling for Musculoskeletal Pain Disorders.

OBJECTIVE: The purpose of this study was to determine the frequency and methods of conflicts of interest (COI) reporting in published dry needling (DN) studies and to determine the frequency of researcher allegiance (RA). METHODS: A pragmatic systematic search was undertaken to identify DN studies that were included in systematic reviews. Information regarding COI and RA were extracted from the full text of the published DN reports, and study authors were sent a survey inquiring about the presence of RA. A secondary analysis also was undertaken based on study quality/risk of bias scores that were extracted from the corresponding systematic reviews and study funding extracted from each DN study. RESULTS: Sixteen systematic reviews were identified, containing 60 studies of DN for musculoskeletal pain disorders, 58 of which were randomized controlled trials. Of the DN studies, 53% had a COI statement. None of these studies disclosed a COI. Nineteen (32%) authors of DN studies responded to the survey. According to the RA survey, 100% of DN studies included at least 1 RA criterion. According to the data extraction, 1 RA criterion was met in 45% of the DN studies. The magnitude of RA per study was 7 times higher according to the surveys than in the published reports. CONCLUSION: These results suggest that COI and RA might be underreported in studies of DN. In addition, authors of DN studies might be unaware of the potential influence of RA on study results and conclusions. IMPACT: Improved reporting of COI/RA might improve credibility of results and help identify the various factors involved in complex interventions provided by physical therapists. Doing so could help optimize treatments for musculoskeletal pain disorders provided by physical therapists.

Researcher allegiance in research on psychosocial interventions: meta-research study protocol and pilot study.

INTRODUCTION: One potential source of bias in randomised clinical trials of psychological interventions is researcher allegiance (RA). The operationalisation of RA differs strongly across studies, and there is not a generally accepted method of operationalising or measuring it. Furthermore, it remains unclear as to how RA affects the outcomes of trials and if it results in better outcomes for a preferred intervention. The aim of this project is to develop and validate a scale that accurately identifies RA, contribute to the understanding of the impact that RA has in a research setting and to make recommendations for addressing RA in practice. METHODS AND ANALYSIS: A scale will first be developed and validated to measure RA in psychotherapy trials. The scale will be validated by surveying authors of psychotherapy trials to assess their opinions, beliefs and preferences of psychotherapy interventions. Furthermore, the scale will be validated for use outside the field of psychotherapy. The validated checklist will then be used to examine two potential mechanisms of how RA may affect outcomes of interventions: publication bias (by assessing grants) and risk of bias (RoB). Finally, recommendations will be developed, and a feasibility study will be conducted at a national mental health agency in The Netherlands. Main analyses comprise inter-rater reliability of checklist items, correlations to examine the relationship between checklist items and author survey (convergent validity) as well as checklist items and trial outcomes and multivariate meta-regression techniques to assess potential mechanisms of how allegiance affects trial outcomes (publication bias and RoB). ETHICS AND DISSEMINATION: This study has been reviewed and approved by the Scientific and Ethical Review Board (VCWE) at the Vrije Universiteit Amsterdam. Study result and advancements will also be published on the Open Science Framework. Furthermore, main findings will be disseminated through articles in international peer-reviewed open access journals. Results and recommendations will be communicated to the Cochrane Collaboration, the Campbell Collaboration and other funding agencies.

How to prove that your therapy is effective, even when it is not: a guideline.

AIMS: Suppose you are the developer of a new therapy for a mental health problem or you have several years of experience working with such a therapy, and you would like to prove that it is effective. Randomised trials have become the gold standard to prove that interventions are effective, and they are used by treatment guidelines and policy makers to decide whether or not to adopt, implement or fund a therapy. METHODS: You would want to do such a randomised trial to get your therapy disseminated, but in reality your clinical experience already showed you that the therapy works. How could you do a trial in order to optimise the chance of finding a positive effect? RESULTS: Methods that can help include a strong allegiance towards the therapy, anything that increases expectations and hope in participants, making use of the weak spots of randomised trials (risk of bias), small sample sizes and waiting list control groups (but not comparisons with existing interventions). And if all that fails one can always not publish the outcomes and wait for positive trials. CONCLUSIONS: Several methods are available to help you show that your therapy is effective, even when it is not.