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      Attenuation of antidepressant and antisuicidal effects of ketamine by opioid receptor antagonism

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          Effects of intravenous ketamine on explicit and implicit measures of suicidality in treatment-resistant depression.

          Intravenous ketamine has shown rapid antidepressant effects in early trials, making it a potentially attractive candidate for depressed patients at imminent risk of suicide. The Implicit Association Test (IAT), a performance-based measure of association between concepts, may have utility in suicide assessment. Twenty-six patients with treatment-resistant depression were assessed using the suicidality item of the Montgomery-Asberg Depression Rating Scale (MADRS-SI) 2 hours before and 24 hours following a single subanesthetic dose of intravenous ketamine. Ten patients also completed IATs assessing implicit suicidal associations at comparable time points. In a second study, nine patients received thrice-weekly ketamine infusions over a 12-day period. Twenty-four hours after a single infusion, MADRS-SI scores were reduced on average by 2.08 points on a 0 to 6 scale (p < .001; d = 1.37), and 81% of patients received a rating of 0 or 1 postinfusion. Implicit suicidal associations were also reduced following ketamine (p = .003; d = 1.36), with reductions correlated across implicit and explicit measures. MADRS-SI reductions were sustained for 12 days by repeated-dose ketamine (p < .001; d = 2.42). These preliminary findings support the premise that ketamine has rapid beneficial effects on suicidal cognition and warrants further study.
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            Opioid receptors: distinct roles in mood disorders.

            The roles of opioid receptors in pain and addiction have been extensively studied, but their function in mood disorders has received less attention. Accumulating evidence from animal research reveals that mu, delta and kappa opioid receptors (MORs, DORs and KORs, respectively) exert highly distinct controls over mood-related processes. DOR agonists and KOR antagonists have promising antidepressant potential, whereas the risk-benefit ratio of currently available MOR agonists as antidepressants remains difficult to evaluate, in addition to their inherent abuse liability. To date, both human and animal studies have mainly examined MORs in the etiology of depressive disorders, and future studies will address DOR and KOR function in established and emerging neurobiological aspects of depression, including neurogenesis, neurodevelopment, and social behaviors. Copyright © 2012 Elsevier Ltd. All rights reserved.
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              Vital Signs: Trends in State Suicide Rates — United States, 1999–2016 and Circumstances Contributing to Suicide — 27 States, 2015

              Introduction Suicide rates in the United States have risen nearly 30% since 1999, and mental health conditions are one of several factors contributing to suicide. Examining state-level trends in suicide and the multiple circumstances contributing to it can inform comprehensive state suicide prevention planning. Methods Trends in age-adjusted suicide rates among persons aged ≥10 years, by state and sex, across six consecutive 3-year periods (1999–2016), were assessed using data from the National Vital Statistics System for 50 states and the District of Columbia. Data from the National Violent Death Reporting System, covering 27 states in 2015, were used to examine contributing circumstances among decedents with and without known mental health conditions. Results During 1999–2016, suicide rates increased significantly in 44 states, with 25 states experiencing increases >30%. Rates increased significantly among males and females in 34 and 43 states, respectively. Fifty-four percent of decedents in 27 states in 2015 did not have a known mental health condition. Among decedents with available information, several circumstances were significantly more likely among those without known mental health conditions than among those with mental health conditions, including relationship problems/loss (45.1% versus 39.6%), life stressors (50.5% versus 47.2%), and recent/impending crises (32.9% versus 26.0%), but these circumstances were common across groups. Conclusions Suicide rates increased significantly across most states during 1999–2016. Various circumstances contributed to suicides among persons with and without known mental health conditions. Implications for Public Health Practice States can use a comprehensive evidence-based public health approach to prevent suicide risk before it occurs, identify and support persons at risk, prevent reattempts, and help friends and family members in the aftermath of a suicide.
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                Author and article information

                Journal
                Molecular Psychiatry
                Mol Psychiatry
                Springer Science and Business Media LLC
                1359-4184
                1476-5578
                August 29 2019
                Article
                10.1038/s41380-019-0503-4
                © 2019

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