Routine treatment pathways in a cohort of patients with major depression and suicidality in Italy: the ARIANNA observational study.

BACKGROUND: Major Depressive Disorder (MDD) with suicidal ideation, intent, or behavior is a psychiatric emergency with controversial care management. Our study describes the comprehensive treatment pathways of this population in Italian routine clinical practice. METHODS: ARIANNA [NCT04463108] is an observational prospective and retrospective cohort study involving both primary data collection and secondary data extract. A total of 137 adult MDD patients with suicidality were enrolled from 24 Italian care sites and followed for 90 days. Other than the description of treatment patterns, the impact of treatment on depressive symptoms and suicidality, the burden on the patient's and caregiver's quality of life, healthcare resource utilization and costs were described. RESULTS: Of the 133 eligible patients, 68.4% were female, and the median age was 47. Approximately half of the study population had a current severe major depressive episode. Treatment strategies at the time of active suicidal ideation with intent definition/confirmation (t0) were heterogeneous, increasing in complexity during observation. According to the MADRS, patients with remission at t0+1 day were 2.6%, with the mean total score decreasing from 37.2 at t0 to 32.3. LIMITATIONS: The study sites were not randomly selected. CONCLUSIONS: To the best of our knowledge, this is the first cohort study that prospectively describes the characteristics of patients with MDD and suicide risk in Italy, and how they are treated in clinical practice. The study confirms this is a difficult-to-treat population. In addition, a lack of rapid, effective treatment for reducing depressive symptoms and suicidality is observed.

Climate Change Perception and Mental Health. Results from a Systematic Review of the Literature.

Climate change is one of the main global challenges and influences various aspects of human health. Numerous studies have indeed demonstrated an association between extreme climate-related events and physical and mental health outcomes, but little is still known about the association between the perception/awareness of climate change and mental health. In accordance with the PRISMA 2020 guidelines, a search was conducted on PubMed and Scopus. The protocol was registered on PROSPERO. The included studies were original observational studies published in English, reporting the association between the perception/awareness of climate change and mental health. A total of 3018 articles were identified. A total of 10 observational studies were included. The period covered in the included studies ranged between 2012 and 2022. Climate change perception is consistently associated with adverse mental health effects across different types of estimates. In particular, the studies identified an association between a higher level of perception/awareness of climate change and depression, anxiety, eco-anxiety, stress, adjustment disorder, substance use, dysphoria, and even thoughts of suicide. Qualitative data underscore the impact on daily activities, contributing to feelings of loss and suicidal ideation. Moreover, climate change perception correlates with lower well-being and resilience. The association between awareness of climate change and mental health is a complex and still poorly explored phenomenon. The main limitations are the high heterogeneity in terms of exposure assessment and data reporting, which hinders quantitative analysis. These results show that climate change perception impacts mental health. Better understanding the phenomenon represents an opportunity to inform public health interventions that promote mental well-being.

Exploring vortioxetine combination with intranasal esketamine: A feasible alternative to SSRI/SNRI? - Insights from the REAL-ESK study.

BACKGROUND: Treatment-Resistant Depression (TRD) affects almost 30 % of patients with Major Depressive Disorder (MDD). Esketamine Nasal Spray (ESK-NS) has recently been approved for TRD in combination with a Serotonin Specific Reuptake Inhibitor/SSRI or a Serotonin-Norepinephrine Reuptake Inhibitor/SNRI. There is a lack of studies investigating the effectiveness and safety of ESK-NS in combination with other oral antidepressants. AIM: To assess the efficacy of Vortioxetine plus ESK-NS in mitigating depressive symptoms and emotional blunting, as well as its tolerability in TRD subjects, compared to the standard-of-care of SSRI/SNRI plus ESK-NS. METHODS: We conducted a post-hoc analysis of the REAL-ESK study. The study included twenty TRD patients, ten subjects taking Vortioxetine as the main oral antidepressant with ESK-NS, and ten subjects taking SSRI or SNRI with ESK-NS. Psychometric assessments (Montgomery-Åsberg Depression Rating Scale/MADRS, Brief Psychiatric Rating Scale/BPRS) were conducted at baseline(T0), one month(T1), and three months after the treatment initiation(T2). RESULTS: The combination of Vortioxetine and ESK-NS was as effective as the standard-of-care in reducing depressive symptoms, with a higher effect size in reducing emotional blunting at T2. The safety and tolerability profile of the Vortioxetine+ESK-NS combination appeared to be better, with a lower rate of treatment-emergent adverse events. CONCLUSION: The combination of Vortioxetine and ESK-NS may be a valuable alternative to the standard-of-care SSRI/SNRI plus ESK-NS in TRD patients, particularly regarding the reduction of emotional blunting and potentially a better safety and tolerability profile. Further randomized controlled trials with larger sample sizes and prospective designs are needed to confirm these findings.

The rapid antidepressant effectiveness of repeated dose of intravenous ketamine and intranasal esketamine: A post-hoc analysis of pooled real-world data.

INTRODUCTION: Intravenous ketamine (KET-IV) and intranasal esketamine (ESK-NS) are effective in the acute treatment of Treatment-Resistant Depression (TRD). Studies comparing KET-IV and ESK-NS concerning their action, safety, and tolerability are currently lacking. MATERIALS AND METHODS: We combined patients' data from two unipolar TRD cohorts that received KET-IV (n = 171) at the Canadian Rapid Treatment Center of Excellence in Toronto, Canada, or ESK-NS (n = 140) at several TRD clinics in Italy. The Quick Inventory for Depression Symptomatology-Self-Report-16/QIDS-SR16 in the KET-IV group and Montgomery-Åsberg Depression Rating Scale/MADRS in the ESK-NS group measured depressive symptoms at baseline (T0) and after the acute treatment phase (T1) (i.e., four infusions of KET-IV and eight administrations of ESK-NS). As different scales were used, the primary outcome was to compare the improvement in depression severity in the two cohorts by measuring effect sizes, response and remission rates. Finally, we compare side effects and discontinuation rates. RESULTS: At T1, KET-IV and ESK-NS significantly reduced depressive symptoms (respectively: QIDS-SR16 mean reduction = 5.65, p < 0.001; MADRS mean reduction = 11.41, p = 0.025). KET-IV showed larger effect sizes compared to ESK-NS (1.666 vs. 1.244). KET-IV had higher response rates (36 % vs. 25 %; p = 0.042) but not superior remission rates (13 % vs. 12 %; p = 0.845) than ESK-NS at T1. Despite more reported side effects, KET-IV did not cause more discontinuations for adverse events (4.6 % vs. 2.12 %; p = 0.228) than ESK-NS. CONCLUSION: KET-IV showed a higher short-term antidepressant effect, whereas ESK-NS exhibited lower side effects. Both were generally well tolerated. Future head-to-head studies should consider the long-term efficacy of these treatments.

Overcoming treatment-resistant depression with machine-learning based tools: a study protocol combining EEG and clinical data to personalize glutamatergic and brain stimulation interventions (SelecTool Project).

Treatment-Resistant Depression (TRD) poses a substantial health and economic challenge, persisting as a major concern despite decades of extensive research into novel treatment modalities. The considerable heterogeneity in TRD's clinical manifestations and neurobiological bases has complicated efforts toward effective interventions. Recognizing the need for precise biomarkers to guide treatment choices in TRD, herein we introduce the SelecTool Project. This initiative focuses on developing (WorkPlane 1/WP1) and conducting preliminary validation (WorkPlane 2/WP2) of a computational tool (SelecTool) that integrates clinical data, neurophysiological (EEG) and peripheral (blood sample) biomarkers through a machine-learning framework designed to optimize TRD treatment protocols. The SelecTool project aims to enhance clinical decision-making by enabling the selection of personalized interventions. It leverages multi-modal data analysis to navigate treatment choices towards two validated therapeutic options for TRD: esketamine nasal spray (ESK-NS) and accelerated repetitive Transcranial Magnetic Stimulation (arTMS). In WP1, 100 subjects with TRD will be randomized to receive either ESK-NS or arTMS, with comprehensive evaluations encompassing neurophysiological (EEG), clinical (psychometric scales), and peripheral (blood samples) assessments both at baseline (T0) and one month post-treatment initiation (T1). WP2 will utilize the data collected in WP1 to train the SelecTool algorithm, followed by its application in a second, out-of-sample cohort of 20 TRD subjects, assigning treatments based on the tool's recommendations. Ultimately, this research seeks to revolutionize the treatment of TRD by employing advanced machine learning strategies and thorough data analysis, aimed at unraveling the complex neurobiological landscape of depression. This effort is expected to provide pivotal insights that will promote the development of more effective and individually tailored treatment strategies, thus addressing a significant void in current TRD management and potentially reducing its profound societal and economic burdens.

Clinical advances in obsessive-compulsive disorder: a position statement by the International College of Obsessive-Compulsive Spectrum Disorders.

In this position statement, developed by The International College of Obsessive-Compulsive Spectrum Disorders, a group of international experts responds to recent developments in the evidence-based management of obsessive-compulsive disorder (OCD). The article presents those selected therapeutic advances judged to be of utmost relevance to the treatment of OCD, based on new and emerging evidence from clinical and translational science. Areas covered include refinement in the methods of clinical assessment, the importance of early intervention based on new staging models and the need to provide sustained well-being involving effective relapse prevention. The relative benefits of psychological, pharmacological and somatic treatments are reviewed and novel treatment strategies for difficult to treat OCD, including neurostimulation, as well as new areas for research such as problematic internet use, novel digital interventions, immunological therapies, pharmacogenetics and novel forms of psychotherapy are discussed.