Association of clinical characteristics, depression remission and suicide risk with discrepancies between self- and clinician-rated suicidal ideation: Two large naturalistic cohorts of outpatients with depression.

Clinician- and self-rating of suicidal ideation (SI) are often discrepant. The aim of this study was to determine: 1) Association between discrepant self- and clinician-rated SI with clinical characteristics, depression remission and SA (SA) risk; 2) which SI assessment (self or clinician) predicted depression remission and risk of SA. LUEUR and GENESE are two large, prospective, naturalistic cohorts of French adult outpatients with unipolar depression treated and followed for 6 weeks. SI presence was assessed and defined with a score to the suicidal item of the Montgomery-Åsberg Depression Rating Scale ≥3. Discordant SI was defined as SI detection by only one of the two evaluators (patient or clinician). In both cohorts, 49.3 % (GENESE) and 34 % (LUEUR) patients had discordant SI. Clinical characteristics were more severe, and risk of SA was higher in patients with current SI (concordant and discordant) than in patients without SI and in the concordant than in the discordant group. Prediction of the risk of SA and of depression non-remission was comparable by the two ratings. Patients with SI (concordant and discordant) have more severe clinical characteristics and patients with concordant SI are the most at risk of SA during the follow-up. It is crucial to assess SI and to improve how it is evaluated.

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.

Factors associated with transitioning from suicidal ideation to suicide attempt in the short-term: Two large cohorts of depressed outpatients.

BACKGROUND: This study explores factors associated with transitioning from recent suicidal ideation (SI) to suicide attempt (SA) in depressed outpatients. METHODS: This is a case-control study nested in two cohorts (LUEUR and GENESE) of depressed adult outpatients recruited in France and followed up for six weeks. SI, depression, anxiety, insomnia, impulsivity, and hopelessness were assessed with validated scales. Differences between patients with SI who attempted suicide during follow up and those who did not were explored using logistic regressions. RESULTS: There was a slight majority of females in both cohorts. Mean age was 47.2 years in LUEUR and 49.4 years in GENESE. Of the 3785 participants in the LUEUR cohort, 72 (2.1 %) attempted suicide within the 6-week period vs. 19 of the 2698 participants (0.7 %) in the GENESE cohort. In LUEUR, factors associated with SA within the 6-week period were lifetime history of SA (OR = 5.35, 95 % CI = 3.30-8.66), high SI at baseline (OR = 3.87, 95 % CI = 2.4-6.24), associated treatments (OR = 3.28, 95 % CI = 2.00-5.38), and less improvement over follow-up in the following symptoms: SI (OR = 3.64, 95 % CI = 1.89-7.02), depression (OR = 3.66, 95 % CI = 1.76-7.62), and anxiety (OR = 3.26, 95 % CI = 1.46-7.27). In GENESE, associated factors were lifetime history of SAs (OR = 9.93, 95 % CI = 3.83-25.80), and less improvement in SI (OR = 9.20, 95 % CI = 3.61-23.44). LIMITATIONS: Heterogeneity of cohorts prevented from performing a pooled analysis with a greater sample size. CONCLUSIONS: In depressed outpatients, lack of improvement was strongly associated with a short-term SA, particularly in patients with a history of previous SAs. Fast acting treatment on SI and depression may help prevent SAs.

Physical and mental health status of former smokers and non-smokers patients with bipolar disorder.

OBJECTIVES: Up to 70% individuals with bipolar disorder (BD) are lifetime tobacco smokers, a major modifiable risk factor for morbidity. However, quitting smoking is rarely proposed to individuals with BD, mainly because of fear of unfavorable metabolic or psychiatric changes. Evaluating the physical and mental impact of tobacco cessation is primordial. The aim of this study was to characterize the psychiatric and nonpsychiatric correlates of tobacco smoking status (never- vs. current vs. former smokers) in individuals with BD. METHODS: 3860 individuals with ascertained BD recruited in the network of Fondamental expert centers for BD between 2009 and 2020 were categorized into current, former, and never tobacco smokers. We compared the sociodemographic and clinical characteristics assessed by standard instruments (e.g., BD type, current symptoms load, and non-psychiatric morbidity-including anthropometric and biological data) of the three groups using multinomial regression logistic models. Corrections for multiple testing were applied. RESULTS: Current smokers had higher depression, anxiety, and impulsivity levels than former and never-smokers, and also higher risk of comorbid substance use disorders with a gradient from never to former to current smokers-suggesting shared liability. Current smokers were at higher risk to have a metabolic syndrome than never-smokers, although this was only evidenced in cases, who were not using antipsychotics. CONCLUSIONS: Tobacco smoking was associated with high morbidity level. Strikingly, as in the general population, quitting smoking seemed associated with their return to the never-smokers' levels. Our findings strongly highlight the need to spread strategies to treat tobacco addiction in the BD population.

Clinical characteristics associated with discrepancies between self- and clinician-rated suicidal ideation in patients with bipolar disorder (FACE-BD cohort).

Suicidal ideation (SI) is a major suicide risk factor; therefore, it is crucial to identify individuals with SI. Discrepancies between the clinicians and patients' estimation of SI may lead to under-evaluating the suicide risk. Yet, studies on discrepancies between self- and clinician-rated SI are lacking, although identifying the patients' sociodemographic and clinical characteristics associated with such discrepancies might help to reduce the under-evaluation risk. Therefore, the aim of this study was to identify features associated with SI rating discrepancies in patients with bipolar disorder (BD) because of the high prevalence of suicide in this population. Among the patients recruited by the French network of FondaMental expert centers for BD, patients with SI (i.e. ≥2 for item 12 of the Quick Inventory of Depressive Symptomatology-Self Report and/or ≥3 for item 10 of the clinician-rated Montgomery and Åsberg Depression Rating Scale) were selected and divided in concordant (i.e. SI in both self- and clinician-rated questionnaires; n = 130; 25.6%), and discordant (i.e. SI in only one questionnaire; n = 377; 74.4%). Depression severity was the feature most associated with SI evaluation discrepancy, especially in patients with SI identified only with the self-rated questionnaire. Clinician may under-evaluate SI presence in patients with low depression level.

Multiple suicide attempts associated with addiction to tramadol.

BACKGROUND: The opioid tramadol is used as analgesic drug, and more recently was also proposed for the management of major depressive disorder. However, growing evidence suggests a link between opioid system dysfunction and suicidal behaviors, raising the question of tramadol use in view of the high addictive and suicidal risk. Here, we present the case of a young adult woman with multiple suicide attempts related to tramadol addiction. CASE PRESENTATION: A 25-year-old woman was admitted for suicide attempt by phlebotomy in the Department of Psychiatric Emergency and Acute Care, Montpellier (France), in March 2020. The suicide attempt occurred 3 days after an abrupt tramadol withdrawal. In 2018, due to spinal disc herniation, she had a first prescription of tramadol to which she became addicted. The patient described an effect on psychological pain and suicidal ideation. However, she had to increase tramadol dose to obtain the desired effects, and for several months her intake was 2 000 mg per day. When she could not obtain tramadol any longer, suicidal ideation and psychological pain increased, leading to the suicide attempt. At the time of a worldwide opioid crisis that contributes to increasing suicidal behaviors, this case raises questions about tramadol prescription (often considered to be less addictive and with lower abuse potential) to individuals at risk of suicide.

Characteristics and treatment outcome of suicidal depression: Two large naturalistic cohorts of depressed outpatients.

OBJECTIVE: The emergence of new drugs for managing suicidal ideation (e.g. ketamine) raises the question of whether suicidal depression (i.e. moderate to severe depression with concomitant suicidal ideation) is a specific depression phenotype. Therefore, this study characterized patients with suicidal depression (baseline clinical characteristics, suicidal ideation and depression evolutions, suicide risk) in two large cohorts of outpatients with depression. METHODS: LUEUR and GENESE are two large, prospective, naturalistic cohorts of French adult outpatients with depression (Diagnostic and Statistical Manual of Mental Disorders, fourth edition, criteria), treated and followed up for 6 weeks. Depression severity was assessed with the Hospital Anxiety and Depression Scale, and suicidal ideation with the suicidal item of the Montgomery-Åsberg Depression Rating Scale. Patients with moderate or severe depression (Hospital Anxiety and Depression Scale-Depression subscale score >11) were selected and classified as without suicidal ideation (suicidal item of the Montgomery-Åsberg Depression Rating Scale <2), with moderate suicidal ideation (suicidal item of the Montgomery-Åsberg Depression Rating Scale [2; 3]) and with severe suicidal ideation (suicidal item of the Montgomery-Åsberg Depression Rating Scale ⩾4). RESULTS: Baseline clinical features were more severe (e.g. higher anxiety and depression scores) in depressed patients with moderate/severe suicidal ideation. Depression remission after treatment was less frequent among patients with severe suicidal ideation. The risk of suicide attempt during the follow-up was threefold higher in patients with suicidal ideation among those 10% had persistent suicidal ideation. CONCLUSION: Suicidal depression could be a specific depression phenotype with more severe clinical characteristics, less frequent depression remission, suicidal ideation persistence and higher suicide attempt risk, despite antidepressant treatment. It seems that novel therapeutic strategies could be needed.

Psilocybin, a Naturally Occurring Indoleamine Compound, Could Be Useful to Prevent Suicidal Behaviors.

The available interventions for people who are at risk of suicide have limited efficacy. Recently, research on new mental health treatments has started to consider psychedelic compounds, particularly psilocybin, a molecule with a few thousand years of history of use in human societies. The possible effects of psilocybin on suicidal ideation and behaviors have not been specifically studied yet; however, the current knowledge on the suicidal process and the available data on es/ketamine suggest that psylocibin could be used to modulate the thoughts and behavioral patterns in individuals who are at risk of suicidal behaviors. Here, we summarize the available evidence on the possible mechanisms underlying psilocybin positive effects on suicide risk. Major pathways related to suicidal behaviors that might be modulated by psylocibin include serotonin receptors. Specifically, psylocibin directly stimulates the serotonin 2A receptor (5HT2A), targeting the inflammatory and oxidative stress pathways and leading to a rapid increase in brain plasticity and inflammation suppression and increases in cognitive flexibility, spirituality, and empathy. We also present preliminary epidemiological data and provide a rationale for studying psilocybin in individuals with suicidal ideation or who are at risk of suicidal behaviors. This review presents a framework to understand the basis for psilocybin use in individuals who are at risk of suicidal behaviors and calls for clinical studies.

Association Between the A118G Polymorphism of the OPRM1 Gene and Suicidal Depression in a Large Cohort of Outpatients with Depression.

BACKGROUND: Growing evidences suggest that depression with suicidal ideation (SI) could be a specific phenotype with its own characteristics. Moreover, opioid system deregulation might be implicated in suicidal behaviour (SB). The aim of this study was to determine whether the A118G polymorphism (rs1799971) in ORPM1 (the gene encoding opioid receptor mu 1) is associated with suicidal depression (ie, moderate to severe depression with SI) in a large cohort of outpatients with depression. METHODS: GENESE is a large, prospective, naturalistic cohort of French adult outpatients with depression (DSM-IV criteria), treated and followed for 6 weeks. Depression severity was assessed with the Hospital Anxiety and Depression Scale (HADS), and SI with the suicidal item of the Montgomery-Åsberg Depression Rating Scale (MADRS-SI). From this cohort, patients with moderate or severe depression (HADS-D subscale score >11) were selected and classified as without SI (MADRS-SI < 2), or with SI (MADRS-SI ≥ 2). RESULTS: The AA/AG genotypes of the A118G polymorphism were significantly associated with suicidal depression in the non-adjusted (OR = 2.32, 95% CI = [1.28; 4.18]; p-value = 0.005) and in the adjusted models (OR = 2.54, 95% CI = [1.35; 4.78]; p-value = 0.004). CONCLUSION: Outpatients with depression harbouring the A allele are at higher risk of SI (and possibly SB) than those carrying the G allele. More studies are needed to better understand the link between this polymorphism and SB.

Effects of Hormonal Contraception Use on Cognitive Functions in Patients With Bulimia Nervosa.

Background: Growing evidences indicate that sex hormones have an effect on cognitive functions, and that Bulimia Nervosa (BN) is associated with cognitive impairment. The aim of this study was to determine the effect of hormonal contraception (HC) use on four cognitive functions that are impaired in patients with BN. Methods: This retrospective exploratory study included 103 women with a diagnosis of BN based on the DSM-5 criteria. Their age ranged from 15 to 45 years, and 46.6% were taking HC (oral, transdermal, or intrauterine). Cognition was assessed with the d2 test (attention), Iowa gambling task (IGT; decision making), Brixton spatial anticipation test (set shifting), and Rey-Osterrieth complex figure test (central coherence). Data were analyzed with logistic regression models to estimate the adjusted odds ratios (OR) and 95% confidence intervals (CI) of HC effect on the neuropsychological test scores. Results: In the multivariate model, HC use was significantly associated with better scores for two d2 test indices: F-score [OR = 0.98, 95% CI = (0.95; 0.99)] and final total score ratio [OR = 0.87, 95% CI = (0.77; 0.99)]. HC was also associated with a better understanding of the IGT explicit rules. No difference between the two groups (HC and non-HC use) was detected for set shifting and central coherence. Conclusions: This exploratory study suggests that HC could have effects on the sustained attention and concentration in women with BN. More studies are needed to confirm these results.

Characterization of depressed bipolar patients with current suicidal ideation.

OBJECTIVE: Bipolar disorder is one of the most frequent psychiatric disorders among suicidal patients. A large part of patients with bipolar disorder (30-50%) will attempt suicide. Suicidal ideation being a major risk factor of suicidal act, it is crucial to better characterize patients with suicidal bipolar depression (i.e. depression with current suicidal ideation). The aim of this study was to characterize suicidal bipolar depressed patients in comparison with non-suicidal depressed patients in terms of clinical characteristics, evolution of depression and suicidal ideation course over time, and risk of suicide attempt during follow-up. METHODS: Among patients with bipolar disorder recruited from the network of FondaMental expert centres for bipolar disorder between 2009 and 2017, we selected patients with at least mild depression (Montgomery-Åsberg Depression Rating Scale total score >11) and without current manic symptomatology (Young Mania Rating Scale total score <7) at baseline (N = 938). Suicidal depression was defined by a baseline score ⩾2 for item 12 of the Quick Inventory of Depressive Symptomatology-Self Report (N = 271, 28.9%). Non-suicidal depression was defined by a baseline item 12 of the Quick Inventory of Depressive Symptomatology-Self Report score <2 (N = 667, 71.1%). A subsample of about 300 patients (with or without suicidal ideation at baseline) was followed up for 2 years. RESULTS: Baseline clinical features (e.g. depression severity, childhood trauma, global functioning) were more severe in patients with than without suicidal depression. Suicidal patients tended to remain more suicidal throughout the follow-up than patients without suicidal ideation at baseline (3.4-fold higher risk of persistent suicidal ideation at the 2-year visit despite an improvement in depressive symptomatology). CONCLUSIONS: Depressed bipolar disorder patients reporting suicidal ideation had more severe clinical features at baseline and were more prone to report persistent suicidal ideation during the follow-up, independently of thymic state. Clinicians should closely monitor this subgroup of patients.

[Let's be more ambitious in treating suicide]. / Soyons plus ambitieux pour traiter le suicide - La vieillesse et la mort, problématiques comportementales et sociétales.

Suicide is a major public health problem. It becomes necessary and essential to identify persons at risk and to offer them an appropriate care. Entry in the DSM 5 of suicidal behavior (SB) as a disease to study is a first step in its recognition as an independent disease with its own physiopathology. Long time considered as a consequence or as a symptom of others psychiatric diseases, there is actually no specific treatment of SB. Nevertheless, new ways of understanding of mechanisms underlying SB are emerging and could consequently lead to find new specific therapeutics. Understanding the role played by psychological pain in SB seems to be a good approach to decipher the physiopathology of SB. Furthermore, we are witnessing the emergence of potential specific therapeutics such as ketamine that has shown promising results in treating SB.

TITLE: Soyons plus ambitieux pour traiter le suicide - La vieillesse et la mort, problématiques comportementales et sociétales. ABSTRACT: Il est difficile de discuter de la mort sans parler de la mort volontaire. Le suicide est en effet un enjeu de santé publique majeur. Il est donc primordial de pouvoir identifier les sujets à risque et de les prendre en charge. Cependant, cet exercice reste complexe. Une première avancée est de considérer les conduites suicidaires (CS) comme une entité diagnostique à part entière avec sa propre physiopathologie. De nouvelles pistes de compréhension sont aussi nécessaires ; le rôle de la douleur tant physique que sociale dans le suicide est une voie prometteuse. Les traitements pharmacologiques actuels visent principalement à traiter les pathologies associées à ces conduites, mais certaines molécules ayant une action anti-suicidaire rapide et spécifique, comme la kétamine, se montrent encourageantes.

Corticotropin releasing hormone receptor CRHR1 gene is associated with tianeptine antidepressant response in a large sample of outpatients from real-life settings.

Polymorphisms of genes involved in the hypothalamic-pituitary-adrenocortical (HPA) axis have been associated with response to several antidepressant treatments in patients suffering of depression. These pharmacogenetics findings have been reported from independent cohorts of patients mostly treated with selective serotonin reuptake inhibitors, tricyclic antidepressant, and mirtazapine. Tianeptine, an atypical antidepressant, recently identified as a mu opioid receptor agonist, which prevents and reverses the stress induced by glucocorticoids, has been investigated in this present pharmacogenetics study. More than 3200 Caucasian outpatients with a major depressive episode (MDE) from real-life settings were herein analyzed for clinical response to tianeptine, a treatment initiated from 79.5% of the subjects, during 6-8 weeks follow-up, assessing polymorphisms targeting four genes involved in the HPA axis (NR3C1, FKPB5, CRHR1, and AVPR1B). We found a significant association (p < 0.001) between CRHR1 gene variants rs878886 and rs16940665, or haplotype rs878886*C-rs16940665*T, and tianeptine antidepressant response and remission according to the hospital anxiety and depression scale. Analyses, including a structural equation model with simple mediation, suggest a moderate effect of sociodemographic characteristics and depressive disorder features on treatment response in individuals carrying the antidepressant responder allele rs8788861 (allele C). These findings suggest direct pharmacological consequences of CRHR1 polymorphisms in the antidepressant tianeptine response and remission, in MDE patients. This study replicates the association of the CRHR1 gene, involved in the HPA axis, with (1) a specificity attributed to treatment response, (2) a lower risk of chance finding, and in (3) an ecological situation.

The Role of Opiates in Social Pain and Suicidal Behavior.

With more than 800,000 deaths by suicide each year and 20 to 30 times more suicide attempts worldwide, suicide is a major public health problem. Current treatments of SB are mainly based on pharmacological treatments that are not specific of SB (e.g. antidepressants), and new therapeutic targets are urgently needed. Recent data strengthen the ancient conception pain (social, psychic, physical) that is at the core of the suicidal process and should be incorporated in the clinical assessment of suicide risk. Then, the mechanisms involved in the regulation of pain may open new avenues regarding therapeutic perspectives. Opiates appear to be a promising candidate in treatment of SB. Indeed, since the last two decades, growing evidences suggest an implication of the opioid system in the pathophysiology of SB, this conduct to the elaboration of randomized controlled trials (RCTs) using opiates in patients with SB. Results suggesting an anti-suicidal effect of buprenorphine and the potential opioidergic-related anti-suicidal effect of ketamine both contribute to the growing interest in opiates use in SB. In this review, we will summarize a large part of the evidence that leads researchers and clinicians to be interested in the use of opiates for SB treatment and discuss on new opioid pharmacological options for suicidal patients.