Patients' perspectives on residual symptoms in bipolar disorder: a focus group study.

Euthymic bipolar patients are often impacted by residual symptoms (RSs) that increase the risk of relapse or low functioning. We aimed to identify the perceptions of RSs, barriers to management, and service needs in euthymic bipolar patients. A qualitative methodology (focus group) was used. The interviews were investigated using a semistructured guide, tape-recorded, transcribed verbatim, and analyzed thematically. Twenty-three bipolar patients expressed concern about several RSs, such as emotional dysregulation, circadian rhythm disruption, cognitive impairment, low self-esteem, and physical symptoms. They reported concern about the impact of RSs on their functioning and about the need for more systematic assessment of RSs during interepisode visits. Selection bias may have occurred because the recruitment was limited to France and there may be cultural differences in the perceptions of RSs. Bipolar patients experienced bipolar disorder as a chronic disorder because they frequently continued to suffer from RSs associated with a functional impact.

Suicidal attempts in bipolar disorder: results from an observational study (EMBLEM).

OBJECTIVES: To compare patients with and without a history of suicidal attempts in a large cohort of patients with bipolar disorder and to identify variables that are associated with suicidal behavior. METHODS: European Mania in Bipolar Longitudinal Evaluation of Medication (EMBLEM) is a two-year, prospective, observational study that enrolled 3,684 adult patients with bipolar disorder and initiated or changed oral treatment for an acute manic/mixed episode. Of those, 2,416 patients were eligible for the two-year follow-up. Only baseline characteristics were studied in the present study, included sociodemographic data, psychiatric history and comorbidities, history of suicide attempts, history of substance use problems, compliance with treatment, inpatient admissions, and functional status. Symptom severity was assessed using the Clinical Global Impression-Bipolar Disorder (CGI-BP) scale, the Young Mania Rating Scale (YMRS), and the 5-item Hamilton Depression Rating Scale (HAMD-5). A logistic regression model identified baseline variables independently associated with a history of suicidal behavior. RESULTS: Of the 2,219 patients who provided data on their lifetime history of suicide attempts, 663 (29.9%) had a history of suicidal behavior (at least one attempt). Baseline factors associated with a history of suicidal behavior included female gender, a history of alcohol abuse, a history of substance abuse, young age at first treatment for a mood episode, longer disease duration, greater depressive symptom severity (HAMD-5 total score), current benzodiazepine use, higher overall symptom severity (CGI-BP: mania and overall score), and poor compliance. CONCLUSIONS: These factors may be considered as potential characteristics to identify subjects at risk for suicidal behavior throughout the course of bipolar disorder.

Patient flow in the largest French psychiatric emergency centre in the context of the COVID-19 pandemic.

To date, we have no French data about the psychiatric consequences of the Covid-19 pandemic and the confinement. In the largest French psychiatric emergency centre, we compared the average number of consultations per day during the confinement with the same period preceding the confinement and with the same periods of previous years, and we observed a significant drop in attendance. Our team had to adapt promptly to these changes in public mental health services, and we set up a telephone hotline dedicated to psychiatric patients and their families, in order to prevent a secondary psychiatric crisis.

Psychological and psychiatric aspects of face transplantation: Lessons learned from the long-term follow-up of six patients.

Since 2005, at least 38 face transplantations have been performed worldwide. Available recommendations on psychological management are based on isolated cases or small case series, either not focused on mental health or with a short follow-up. We propose herein a clinical commentary on psychological and psychiatric outcomes from the follow-up of a prospective single-center cohort of six patients over a period of 3.5 to 9 years. Seven patients received a face transplant between January 2007 and April 2011: two patients with neurofibromatosis, four with self-inflicted ballistic trauma, one with self-immolation. One patient died at 63 days of cerebral sequelae from cardiac arrest in the setting of bacterial infection. The six other patients were routinely evaluated with unstructured psychological interviews up to May 2016 and with the Short Form 36-item health survey and the Mini-International Neuropsychiatric Interview at one year and at the end of the follow-up. Clinically meaningful observations were the following: a history of mental disorders before disfigurement was associated with poor physical and mental outcomes, including poor adherence and one suicide; untreated depression was associated with poor adherence; acceptance of the new face occurred rapidly and without significant distress in all of the patients; fear of transplant rejection was present to some degree in all of the patients and did not substantially differ from other transplantation settings; media exposure may be disturbing but may also have had positive psychological effects on some of the patients. Mental health issues related to chronic rejection and re-transplantation remain to be explored.

Exploring venlafaxine pharmacokinetic variability with a phenotyping approach, a multicentric french-swiss study (MARVEL study).

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.

Significant Need for a French Network of Expert Centers Enabling a Better Characterization and Management of Treatment-Resistant Depression (Fondation FondaMental).

BACKGROUND: Major depression is characterized by (i) a high lifetime prevalence of 16-17% in the general population; (ii) a high frequency of treatment resistance in around 20-30% of cases; (iii) a recurrent or chronic course; (iv) a negative impact on the general functioning and quality of life; and (v) a high level of comorbidity with various psychiatric and non-psychiatric disorders, high occurrence of completed suicide, significant burden along with the personal, societal, and economic costs. In this context, there is an important need for the development of a network of expert centers for treatment-resistant depression (TRD), as performed under the leadership of the Fondation FondaMental. METHODS: The principal mission of this national network is to establish a genuine prevention, screening, and diagnosis policy for TRD to offer a systematic, comprehensive, longitudinal, and multidimensional evaluation of cases. A shared electronic medical file is used referring to a common exhaustive and standardized set of assessment tools exploring psychiatric, non-psychiatric, metabolic, biological, and cognitive dimensions of TRD. This is paralleled by a medico-economic evaluation to examine the global economic burden of the disease and related health-care resource utilization. In addition, an integrated biobank has been built by the collection of serum and DNA samples for the measurement of several biomarkers that could further be associated with the treatment resistance in the recruited depressed patients. A French observational long-term follow-up cohort study is currently in progress enabling the extensive assessment of resistant depressed patients. In those unresponsive cases, each expert center proposes relevant therapeutic options that are classically aligned to the international guidelines referring to recognized scientific societies. DISCUSSION: This approach is expected to improve the overall clinical assessments and to provide evidence-based information to those clinicians most closely involved in the management of TRD thereby facilitating treatment decisions and choice in everyday clinical practice. This could contribute to significantly improve the poor prognosis, the relapsing course, daily functioning and heavy burden of TRD. Moreover, the newly created French network of expert centers for TRD will be particularly helpful for a better characterization of sociodemographic, clinical, neuropsychological, and biological markers of treatment resistance required for the further development of personalized therapeutic strategies in TRD.

Residual symptoms and functional performance in a large sample of euthymic bipolar patients in France (the OPTHYMUM study).

BACKGROUND: Some residual symptoms were found to be associated with impaired functioning in euthymic bipolar patients, but their impact and relevance are unclear in clinical practice. We re-examined the functional influence of a large set of residual symptoms in 525 euthymic bipolar outpatients using self- and clinician-rated questionnaires (OPTHYMUM study). METHODS: This was a multi-centre, cross-sectional, non-interventional study of adult bipolar outpatients. All patients were euthymic at the time of assessment (YMRS score <8 and BDRS ≤8). Patients with low functioning (GAF score <60) were compared with the rest of the sample. Patients filled in specific questionnaires concerning their perceptions of different residual and subsyndromal symptoms. RESULTS: Ninety-seven (97) psychiatrists included 525 patients. Of them, 35 patients had a GAF score <60. These "low functioning patients" were more frequently unemployed, had presented more manic episodes and psychotic symptoms, used more atypical antipsychotics or benzodiazepines and received less adjunctive psychotherapy. Concerning residual symptoms, they had more frequent emotional subsyndromal symptoms, disruption of circadian rhythms and sexual disorders. They perceived some cognitive deficits and suffered more social and family stigma. LIMITATIONS: Our study used an arbitrary GAF cut-off score (60) to separate bipolar patients in two groups (low and satisfactory functioning). CONCLUSIONS: Residual symptoms are associated with functional impairment and may represent specific treatment targets. A personalized approach through specific psychotherapeutic programs may lead to more efficient support by the clinician.

Factor analyses of the Suicidal Intent Scale (SIS) and the Risk-Rescue Rating Scale (RRRS): toward the identification of homogeneous subgroups of suicidal behaviors.

BACKGROUND: Suicidal behavior is a heterogeneous entity, determined by multiple factors. This heterogeneity has major implications for clinical management of patients and identification of risk factors. Our study aims at identifying homogeneous subgroups of patients with suicidal behavior. METHODS: We used two validated questionnaires to assess the intent (Suicidal Intent Scale, SIS) and lethality (Risk-Rescue Rating Scale, RRRS) of the most severe suicide attempt in a sample of 608 patients recruited consecutively. We first explored the factorial structure of the two scales, using a principal component analysis, and then tested the relationship between sub-scores identified and subtypes of suicide attempts (violent, serious overdose) using a backward logistic regression. RESULTS: A four-factor structure was retained for the SIS (conception, preparation, precautions and communication). The RRRS, for which a factorial structure has not been previously published, had a three-factor structure (medical damage, implementation and rescue conditions). This structure was valid, stable and clinically relevant. Serious suicide attempts were characterized by less communication and more precautions against discovery, whereas violent attempts were associated with higher risk acts. Neither violent nor serious attempts were characterized by more planning. LIMITATIONS: The SIS and RRRS were assessed retrospectively, and so could have been influenced by recall bias. Finally, censoring bias may have affected our results. CONCLUSIONS: The characterization of suicidal behaviors using SIS and RRRS sub-scores constitutes a first step toward the identification of homogeneous subgroups of suicide attempters. Prospective studies are needed to test the predictive value of these sub-scores for subsequent suicidal acts.

Admixture analysis of age at first suicide attempt.

OBJECTIVE: Clinical and familial studies have suggested that age at first suicide attempt (SA) is a marker for different subtypes of suicidal behaviors. However, none of the various thresholds used to define subgroups according to the age at first suicide attempt have been validated. The aim of this study was to try to define different subgroups according to age at first SA subtypes using admixture analysis. METHOD: In a sample of 368 consecutively recruited patients from Sept. 2001 to Sept. 2005 with a personal history of suicide attempt, admixture analysis was used to determine the best-fitting model for the observed distribution of age at first SA. RESULTS: The theoretical model that best explains the observed distribution of age at first SA was a mixture of two Gaussian distributions with mean ages (+/-SD) of 19.5 +/- 4.3 and 38.5 +/- 12.4 years with a cut-off point of 26 years for the two subgroups. In multivariate analyses, the early onset subgroup was characterized by more frequent comorbid anxiety disorders, cannabis misuse and personal history of emotional and sexual abuse. Patients belonging to the late onset subgroup were more likely to suffer from major depressive disorders (single or recurrent). CONCLUSION: This study provides a mathematical modelisation suggesting the existence of two age at onset subgroups in suicidal behaviors with different clinical picture and history of childhood trauma. Given the heterogeneity of suicidal behavior, these results suggest that the age at first SA may represent a valid 'candidate symptom' for future investigations of vulnerability factors.