Real-world demographic and clinical profiles of patients with treatment-resistant depression initiated on esketamine nasal spray.

OBJECTIVE: ESKALE is a French, multicentre, observational study of adults with treatment-resistant depression (TRD) treated with esketamine. This interim analysis describes baseline demographic and clinical characteristic evolution in patients included and treated from early access program to post-marketing launch. METHODS: Data were collected from medical records and included patient characteristics, disease history at esketamine initiation, use of neurostimulation, the patient's care pathway, and the number of antidepressant treatment lines prescribed prior to esketamine initiation. Descriptive statistics were used for each cohort: the early access program 'Temporary Authorisation for Use' (ATU), post-ATU, and post-launch cohorts. RESULTS: The overall ESKALE cohort (N = 160 included; n = 157 treated with esketamine; average age 49.0 years; 66.2% female) demonstrated moderate-to-severe depression according to clinical assessment and a mean Montgomery-Åsberg Depression Rating Scale score of 32.6 (8.0); however, severity, subtype, and comorbidities were heterogeneous across the cohorts. Earlier use of esketamine and prior to alternative treatments occurred during the later cohorts. CONCLUSION: These findings demonstrated a high burden of TRD in these patients and that esketamine is used in TRD treatment regardless of their disease severity, subtype, or existing comorbidities. These results also suggest that esketamine is potentially a clinically useful alternative treatment, particularly with healthcare professionals gaining greater familiarity with and easier access to esketamine.

ESKALE is a long-term, French, multicentre, observational study based on secondary data in adult patients with treatment-resistant depression (TRD) who initiated esketamine treatment in one of three mutually exclusive cohorts: the Temporary Authorisation for Use (ATU), post-ATU, and post-launch cohorts.ESKALE is one of the largest European real-world studies investigating the profiles of more than 150 patients and their treatment with esketamine before and after marketing authorisation.A majority of patients had moderate to severe TRD, with multiple treatment failures with medications and/or neurostimulation prior to esketamine initiation.Esketamine nasal spray administration was undertaken more frequently in an outpatient setting, with the post-administration period monitoring being undertaken mostly by nurses.Esketamine was used in patients with TRD in real-world conditions regardless of their disease severity and subtype or existing comorbidities.These results highlight both the need for an effective treatment for TRD and the adoption of esketamine by multidisciplinary teams that are involved in esketamine prescription and administration.

Identifying digital biomarkers of illness activity and treatment response in bipolar disorder with a novel wearable device (TIMEBASE): protocol for a pragmatic observational clinical study.

BACKGROUND: Bipolar disorder is highly prevalent and consists of biphasic recurrent mood episodes of mania and depression, which translate into altered mood, sleep and activity alongside their physiological expressions. AIMS: The IdenTifying dIgital bioMarkers of illnEss activity and treatment response in BipolAr diSordEr with a novel wearable device (TIMEBASE) project aims to identify digital biomarkers of illness activity and treatment response in bipolar disorder. METHOD: We designed a longitudinal observational study including 84 individuals. Group A comprises people with acute episode of mania (n = 12), depression (n = 12 with bipolar disorder and n = 12 with major depressive disorder (MDD)) and bipolar disorder with mixed features (n = 12). Physiological data will be recorded during 48 h with a research-grade wearable (Empatica E4) across four consecutive time points (acute, response, remission and episode recovery). Group B comprises 12 people with euthymic bipolar disorder and 12 with MDD, and group C comprises 12 healthy controls who will be recorded cross-sectionally. Psychopathological symptoms, disease severity, functioning and physical activity will be assessed with standardised psychometric scales. Physiological data will include acceleration, temperature, blood volume pulse, heart rate and electrodermal activity. Machine learning models will be developed to link physiological data to illness activity and treatment response. Generalisation performance will be tested in data from unseen patients. RESULTS: Recruitment is ongoing. CONCLUSIONS: This project should contribute to understanding the pathophysiology of affective disorders. The potential digital biomarkers of illness activity and treatment response in bipolar disorder could be implemented in a real-world clinical setting for clinical monitoring and identification of prodromal symptoms. This would allow early intervention and prevention of affective relapses, as well as personalisation of treatment.

Diet quality and associations with lactate and metabolic syndrome in bipolar disorder.

BACKGROUND: Nutrition is largely affected in bipolar disorder (BD), however, there is a lack of understanding on the relationship between dietary categories, BD, and the prevalence of metabolic syndrome. The objective of this study is to examine dietary trends in BD and it is hypothesized that diets with increased consumption of seafood and high-fiber carbohydrates will be correlated to improved patient outcomes, and a lower frequency of metabolic syndrome. METHODS: This retrospective cohort study includes two French cohorts. The primary cohort, FACE-BD, includes 268 stable BD patients. The second cohort, I-GIVE, includes healthy controls, both stable and acute BD and schizophrenia patients. Four dietary categories were assessed: meat, seafood, low-fiber and high-fiber carbohydrates. Dietary data from two food frequency questionnaires were normalized using min-max scaling and assessed using various statistical analyses. RESULTS: In our primary cohort, the increased high-fiber carbohydrate consumption was correlated to lower prevalence of metabolic syndrome and improved mood. Low-fiber carbohydrate consumption is associated with higher BMI, while higher seafood consumption was correlated to improved mood and delayed age of onset. Results were not replicated in our secondary cohort. LIMITATIONS: Our populations were small and two different dietary questionnaires were used; thus, results were used to examine similarities in trends. CONCLUSIONS: Overall, various dietary trends were associated with metabolic syndrome, BMI, lactate, mood and age of onset. Improving our understanding of nutrition in BD can provide mechanistic insight, clinically relevant nutritional guidelines for precision medicine and ultimately improve the quality of lives for those with BD.

Mitochondrial Biomarkers and Metabolic Syndrome in Bipolar Disorder.

The object of this study is test whether mitochondrial blood-based biomarkers are associated with markers of metabolic syndrome in bipolar disorder, hypothesizing higher lactate but unchanged cell-free circulating mitochondrial DNA levels in bipolar disorder patients with metabolic syndrome. In a cohort study, primary testing from the FondaMental Advanced Centers of Expertise for bipolar disorder (FACE-BD) was conducted, including 837 stable bipolar disorder patients. The I-GIVE validation cohort consists of 237 participants: stable and acute bipolar patients, non-psychiatric controls, and acute schizophrenia patients. Multivariable regression analyses show significant lactate association with triglycerides, fasting glucose and systolic and diastolic blood pressure. Significantly higher levels of lactate were associated with presence of metabolic syndrome after adjusting for potential confounding factors. Mitochondrial-targeted metabolomics identified distinct metabolite profiles in patients with lactate presence and metabolic syndrome, differing from those without lactate changes but with metabolic syndrome. Circulating cell-free mitochondrial DNA was not associated with metabolic syndrome. This thorough analysis mitochondrial biomarkers indicate the associations with lactate and metabolic syndrome, while showing the mitochondrial metabolites can further stratify metabolic profiles in patients with BD. This study is relevant to improve the identification and stratification of bipolar patients with metabolic syndrome and provide potential personalized-therapeutic opportunities.

Does BioAge identify accelerated aging in individuals with bipolar disorder? An exploratory study in the FACE-BD cohort.

BACKGROUND: Individuals with bipolar disorders (BD) have an estimated loss of life expectancy around 10-15 years. Several laboratory-measured biomarkers of accelerated aging exist (e.g., telomere length), however with a questionable transferability to bedside. There is a need for easily and inexpensively measurable markers of aging, usable in routine practice, such as BioAge. METHODS: We calculated BioAge that estimates biological age based on routine blood tests and a physical exam, in a sample of 2220 outpatients with BD. We investigated associations between BioAge Acceleration (BioAgeAccel), which is an indicator of accelerated aging, and sociodemographic variables, clinical variables, and current psychotropic medication use. RESULTS: Mean chronological age was 40.2 (±12.9). Mean BioAge was 39.1 (±12.4). Mean BioAgeAccel was 0.08 (±1.8). A minority of individuals (15%) had a BioAgeAccel above 2 years. Multivariable analyses suggested strong associations between a higher BioAgeAccel and younger age, male sex, overweight and sleep disturbances. Regarding current psychotropic medication use, discrepancies between univariate and multivariate analyses were observed. CONCLUSIONS: A minority of individuals with BD had an accelerated aging as measured by BioAge. We identified associations with potentially modifiable factors, such as higher body mass index and sleep disturbances, that are however nonspecific to BD. These results require replications in independent samples of individuals with BD, and comparisons with a control group matched for age and gender. Longitudinal studies are also required to test whether any change in metabolic health, or sleep might decrease BioAgeAccel.

Adherence to clinical practice guidelines for using electroconvulsive therapy in elderly depressive patients.

OBJECTIVES: Electroconvulsive therapy (ECT) is one of the most effective treatments in mood disorders, mainly in major depressive episode (MDE) in the context of either unipolar (MDD) or bipolar disorder (BD). However, ECT remains a neglected and underused treatment. Older people are at high risk patients for the development of adverse drug reactions. In this context, we sought to determine the duration of MDEs and the number of lines of treatment before the initiation of ECT in patients aged 65 years or over according to the presence or absence of first-line indications for using ECT from international guidelines. METHODS: In this multicenter, retrospective study including patients aged 65 years or over with MDEs in MDD or BD who have been treated with ECT for MDEs, data on the duration of MDEs and the number of lines of treatment received before ECT were collected. The reasons for using ECT, specifically first-line indications (suicidality, urgency, presence of catatonic and psychotic features, previous ECT response, patient preference) were recorded. Statistical comparisons between groups used standard statistical tests. RESULTS: We identified 335 patients. The mean duration of MDEs before ECT was about 9 months. It was significantly shorter in BD than in MDD- about 7 and 10 months, respectively. The co-occurrence of chronic medical disease increased the duration before ECT in the MDD group. The presence of first-line indications for using ECT from guidelines did not reduce the duration of MDEs before ECT, except where there was a previous response to ECT. The first-line indications reduced the number of lines of treatment before starting ECT. CONCLUSION: Even if ECT seems to be a key treatment in the elderly population due to its efficacity and safety for MDEs, the delay before this treatment is still too long.

Psychometric Assessment of an Item Bank for Adaptive Testing on Patient-Reported Experience of Care Environment for Severe Mental Illness: Validation Study.

BACKGROUND: The care environment significantly influences the experiences of patients with severe mental illness and the quality of their care. While a welcoming and stimulating environment enhances patient satisfaction and health outcomes, psychiatric facilities often prioritize staff workflow over patient needs. Addressing these challenges is crucial to improving patient experiences and outcomes in mental health care. OBJECTIVE: This study is part of the Patient-Reported Experience Measure for Improving Quality of Care in Mental Health (PREMIUM) project and aims to establish an item bank (PREMIUM-CE) and to develop computerized adaptive tests (CATs) to measure the experience of the care environment of adult patients with schizophrenia, bipolar disorder, or major depressive disorder. METHODS: We performed psychometric analyses including assessments of item response theory (IRT) model assumptions, IRT model fit, differential item functioning (DIF), item bank validity, and CAT simulations. RESULTS: In this multicenter cross-sectional study, 498 patients were recruited from outpatient and inpatient settings. The final PREMIUM-CE 13-item bank was sufficiently unidimensional (root mean square error of approximation=0.082, 95% CI 0.067-0.097; comparative fit index=0.974; Tucker-Lewis index=0.968) and showed an adequate fit to the IRT model (infit mean square statistic ranging between 0.7 and 1.0). DIF analysis revealed no item biases according to gender, health care settings, diagnosis, or mode of study participation. PREMIUM-CE scores correlated strongly with satisfaction measures (r=0.69-0.78; P<.001) and weakly with quality-of-life measures (r=0.11-0.21; P<.001). CAT simulations showed a strong correlation (r=0.98) between CAT scores and those of the full item bank, and around 79.5% (396/498) of the participants obtained a reliable score with the administration of an average of 7 items. CONCLUSIONS: The PREMIUM-CE item bank and its CAT version have shown excellent psychometric properties, making them reliable measures for evaluating the patient experience of the care environment among adults with severe mental illness in both outpatient and inpatient settings. These measures are a valuable addition to the existing landscape of patient experience assessment, capturing what truly matters to patients and enhancing the understanding of their care experiences. TRIAL REGISTRATION: ClinicalTrials.gov NCT02491866; https://clinicaltrials.gov/study/NCT02491866.

Decreased telomere length in a subgroup of young individuals with bipolar disorders: replication in the FACE-BD cohort and association with the shelterin component POT1.

Bipolar disorder (BD) has been associated with premature cellular aging with shortened telomere length (TL) as compared to the general population. We recently identified a subgroup of young individuals with prematurely shortened TL. The aims of the present study were to replicate this observation in a larger sample and analyze the expression levels of genes associated with age or TL in a subsample of these individuals. TL was measured on peripheral blood DNA using quantitative polymerase chain reaction in a sample of 542 individuals with BD and clustering analyses were performed. Gene expression level of 29 genes, associated with aging or with telomere maintenance, was analyzed in RNA samples from a subsample of 129 individuals. Clustering analyses identified a group of young individuals (mean age 29.64 years), with shorter TL. None of the tested clinical variables were significantly associated with this subgroup. Gene expression level analyses showed significant downregulation of MYC, POT1, and CD27 in the prematurely aged young individuals compared to the young individuals with longer TL. After adjustment only POT1 remained significantly differentially expressed between the two groups of young individuals. This study confirms the existence of a subgroup of young individuals with BD with shortened TL. The observed decrease of POT1 expression level suggests a newly described cellular mechanism in individuals with BD, that may contribute to telomere shortening.

French Society for Biological Psychiatry and Neuropsychopharmacology and French-speaking Marcé Society guidelines for the management of mood disorders in women before, during, and after pregnancy.

PURPOSE: The French Society for Biological Psychiatry and Neuropsychopharmacology and the French-speaking Marcé Society have joined forces to establish expert recommendations on the prescription of psychotropic drugs before, during, and after pregnancy in women with major depressive disorder (MDD) and bipolar disorder (BD). METHODS: To elaborate recommendations, we used the RAND/UCLA Appropriateness Method, which combines scientific evidence and expert clinicians' opinions. A written survey was completed by 48 psychiatrists, who have expertise in the management of mood disorders and/or in perinatal psychiatry. Key recommendations are provided by the scientific committee based on data analysis and interpretation of the results of the survey. RESULTS: The recommendations address the following three areas that are deemed essential in women with mood disorders, with an emphasis on screening, treatment options, and monitoring: (i) management of mood disorders in women of childbearing age, (ii) management during pregnancy, (iii) management during the post-partum period. As first-line strategies, experts recommend treating mood symptoms during pregnancy and maintaining a pharmacological treatment, even in euthymic or stabilized patients. First-line options include only medications with no teratogenic risk, and during breastfeeding, only medications without evidence of adverse effects in nursing infants. CONCLUSION: The expert consensus guidelines will help facilitate treatment decisions for clinicians in the daily assessment and management of mood disorders in women of childbearing age, during pregnancy, and in the post-partum period.

Evaluating the efficacy and safety of the currently available once-every-two months long-acting injectable formulations of aripiprazole for the treatment of schizophrenia or as a maintenance monotherapy for bipolar I disorder in adults.

INTRODUCTION: An aripiprazole long-acting injectable (LAI) antipsychotic is now available for gluteal administration every 2 months via two different formulations: aripiprazole lauroxil (AL) and aripiprazole monohydrate (Ari 2MRTU). These longer dosing regimens of aripiprazole LAI offer new potential benefits for patients. AREAS COVERED: The authors review the evidence supporting the efficacy and safety of aripiprazole LAIs given every 2 months for the treatment of schizophrenia or bipolar disorder (BD) in adults. The article culminates with the authors' expert perspectives on the subject. EXPERT OPINION: AL 1064 mg every 2 months has established efficacy for the treatment of schizophrenia based on pharmacokinetic bridging studies and prospective data for treatment of an acute exacerbation of schizophrenia. In an open-label trial, Ari 2MRTU showed efficacy for the treatment of schizophrenia and BD type I based on pharmacokinetic parameters (comparable to aripiprazole once-monthly 400 mg); it also showed efficacy regarding the secondary endpoints. Multiple doses of AL 1064 mg or Ari 2MRTU 960 mg are generally well tolerated, in line with the safety profile of oral aripiprazole, with the exception of the injection-site reactions. While AL may require a 1-day initiation regimen, Ari 2MRTU 960 covers all the recommended doses of oral aripiprazole (10-20 mg).

French Society for Biological Psychiatry and Neuropsychopharmacology (AFPBN) guidelines for the management of patients with partially responsive depression and treatment-resistant depression: Update 2024.

INTRODUCTION: The purpose of this update is to add newly approved nomenclatures and treatments as well as treatments yet to be approved in major depressive disorder, thus expanding the discussions on the integration of resistance factors into the clinical approach. METHODS: Unlike the first consensus guidelines based on the RAND/UCLA Appropriateness Method, the French Association for Biological Psychiatry and Neuropsychopharmacology (AFPBN) developed an update of these guidelines for the management of partially responsive depression (PRD) and treatment-resistant depression (TRD). The expert guidelines combine scientific evidence and expert clinicians' opinions to produce recommendations for PRD and TRD. RESULTS: The recommendations addressed three areas judged as essential for updating the previous 2019 AFPBN guidelines for the management of patients with TRD: (1) the identification of risk factors associated with TRD, (2) the therapeutic management of patients with PRD and TRD, and (3) the indications, the modalities of use and the monitoring of recent glutamate receptor modulating agents (esketamine and ketamine). CONCLUSION: These consensus-based guidelines make it possible to build bridges between the available empirical literature and clinical practice, with a highlight on the 'real world' of the clinical practice, supported by a pragmatic approach centred on the experience of specialised prescribers in TRD.

Esketamine-induced post-traumatic stress disorder flashbacks during treatment-resistant depression indication: is it just a side effect?

Background: Posttraumatic stress disorder (PTSD) is a severe and frequent affection that is highly comorbid to major depressive disorder. Comorbid PTSD and depression are usually treatment-resistant, with a high risk of functional impairment and suicide. Esketamine nasal spray is a recent validated treatment for treatment-resistant depression (TRD), but its efficacy on comorbid TRD-PTSD remains insufficiently documented. In particular, flashbacks can occur during esketamine administration and their influence on clinical outcomes is unknown. Objectives: Our main objective was to describe esketamine-induced traumatic flashbacks and their impact on clinical trajectories within a sample of patients with comorbid TRD-PTSD. Methods: We retrospectively collected clinical data of patients receiving esketamine nasal spray for TRD with comorbid PTSD who experienced at least one flashback of their trauma during esketamine sessions across 11 psychiatric departments. Results: Between February 2020 and March 2023, 22 adult patients with TRD met inclusion criteria. In sixteen patients (72.7%) flashbacks disappeared as the sessions progressed. In six patients (27.3%), esketamine treatment was stopped because of persistent flashbacks. When esketamine was continued, clinical response was observed both for depression and PTSD (depression response rate: 45.5% and remission rate: 22.7%; PTSD response rate: 45.5% and remission: 18.2%). Limitations: The retrospective design of the study and the absence of a comparator group are the main limitations of our study. Conclusions: Our results suggest that the occurrence of esketamine-induced traumatic flashbacks does not hinder clinical response. On the contrary, when managed appropriately and combined with targeted psychotherapy, it could even contribute to positive outcomes.

Subjects suffering from bipolar disorder taking lithium are less likely to report physical pain: a FACE-BD study.

BACKGROUND: Physical pain is a common issue in people with bipolar disorder (BD). It worsens mental health and quality of life, negatively impacts treatment response, and increases the risk of suicide. Lithium, which is prescribed in BD as a mood stabilizer, has shown promising effects on pain. METHODS: This naturalistic study included 760 subjects with BD ( FACE-BD cohort) divided in two groups: with and without self-reported pain (evaluated with the EQ-5D-5L questionnaire). In this sample, 176 subjects were treated with lithium salts. The objectives of the study were to determine whether patients receiving lithium reported less pain, and whether this effect was associated with the recommended mood-stabilizing blood concentration of lithium. RESULTS: Subjects with lithium intake were less likely to report pain (odds ratio [OR] = 0.59, 95% confidence interval [CI], 0.35-0.95; p = 0.036) after controlling for sociodemographic variables, BD type, lifetime history of psychiatric disorders, suicide attempt, personality traits, current depression and anxiety levels, sleep quality, and psychomotor activity. Subjects taking lithium were even less likely to report pain when lithium concentration in blood was ≥0.5 mmol/l (OR = 0.45, 95% CI, 0.24-0.79; p = 0.008). CONCLUSIONS: This is the first naturalistic study to show lithium's promising effect on pain in subjects suffering from BD after controlling for many confounding variables. This analgesic effect seems independent of BD severity and comorbid conditions. Randomized controlled trials are needed to confirm the analgesic effect of lithium salts and to determine whether lithium decreases pain in other vulnerable populations.

The Efficacy and Safety of Intranasal Formulations of Ketamine and Esketamine for the Treatment of Major Depressive Disorder: A Systematic Review.

Ketamine and its enantiomers represent an innovative glutamatergic agent as a treatment for individuals with treatment-resistant depression (TRD) and major depressive disorder (MDD) with suicidal ideation and behavior. Intranasal (IN) formulations could allow for quick onset of action on depressive symptoms as well as a reduction in side effects by bypassing the blood-brain barrier compared with administration via the intravenous route. The aim of this review was to provide an up-to-date analysis of the data on the efficacy and safety of IN ketamine and IN esketamine for the treatment of MDD. A systematic review following PRISMA guidelines was conducted. Databases (PubMed, Embase, MEDLINE, PsycINFO, and Google Scholar) were searched to capture articles about IN ketamine or IN esketamine for MDD. This systematic review highlighted the interest in IN routes of ketamine and esketamine for MDD patients with TRD or active suicidal ideation. They provide a rapid onset of antidepressant action within the first hours after administration. Nevertheless, the evidence of efficacy is stronger for IN esketamine than for IN ketamine in MDD patients. The safety profile appears to be acceptable for IN esketamine but requires further studies, and a more accurate IN delivery device is required for ketamine.

Development of the PREMIUM computerized adaptive testing for measuring the access and care coordination for patients with severe mental illness.

Severe mental illness (SMI) patients often have complex health needs, which makes it difficult to access and coordinate their care. This study aimed to develop a computerized adaptive testing (CAT) tool, PREMIUM CAT-ACC, to measure SMI patients' experience with access and care coordination. This multicenter and cross-sectional study included 496 adult in- and out-patients with SMI (i.e., schizophrenia, bipolar disorder, or major depressive disorder). Psychometric analysis of the 13-item bank showed adequate properties, with preliminary evidence of external validity and no substantial differential item functioning for sex, age, care setting, and diagnosis, making it suitable for CAT administration. A post-hoc CAT simulation demonstrated that the tool was efficient and accurate, with an average of seven items, compared to the full item bank administration. Its use by clinicians can contribute to optimizing patient care pathways and transitioning towards more person-centered healthcare.

[Validated care programs for patients with functional neurological disorders]. / Modèles de soins validés pour les patients souffrant de troubles neurologiques fonctionnels.

Functional neurological disorder (FND) is a common cause of persistent and disabling neurological symptoms. Diagnostic delay may lead to no treatment, inappropriate treatment or even iatrogenic symptoms. Yet, several treatments significantly reduce physical symptoms and improve functioning in FND patients even though not all patients respond to the currently available treatments. This review aims to describe the range of evidence-based rehabilitative and/or psychological therapeutic approaches available for FND patients. The most effective treatments are multidisciplinary and coordinated; using an outpatient or inpatient setting. Building a network of FND-trained healthcare professionals around the patient is an essential aspect of optimal patient management. Indeed, a supportive environment coupled with a collaborative therapeutic relationship improves understanding of FND and appears to help patients engage in appropriate treatments. Patients need to be invested in their own care and have to understand that recovery may depend on their commitment. The conventional treatment combines psychoeducation, physical rehabilitation and psychotherapy (cognitive and behavioral therapy, hypnosis, psychodynamic interpersonal therapy). Early referral of patients to physical therapy is recommended; however, the optimal parameters of treatment, duration and intensity are unknown and seem to vary with the severity and chronicity of symptoms. The goal is to minimize self-awareness by diverting attention or by stimulating automatically generated movements with non-specific and gradual exercises. The use of compensatory technical aids should be avoided as much as possible. Psychotherapeutic management should encourage self-evaluation of cognitive distortions, emotional reactions and maladaptive behaviors while empowering the patient in managing symptoms. Symptom management can use anchoring strategies to fight against dissociation. The aim is to connect to the immediate environment and to enrich one's sensoriality. The psychological interventions should then be adapted to the individual psychopathology, cognitive style and personality functioning of each patient. There is currently no known curative pharmacological treatment for FND. The pharmacological approach rather consists of progressively discontinuing medication that was introduced by default and that could lead to undesirable side effects. Finally, neurostimulation (transcranial magnetic stimulation, transcranial direct current stimulation) can be effective on motor FND.

Crossed clinical features between eating disorders and types of bipolar disorder: Results from the FondaMental Advanced Centers of Expertise - Bipolar Disorder cohort.

BACKGROUND: Eating disorders (EDs) are liable to alter the disease course of bipolar disorder (BD). We explored the crossed clinical features between EDs and BD, particularly as a function of BD type (BD1 vs. BD2). METHODS: 2929 outpatients attending FondaMental Advanced Centers of Expertise were assessed for BD and lifetime EDs with a semi-structured interview, and their sociodemographic, dimensional and clinical data were collected according to a standardized procedure. For each ED type, bivariate analyses were used to investigate associations between these variables and the type of BD type followed by multinomial regressions with the variables associated with EDs and BDs after Bonferroni correction. RESULTS: Comorbid EDs were diagnosed in 478 (16.4 %) cases, and were more prevalent in patients with BD2 than in those with BD1 (20.6 % vs. 12.4 %, p < 0.001). Regression models showed no difference according to the subtype of bipolar disorder on the characteristics of patients with anorexia nervosa (AN), bulimia nervosa (BN) or binge eating disorder (BED). After multiple adjustments, the factors differentiating BD patients with versus without ED were primarily age, gender, body mass index, more affective lability and comorbidity with anxiety disorders. BD patients with BED also scored higher regarding childhood trauma. BD patients with AN also showed higher risk of past suicide attempts than those with BED. CONCLUSIONS: In a large sample of patients with BD, we found a high prevalence of lifetime EDs, especially for the BD2 type. EDs were associated with several severity indicators, but not with BD type-specific characteristics. This should prompt clinicians to carefully screen patients with BD for EDs, regardless of BD and ED types.

Clinicians' preferences and attitudes towards the use of lithium in the maintenance treatment of bipolar disorders around the world: a survey from the ISBD Lithium task force.

BACKGROUND: Lithium has long been considered the gold-standard pharmacological treatment for the maintenance treatment of bipolar disorders (BD) which is supported by a wide body of evidence. Prior research has shown a steady decline in lithium prescriptions during the last two decades. We aim to identify potential factors explaining this decline across the world with an anonymous worldwide survey developed by the International Society for Bipolar Disorders (ISBD) Task Force "Role of Lithium in Bipolar Disorders" and distributed by diverse academic and professional international channels. RESULTS: A total of 886 responses were received of which 606 completed the entire questionnaire while 206 completed it partially. Respondents were from 43 different countries comprising all continents. Lithium was the most preferred treatment option for the maintenance of BD patients (59%). The most relevant clinical circumstances in which lithium was the preferred option were in patients with BD I (53%), a family history of response (18%), and a prior response during acute treatment (17%). In contrast, Lithium was not the preferred option in case of patients´ negative beliefs and/or attitudes towards lithium (13%), acute side-effects or tolerability problems (10%) and intoxication risk (8%). Clinicians were less likely to prefer lithium as a first option in BD maintenance phase when practising in developing economy countries [X2 (1, N = 430) = 9465, p = 0.002) ] and private sectors [X2 (1, N = 434) = 8191, p = 0.004)]. CONCLUSIONS: Clinicians' preferences and attitudes towards the use of lithium in the maintenance treatment of bipolar disorders appear to be affected by both the patients' beliefs and the professional contexts where clinicians provide their services. More research involving patients is needed for identifying their attitudes toward lithium and factors affecting its use, particularly in developing economies.

Childhood maltreatment contributes to the medical morbidity of individuals with bipolar disorders.

BACKGROUND: Individuals with bipolar disorders (BD) are at risk of premature death, mainly due to medical comorbidities. Childhood maltreatment might contribute to this medical morbidity, which remains underexplored in the literature. METHODS: We assessed 2891 outpatients with BD (according to DSM-IV criteria). Childhood maltreatment was assessed using the Childhood Trauma Questionnaire. Lifetime diagnoses for medical disorders were retrospectively assessed using a systematic interview and checked against medical notes. Medical morbidity was defined by the sum of medical disorders. We investigated associations between childhood maltreatment (neglect and abuse) and medical morbidity while adjusting for potential confounders. RESULTS: One quarter of individuals had no medical comorbidities, while almost half of them had at least two. Multivariable regression showed that childhood maltreatment (mainly abuse, but also sexual abuse) was associated with a higher medical morbidity. Medical morbidity was also associated with sex, age, body mass index, sleep disturbances, lifetime anxiety disorders and lifetime density of mood episodes. Childhood maltreatment was associated with an increased prevalence of four (i.e. migraine/headache, drug eruption, duodenal ulcer, and thyroid diseases) of the fifteen most frequent medical disorders, however with no difference in terms of age at onset. CONCLUSIONS: This large cross-sectional study confirmed a high medical morbidity in BD and its association with childhood maltreatment. The assessment of childhood maltreatment in individuals with BD should be systematically included in routine care and the potential impact on physical health of psycho-social interventions targeting childhood maltreatment and its consequences should be evaluated.