Statistical Machine Learning Meets High-Dimensional Spatiotemporal Challenges -- A Case Study of COVID-19 Modeling (preprint)

Diverse non-pharmacological interventions (NPIs), serving as the primary approach for COVID-19 control prior to pharmaceutical interventions, showed heterogeneous spatiotemporal effects on pandemic management. Investigating the dynamic compounding impacts of NPIs on pandemic spread is imperative. However, the challenges posed by data availability of high-dimensional human behaviors and the complexity of modeling changing and interrelated factors are substantial. To address these challenges, this study analyzed social media data, COVID-19 case rates, Apple mobility data, and the stringency of stay-at-home policies in the United States throughout the year 2020, aiming to (1) uncover the spatiotemporal variations in NPIs during the COVID-19 pandemic utilizing geospatial big data; (2) develop a statistical machine learning model that incorporates spatiotemporal dependencies and temporal lag effects for the detection of relationships; (3) dissect the impacts of NPIs on the pandemic across space and time. Three indices were computed based on Twitter (currently known as X) data: the Negative and Positive Sentiments Adjusted by Demographics (N-SAD and P-SAD) and the Ratio Adjusted by Demographics (RAD), representing negative sentiment, positive sentiment, and public awareness of COVID-19, respectively. The Multivariate Bayesian Structural Time Series Time Lagged model (MBSTS-TL) was proposed to investigate the effects of NPIs, accounting for spatial dependencies and temporal lag effects. The developed MBSTS-TL model exhibited a high degree of accuracy. Determinants of COVID-19 health impacts transitioned from an emphasis on human mobility during the initial outbreak period to a combination of human mobility and stay-at-home policies during the rapid spread phase, and ultimately to the compound of human mobility, stay-at-home policies, and public awareness of COVID-19.

The impact of depression and childhood maltreatment experiences on psychological adaptation from lockdown to relaxation periods during the COVID-19 pandemic (preprint)

The COVID-19 pandemic has presented a significant challenge to societal mental health. Yet, it remains unknown which factors influence the mental adaptation from lockdown to subsequent relaxation periods, particularly for vulnerable groups. This study used smartphone-based monitoring to explore how 74 individuals with major depression (MDD) and 77 healthy controls (HCs) responded to the transition from lockdown to relaxation during the first wave of the COVID-19 pandemic (March 21 to November 01, 2020) regarding interpersonal interactions, COVID-19-related fear (fear of participants' own health, the health of close relatives, and the pandemics' economic impact), and the feeling of isolation. Furthermore, we investigated the effect of a diagnosis of MDD and the experience of childhood maltreatment (CM) on adaptive functioning. During the transition from lockdown to relaxation, we observed an increase in direct contacts and a decrease in indirect contacts and self-perceived isolation in the study population. The diagnosis of MDD and the experience of CM moderated a maintenance of COVID-19-related fear: HCs and participants without the experience of CM showed a decrease in fear, while fear of participants with MDD and with an experience of CM did not change significantly. The finding that elevated COVID-19-related fear was sustained in vulnerable groups after lockdown measures were lifted could help guide psychosocial prevention efforts in future pandemic emergencies.

Poor Hemorrhagic Stroke Outcomes During the COVID-19 Pandemic Are Driven by Socioeconomic Disparities (preprint)

Background Nationally representative data demonstrating the impact of the COVID-19 pandemic on hemorrhagic stroke outcomes are lacking. Methods In this pooled cross-sectional analysis, we used the National Inpatient Sample (2016-2020) to identify adults (>=18 years) with primary intracerebral hemorrhage (ICH) or subarachnoid hemorrhage (SAH). We fit segmented logistic regression models to evaluate the differences in the rates of in-hospital outcomes (in-hospital mortality, home discharge, and receiving neurosurgical procedures) between the pre-pandemic (January 2016-February 2020) and pandemic periods (March 2020-December 2020). We used multivariable logistic regression models to evaluate the differences in mortality between patients admitted from April to December 2020, with and without COVID-19, and those admitted during a similar period in 2019. Stratified analyses were conducted among patients residing in low and high-income zip codes and among patients with extreme loss of function (E-LoF) and those with minor to major loss of function (MM-LoF). Results Overall, 309,965 ICH patients (mean age [SD]: 68[14.8], 47% female, 56% low-income) and 112,210 SAH patients (mean age [SD]: 60.2[15.4], 62% female, 55% low-income) were analyzed. Pre-pandemic, ICH mortality was decreasing by {approx}1% per month (adjusted odds ratio, 95% confidence interval: 0.99, 0.99-1.00). However, during the pandemic, the overall ICH mortality rate increased by {approx}2% per month (1.02, 1.00-1.02) and {approx}4% per month among low-income patients (1.04, 1.01-1.07). However, there was no change in trend among high-income ICH patients during the pandemic (1.00, 0.97-1.03). Patients with comorbid COVID-19 in 2020 had significantly higher odds of mortality compared to the 2019 comparison cohort, overall (ICH: 1.83, 1.33-2.51; SAH: 2.76, 1.68-4.54), and among patients with MM-LoF (ICH: 2.15, 1.12-4.16; SAH: 5.77, 1.57-21.17). However, patients with E-LoF and comorbid COVID-19 had similar mortality rates with the 2019 cohort. Conclusion Sustained efforts are needed to address socioeconomic disparities in healthcare access, quality, and outcomes during public health emergencies.

Major Depressive Disorder and Chronic Fatigue Syndrome Show Characteristic Heart Rate Variability Profiles Reflecting Autonomic Dysregulations: Differentiation by Linear Discriminant Analysis.

Major depressive disorder (MDD) and chronic fatigue syndrome (CFS) have overlapping symptoms, and differentiation is important to administer the proper treatment. The present study aimed to assess the usefulness of heart rate variability (HRV) indices. Frequency-domain HRV indices, including high-frequency (HF) and low-frequency (LF) components, their sum (LF+HF), and their ratio (LF/HF), were measured in a three-behavioral-state paradigm composed of initial rest (Rest), task load (Task), and post-task rest (After) periods to examine autonomic regulation. It was found that HF was low at Rest in both disorders, but was lower in MDD than in CFS. LF and LF+HF at Rest were low only in MDD. Attenuated responses of LF, HF, LF+HF, and LF/HF to task load and an excessive increase in HF at After were found in both disorders. The results indicate that an overall HRV reduction at Rest may support a diagnosis of MDD. HF reduction was found in CFS, but with a lesser severity. Response disturbances of HRV to Task were observed in both disorders, and would suggest the presence of CFS when the baseline HRV has not been reduced. Linear discriminant analysis using HRV indices was able to differentiate MDD from CFS, with a sensitivity and specificity of 91.8% and 100%, respectively. HRV indices in MDD and CFS show both common and different profiles, and can be useful for the differential diagnosis.

Disparities in COVID-19 infection, hospitalisation and death in people with schizophrenia, bipolar disorder, and major depressive disorder: a cohort study of the UK Biobank.

People with severe mental illness (SMI; including schizophrenia/psychosis, bipolar disorder (BD), major depressive disorder (MDD)) experience large disparities in physical health. Emerging evidence suggests this group experiences higher risks of infection and death from COVID-19, although the full extent of these disparities are not yet established. We investigated COVID-19 related infection, hospitalisation and mortality among people with SMI in the UK Biobank (UKB) cohort study. Overall, 447,296 participants from UKB (schizophrenia/psychosis = 1925, BD = 1483 and MDD = 41,448, non-SMI = 402,440) were linked with healthcare and death records. Multivariable logistic regression analysis was used to examine differences in COVID-19 outcomes by diagnosis, controlling for sociodemographic factors and comorbidities. In unadjusted analyses, higher odds of COVID-19 mortality were seen among people with schizophrenia/psychosis (odds ratio [OR] 4.84, 95% confidence interval [CI] 3.00-7.34), BD (OR 3.76, 95% CI 2.00-6.35), and MDD (OR 1.99, 95% CI 1.69-2.33) compared to people with no SMI. Higher odds of infection and hospitalisation were also seen across all SMI groups, particularly among people with schizophrenia/psychosis (OR 1.61, 95% CI 1.32-1.96; OR 3.47, 95% CI 2.47-4.72) and BD (OR 1.48, 95% CI 1.16-1.85; OR 3.31, 95% CI 2.22-4.73). In fully adjusted models, mortality and hospitalisation odds remained significantly higher among all SMI groups, though infection odds remained significantly higher only for MDD. People with schizophrenia/psychosis, BD and MDD have higher risks of COVID-19 infection, hospitalisation and mortality. Only a proportion of these disparities were accounted for by pre-existing demographic characteristics or comorbidities. Vaccination and preventive measures should be prioritised in these particularly vulnerable groups.

Acute eosinophilic pneumonia-like syndrome post-initiation of vortioxetine.

A man in his mid-30s presented to the emergency department with a 1-week history of fatigue, loss of appetite, fever and productive (yellow) cough. This progressed to requiring admission to intensive care needing a oxygen therapy via high-flow nasal cannula for acute hypoxaemic respiratory failure. He had recently started vortioxetine for major depressive disorder, and his acute symptoms correlated with an increase in the dose of vortioxetine. For more than 20 years, rare but consistent reports of serotonergic medications have been implicated in eosinophilic pulmonary conditions. During this same period, serotonergic medications have become a mainstay solution for a wide range of depressive symptoms and disorders. This is the first report of an eosinophilic pneumonia-like syndrome occurring while consuming the novel serotonergic medication vortioxetine.

Identification of major depression patients using machine learning models based on heart rate variability during sleep stages for pre-hospital screening.

With the COVID-19 pandemic causing challenges in hospital admissions globally, the role of home health monitoring in aiding the diagnosis of mental health disorders has become increasingly important. This paper proposes an interpretable machine learning solution to optimise initial screening for major depressive disorder (MDD) in both male and female patients. The data is from the Stanford Technical Analysis and Sleep Genome Study (STAGES). We analyzed 5-min short-term electrocardiogram (ECG) signals during nighttime sleep stages of 40 MDD patients and 40 healthy controls, with a 1:1 gender ratio. After preprocessing, we calculated the time-frequency parameters of heart rate variability (HRV) based on the ECG signals and used common machine learning algorithms for classification, along with feature importance analysis for global decision analysis. Ultimately, the Bayesian optimised extremely randomized trees classifier (BO-ERTC) showed the best performance on this dataset (accuracy 86.32%, specificity 86.49%, sensitivity 85.85%, F1-score 0.86). By using feature importance analysis on the cases confirmed by BO-ERTC, we found that gender is one of the most important factors affecting the prediction of the model, which should not be overlooked in our assisted diagnosis. This method can be embedded in portable ECG monitoring systems and is consistent with the literature results.

Treatment-Resistant Late-Life Depression: A Review of Clinical Features, Neuropsychology, Neurobiology, and Treatment.

Major depression is common in older adults (≥ 60 years of age), termed late-life depression (LLD). Up to 30% of these patients will have treatment-resistant late-life depression (TRLLD), defined as depression that persists despite two adequate antidepressant trials. TRLLD is challenging for clinicians, given several etiological factors (eg, neurocognitive conditions, medical comorbidities, anxiety, and sleep disruption). Proper assessment and management is critical, as individuals with TRLLD often present in medical settings and suffer from cognitive decline and other marks of accelerated aging. This article serves as an evidence-based guide for medical practitioners who encounter TRLLD in their practice.

The effects of COVID-19 on European healthcare provision for working-age adults with major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is a leading cause of disability worldwide, and yet delivery of care for this illness is rife with gaps. The COVID-19 pandemic has had far reaching implications for every facet of healthcare, and MDD is no exception. This scoping review aimed to ascertain the impacts of COVID-19 on the delivery of MDD care in Europe, as well as to evaluate any novel MDD care strategies trialled in this period. METHODS: We searched the PubMed and PsycINFO databases up to January 2022 with a strategy centred around COVID-19 and MDD. Full texts of eligible studies examining working-age adults and conducted in Europe were evaluated against several criteria. All outcomes were then extracted and a narrative synthesis was constructed to summarise identified themes. RESULTS: Of 1,744 records identified in our search, 11 articles were eligible for inclusion in the review. In general, these studies reported a decrease in treatment rates, access to care, and perceived access to care during the COVID-19 pandemic. In addition, digital interventions trialled during the pandemic were broadly well-received by users, though their efficacy in improving MDD care was ambiguous. CONCLUSIONS: Despite a limited number of pertinent studies, this scoping review identified a trend of exacerbated treatment gaps in MDD care during the pandemic. Several of our pre-specified gaps, including delays to detection or treatment of depression and rates of follow-up contacts, remained unexplored in the context of COVID-19. This highlights the need for further investigation to obtain a full understanding of the relationship between COVID-19 and MDD care in Europe.

Intertwined associations between oxytocin, immune system and major depressive disorder.

Major depressive disorder (MDD) is a prominent psychiatric disorder with a high prevalence rate. The recent COVID-19 pandemic has exacerbated the already high prevalence of MDD. Unfortunately, a significant proportion of patients are unresponsive to conventional treatments, necessitating the exploration of novel therapeutic strategies. Oxytocin, an endogenous neuropeptide, has emerged as a promising candidate with anxiolytic and antidepressant properties. Oxytocin has been shown to alleviate emotional disorders by modulating the hypothalamic-pituitary-adrenal (HPA) axis and the central immune system. The dysfunction of the immune system has been strongly linked to the onset and progression of depression. The central immune system is believed to be a key target of oxytocin in ameliorating emotional disorders. In this review, we examine the evidence regarding the interactions between oxytocin, the immune system, and depressive disorder. Moreover, we summarize and speculate on the potential roles of the intertwined association between oxytocin and the central immune system in treating emotional disorders.

Randomized trial of brief interpersonal psychotherapy and cognitive behavioral therapy for depression delivered both in-person and by telehealth.

BACKGROUND: Expert consensus guidelines recommend Cognitive Behavioral Therapy (CBT) and Interpersonal Psychotherapy (IPT), interventions that were historically delivered face-to-face, as first-line treatments for Major Depressive Disorder (MDD). Despite the ubiquity of telehealth following the COVID-19 pandemic, little is known about differential outcomes with CBT versus IPT delivered in-person (IP) or via telehealth (TH) or whether working alliance is affected. METHODS: Adults meeting DSM-5 criteria for MDD were randomly assigned to either 8 sessions of IPT or CBT (group). Mid-trial, COVID-19 forced a change of therapy delivery from IP to TH (study phase). We compared changes in Hamilton Rating Scale for Depression (HRSD-17) and Working Alliance Inventory (WAI) scores for individuals by group and phase: CBT-IP (n = 24), CBT-TH (n = 11), IPT-IP (n = 25) and IPT-TH (n = 17). RESULTS: HRSD-17 scores declined significantly from pre to post treatment (pre: M = 17.7, SD = 4.4 vs. post: M = 11.7, SD = 5.9; p < .001; d = 1.45) without significant group or phase effects. WAI scores did not differ by group or phase. Number of completed therapy sessions was greater for TH (M = 7.8, SD = 1.2) relative to IP (M = 7.2, SD = 1.6) (Mann-Whitney U = 387.50, z = -2.24, p = .025). LIMITATIONS: Participants were not randomly assigned to IP versus TH. Sample size is small. CONCLUSIONS: This study provides preliminary evidence supporting the efficacy of both brief IPT and CBT, delivered by either TH or IP, for depression. It showed that working alliance is preserved in TH, and delivery via TH may improve therapy adherence. Prospective, randomized controlled trials are needed to definitively test efficacy of brief IPT and CBT delivered via TH versus IP.

The risks of adverse events with venlafaxine and mirtazapine versus 'active placebo', placebo, or no intervention for adults with major depressive disorder: a protocol for two separate systematic reviews with meta-analysis and Trial Sequential Analysis.

BACKGROUND: Major depressive disorder causes a great burden on patients and societies. Venlafaxine and mirtazapine are commonly prescribed as second-line treatment for patients with major depressive disorder worldwide. Previous systematic reviews have concluded that venlafaxine and mirtazapine reduce depressive symptoms, but the effects seem small and may not be important to the average patient. Moreover, previous reviews have not systematically assessed the occurrence of adverse events. Therefore, we aim to investigate the risks of adverse events with venlafaxine or mirtazapine versus 'active placebo', placebo, or no intervention for adults with major depressive disorder in two separate systematic reviews. METHODS: This is a protocol for two systematic reviews with meta-analysis and Trial Sequential Analysis. The assessments of the effects of venlafaxine or mirtazapine will be reported in two separate reviews. The protocol is reported as recommended by Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols, risk of bias will be assessed with the Cochrane risk-of-bias tool version 2, clinical significance will be assessed using our eight-step procedure, and the certainty of the evidence will be assessed with the Grading of Recommendations Assessment, Development and Evaluation approach. We will search for published and unpublished trials in major medical databases and trial registers. Two review authors will independently screen the results from the literature searches, extract data, and assess risk of bias. We will include published or unpublished randomised clinical trial comparing venlafaxine or mirtazapine with 'active placebo', placebo, or no intervention for adults with major depressive disorder. The primary outcomes will be suicides or suicide attempts, serious adverse events, and non-serious adverse events. Exploratory outcomes will include depressive symptoms, quality of life, and individual adverse events. If feasible, we will assess the intervention effects using random-effects and fixed-effect meta-analyses. DISCUSSION: Venlafaxine and mirtazapine are frequently used as second-line treatment of major depressive disorder worldwide. There is a need for a thorough systematic review to provide the necessary background for weighing the benefits against the harms. This review will ultimately inform best practice in the treatment of major depressive disorder. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022315395.

Major depressive episode in hospital workers during the Covid-19 pandemic in Brazil.

OBJECTIVES: To estimate prevalence and factors associated with major depressive episode (MDE), emphasizing occupational aspects, in workers of a public teaching hospital that is a reference for Covid-19 treatment. METHODS: A cross-sectional study was carried out between October and December 2020, after the first peak of the pandemic, interviewing 1,155 workers. The prevalence of MDE was estimated using the Patient Health Questionnaire (PHQ-9) algorithm. Multivariate hierarchical analysis was conducted using Poisson regression to assess associated factors. RESULTS: MDE prevalence was 15.3% (95%CI: 13.3-17.5) and was higher among young, white and female workers, those with a family history of depression, resident professionals, nursing professionals, workers who were exposed to three or more situations of moral dilemma, and those who had to put off a physiological need until later. Having a risk factor for Covid-19, being a smoker and being physically inactive were also positively associated with MDE. CONCLUSIONS: The study points to the considerable prevalence of MDE among tertiary health care workers; reviewing work processes is essential to reduce occupational stress and minimize the effects of the pandemic on mental health, preventing those problems from becoming chronic.

The Role of Probiotics and Their Metabolites in the Treatment of Depression.

Depression is a common and complex mental and emotional disorder that causes disability, morbidity, and quite often mortality around the world. Depression is closely related to several physical and metabolic conditions causing metabolic depression. Studies have indicated that there is a relationship between the intestinal microbiota and the brain, known as the gut-brain axis. While this microbiota-gut-brain connection is disturbed, dysfunctions of the brain, immune system, endocrine system, and gastrointestinal tract occur. Numerous studies show that intestinal dysbiosis characterized by abnormal microbiota and dysfunction of the microbiota-gut-brain axis could be a direct cause of mental and emotional disorders. Traditional treatment of depression includes psychotherapy and pharmacotherapy, and it mainly targets the brain. However, restoration of the intestinal microbiota and functions of the gut-brain axis via using probiotics, their metabolites, prebiotics, and healthy diet may alleviate depressive symptoms. Administration of probiotics labeled as psychobiotics and their metabolites as metabiotics, especially as an adjuvant to antidepressants, improves mental disorders. It is a new approach to the prevention, management, and treatment of mental and emotional illnesses, particularly major depressive disorder and metabolic depression. For the effectiveness of antidepressant therapy, psychobiotics should be administered at a dose higher than 1 billion CFU/day for at least 8 weeks.

Pre- and peri-traumatic event stressors drive gender differences in chronic stress-related psychological sequelae: A prospective cohort study of COVID-19 frontline healthcare providers.

Women are at heightened risk for chronic stress-related psychological sequelae (SRPS), including major depressive disorder (MDD), generalized anxiety disorder (GAD), and posttraumatic stress disorder (PTSD) in response to potentially traumatic events, including the COVID-19 pandemic. However, few studies have examined pre- and peri-event stressors that could account for gender differences in chronic SRPS. To address this gap, we conducted a prospective cohort study of healthcare providers (HCPs) caring for patients with COVID-19 at a large tertiary care hospital in New York City, and measured mental health risk factors and symptoms of MDD, GAD, and PTSD at baseline (April 2020) and at a 7-month follow-up (December 2020). We defined chronic SRPS as the presence of probable MDD, GAD, and/or PTSD at both timepoints. We conducted a mediation analysis to evaluate whether pre- and peri-event stressors explained women's increased risk for chronic SRPS. Among our sample of 786 HCPs, 571 (72.6%) were women. Compared with men, women were twice as likely to have chronic SRPS (18.7% vs. 8.8%, χ2[1] = 11.38, p < 0.001). However, after accounting for pre- and peri-event stressors, being a woman was no longer associated with chronic SRPS (p = 0.58). The pre- and peri-event stressors that accounted for this heightened risk among women included being in a woman-prevalent profession (specifically nursing; estimate = 0.08, SE = 0.04, p = 0.05), pre-pandemic burnout (estimate = 0.11, SE = 0.05, p = 0.04), greater family-related (estimate = 0.09, SE = 0.03, p = 0.004), infection-related (estimate = 0.06, SE = 0.02, p = 0.007), and work-related concerns (estimate = 0.11, SE = 0.03, p < 0.001), and lower leadership support (estimate = 0.07, SE = 0.03, p = 0.005). These findings can inform institutional interventions to mitigate the risk of chronic SRPS among women HCPs.

Treating depression with a smartphone-delivered self-help cognitive behavioral therapy for insomnia: a parallel-group randomized controlled trial.

BACKGROUND: Despite its efficacy in treating comorbid insomnia and depression, cognitive behavioral therapy for insomnia (CBT-I) is limited in its accessibility and, in many countries, cultural compatibility. Smartphone-based treatment is a low-cost, convenient alternative modality. This study evaluated a self-help smartphone-based CBT-I in alleviating major depression and insomnia. METHODS: A parallel-group randomized, waitlist-controlled trial was conducted with 320 adults with major depression and insomnia. Participants were randomized to receive either a 6-week CBT-I via a smartphone application, proACT-S, or waitlist condition. The primary outcomes included depression severity, insomnia severity, and sleep quality. The secondary outcomes included anxiety severity, subjective health, and acceptability of treatment. Assessments were administered at baseline, post-intervention (week 6) follow-up, and week 12 follow-up. The waitlist group received treatment after the week 6 follow-up. RESULTS: Intention to treat analysis was conducted with multilevel modeling. In all but one model, the interaction between treatment condition and time at week 6 follow-up was significant. Compared with the waitlist group, the treatment group had lower levels of depression [Center for Epidemiologic Studies Depression Scale (CES-D): Cohen's d = 0.86, 95% CI (-10.11 to -5.37)], insomnia [Insomnia Severity Index (ISI): Cohen's d = 1.00, 95% CI (-5.93 to -3.53)], and anxiety [Hospital Anxiety and Depression Scale - Anxiety subscale (HADS-A): Cohen's d = 0.83, 95% CI (-3.75 to -1.96)]. They also had better sleep quality [Pittsburgh Sleep Quality Index (PSQI): Cohen's d = 0.91, 95% CI (-3.34 to -1.83)]. No differences across any measures were found at week 12, after the waitlist control group received the treatment. CONCLUSION: proACT-S is an efficacious sleep-focused self-help treatment for major depression and insomnia. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04228146. Retrospectively registered on 14 January 2020. http://www.w3.org/1999/xlink">https://clinicaltrials.gov/ct2/show/NCT04228146.

Does insomnia treatment prevent depression?

Rates of major depressive disorder (MDD) are increasing globally, in part due to the coronavirus disease 2019 pandemic, contributing to disease burden. It has long been known that insomnia is intricately connected with depression as indicated by greater depression severity and lower treatment response. Furthermore, insomnia is a significant risk factor for new-onset depression. Treatment of insomnia is thus a logical target for prevention of incidents and recurrent MDD. This systematic review sought to evaluate the current evidence for the preventive effects of insomnia treatment on depression onset. A database search yielded 186 studies, six of which met criteria for inclusion in this review. All of the studies utilized cognitive behavioral treatment for insomnia (CBT-I) as the target intervention and most delivered treatment via a digital platform. Four of the studies found significantly lower rates of MDD onset in those who received CBT-I compared to a control condition. The two remaining studies failed to confirm these effects in primary analyses but secondary analyses suggested evidence of a preventive effect. There was significant methodologic heterogeneity across studies in terms of sample selection, outcomes, and follow-up periods, limiting the ability to draw firm conclusions. The evidence overall is in the direction of insomnia treatment reducing the risk for onset of MDD, but further research is warranted.

Clinical experiences with intranasal esketamine for major depressive disorder resistant to treatment and with a psychiatric emergency: case presentations.

Recently, esketamine became availableas an intranasal formulation, proposed for treatment-resistant depression (TRD). Three cases of TRD are presented, two with features of a psychiatric emergency. The first case is a 35-year-old man with MDD onset at the age of 27 years, with five previous failed therapies. The second patient is a middle-aged man with a 21-year MDD onset and six previous antidepressant treatments discontinued for poor therapeutic effects and tolerability. He also presented suicidal ideation with intent and a history of a failed suicide attempt by self-cutting his forearms. The third case is a 28-year-old female with a first MDD episode in 2020, treated first with amitriptyline and then with intravenous clomipramine. She had a history of a previous suicide attempt by self-cutting and, by her admission, showed active suicidal ideation with intent. In all three cases, a rapid reduction of depressive symptoms was observed with a subsequent complete resolution of suicidal ideation and intent in the two patients with such risk. Intranasal esketamine treatment was carried out with concomitant oral antidepressant therapy. The third patient reported the only recorded side effect: dissociation 20 min after every esketamine administration. Our preliminary experience proved esketamine's effectiveness on TRD symptoms and successful outcomes in psychiatric emergencies such as suicide risk.