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Glucagon-like peptide-1 (GLP-1) agonists have been successfully used in clinical practice for the treatment of diabetes and obesity, offering significant clinical benefits. However, concerns regarding their potential link to psychiatric side effects, like suicidal thoughts and behaviours (STB) have emerged. This narrative review investigates the complex interplay between GLP-1 agonists and STB, focusing on the biological stress induced by rapid weight loss, psychological and social consequences, similar mechanism with addiction, and the evaluative lens of the Bradford Hill criteria on causality. While GLP-1 agonists can contribute to substantial health improvements, they also introduce biological and psychological stressors. Disruptions in homeostasis from quick weight reduction can elevate cortisol and norepinephrine levels, heightening the risk for, or exacerbation of STB. Psychological factors, including unfulfilled expectations and identity changes after significant weight loss, compound these risks. Utilizing the Bradford Hill criteria reveals insufficient evidence for a direct causal link between GLP-1 agonists and STB. Yet, the indirect effects related to the metabolic and psychological disturbances associated with rapid weight loss call for a cautious approach. Used carefully in targeted populations GLP-1 agonists may even emerge as protective agents against STB. Therefore, it is crucial to monitor patients during the treatment and screen for preexisting mental health conditions. If detected, appropriate clinical management should be applied. Future studies should aim at optimizing dosing schedules to mitigate the adverse effects of rapid weight loss and further investigate GLP-1 agonists in possible STB prevention.
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BACKGROUND: Identifying circulating biomarkers associated with prospective suicidal ideation (SI) and depression could help better understand the dynamics of these phenomena and identify people in need of intense care. In this study, we investigated the associations between baseline peripheral biomarkers implicated in neuroplasticity, vascular homeostasis and inflammation, and prospective SI and depression severity during 6 months of follow-up in patients with mood disorders. METHODS: 149 patients underwent a psychiatric evaluation and gave blood to measure 32 plasma soluble proteins. At follow-up, SI incidence over six months was measured with the Columbia Suicide Severity Rating Scale, and depressive symptoms were assessed with the Inventory for Depressive Symptomatology. Ninety-six patients provided repeated blood samples. Statistical analyses included Spearman partial correlation and Elastic Net regression, followed by the covariate-adjusted regression models. RESULTS: 51.4â¯% (N = 71) of patients reported SI during follow-up. After adjustment for covariates, higher baseline levels of interferon-γ were associated with SI occurrence during follow-up. Higher baseline interferon-γ and lower orexin-A were associated with increased depression severity, and atypical and anxious, but not melancholic, symptoms. There was also a tendency for associations of elevated baseline levels of interferon-γ, interleukin-1ß, and lower plasma serotonin levels with SI at the six-month follow-up time point. Meanwhile, reduction in transforming growth factor- ß1 (TGF-ß1) plasma concentration correlated with atypical symptoms reduction. CONCLUSION: We identified interferon-γ and orexin-A as potential predictive biomarkers of SI and depression, whereas TGF-ß1 was identified as a possible target of atypical symptoms.
Subject(s)
Biomarkers , Depression , Mood Disorders , Severity of Illness Index , Suicidal Ideation , Humans , Male , Female , Biomarkers/blood , Prospective Studies , Middle Aged , Adult , Depression/blood , Depression/psychology , Mood Disorders/blood , Mood Disorders/psychology , Interferon-gamma/blood , Orexins/blood , Interleukin-1beta/blood , Follow-Up Studies , Serotonin/bloodABSTRACT
Introduction: Suicidal ideation, an important risk factor for suicide attempts, has an unclear neurobiological basis and is potentially linked to the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and immune-inflammatory systems. While inflammatory markers have been associated with suicide attempts and, to a lower extent suicidal ideation, the data on the role of a stress-response system is less robust, with most studies carried out with cortisol showing inconsistent results. The present study extends on the previous studies implicating stress-response and immune-inflammatory systems in suicidal thoughts and behaviours, focusing on the associations of several stress-response (adrenocorticotropic hormone (ACTH), cortisol, and dehydroepiandrosterone (DHEA)) and immune-inflammatory (C-reactive protein (CRP),interle ukin-6 (IL-6), and tumour necrosis factor-alpha (TNF-alpha)) with suicidal ideation severity in recent suicide attempters, patients with major depressive disorder, and non-psychiatric controls. Methods: This observational study included 156 adults from three Vilnius hospitals, recruited into one of the three groups in equal parts: recent suicide attempters, patients with major depressive disorder in current depressive episode, and non-psychiatric controls. Measures included the Hamilton Depression Rating Scale (HDRS-17) and the Beck Scale for Suicide Ideation/Suicide Severity Index (BSS/SSI), alongside sociodemographic data, alcohol, tobacco use, and morning blood samples, measuring plasma ACTH, cortisol, DHEA, CRP, and IL-6. Data were analysed with non-parametric tests, Kendall's tau correlation, and multivariate linear regression adjusted for confounders. Results: We found a negative correlation between the plasma ACTH levels and suicidal ideation severity (tau = -0.130, p = 0.033), which was driven by the patients with major depressive disorder (tau = -0.237, p = 0.031). Suicidal ideation severity was also negatively correlated with TNF-alpha (tau = -0.231; p < 0.001), positively correlated with IL-6 (tau = 0.154, p = 0.015), and CRP levels (tau = 0.153, p = 0.015), but no differences were observed in group-stratified analyses. The association between plasma ACTH levels and suicidal ideation severity in patients with major depressive disorder remained robust to adjustment for major confounders (adjusted for age, sex, education years, body mass index, smoking status, plasma CRP and PEth concentration (measuring chronic alcohol exposure), and antidepressant use) in the linear regression model (t = -2.71, p = 0.011), as well as additionally adjusting for depression severity (t = -2.99, p = 0.006). Discussion: The present study shows an association between plasma ACTH levels and suicidal ideation severity in patients with major depressive disorder, robust to adjustment for antidepressant use and depression severity. This finding highlights the potential role of ACTH, in elucidating the effects of stress and mental health disorders. Our findings underscore the importance of the HPA axis in the diagnosis and treatment of suicidal ideation in major depressive disorder and invite further research on interventions targeting this pathway.
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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.
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INTRODUCTION: Managing patient with suicidal thoughts and behaviours presents significant challenges due to the scarcity of robust evidence and clear guidance. This study sought to develop a comprehensive set of practical guidelines for the assessment and management of suicidal crises. MATERIALS AND METHODS: Utilizing the Delphi methodology, 80 suicide clinician and research experts agreed on a series of recommendations. The process involved two iterative rounds of surveys to assess agreement with drafted recommendations, inviting panellists to comment and vote, culminating in 43 consensus recommendations approved with at least 67% agreement. These consensus recommendations fall into three main categories: clinical assessment, immediate care, and long-term approaches. RESULTS: The panel formulated 43 recommendations spanning suicidal crisis recognition to continuous long-term care. These guidelines underscore systematic proactive suicide risk screening, in-depth medical and toxicological assessment, and suicide risk appraisal considering personal, clinical factors and collateral information from family. The immediate care directives emphasize a secure environment, continuous risk surveillance, collaborative decision-making, including potential hospitalization, sensible pharmacological management, safety planning, and lethal means restriction counselling. Every discharge should be accompanied by prompt follow-up care incorporating proactive case management and multi-modal approach involving crisis lines, brief contact, and psychotherapeutic and pharmacological interventions. CONCLUSIONS: This study generated comprehensive guidelines addressing care for individuals in suicidal crises, covering pre- to post-discharge care. These practical recommendations can guide clinicians in managing patients with suicidal thoughts and behaviours, improve patient safety, and ultimately contribute to the prevention of future suicidal crises.
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In France, suicidal behaviors remain a major public health issue. Depressed patients with suicidal ideation have more severe depressive symptoms, a more unfavorable disease course, and a greater number of suicide attempts than patients without suicidal ideation. Unfortunately, conventional antidepressants tend to be less effective in patients with suicidal tendencies than in those without. Nevertheless, promising advancements have emerged with the use of ketamine, which has shown significant and rapid efficacy in reducing the intensity of suicidal ideation in depressed patients within the first 72 h after its administration. Several mechanisms are potentially involved: (1) reduction of anhedonia. It has been demonstrated that ketamine reduces both anhedonia and suicidal ideation. In depressed patients, the reduction of anhedonia observed 2 h after ketamine administration is associated with metabolic changes in the anterior cingulate cortex involved in suicidal ideation; (2) activation of neuroplasticity cascades. The reduction in suicidal ideation within 24 h following ketamine administration is correlated with changes in plasma BDNF levels and is modulated by the Val66Met functional polymorphism of the BDNF gene. Moreover, preclinical and clinical studies have shown that ketamine induces functional and connectivity changes in the prefrontal and anterior cingulate regions, which are strongly implicated in suicidal behaviors; (3) reduction of inflammation. It is now widely accepted that suicidal behaviors are associated with low-grade inflammation, and with elevated quinolinic acid and reduced kynurenic acid levels. Interestingly, predictors of a reduction in suicidal ideation after ketamine infusion include initial severity of suicidal thoughts and depression, as well as baseline blood levels of kynurenic acid; (4) involvement of the opioidergic system. Post-mortem studies have indicated alterations in the opioidergic system related to suicidal behaviors. A recent study suggested that the antisuicidal effect of ketamine may depend on this system because naltrexone, an antagonist of mu opioid receptors, abolished the typical antidepressant effect and reduction in suicidal ideation observed following ketamine administration. In conclusion, ketamine exhibits promising potential in mitigating suicidal ideation - its effects are specific, rapid, albeit temporary. The suggested mechanisms driving its efficacy are multifaceted. Nevertheless, it is yet to be determined whether ketamine administration can effectively prevent suicidal behaviors.
Title: Comment la kétamine peut-elle aider à mieux prendre en charge le risque suicidaire ? Abstract: Les patients souffrant de dépression suicidaire répondent moins bien aux traitements antidépresseurs conventionnels que ceux qui n'ont pas d'idées suicidaires. Une avancée prometteuse dans ce domaine est l'utilisation de la kétamine, qui a montré une efficacité significative et rapide dans la réduction de l'intensité des idées suicidaires chez les patients déprimés. Des études ont montré qu'une seule perfusion intraveineuse de kétamine à faible dose pouva3it réduire de manière significative et durable les idées de suicide. De plus, la kétamine semble également réduire l'anhédonie, un symptôme associé aux idées suicidaires. Les mécanismes d'action de la kétamine sont multiples. Elle stimule la neuroplasticité via l'activation de la voie du BDNF (facteur neurotrophique du cerveau) et réduit l'inflammation. De plus, la kétamine semble agir sur le système opioïdergique, qui est impliqué dans les conduites suicidaires. En conclusion, la kétamine présente un intérêt dans la réduction des idées suicidaires chez les patients déprimés. Cependant, il est nécessaire de déterminer si son administration permet de prévenir les actes suicidaires. De plus amples recherches sont nécessaires pour mieux comprendre les mécanismes d'action de la kétamine et développer des stratégies thérapeutiques ciblées pour prévenir les conduites suicidaires.
Subject(s)
Depressive Disorder, Major , Ketamine , Humans , Ketamine/adverse effects , Anhedonia , Suicidal Ideation , Kynurenic Acid/therapeutic use , Brain-Derived Neurotrophic Factor/therapeutic use , Depressive Disorder, Major/drug therapy , Antidepressive Agents/adverse effects , InflammationABSTRACT
A growing body of evidences suggests that suicidal ideation (SI) and suicidal behaviors have biological bases. However, no biological marker is currently available to evaluate the suicide risk in individuals with SI or suicide attempt (SA). Moreover, the current risk assessment techniques poorly predict future suicidal events. The aim of this study was to examine the association of 39 new and already described peripheral cells and proteins (implicated in the immune system, oxidative stress and plasticity) with lifetime SA, past month SA, current SI, and future suicidal events (visit to the Emergency Department for SI or SA) in 266 treatment-seeking individuals with mood disorders. Equal parts of patients with and without past history of SA were recruited. All individuals at inclusion gave blood, were evaluated for SA recency, current SI, and were followed for two years afterwards. The 39 peripheral blood cellular and protein markers were entered separately for each outcome in Elastic Net models with 10-fold cross-validation, followed by single-analyte covariate-adjusted regression analyses for pre-selected analytes. Past month SA was associated with increased plasma levels of thrombospondin-2 and C-reactive protein, whereas current SI was associated with lower plasma serotonin levels. These associations were robust to adjustments for key covariates and corrections for multiple testing. The Cox proportional hazards regression showed that higher levels of thrombospondin-1 and of platelet-derived growth factor-AB predicted a future suicidal event. These two associations remained after adjustment for sex, age, and SA history, and outperformed the predictive value of past SA. Thrombospondins and platelet-derived growth factors have never been investigated in the context of suicide. Altogether, our results highlight the involvement in the suicidal process of platelet biological response and plasticity modifiers and also of inflammatory factors. They also suggest that SI and SA may have different biological correlates and that biomarkers associated with past SA or current SI do not automatically also predict future events.
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INTRODUCTION: Suicide is a complex transdiagnostic phenomenon. It is strongly associated with, but not exclusive to major depressive disorder (MDD). Hazardous alcohol drinking has also been linked to an increased risk of suicidal behaviours, however, it is often underreported. The study aimed to evaluate whether an objective measure of chronic alcohol use, phosphatidylethanol (PEth) could be useful as a biomarker in clinical practice. METHOD: ology. The present case-control multi-centric study recruited 156 participants into three study groups: 52 patients treated for major depressive disorder (MDD), 51 individuals immediately following a suicide attempt (SA), and 53 volunteers. Sociodemographic data, medical history, and laboratory data, including PEth concentrations and C-reactive protein levels, were collected from study participants. RESULTS: PEth concentrations were the highest in suicide attempters (232,54 ± 394,01 ng/ml), followed by patients with MDD (58,39 ± 135,82 ng/ml), and the control group (24,45 ± 70,83 ng/ml) (Kruskall Wallis χ2 = 12.23, df = 2, p = .002). In a multinomial logistic regression model with adjustments, PEth concentration was able to predict belonging to suicide attempters' group, but not to depression group (p = .01). Suicide attempters were also more likely to underreport their recent alcohol consumption. LIMITATIONS: We did not analyze SA methods, psychiatric comorbidity and several other factors that might be associated with PEth levels, such as body mass index, race, and haemoglobin levels. Sample recruited in hospital settings may not be representative of the whole population. The results of this adult-only study cannot be generalized to adolescents. CONCLUSIONS: PEth levels in recent suicide attempters significantly exceeded those of patients with MDD and controls. Suicide attempters also were more likely to underreport their alcohol consumption when questioned about their consuption. PEth might be an interesting biomarker to evaluate individuals at risk of SA.
Subject(s)
Glycerophospholipids , Suicide, Attempted , Adult , Humans , Alcohol Drinking , Biomarkers/blood , Depressive Disorder, Major/blood , Healthy Volunteers , Glycerophospholipids/bloodABSTRACT
Evidences suggest that inflammation is increased in a subgroup of patients with depression. Moreover, increased peripheral inflammatory markers (cells and proteins) are associated with some, but not all depressive symptoms. On the other hand, similar studies on bipolar disorders mainly focused on blood cytokines. Here, we analysed data from a large (N = 3440), well-characterized cohort of individuals with bipolar disorder using Kendall partial rank correlation, multivariate linear regression, and network analyses to determine whether peripheral blood cell counts are associated with depression severity, its symptoms, and dimensions. Based on the self-reported 16-Item Quick Inventory of Depressive Symptomatology questionnaire scores, we preselected symptom dimensions based on literature and data-driven principal component analysis. We found that the counts of all blood cell types were only marginally associated with depression severity. Conversely, white blood cell count was significantly associated with the sickness dimension and its four components (anhedonia, slowing down, fatigue, and appetite loss). Platelet count was associated with the insomnia/restlessness dimension and its components (initial, middle, late insomnia and restlessness). Principal component analyses corroborated these results. Platelet count was also associated with suicidal ideation. In analyses stratified by sex, the white blood cell count-sickness dimension association remained significant only in men, and the platelet count-insomnia/restlessness dimension association only in women. Without implying causation, these results suggest that peripheral blood cell counts might be associated with different depressive symptoms in individuals with bipolar disorder, and that white blood cells might be implicated in sickness symptoms and platelets in insomnia/agitation and suicidal ideation.
Subject(s)
Bipolar Disorder , Sleep Initiation and Maintenance Disorders , Male , Humans , Female , Bipolar Disorder/diagnosis , Depression , Platelet Count , Psychomotor Agitation , Suicidal Ideation , LeukocytesABSTRACT
One of the biggest ambitions in the field of anorexia nervosa (AN) research is to find a reliable and effective pharmacological treatment. The fact that currently no pharmacological treatment is safe and effective in this disease is worrying and also challenging. On the basis of the progress in our understanding of AN neurobiology, we propose that escitalopram, a widely available drug, might be a safe and effective option that needs to be investigated. Escitalopram is the only selective serotonin reuptake inhibitor, without any catecholaminergic effect. As studies have shown decreased serotonergic and increased dopaminergic transmission in AN, we hypothesized that an ideal drug for AN management should boost serotonin levels to increase serotonergic and decrease dopaminergic transmission, the two main features of escitalopram action. Here, we present a short overview of pharmacological research in AN and discuss the theoretical rationale for escitalopram use in AN. We also call for double-blind, randomized, placebo-controlled trials to test whether this theoretical framework translates into clinical efficacy.
Subject(s)
Anorexia Nervosa , Selective Serotonin Reuptake Inhibitors , Anorexia Nervosa/drug therapy , Citalopram/pharmacology , Citalopram/therapeutic use , Double-Blind Method , Escitalopram , Humans , Serotonin , Selective Serotonin Reuptake Inhibitors/pharmacology , Selective Serotonin Reuptake Inhibitors/therapeutic useABSTRACT
Marked heterogeneity in suicide attempters has been observed, with earlier onset being linked to stronger heritability, more childhood maltreatment. Nitric oxide signalling system might be implicated in this relationship through its role in the stress response/adaptation. This study examined how NOS genetic variants and childhood maltreatment were associated with age at first suicide attempt (SA). Adult patients with SA history (N = 414) filled in the Childhood Trauma Questionnaire, and six functionally relevant NOS2 and NOS3 polymorphisms were genotyped. Analyses included χ2, Mann-Whitney U tests, Kendall's regression, multivariate linear and Cox survival regressions, and a moderation analysis. The NOS3 promotor 27-bp variable number tandem repeat (VNTR) bb homozygous state and childhood emotional abuse were independently associated with earlier age at first SA, which was robust after controlling for confounders [regression coefficient - 3.975, 95% CI -6.980 - (-0.970), p = 0.010, and - 1.088, 95% CI -2.172 - (-0.004), p = 0.049]. No interaction was observed. In the Cox proportional hazards model for age at first SA, the hazard ratio for patients with childhood emotional abuse and NOS3 27-bp VNTR bb was 0.533 (95% CI 0.394-0.720, p < 0.001) compared to patients without. Intermediate scores were observed with either only the risk genotype or only childhood emotional abuse. A graded relationship was also observed for repeated SA, family history of SA, and severe SA history. These results are preliminary due to a low statistical power and call for replication and further characterization of the role of nitric oxide system in the susceptibility to early-onset SB.
Subject(s)
Child Abuse , Suicidal Ideation , Adult , Child , Emotional Abuse , Genotype , Humans , Nitric Oxide , Nitric Oxide Synthase Type III , Suicide, AttemptedABSTRACT
OBJECTIVES: Pre-electroconvulsive therapy (ECT) evaluation is an essential part of ECT preparation, a standard treatment in the psychiatric field. However, no routine pre-ECT evaluation has been published so far. This preliminary study aimed to explore different practices in pre-ECT evaluation across European countries. METHODS: The data were collected as a snowball sample approach using an online survey from September 2019 to April 2020. The final analysis included data from 18 clinics placed in 16 European countries. RESULTS: Regulations on the pre-ECT evaluation were found in 9 countries. All clinics reported doing complete blood count, serum electrolytes, and renal function analysis as a part of regular laboratory testing, alongside with a cardiovascular assessment. Ten clinics reported using psychiatric scales. Six clinics reported doing a cognitive assessment, of which all had regulations on the pre-ECT evaluation. Not one evaluation had the same sets of procedures and diagnostics. CONCLUSIONS: The differences in assessment approaches mirror high variability of the pre-ECT evaluation practice across Europe. Cognitive assessment and objectification of psychiatric symptoms should be a regular part of the pre-ECT evaluation because of the monitoring of the most common adverse effect and observing the clinical response to ECT. Standardization of the pre-ECT evaluation and ECT in general would remove criticisms and opposition to the treatment, make it based on the best of our knowledge, and provide a method respectful of patients' best interests and rights.
Subject(s)
Electroconvulsive Therapy , Mental Disorders , Humans , Electroconvulsive Therapy/methods , Mental Disorders/diagnosis , Mental Disorders/therapy , Mental Disorders/psychology , Surveys and Questionnaires , EuropeABSTRACT
BACKGROUND & AIMS: Patients with Anorexia Nervosa (AN) present many nutritional deficiencies (macro- and often also micro-nutrients), possibly explained by their inadequate food intake. Previous studies reported that selenium (Se) deficiency is common in the general population. As Se can be easily added as a supplement, the goal of this study was to evaluate the clinical impact of Se deficiency in patients with AN. METHODS: This cross-sectional study concerned 153 patients with AN (92.9% women) followed at the Eating Disorder Unit of Lapeyronie Academic Hospital, Montpellier, France. Patients underwent an extensive neuropsychological assessment, and completed validated questionnaires. Blood samples were collected for Se quantification. Results were compared with the t-test, Mann-Whitney U, and Chi square tests, and univariate linear and multivariate logistic regression models. RESULTS: Se plasma levels were below the cut-off of 80 µg/L in 53.6% (N = 82) of patients. AN onset was earlier in patients with Se deficiency, (p = .005), whereas disease duration was comparable between groups (p = .77). General eating disorder symptomatology in the past 28 days (Eating Disorder Examination Questionnaire) was more severe in patients with Se deficiency (p = .010). The suicide risk (MINI International Neuropsychiatric Evaluation) tended to be higher (p = .037), and suicide attempt history was more frequent (28.39% vs 9.85%, p = .004) in patients with low Se levels. Se plasma concentration was negatively correlated with the performance in the temporal delayed discounting task (p = .006). CONCLUSIONS: Our findings suggest that in patients with AN, Se plasma concentration might be implicated in disease severity and suicide risk. The finding that Se deficiency in patients with AN was associated only with reward-related processes, but not with other psychological functions suggests the selective involvement of dopamine-related pathways. Our results suggest that it might be useful to monitor the plasma micronutrient profile in patients with AN. Future studies should determine whether Se supplementation in AN might improve clinical outcomes.
Subject(s)
Anorexia Nervosa , Malnutrition , Selenium , Anorexia Nervosa/complications , Anorexia Nervosa/psychology , Cross-Sectional Studies , Disease Susceptibility , Female , Humans , Male , Malnutrition/complications , Reward , Severity of Illness Index , Suicide, AttemptedABSTRACT
Currently, only a limited number of interventions can rapidly relieve depressive symptomatology in patients with major depressive disorder or bipolar disorder experiencing extreme distress. Such crises, especially when suicide attempt or ideation is involved, are a major risk factor of suicide. Ketamine, a N-methyl-d-aspartate glutamate receptor antagonist, and its enantiomer esketamine rapidly reduce depressive symptoms in depressed patients with current suicidal ideation. Recently, esketamine has been approved for use in patients with depression at risk of suicide and for psychiatric emergency by major medical agencies in the United States and Europe, whereas ketamine is increasingly used off-label. However, there is currently limited guidance on why, when, and how to use these drugs in patients with depression to treat a crisis. In this review article, we provide a succinct overview of the cellular and molecular mechanisms of action of ketamine and esketamine, and of the functional brain changes following their administration. We also summarize the major clinical studies on ketamine and esketamine efficacy in patients experiencing a crisis (generally, suicidal ideation), and propose a profile of patients who can benefit most from such drugs, on the basis of neurobiological and clinical observations. Finally, we describe the administration mode, the efficacy and tolerability profiles, the side effect management, possible concomitant treatments and the issue of deprescribing.
Subject(s)
Depressive Disorder, Major , Ketamine , Antidepressive Agents/adverse effects , Depression/drug therapy , Depressive Disorder, Major/drug therapy , Depressive Disorder, Major/psychology , Humans , Ketamine/adverse effects , Suicidal IdeationABSTRACT
OBJECTIVE: Eating disorders (ED) are associated with an in increased risk of suicidal behaviours. Laxative abuse might alter the gut-brain axis signaling, that might be implicated in the pathophysiology of suicide. This study aims to determine the association between laxative misuse and suicide attempt (SA) and suicidal ideation (SI) in patients with ED. METHODS: 277 patients with ED were recruited from an Eating Disorder Unit of Lapeyronie Academic Hospital, Montpellier, France. Sociodemographic and clinical data were collected. Chi-square and t test were used, with Bonferroni corrections where required. Multiple regression models assessed the relationships between laxative misuse, SA, and SI. RESULTS: 62 (22.4%) patients reported lifetime laxative misuse. They were more likely to have a history of SA than non-misusers [43.83 vs 19.9%, p < 0.001, odds ratio (OR) 3.68]. In the multivariate model, adjusted for other confounders, lifetime laxative misuse remained associated with SA (adjusted OR 3.79, p = 0.041). In past 28 days, patients with SA history reported misusing laxatives for more days than patients without SA history (6 vs 1.5 days, p = 0.01, adjusted for vomiting and ED severity). Laxative use days during past 28 days was associated with current SI, adjusted for vomiting in the same period (p = 0.017). CONCLUSIONS: Current and lifetime laxative misuse were associated with SA history and current SI in patients with ED, at least in part independently of other suicide-related factors. LEVEL OF EVIDENCE: Level III cohort, cross-sectional study.
Subject(s)
Anorexia Nervosa , Bulimia Nervosa , Feeding and Eating Disorders , Cross-Sectional Studies , Humans , Laxatives/adverse effects , Suicidal IdeationABSTRACT
BACKGROUND: Bipolar disorder (BD) is a chronic, lifelong condition, associated with increased risk of obesity, cognitive impairment, and suicidal behaviors. Abdominal obesity and a higher risk of violent suicide attempt (SA) seem to be shared correlates with older age, BD, and male sex until middle age when menopause-related female body changes occur. This study aimed at assessing the role of abdominal obesity and cognition in the violent SA burden of individuals with BD. METHODS: From the well-defined nationwide cohort FACE-BD (FondaMental Advanced center of Expertise for Bipolar Disorders), we extracted data on 619 euthymic BD patients that were 50 years or older at inclusion. Cross-sectional clinical, cognitive, and metabolic assessments were performed. SA history was based on self-report. RESULTS: Violent SA, in contrast to non-violent and no SA, was associated with higher waist circumference, abdominal obesity and poorer California Verbal Learning Test short-delay free recall (CVLT-SDFR) (ANOVA, p < .001, p = .014, and p = .006). Waist circumference and abdominal obesity were associated with violent SA history independently of sex, BD type and anxiety disorder (Exp(B) 1.02, CI 1.00-1.05, p = .018; Exp(B) 2.16, CI 1.00-4.64, p = .009, accordingly). In an exploratory model, waist circumference and CVLT-SDFR performance mediated the association between male sex and violent SA. LIMITATIONS: Cross-sectional design and retrospective reporting. CONCLUSIONS: Violent SA history was associated with abdominal obesity and poorer verbal memory in older age BD patients. These factors were interlinked and might mediate the association between male sex and violent SA.