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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. 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. 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. 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. • KET-IV and ESK-NS treat acute TRD effectively; comparative studies lacking. • Data from two TRD cohorts compared for depression improvement and side effects. • KET-IV reduced symptoms more but had similar remission rates to ESK-NS. • More side effects in KET-IV but same discontinuation rates as ESK-NS. • KET-IV had higher short-term effects; ESK-NS had lower side effects; both well tolerated. [ABSTRACT FROM AUTHOR]

Depression affects approximately 4 % of the global population and has huge social and economic implications. Social factors, including support, engagement, and stigma, play a crucial role in the development and severity of depression. We provide a synthesis of the consistency and magnitude of the association between measures of social connection and depression. We searched PubMed, PsycINFO, Cochrane Library, and EMBASE and 47 meta-analyses were included in the umbrella review. The strength of the associations was extracted and compared among different populations. The quality/certainty of evidence was assessed using AMSTAR-2 and GRADE tool. Results indicate that social support serves as a protective factor against depression, particularly in peripartum populations, while its impact is weaker in clinical populations. No association was found between social support and depression in post-disaster populations. Stigma and discrimination favour the development and maintenance of depressive symptoms in clinical populations, but have a weaker effect in ethnic minorities. The quality and certainty of evidence should be taken into account when interpreting our findings. Further research with more rigorous methodology and higher-quality evidence is needed to better understand the complex relationship between depression and social connection across various populations and contexts. Our findings confirm the role of social determinants in the emergence and severity of depression, particularly in the case of vulnerable populations. Efforts to counteract disconnection at the societal and individual levels and to reduce stigma should be central to an effective depression prevention agenda. • Social determinants play a significant role in influencing health. • Social connection represents a major protective/risk factors for depression. • Social support is protective against depression, especially in peripartum populations. • Stigma/discrimination represents risk factors for depression in clinical populations. • Social determinants should be central to an effective depression prevention agenda. [ABSTRACT FROM AUTHOR]

Introduction: Late-life major depression (MD) is a frequent and high-cost psychiatric disorder. Our purpose was to detect clinical and biological factors possibly associated with this condition to better prevent and treat it. Methods: We recruited 343 patients, consecutively admitted for a Major Depressive Episode to the inpatient clinic of Policlinico of Milan and ASST Monza, Italy. A large set of clinical and biochemical variables was collected from clinical charts. Univariate analyses were performed both dividing the sample into two groups (age < or >65) and considering age as a continuous quantitative variable. Regression analyses were then performed considering as independent variables only those statistically significant at univariate analyses. Results: Patients aged > 65 resulted in having longer duration of illness, shorter duration of last antidepressant therapy, higher number of antidepressants assumed in the past, higher frequency of treatment-resistant depression, higher frequency of overweight/obesity and diabetes. As for biochemical parameters, patients > 65 showed lower total plasmatic proteins and albumin, higher uric acid and creatinine. Conclusions: These preliminary results suggest less effectiveness of antidepressants, more susceptibility to metabolic disorders and poor nutritional status in patients with late-life depression; such aspects may consequently be taken into consideration for a proper therapeutic approach. [ABSTRACT FROM AUTHOR]

Esketamine, the S-enantiomer of ketamine, has recently emerged as a therapy for treatment-resistant depression (TRD), showing both rapid antidepressant action and good efficacy and high safety. It is also indicated for the acute short-term treatment of psychiatric emergency due to major depressive disorder (MDD) and for depressive symptoms in adults with MDD with acute suicidal thoughts/behavior. We here provide preliminary insights on esketamine nasal spray (ESK-NS) effectiveness and safety among patients with a substance use disorder (SUD) within the sample of patients with TRD collected for the observational, retrospective, multicentre REAL-ESK study. Twenty-six subjects were retrospectively selected according to the presence of a SUD in comorbidity. Subjects enrolled completed the three different follow-up phases (T0/baseline, T1/after one month, and T2/after three months) and there were no dropouts. A decrease in Montgomery-Asberg depression rating scale (MADRS) scores was recorded, thus highlighting the antidepressant efficacy of ESK-NS (MADRS decreased from T0 to T1, t = 6.533, df=23, p <0.001, and from T1 to T2, t = 2.029, df=20, p = 0.056). Considering tolerability and safety issues, one or more side effects were reported by 19/26 subjects (73%) after treatment administration. All reported side effects were time-dependent and did not cause significant sequelae; among them, dissociative symptoms (38%) and sedation (26%) were the most frequently reported. Finally, no cases of abuse or misuse of ESK-NS were reported. Despite study limitations related to the inherent nature of the study, a limited number of patients, and a short follow-up period, ESK-NS showed to be effective and safe in patients diagnosed with TRD comorbid with a SUD. [ABSTRACT FROM AUTHOR]

Background: Bipolar depression accounts for most of the disease duration in type I and type II bipolar disorder (BD), with few treatment options, often poorly tolerated. Many individuals do not respond to first‐line therapeutic options, resulting in treatment‐resistant bipolar depression (B‐TRD). Esketamine, the S‐enantiomer of ketamine, has recently been approved for treatment‐resistant depression (TRD), but no data are available on its use in B‐TRD. Objectives: To compare the efficacy of esketamine in two samples of unipolar and bipolar TRD, providing preliminary indications of its effectiveness in B‐TRD. Secondary outcomes included the evaluation of the safety and tolerability of esketamine in B‐TRD, focusing on the average risk of an affective switch. Methods: Thirty‐five B‐TRD subjects treated with esketamine nasal spray were enrolled and compared with 35 TRD patients. Anamnestic data and psychometric assessments (Montgomery‐Asberg Depression Rating Scale/MADRS, Hamilton‐depression scale/HAM‐D, Hamilton‐anxiety scale/HAM‐A) were collected at baseline (T0), at one month (T1), and three months (T2) follow up. Results: A significant reduction in depressive symptoms was found at T1 and T2 compared to T0, with no significant differences in response or remission rates between subjects with B‐TRD and TRD. Esketamine showed a greater anxiolytic action in subjects with B‐TRD than in those with TRD. Improvement in depressive symptoms was not associated with treatment‐emergent affective switch. Conclusions: Our results supported the effectiveness and tolerability of esketamine in a real‐world population of subjects with B‐TRD. The low risk of manic switch in B‐TRD patients confirmed the safety of this treatment. [ABSTRACT FROM AUTHOR]

Repetitive Transcranial Magnetic Stimulation (rTMS) has been approved by the FDA as an effective intervention for Treatment-Resistant Depression (TRD). However, there is little evidence about maintenance protocol necessity. The aim of this systematic review is to identify, characterize, and evaluate the current maintenance TMS protocols for MDD and TRD patients who have received acute treatment. A literature search was conducted following the PRISMA guidelines of 2015 on PubMed, Scopus, and Web of Science databases for publications up to March 2022. Fourteen articles were included. High protocol heterogeneity was observed. Most studies highlighted significant efficacy of maintenance protocols in decreasing relapse risk, suggesting that administering two or fewer stimulations per month is ineffective in sustaining an antidepressant effect or in reducing the risk of relapse in responder patients. The risk of relapse was most pronounced after five months from the acute treatment. Maintenance TMS appears to be a resourceful strategy to maintain acute antidepressant treatment effects, significantly reducing relapse risk. The ease of administering and the ability to monitor treatment adherence should be considered when evaluating the future use of maintenance TMS protocols. Further studies are needed to clarify the clinical relevance of overlapping acute TMS effects with maintenance protocols and to evaluate their long-term effectiveness. [ABSTRACT FROM AUTHOR]

• esketamine represent a novel agent for TRD with several RCTs proven its efficacy. • TRD subjects in real-world often include challenging cases excluded from RCTs. • REAL-ESK study comprised 116 TRD patients from several Italian real-world settings. • 3-month response (64.2 %) and remission (40.6 %) were similar to RCTs reports. • Only 3/116 subjects (2.58 %) dropped out for side effects. [ABSTRACT FROM AUTHOR]

Background: Since mothers who undergo in vitro fertilization (IVF) may experience more anxiety and depressive symptoms than mothers who conceive naturally, a review of the literature was conducted to investigate whether IVF may be considered a risk factor for the development of anxiety or depression during pregnancy and post-partum.Methods: A thorough search of articles in Pubmed, PsycINFO and Isi Web of Knowledge was performed in order to produce a comprehensive review regarding the potential association of in vitro fertilization and anxiety/depression.Results: The search resulted in a total of 10 articles. Contradictory results were reported in the articles about the possible association between IVF and the occurrence of anxiety and depressive symptoms both during pregnancy and postpartum period. Three studies found that women who resorted to IVF showed less anxiety and depressive symptoms than those who conceived naturally especially with the progression of pregnancy and in the postpartum.Limitations: Vulnerability to affective disorders of women affected by infertility may be independent from the outcome of IVF. Other limits are the limited research in this area, the small sample sizes, the heterogeneity of the tools used to assess affective symptoms.Conclusions: The available data indicate that IVF is not associated with perinatal affective symptoms. Women who resorted to IVF could have less perinatal depressive symptoms as the result of a positive outcome of the technique and the satisfaction of the desire to become mothers. Further studies are necessary in order to draw definitive conclusions about this topic. [ABSTRACT FROM AUTHOR]

Background: Intensive Short-Term Dynamic Psychotherapy (ISTDP) is an intervention introduced by Davanloo in order to treat anxiety, mood and somatic symptom, and personality disorders. It is a brief intervention aiming to identify and process painful or forbidden emotions and consequently to override symptoms and self-destructive tendencies. In this review we examine the efficacy of ISTDP on symptoms in patients with Major Depressive Disorder (MDD) and Bipolar Disorder (BD).Methods: A thorough search of articles in Pubmed, PsycINFO, Isi Web of Knowledge was carried out in order to obtain available studies of ISTDP for BD and MDD. We included all studies conducted on patients with a diagnosis of MDD or BD and who received ISTDP.Results: Eight studies were included. These were two randomized controlled trials and six observational studies. Overall the results of the included manuscripts suggest a positive effect of ISTDP on depressive symptoms for patients affected by mood disorders. Furthermore, they suggest ISTDP may be cost-effective through reducing doctor visits and hospitalizations in follow-up.Limitations: Most studies had small samples and consisted of non-randomized trials.Conclusions: These are preliminary positive results on the effectiveness of this approach for the treatment of depressive symptoms. They have to be confirmed by studies with larger sample sizes and by comparing this technique with other psychological treatments such as cognitive-behavioral therapy. [ABSTRACT FROM AUTHOR]

Pathophysiological mechanisms of major depressive disorder (MDD) seem to be associated with oxidative stress pathways and altered purinergic metabolism. We conducted a systematic review and meta-analysis to estimate if subjects with MDD might have reduced levels of antioxidant uric acid, considering also potential influence of antidepressant treatment. We searched the main Electronic Databases, identifying 14 studies that met our inclusion criteria. Meta-analyses were carried out generating pooled Hedges’ g and mean differences (MDs), using random-effects models. Heterogeneity across studies and risk of publication bias were estimated using standard methods. Relevant sensitivity and meta-regression analyses were conducted. Subjects with MDD had levels of uric acid lower than healthy controls (Hedges’ g = −0.30; p = 0.003). Overall between-study heterogeneity was high (I2 = 76.3%). The effect was significant among studies including drug naïve/free MDD individuals (Hedges’ g = −0.55; p = 0.023), but not among those involving treated subjects (Hedges’ g = −0.15; p = 0.062). Relevant quality- and heterogeneity-based sensitivity analyses, as well as meta-regressions, confirmed these findings. In addition, uric acid levels significantly, though inconsistently (I2 = 79.2%), increased after treatment (MD = +0.71 mg/dL; p < 0.001), regardless of follow-up duration (p = 0.518). Our meta-analysis shows that subjects with MDD have lower levels of uric acid. Since antidepressant treatment seems to influence this association, our findings support the hypothesis that uric acid levels may represent a state marker of MDD. Nevertheless, the potential role of additional factors that might clarify the nature of this association deserves further research. [ABSTRACT FROM AUTHOR]

Objectives We tested whether serum total cholesterol levels might be associated with recent suicide attempts in subjects with major depressive disorder, after controlling for relevant individual characteristics. Design and methods We conducted a comparative cross-sectional study including consecutive inpatients with major depressive disorder. We differentiated subjects admitted for a recent serious (violent or non-violent) suicide attempt and those without such recent history. Total cholesterol was measured from fasting blood tests. Results At univariate analyses, suicide attempters had levels of total cholesterol (174.0 ± 45.7 mg/dL) lower than non-attempters (193.9 ± 42.6 mg/dL) ( p = 0.004). This was confirmed among both violent (174.1 ± 46.2 mg/dL) and non-violent (173.8 ± 46.1 mg/dL) suicide attempters ( p = 0.035 and 0.016, respectively). However, logistic regression analyses, sequentially including demographic, clinical (comorbid alcohol and personality disorders), and biochemical factors, did not show any association between serum cholesterol and recent suicide attempts ( p = 0.172). Similar findings were observed in multinomial logistic regression analyses, for both violent ( p = 0.512) and non-violent ( p = 0.157) suicide attempts. Conclusions Our findings do not support the hypothesis that serum cholesterol and suicide attempts are associated among subjects with major depressive disorder. The identification of valid and accessible biological markers of suicidal behaviors still represents a challenge for future research. [ABSTRACT FROM AUTHOR]

Background and Objectives: Since significant differences have been reported, we estimated agreement between DSM-5 and DSM-IV criteria for alcohol use disorder (AUD).Methods: We assessed 327 outpatients (mean age: 45.2 ± 13.4) with depressive or anxiety disorders.Results: Absolute differences in prevalence rates between DSM-5 and DSM-IV AUD ranged from -1.1% (subjects with anxiety disorders) to +1.8% (tobacco smokers). The agreement was excellent (k = 0.88), also accounting for specific subgroups (relevant k coefficients >0.80).Discussion and Conclusions: DSM-5 criteria did not inflate AUD rates.Scientific Significance: Our results have epidemiological significance since, unlike previous reports, we found diagnostic stability between new and old AUD criteria in this clinical population. (Am J Addict 2017;26:53-56). [ABSTRACT FROM AUTHOR]

Previous research has hypothesised increased uric acid levels, possibly because of an amplified purinergic metabolism and a reduced adenosine activity, in subjects with bipolar disorder. This systematic review and meta-analysis aimed at estimating if individuals with bipolar disorder had uric acid levels higher than both healthy controls and subjects with major depression (trait marker hypothesis). It also tested if uric acid levels could differ in different phases of bipolar disorder (state marker hypothesis). Meta-analyses were carried out generating pooled standardized mean differences (SMDs), using random-effects models. Heterogeneity between studies was estimated using the I 2 index. Relevant sensitivity and meta-regression analyses were conducted. We searched main Electronic Databases, identifying twelve studies that met our inclusion criteria. Meta-analyses showed increased uric acid levels in individuals with bipolar disorder as compared with both healthy controls (SMD = 0.65, p < 0.001, I 2 = 82.9%) and those with major depression (SMD = 0.46, p < 0.001; I 2 = 68.7%). However, meta-regression analyses confirmed this association only as compared with healthy controls. Finally, though uric acid levels were higher in manic/mixed phases as compared with depressive ones (SMD = 0.34; p = 0.04, I 2 = 58.8%), a sensitivity analysis did not confirm the association. In sum, our meta-analysis shows that subjects with bipolar disorder have uric acid levels higher than healthy controls. The potential role of factors that might clarify the nature of this association deserves additional research. [ABSTRACT FROM AUTHOR]

Background: There is a lack of studies testing accuracy of fast screening methods for alcohol use disorder in mental health settings. We aimed at estimating clinical utility of a standard single-item test for case finding and screening of DSM-5 alcohol use disorder among individuals suffering from anxiety and mood disorders.Methods: We recruited adults consecutively referred, in a 12-month period, to an outpatient clinic for anxiety and depressive disorders. We assessed the National Institute on Alcohol Abuse and Alcoholism (NIAAA) single-item test, using the Mini- International Neuropsychiatric Interview (MINI), plus an additional item of Composite International Diagnostic Interview (CIDI) for craving, as reference standard to diagnose a current DSM-5 alcohol use disorder. We estimated sensitivity and specificity of the single-item test, as well as positive and negative Clinical Utility Indexes (CUIs).Results: 242 subjects with anxiety and mood disorders were included. The NIAAA single-item test showed high sensitivity (91.9%) and specificity (91.2%) for DSM-5 alcohol use disorder. The positive CUI was 0.601, whereas the negative one was 0.898, with excellent values also accounting for main individual characteristics (age, gender, diagnosis, psychological distress levels, smoking status).Discussion: Testing for relevant indexes, we found an excellent clinical utility of the NIAAA single-item test for screening true negative cases. Our findings support a routine use of reliable methods for rapid screening in similar mental health settings. [ABSTRACT FROM AUTHOR]

Objective: Depression and neuropathy are frequent complications of type 2 diabetes. The current meta-analysis aimed to estimate the association between depression and neuropathy in subjects with type 2 diabetes.Methods: We systematically searched electronic databases for articles published up to February 2015, providing data on the association between depression and neuropathy in individuals with type 2 diabetes. No language restrictions were applied. The meta-analysis generated random-effect odds ratios with 95% confidence intervals (95% CI). Risk of publication bias and heterogeneity were estimated using the Egger test and I(2) index, respectively. Leave-one-out analysis was performed. Data were analysed using stata.Results: Thirteen studies were included in the meta-analysis. Data on the association between depression and neuropathy were available for 3898 individuals with type 2 diabetes. Pooled analysis showed an association between depression and neuropathy, with an odds ratio of 2.01 (95% CI: 1.60-2.54; p < 0.001). There was no risk of publication bias (p = 0.064), and heterogeneity was moderate (I(2)  = 44.5%). Leave-one-out analysis confirmed consistency of the findings. The association appeared partly influenced by age, because studies selecting older people (sample mean age > 65 years) showed a slightly higher estimate for the association.Conclusions: We found an association between depression and neuropathy among people with type 2 diabetes. Because of the cross-sectional nature of included studies, the relationship between these two conditions might be bidirectional. Further research exploring factors that might moderate or mediate this association is needed. Targeted interventions for comorbid depression and neuropathy should be implemented in clinical practice. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: Treatment-resistant depression (TRD) is a debilitating condition associated with unmet clinical needs. Few studies have explored clinical characteristics and serum biomarkers associated with TRD. Aims: We investigated whether there were differences in clinical and biochemical variables between patients affected by TRD than those without. Methods: We recruited 343 patients (165 males and 178 females) consecutively hospitalized for MDD to the inpatient clinics affiliated to the Fondazione IRCCS Policlinico, Milan, Italy (n = 234), and ASST Monza, Italy (n = 109). Data were obtained through a screening of the clinical charts and blood analyses conducted during the hospitalization. Results: TRD versus non-TRD patients resulted to be older (p = 0.001), to have a longer duration of illness (p < 0.001), to be more currently treated with a psychiatric poly-therapy (p < 0.001), to have currently more severe depressive symptoms as showed by the Hamilton Depression Rating Scale (HAM-D) scores (p = 0.016), to have lower bilirubin plasma levels (p < 0.001). In addition, more lifetime suicide attempts (p = 0.035), more antidepressant treatments before the current episode (p < 0.001), and a lower neutrophil to lymphocyte ratio at borderline statistically significant level (p = 0.060) were all associated with the TRD group. Conclusion: We identified candidate biomarkers associated with TRD such as bilirubin plasma levels and NLR, to be confirmed by further studies. Moreover, TRD seems to be associated with unfavorable clinical factors such as a predisposition to suicidal behaviors. Future research should replicate these results to provide robust data in support of the identification of new targets of treatment and implementation of prevention strategies for TRD. [ABSTRACT FROM AUTHOR]

Abstract: Background: Assessing factors associated with non-fatal overdose is important as these could be useful to identify individuals with substance use disorders at high risk of adverse outcomes and consequences. Depression may play an important role in terms of overdose risk. We aimed to test if drug users suffering from a depressive disorder might have significantly higher risk of non-fatal overdose as compared with drug users without depression. Methods: We conducted a systematic review and meta-analysis. PubMed, Embase and Web of Knowledge were searched. The pooled analyses were based on prevalence rates, risk difference (RD) and odds ratio (OR), reporting 95% confidence intervals (CIs). The combined estimates were obtained weighting each study according to random effects model for meta-analysis. Results: Seven articles, involving 12,019 individuals, and run in the US, Canada, Sweden, Norway, and Australia, were included. Pooled analyses comparing depressed with not depressed individuals highlighted a RD (95% CIs) for non-fatal overdose of 7.3% (4.8–9.7%) and an OR (95% CIs) of 1.45 (1.17–1.79). The subgroups analyses based on specific characteristics of included studies confirmed the association between depression and overdose. Conclusions: Depressive disorders seem to be important factors associated to the risk of non-fatal overdose. Longitudinal studies might appropriately clarify causal inference issues. Future research should address the role of depressive disorders as predictors of subsequent non-fatal overdoses. [Copyright &y& Elsevier]

Treatment resistant depression (TRD) is associated with poor outcomes, but a consensus is lacking in the literature regarding which compound represents the best pharmacological augmentation strategy to antidepressants (AD). In the present review, we identify the available literature regarding the pharmacological augmentation to AD in TRD. Research in the main psychiatric databases was performed (PubMed, ISI Web of Knowledge, PsychInfo). Only original articles in English with the main topic being pharmacological augmentation in TRD and presenting a precise definition of TRD were included. Aripiprazole and lithium were the most investigated molecules, and aripiprazole presented the strongest evidence of efficacy. Moreover, olanzapine, quetiapine, cariprazine, risperidone, and ziprasidone showed positive results but to a lesser extent. Brexpiprazole and intranasal esketamine need further study in real-world practice. Intravenous ketamine presented an evincible AD effect in the short-term. The efficacy of adjunctive ADs, antiepileptic drugs, psychostimulants, pramipexole, ropinirole, acetyl-salicylic acid, metyrapone, reserpine, testosterone, T3/T4, naltrexone, SAMe, and zinc cannot be precisely estimated in light of the limited available data. Studies on lamotrigine and pindolol reported negative results. According to our results, aripiprazole and lithium may be considered by clinicians as potential effective augmentative strategies in TRD, although the data regarding lithium are somewhat controversial. Reliable conclusions about the other molecules cannot be drawn. Further controlled comparative studies, standardized in terms of design, doses, and duration of the augmentative treatments, are needed to formulate definitive conclusions. [ABSTRACT FROM AUTHOR]

Background. Depression after stroke may have great burden on the likelihood of functional recovery and long-term outcomes. Objective. To estimate the association between depression after stroke and subsequent mortality. Methods. A systematic search of articles using PubMed and Web of Science databases was performed. Odds ratios (ORs) and hazard ratios (HRs) were used as association measures for pooled analyses, based on random-effects models. Results. Thirteen studies, involving 59,598 subjects suffering from stroke (6,052 with and 53,546 without depression), had data suitable for meta-analysis. The pooled OR for mortality at followup in people suffering from depression after stroke was 1.22 (1.02-1.47). Subgroups analyses highlighted that only studies with medium-term followup (2-5 years) showed a statistically significant association between depression and risk of death. Four studies had data suitable for further analysis of pooled HR. The meta-analysis revealed a HR for mortality of 1.52 (1.02-2.26) among people with depression after stroke. Conclusions. Despite some limitations, this paper confirms the potential role of depression on post stroke mortality. The relationship between depression and mortality after stroke seems to be related to the followup duration. Further research is needed to clarify the nature of the association between depression after stroke and mortality. [ABSTRACT FROM AUTHOR]

Esketamine (ESK) has been approved as a rapid-acting intranasal treatment for treatment-resistant depression (TRD). Although existing studies have investigated the efficacy of ESK in the 4-week induction phase, our knowledge about long-term ESK efficacy remains poor. The aim of this systematic review was to summarize the available data on long-term ESK efficacy for TRD. A systematic search was performed including articles in English, up to 31 March 2021. The search found 7 relevant studies, involving 1024 adult TRD patients. Continuing treatment with ESK after the 4-week induction phase may be associated with stable efficacy in relapse prevention among TRD patients. Conversely, the long-term antidepressant effectiveness upon discontinuation of ESK might be limited, although data from three studies had a moderate to high risk of bias. Overall, the results on the effectiveness of this compound in the long term are mixed. According to our findings, ESK treatment should be continued following the induction phase to reach a stable efficacy in relapse prevention, while the long-term antidepressant and anti-suicidal effects of ESK after discontinuation are inconsistent. Currently, the level of proof of ESK efficacy in long-term TRD treatment remains low and more RCTs with larger sample sizes and active comparators are needed. [ABSTRACT FROM AUTHOR]