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Background Shared decision-making (SDM) is a model of interaction between doctors and patients in which both actors contribute to the medical decision-making process. SDM has raised great interest in mental healthcare over the last decade, as it is considered a fundamental part of patient-centered care. However, there is no research evaluating the efficacy of SDM compared to usual care (CAU), as it relates to quality of care and more specifically treatment adherence, in bipolar disorder (BD). Methods/Design This is a 12-month multi-centre, cluster-randomized controlled trial comparing the efficacy of SDM to CAU. Adult BD patients ( n  = 300) will be eligible after stabilization for at least 4 weeks following an acute mood episode. The intervention will consist of applying the standardized SDM process as developed by the Ottawa Hospital Research Institute in order to choose the maintenance treatment of BD. A multidisciplinary team developed a decision aid “choose my long-term treatment with my doctor” for BD patients to clarify possible therapeutic options. Primary outcome will assess the patient’s level of adherence (based on hetero-evaluation) of ongoing treatment at 12 months. Secondary outcomes will assess the difference between the 2 groups of patients in terms of adherence to maintenance drug therapy based on other measures (self-assessment scale and plasma levels of mood stabilizers). Additionally, other dimensions will be assessed: decisional conflict, satisfaction with care and involvement in decision making, beliefs about treatment, therapeutic relationship, knowledge about information for medical decision and clinical outcomes (depression, mania, functioning and quality of life). The primary endpoint will be analysed without adjustment by comparison of adherence scores between the two groups using Student t -tests or Mann–Whitney tests according to the variable distribution. A set of secondary analyses will be adjusted for covariates of clinical interest using generalized linear mixed regression models. Discussion This will be the first study evaluating the effect of an SDM intervention on patient adherence in BD. This is also an innovative protocol because it proposes the development of an evidence-based tool that should help patients and clinicians to initiate discussions regarding the use of BD treatment. Trial registration The study has been registered with ClinicalTrials.gov as NCT03245593 .

IntroductionTreatment resistant depression (TRD) affects a substantial proportion of patients with depression and carries a large unmet need. Esketamine nasal spray (NS), in combination with a selective serotonin reuptake inhibitor (SSRI) or serotonin norepinephrine reuptake inhibitor (SNRI), has been shown to reduce depressive symptoms and risk of relapse, in patients with TRD (Popova, V., et al. 2019. Am J Psychiatry; Daly, E.J., et al. 2019. JAMA Psychiatry). Esketamine NS has been authorised by European Medicines Agency as treatment for resistant depression since December 2019. ESKALE, is the first French observational study to describe TRD patients treated with Esketamine NS under real-world settings and to provide data on this innovative solution for patients.ObjectivesTo describe patients with TRD at Esketamine NS initiation and during the following 12-month period in real-world clinical practice.MethodsESKALE is a French, observational, multicentre, retrospective study of adult patients with moderate to severe TRD defined as a non-response to ≥ 2 oral antidepressant. Each patient was included in one of the 3 cohorts according to Esketamine NS start date: Temporary Authorisation for Use (ATUc) cohort, post-ATU cohort or post-launch period cohort. Data were collected from medical records of patients treated with Esketamine NS between 10-29-2019 and 06-14-2022. Primary objective is to describe patients’ profile and Esketamine NS conditions of use at esketamine initiation and during the 12-month period after esketamine initiation in real-world clinical practice (either patient had stop or not the treatment). Secondary objectives are to describe Esketamine NS management, safety profile and patient pathway.ResultsTwo standard descriptive statistical interim analysis were conducted and published in several conferences (Samalin L, et al. Presented at EPA Hybrid congress June 2022. P.2482; Samalin L, et al. Presented at ECNP Vienna, October 2022. P.0122). This final analysis describes the data collected from medical records of patients included in the study from 04-08-2020 to 06-30-2021. 157 patients were included from 26 French centers, the majority (>65%) of patients were females. Average age was 49 years old with 27 patients > 65 years old. Duration of the current depressive episode was up to 2,5 years (mean) with an average of more than three episode in the patient’s entire life (mean). At esketamine initiation, 3 patients out of 4 were clinically perceived to have severe depression with a MADRS score of 32.0 (median). Patients had mainly depression with anxious distress specifier. Esketamine NS dose at initiation was mainly 56mg.ConclusionsEskale is the first French cohort study generating real-world evidence on treatment resistant depression patients treated with Esketamine nasal spray. Results of the final analysis confirmed the 2 interim analysis results already published.Disclosure of InterestNone Declared

IntroductionA 10-15 years decrease in life expectancy has been observed in individuals with bipolar disorder (BD) and has been associated with premature cellular aging, but mechanisms involved remain unclear. Our team recently identified a subgroup of young individuals with prematurely shortened telomere length (TL).ObjectivesThe aims of the present study were to replicate this observation in a larger sample and to analyze the expression levels of genes associated with age or TL in a subsample of these individuals.MethodsTL was measured by qPCR using peripheral blood DNA from 542 individuals with BD. Clustering analyzes were performed with age and TL as classification variables to identify similar groups.Gene expression of 29 genes, including 20 associated with age and 9 with TL, was analyzed by RT-qPCR using peripheral blood RNA in a subgroup of 129 individuals. Gene expressions were compared between groups obtained from the previous clustering analyzes by Kruskal-Wallis and Mann-Whitney tests.ResultsClustering analyzes identified 3 subgroups and replicated the clustering previously described: a subgroup of aged individuals with a low TL (mean age : 51.73 years ; mean TL : 2), a subgroup of young individuals with a high TL (mean age : 29.02 years ; mean TL : 4.36) and a subgroup of young individuals but with a low TL (mean age : 29.64 years ; mean TL : 1.96). None of the tested clinical variables were significantly associated with this subgroup.Furthermore, gene expression level analyzes showed that only POT1 expression was different between the two subgroups of young individuals, with a downregulation of POT1 expression in the subgroup with a lower TL level. POT1 is a protein involved in the maintenance of TL. POT1 binds to another protein TPP1 allowing the recruitment of telomerase, the enzyme which extends TL. Our hypothesis is that in the subgroup presenting a lower POT1 expression, the POT1-TPP1 complex cannot form and thus prevents telomerase recruitment and TL elongation.ConclusionsThis study confirms, on a larger sample, the existence of a subgroup of young individuals with BD presenting accelerated cellular aging. The observed decrease of POT1 expression level suggests a newly described cellular mechanism in individuals with BD, that may contribute to telomere shortening.Disclosure of InterestNone Declared

Introduction Migraine and bipolar disorder (BD) are two chronic and recurrent disorders with a major impact on patient’s quality of life. It is now well known that affective disorders and migraine are often comorbid (Leo et al. Scand J Pain. 2016; 11:136-145). Starting from these observations, we can hypothesis that BD patients with comorbid migraine might have specifical clinical and biological features. Objectives The aim of this study was to estimate the prevalence of migraine in a cohort of French BD patients; determine sociodemographic, clinical, and biological features associated BD-migraine comorbidity. Methods 4348 BD patients from the FACE-BD cohort were included from 2009 to 2022. Sociodemographic and clinical characteristics, lifestyle information, and data on antipsychotic treatment and comorbidities were collected, and a blood sample was drawn. The Structured Clinical Interview for DSM-IV Axis I Disorders was used to confirm the diagnosis of BD. Migraine diagnosis was established according to a clinician-assessed questionnaire. Results 20.1% of individuals with BD had comorbid migraine. Half of these patients received treatment for migraine. Multivariate logistic regression model showed that risk of migraine in women was nearly twice that in men (OR = 1.758; 95% CI, 1.345-2.298). Anxiety disorder, sleep disturbances and childhood trauma were also associated with an increased risk of migraine comorbidity. Patients receiving antipsychotic treatment had less risk of developing migraine than those not receiving those treatment (OR 0.716, 95% CI, 0.554-0.925), independent of other potential confounders. Conclusions The prevalence of migraine in our cohort was lower than those previously reported in other studies. This result might suggest an overestimation of migraine diagnosis in BD patients population studies. However, BD-migraine comorbidity could constitute a subphenotype of bipolar disorder requiring specific treatments. Disclosure of Interest None Declared

Background: The objective of this study was to develop a conceptual framework to define a domain map describing the experience of patients with severe mental illnesses (SMIs) on the quality of mental health care. Methods: This study used an exploratory qualitative approach to examine the subjective experience of adult patients (18-65 years old) with SMIs, including schizophrenia (SZ), bipolar disorder (BD) and major depressive disorder (MDD). Participants were selected using a purposeful sampling method. Semistructured interviews were conducted with 37 psychiatric inpatients and outpatients recruited from the largest public hospital in southeastern France. Transcripts were subjected to an inductive analysis by using two complementary approaches (thematic analysis and computerized text analysis) to identify themes and subthemes. Results: Our analysis generated a conceptual model composed of 7 main themes, ranked from most important to least important as follows: interpersonal relationships, care environment, drug therapy, access and care coordination, respect and dignity, information and psychological care. The interpersonal relationships theme was divided into 3 subthemes: patient-staff relationships, relations with other patients and involvement of family and friends. All themes were spontaneously raised by respondents. Conclusion: This work provides a conceptual framework that will inform the subsequent development of a patient-reported experience measure to monitor and improve the performance of the mental health care system in France. The findings showed that patients with SMIs place an emphasis on the interpersonal component, which is one of the important predictors of therapeutic alliance. Trial registration: NCT02491866

AbstractObjectiveTo confirm the rapid onset anti-suicidal benefits of ketamine in the short term and at six weeks, overall and according to diagnostic group.DesignProspective, double blind, superiority, randomised placebo controlled trial.SettingSeven French teaching hospitals between 13 April 2015 and 12 March 2019.Eligibility criteria for participantsAged 18 or older with current suicidal ideation, admitted to hospital voluntarily. Exclusion criteria included a history of schizophrenia or other psychotic disorders, substance dependence, and contraindications for ketamine.Participants156 participants were recruited and randomised to placebo (n=83) or ketamine (n=73), stratified by centre and diagnosis: bipolar, depressive, or other disorders.InterventionTwo 40 minute intravenous infusions of ketamine (0.5 mg/kg) or placebo (saline) were administered at baseline and 24 hours, in addition to usual treatment.Main outcome measuresThe primary outcome was the rate of patients in full suicidal remission at day 3, according to the scale for suicidal ideation total score ≤3. Analyses were conducted on an intention-to-treat basis.ResultsMore participants receiving ketamine reached full remission of suicidal ideas at day 3 than those receiving placebo: 46 (63.0%) of 83 participants in the ketamine arm and 25 (31.6%) of 73 in the placebo arm (odds ratio 3.7 (95% confidence interval 1.9 to 7.3), P<0.001). This effect differed according to the diagnosis (treatment: P<0.001; interaction: P=0.02): bipolar (odds ratio 14.1 (95% confidence interval 3.0 to 92.2), P<0.001), depressive (1.3 (0.3 to 5.2), P=0.6), or other disorders (3.7 (0.9 to 17.3, P=0.07)). Side effects were limited. No manic or psychotic symptom was seen. Moreover, a mediating effect of mental pain was found. At week 6, remission in the ketamine arm remained high, although non-significantly versus placebo (69.5% v 56.3%; odds ratio 0.8 (95% confidence interval 0.3 to 2.5), P=0.7).ConclusionsThe findings indicate that ketamine is rapid, safe in the short term, and has persistent benefits for acute care in suicidal patients. Comorbid mental disorders appear to be important moderators. An analgesic effect on mental pain might explain the anti-suicidal effects of ketamine.Trial registrationClinicalTrials.gov NCT02299440.

Lurasidone is a new second-generation antipsychotic approved in October 2010 by the Food and Drug Administration for the treatment of schizophrenia. Like other second-generation antipsychotics, lurasidone is a powerful antagonist of D(2) dopamine and 5HT(2A) serotonin receptors, but differs from the other second-generation antipsychotics in its action profile for certain receptors. Lurasidone is the second-generation antipsychotic with the greatest affinity for 5HT(7) receptors and has a high affinity for 5HT(1A) serotonin receptors, compatible with favorable effects on cognitive function and an antidepressant action. By contrast, lurasidone has a low affinity for and α(1) α(2C)-adrenergic and 5HT(2C) serotonin receptors, and no affinity for histaminergic H(1) or muscarinic M(1) receptors, suggesting a better tolerability profile than the other second-generation antipsychotics. Lurasidone has demonstrated its efficacy in several short-term trials in acute schizophrenia, promptly and significantly reducing total Positive and Negative Syndrome Scale and Brief Psychiatric Rating Scale scores compared with placebo. Several long-term studies are in progress to assess its efficacy in the maintenance treatment of schizophrenic patients. The efficacy of lurasidone with regard to cognitive functions and depressive symptoms seems good, but requires further work. Lurasidone differs from the other second-generation antipsychotics by having a good tolerability profile, in particular for cardiometabolic tolerability. However, it seems to have a significant although moderate link with the occurrence of akathisia, extrapyramidal symptoms, and hyperprolactinemia at the start of treatment. This tolerance profile greatly broadens the scope of second-generation antipsychotics and so supports the view of some authors that the term \"second-generation antipsychotic\" is now outdated. Other therapeutic perspectives of lurasidone are assessed here, in particular bipolar depression.

In the last few years, oral second-generation antipsychotics have demonstrated mood-stabilizing properties and are now widely used in the treatment of bipolar disorder. Unfortunately, treatment of this chronic and complex illness is hampered with poor adherence on the part of patients. Long-acting injectable formulations of second-generation antipsychotics could combine the effect of oral second-generation antipsychotics in patients with bipolar disorder and the benefits of depot formulation with the assurance of steady medication delivery and thereby improve adherence. In this context, the efficacy and tolerance of risperidone long-acting injection (RLAI) for maintenance treatment in patients with bipolar disorder is assessed. The relevant studies found RLAI to be effective in preventive treatment of manic but not depressive recurrences in bipolar patients, with good tolerance. RLAI appeared to be particularly suitable for patients with known poor adherence to treatment or severe bipolar disorder (such as patients who relapse frequently). Lastly, if RLAI, unlike the first-generation antipsychotics, does not induce depressive symptoms, the different studies do not enable us to consider its use in monotherapy in the preventive treatment of patients with depressive polarity. Long-acting second-generation antipsychotics in bipolar patients are therefore associated with long-term benefits, but their use in clinical practice needs to be improved.

Internet-based cognitive behavioral therapy (iCBT) services for common mental health disorders have been found to be effective. There is a need for strategies that improve implementation in routine practice. One-size-fits-all strategies are likely to be ineffective. Tailored implementation is considered as a promising approach. The self-guided integrated theory-based Framework for intervention tailoring strategies toolkit (ItFits-toolkit) supports local implementers in developing tailored implementation strategies. Tailoring involves identifying local barriers; matching selected barriers to implementation strategies; developing an actionable work plan; and applying, monitoring, and adapting where necessary. This study aimed to compare the effectiveness of the ItFits-toolkit with implementation-as-usual (IAU) in implementing iCBT services in 12 routine mental health care organizations in 9 countries in Europe and Australia. A stepped-wedge cluster randomized trial design with repeated measures was applied. The trial period lasted 30 months. The primary outcome was the normalization of iCBT delivery by service providers (therapists, referrers, IT developers, and administrators), which was measured with the Normalization Measure Development as a proxy for implementation success. A 3-level linear mixed-effects modeling was applied to estimate the effects. iCBT service uptake (referral and treatment completion rates) and implementation effort (hours) were used as secondary outcomes. The perceived satisfaction (Client Satisfaction Questionnaire), usability (System Usability Scale), and impact of the ItFits-toolkit by implementers were used to assess the acceptability of the ItFits-toolkit. In total, 456 mental health service providers were included in this study. Compared with IAU, the ItFits-toolkit had a small positive statistically significant effect on normalization levels in service providers (mean 0.09, SD 0.04; P=.02; Cohen d=0.12). The uptake of iCBT by patients was similar to that of IAU. Implementers did not spend more time on implementation work when using the ItFits-toolkit and generally regarded the ItFits-toolkit as usable and were satisfied with it. The ItFits-toolkit performed better than the usual implementation activities in implementing iCBT services in routine practice. There is practical utility in the ItFits-toolkit for supporting implementers in developing and applying effective tailored implementation strategies. However, the effect on normalization levels among mental health service providers was small. These findings warrant modesty regarding the effectiveness of self-guided tailored implementation of iCBT services in routine practice. ClinicalTrials.gov NCT03652883; https://clinicaltrials.gov/ct2/show/NCT03652883. RR2-10.1186/s13063-020-04686-4.

There is growing concern about measuring patient experience with mental health care. There are currently numerous patient-reported experience measures (PREMs) available for mental health care, but there is little guidance for selecting the most suitable instruments. The objective of this systematic review was to provide an overview of the psychometric properties and the content of available PREMs. A comprehensive review following the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines was conducted using the MEDLINE database with no date restrictions. The content of PREMs was analyzed using an inductive qualitative approach, and the methodological quality was assessed according to Pesudovs quality criteria. A total of 86 articles examining 75 PREMs and totaling 1932 items were included. Only four PREMs used statistical methods from item response theory (IRT). The 1932 items covered seven key mental health care domains: interpersonal relationships (22.6%), followed by respect and dignity (19.3%), access and care coordination (14.9%), drug therapy (14.1%), information (9.6%), psychological care (6.8%) and care environment (6.1%). Additionally, a few items focused on patient satisfaction (6.7%) rather than patient experience. No instrument covered the latent trait continuum of patient experience, as defined by the inductive qualitative approach, and the psychometric properties of the instruments were heterogeneous. This work is a critical step in the creation of an item library to measure mental health care patient-reported experience that will be used in France to develop, validate, and standardize item banks and computerized adaptive testing (CAT) based on IRT. It will also provide internationally replicable measures that will allow direct comparisons of mental health care systems. NCT02491866.