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Background: The process of tailored implementation is ill-defined and under-explored. The ItFits-toolkit was developed and subsequently tested as a self-guided online platform to facilitate implementation of tailored strategies for internet-based cognitive behavioural therapy (iCBT) services. In ImpleMentAll, ItFits-toolkit had a small but positive effect on the primary outcome of iCBT normalisation. This paper investigates, from a qualitative perspective, how implementation teams developed and undertook tailored implementation using the toolkit within the trial. Methods: Implementation teams in thirteen sites from nine countries (Europe and Australia) used the ItFits-toolkit for six months minimum, consistent with the trial protocol. A qualitative process evaluation was conducted. Descriptive data regarding goals, barriers, strategies, and implementation plans collected within the toolkit informed qualitative data collection in real time. Qualitative data included remote longitudinal interviews (n = 55) with implementation team members (n = 30) and observations of support calls (n = 19) with study sites. Qualitative data were analysed thematically, using a team-based approach. Results: Implementation teams developed and executed tailored implementation projects across all steps in the toolkit process. Working in a structured way but with room for flexibility, decisions were shaped by team members' ideas and goals, iterative stakeholder engagement, internal and external influences, and the context of the ImpleMentAll project. Although teams reported some positive impacts of their projects, 'time', both for undertaking the work, and for seeing project impacts, was described as a key factor in decisions about implementation strategies and assessments of success. Conclusion: This study responds directly to McHugh et al.'s (2022) call for empirical description of what implementation tailoring looks like in action, in service settings. Self-guided facilitation of tailored implementation enables implementers in service settings to undertake tailoring within their organisations. Implementation tailoring takes considerable time and involves detailed work but can be supported through the provision of implementation science informed guidance and materials, iterative and ongoing stakeholder engagement, and working reflectively in response to external influencing factors. Directions for advancement of tailored implementation are suggested. [ABSTRACT FROM AUTHOR]

Background: Although clozapine is the most effective antipsychotic drug for treatment-resistant schizophrenia, it leads to a poor or partial response in 40 to 70% of patients. Augmentation of clozapine with electroconvulsive therapy (ECT) is a highly effective and relatively safe treatment for these clozapine-resistant patients. However, parameters are not yet well specified, such as the optimal number of sessions, their frequency, and the relevance of maintenance ECT. Our objective is to compare the efficacy and tolerance between two protocols of combined ECT and clozapine treatment in patients with ultra-resistant schizophrenia (URS): a 6-month protocol (short protocol with 20 ECT sessions) and a 12-month protocol (long protocol with 40 ECT sessions).Methods: Sixty-four patients with schizophrenia with persistent psychotic symptoms despite clozapine treatment will be enrolled in a prospective multicentric assessor-blinded randomized controlled trial. Patients will be randomly assigned to the short or the long protocol. The main outcome is the response rate assessed by the Positive and Negative Symptoms Scale (PANSS) 3 months after the end of the treatment in patients following the long protocol compared to those following the short protocol. The response was defined as a 30% reduction on the PANSS baseline. Clinical assessments (PANSS, BPRS, HAMD-21, YMRS, CGI, GAF, Modified Overt Aggression Scale (MOAS), and Subjective Scale to Investigate Cognition in Schizophrenia (SSTICS)) and plasma clozapine concentration will be performed at baseline and at 2, 4, 6, 9, 12, and 15 months. Neuropsychological measures (MMSE, RL/RI-16, Doors test, D2 Test of Attention, Copy of the Rey-Osterrieth complex figure) will be performed at baseline and at 6 and 15 months.Discussion: The aims of this research are to optimize protocols of combined ECT with clozapine in patients with URS and to offer specific recommendations for these patients' care.Trial Registration: ClinicalTrials.gov NCT03542903 . Registered on May 31, 2018. Id RCB: 2017-A02657-46. [ABSTRACT FROM AUTHOR]

Background: It is well known that the standard doses of a given drug may not have equivalent effects in all patients. To date, the management of depression remains mainly empirical and often poorly evaluated. The development of a personalized medicine in psychiatry may reduce treatment failure, intolerance or resistance, and hence the burden and costs of mood depressive disorders. The Geneva Cocktail Phenotypic approach presents several advantages including the "in vivo" measure of different cytochromes and transporter P-gp activities, their simultaneous determination in a single test, avoiding the influence of variability over time on phenotyping results, the administration of low dose substrates, a limited sampling strategy with an analytical method developed on DBS analysis. The goal of this project is to explore the relationship between the activity of drug-metabolizing enzymes (DME), assessed by a phenotypic approach, and the concentrations of Venlafaxine (VLX) + O-demethyl-venlafaxine (ODV), the efficacy and tolerance of VLX. Methods/design: This study is a multicentre prospective non-randomized open trial. Eligible patients present a major depressive episode, MADRS over or equal to 20, treatment with VLX regardless of the dose during at least 4 weeks. The Phenotype Visit includes VLX and ODV concentration measurement. Following the oral absorption of low doses of omeprazole, midazolam, dextromethorphan, and fexofenadine, drug metabolizing enzymes activity is assessed by specific metabolite/probe concentration ratios from a sample taken 2 h after cocktail administration for CYP2C19, CYP3A4, CYP2D6; and by the determination of the limited area under the curve from the capillary blood samples taken 2-3 and 6 h after cocktail administration for CYP2C19 and P-gp. Two follow-up visits will take place between 25 and 40 days and 50-70 days after inclusion. They include assessment of efficacy, tolerance and observance. Eleven french centres are involved in recruitment, expected to be completed within approximately 2 years with 205 patients. Metabolic ratios are determined in Geneva, Switzerland. Discussion: By showing an association between drug metabolism and VLX concentrations, efficacy and tolerance, there is a hope that testing drug metabolism pathways with a phenotypical approach would help physicians in selecting and dosing antidepressants. The MARVEL study will provide an important contribution to increasing the knowledge of VLX variability and in optimizing the use of methods of personalized therapy in psychiatric settings. Trial registration: ClinicalTrials.gov NCT02590185 (10/27/2015). This study is currently recruiting participants. [ABSTRACT FROM AUTHOR]