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Ketamine

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81. Predictors of response to repeated ketamine infusions in depression with suicidal ideation: An ROC curve analysis. Full Text available with Trip Pro

Predictors of response to repeated ketamine infusions in depression with suicidal ideation: An ROC curve analysis. Ketamine has rapid-acting antidepressant and antisuicidal properties, while a proportion of patients do not adequately achieve a complete response to ketamine. Our aim was to explore the applicability of using clinical factors and serum tryptophan (TRP) metabolites to predict the response to six doses of ketamine for depression with suicidal ideation.Seventy-three depressed (...) patients with suicidal ideation received a thrice-weekly infusion regimen of subanaesthetic doses of ketamine. Clinical symptoms were assessed by the Montgomery-Asberg Depression Rating Scale (MADRS), Beck's Scale for Suicide Ideation (SSI) and Patient Health Questionnaire-9 (PHQ-9), and serum levels of TRP, kynurenine (KYN) and kynurenic acid (KYNA) were detected by liquid chromatography-tandem mass spectrometry at baseline and day 1 (1 day after the first infusion). The potential predictors

2020 Journal of Affective Disorders

82. A Single Ketamine Infusion Combined With Motivational Enhancement Therapy for Alcohol Use Disorder: A Randomized Midazolam-Controlled Pilot Trial. (Abstract)

A Single Ketamine Infusion Combined With Motivational Enhancement Therapy for Alcohol Use Disorder: A Randomized Midazolam-Controlled Pilot Trial. Pharmacotherapy and behavioral treatments for alcohol use disorder are limited in their effectiveness, and new treatments with innovative mechanisms would be valuable. In this pilot study, the authors tested whether a single subanesthetic infusion of ketamine administered to adults with alcohol dependence and engaged in motivational enhancement (...) therapy affects drinking outcomes.Participants were randomly assigned to a 52-minute intravenous administration of ketamine (0.71 mg/kg, N=17) or the active control midazolam (0.025 mg/kg, N=23), provided during the second week of a 5-week outpatient regimen of motivational enhancement therapy. Alcohol use following the infusion was assessed with timeline followback method, with abstinence confirmed by urine ethyl glucuronide testing. A longitudinal logistic mixed-effects model was used to model daily

2020 American Journal of Psychiatry

83. Vascular endothelial growth factor and pigment epithelial-derived factor in the peripheral response to ketamine. (Abstract)

Vascular endothelial growth factor and pigment epithelial-derived factor in the peripheral response to ketamine. Ketamine is a rapid-acting antidepressant but its mechanism remains unclear. Vascular endothelial growth factor growth factor (VEGF) has been reported in the antidepressant action of ketamine in rodents. VEGF and pigment epithelial-derived factor (PEDF) signalling are closely linked and both are dysregulated in depression. We explored the effect of a single infusion of ketamine (...) , with midazolam as comparison, on peripheral whole blood mRNA levels of vascular endothelial growth factor A (VEGFA) and PEDF, and the VEGFA/PEDF ratio, in patients with depression.Twenty-five patients with depression were randomised to either ketamine (0.5 mg/kg) or midazolam (0.045 mg/kg) infusions over 40 min. Blood plasma samples were taken 1 h before the first infusion and 4 h after the infusion start. mRNA was extracted and qRT-PCR performed to analyse gene expression.Single infusions of ketamine

2020 Journal of Affective Disorders

84. A preliminary study of adjunctive ketamine for treatment-resistant bipolar depression. (Abstract)

A preliminary study of adjunctive ketamine for treatment-resistant bipolar depression. Ketamine has shown rapid antidepressant effects in depressed patients. However, the antidepressant and antisuicidal effects of repeated ketamine infusions in patients with treatment-resistant bipolar depression (TRBD) are not known.TRBD patients received six intravenous infusions of 0.5 mg/kg ketamine over 40 min on a Monday-Wednesday-Friday schedule during a 12-day period followed by a 2-week follow-up (...) period. Depressive symptoms were measured by the Montgomery-Asberg Depression Rating Scale (MADRS) at baseline and at each follow-up visit.Nineteen patients with TRBD were enrolled in the study, and 16 patients (84.2%) received all six ketamine infusions. After the first infusion, the rates of response and remission were 21.1% (95% CI: 0.9 to 21.2) and 15.8% (95% CI: 0 to 33.9), respectively, and after the sixth infusion, the rates of response and remission were 73.7% (95% CI: 51.9 to 95.5) and 63.2

2020 Journal of Affective Disorders

85. Guanosine potentiates the antidepressant-like effect of subthreshold doses of ketamine: Possible role of pro-synaptogenic signaling pathway. (Abstract)

Guanosine potentiates the antidepressant-like effect of subthreshold doses of ketamine: Possible role of pro-synaptogenic signaling pathway. Background Augmentation therapies may be effective strategies to potentiate the ketamine's actions with lower potential for knock-on effects. Thus, this study investigated the ability of combined administration of guanosine plus ketamine to elicit an antidepressant-like effect associated with mTOR pathway modulation. The ability of this combined (...) administration to exert an antidepressant-like effect in a model of depression was also evaluated. Methods Mice were administered with subthreshold doses of ketamine (0.1 mg/kg, i.p.) and guanosine (0.01 mg/kg, p.o.) and submitted to the tail suspension test, and immunoblotting analyses (p-mTOR, p-p70S6K, PSD-95, GluA1, and synapsin) in the hippocampus and prefrontal cortex. The antidepressant-like effect of ketamine plus guanosine in mice subjected to administration of corticosterone (20 mg/kg, p.o., 21

2020 Journal of Affective Disorders

86. Baseline insomnia as a predictor of antidepressant efficacy to repeated intravenous ketamine for unipolar and bipolar depression: A preliminary study. (Abstract)

Baseline insomnia as a predictor of antidepressant efficacy to repeated intravenous ketamine for unipolar and bipolar depression: A preliminary study. Ketamine has been demonstrated to have robust and rapid antidepressant effects, and few studies have focused on the relationship between insomnia and the efficacy of ketamine. The objective of this study was to examine whether baseline insomnia predicted the antidepressant efficacy of repeated intravenous ketamine infusions for unipolar (...) and bipolar depression.Patients with high insomnia (n = 64) or low insomnia (n = 68) received six intravenous infusions of ketamine (0.5 mg/kg over 40 min) over 12 days (Monday-Wednesday-Friday). The Montgomery-Asberg Depression Rating Scale (MADRS) without sleep item was used to assess depressive symptoms. Response was defined as a MADRS total score ≥ 50%, and remission was defined as a MADRS total score ≤ 10.There were no differences in response or remission rates between patients with high and low

2020 Journal of Affective Disorders

87. mGluR5 mediates ketamine antidepressant response in susceptible rats exposed to prenatal stress. (Abstract)

mGluR5 mediates ketamine antidepressant response in susceptible rats exposed to prenatal stress. New insights have recently been gained into ketamine's potential anti-depressive effects. However, the mechanisms that underlie ketamine's rapid antidepressant activity still remain a mystery.We used a rat prenatal stress (PS) model of depression to explore the functional role of mGluR5 in ketamine's rapidly induced antidepressant activity. Effects of the antidepressants imipramine, escitalopram (...) , ketamine, and fluoxetine were compared. AAV-mGluR5 and AAV-shRNA-mGluR5 were constructed to overexpress and knockdown hippocampal mGluR5 respectively.This study shows that mGluR5, which is associated with depression-like behaviors, is increased in susceptible rats exposed to prenatal stress, and that ketamine could significantly alleviate these stress-induced effects. RU-38486 down-regulated expression of mGluR5 and up-regulated NR1. MPEP and CHPG also altered expression of both mGluR5 and NR1. Notably

2020 Journal of Affective Disorders

88. Efficacy and safety of adjunctive therapy using esketamine or racemic ketamine for adult treatment-resistant depression: A randomized, double-blind, non-inferiority study. (Abstract)

Efficacy and safety of adjunctive therapy using esketamine or racemic ketamine for adult treatment-resistant depression: A randomized, double-blind, non-inferiority study. Ketamine and its enantiomers have recently been highlighted as one of the most effective therapeutic options in refractory depression. However, racemic ketamine and esketamine have not been directly compared. The aim of this study is to assess the efficacy and safety of esketamine compared to ketamine in patients (...) with treatment-resistant depression (TRD).This is a randomized, double-blind, active-controlled, bicentre, non-inferiority clinical trial, with two parallel groups. Participants were randomly assigned to a 40-min single intravenous infusion of ketamine 0.5 mg/kg or esketamine 0.25 mg/kg. The primary outcome was the difference in remission rates for depression 24 h following intervention using the Montgomery-Åsberg Depression Rating Scale (MADRS), with a non-inferiority margin of 20%.63 subjects were included

2020 Journal of Affective Disorders

89. Comprehensive assessment of side effects associated with a single dose of ketamine in treatment-resistant depression. (Abstract)

Comprehensive assessment of side effects associated with a single dose of ketamine in treatment-resistant depression. Concerns about ketamine for treating depression include abuse potential and the occurrence of psychotomimetic effects. This study sought to comprehensively assess side effects (SEs) associated with a single subanesthetic-dose intravenous ketamine infusion. A secondary aim was to examine the relationship between Clinician-Administered Dissociative States Scale (CADSS) scores (...) and dissociative symptoms reported on a comprehensive, clinician-administered SE questionnaire.Data from 188 participants were pooled from four placebo-controlled, crossover ketamine trials and one open-label study (n = 163 with either treatment-resistant major depressive disorder or bipolar disorder and 25 healthy controls). SEs were actively solicited in a standardized fashion and monitored over the time-course of each study. Statistical analyses assessed the effect of drug (ketamine, placebo) on SEs

2020 Journal of Affective Disorders

90. Rapid and sustained improvement in treatment-refractory depression through use of acute intravenous ketamine and concurrent transdermal selegiline: A case series. (Abstract)

Rapid and sustained improvement in treatment-refractory depression through use of acute intravenous ketamine and concurrent transdermal selegiline: A case series. Treatment resistant depression is a significant source of morbidity and mortality. For patients having failed or unable to undergo the electroconvulsive therapy procedure few effective alternative treatments exist.A case series is presented where six patients with treatment resistant depression failing both electroconvulsive therapy (...) and oral antidepressants are concomitantly treated with short course intravenous ketamine and longer term selegiline transdermal system.All six patients experienced clinical improvement with intravenous ketamine, with resolution of suicidality, increased food intake, and commitment to treatment adherence. Five patients showed sustained improvement with the selegiline transdermal system. One patient discontinued selegiline after developing peripheral edema and palpitations.This case series included only

2020 Journal of Affective Disorders

91. The effects of ketamine on typical and atypical depressive symptoms. (Abstract)

The effects of ketamine on typical and atypical depressive symptoms. Ketamine's effects on different dimensions of depressive symptomatology, including typical/melancholic and atypical depression, remain largely unknown. This study examined the effects of a single intravenous dose of ketamine on general depressive symptoms (measured using the Montgomery-Asberg Depression Rating Scale (MADRS), typical/melancholic symptoms (measured using the MADRS5), and atypical symptoms (measured using (...) the Scale for Atypical Symptoms (SAS)).Data from 68 participants with treatment-resistant major depressive disorder (MDD) or bipolar depression were pooled from three separate, double-blind, placebo-controlled, crossover studies investigating ketamine's efficacy in depression. MDD participants were unmedicated; bipolar participants received therapeutic-dose lithium or valproate. Clinical symptoms were collected preinfusion and up to 14 days postinfusion. Effect sizes were calculated for days 1 and 3

2020 Acta Psychiatrica Scandinavica

92. Ketamine Versus Etomidate and Peri-intubation Hypotension: A National Emergency Airway Registry Study. (Abstract)

Ketamine Versus Etomidate and Peri-intubation Hypotension: A National Emergency Airway Registry Study. The hemodynamic impact of induction agents is a critically important consideration in emergency intubations. We assessed the relationship between peri-intubation hypotension and the use of ketamine versus etomidate as an induction agent for emergency department (ED) intubation.We analyzed ED intubation data for patients aged >14 years from the National Emergency Airway Registry performed in 25 (...) 738 encounters with ketamine and 6,068 with etomidate. Patients receiving ketamine were more likely to have difficult airway characteristics (effect size difference = 8.8%, 95% confidence interval [CI] = 5.3% to 12.4%) and to undergo intubation with video laryngoscopy (8.1%, 95% CI = 4.4% to 12.0%). Peri-intubation hypotension incidence was 18.3% among patients receiving ketamine and 12.4% among patients receiving etomidate (effect size difference = 5.9%, 95% CI = 2.9% to 8.8%). Patients receiving

2020 Academic Emergency Medicine

93. Etomidate Use Is Associated With Less Hypotension Than Ketamine for Emergency Department Sepsis Intubations: A NEAR Cohort Study. (Abstract)

Etomidate Use Is Associated With Less Hypotension Than Ketamine for Emergency Department Sepsis Intubations: A NEAR Cohort Study. The objectives of this study were 1) to describe the current use of etomidate and other induction agents in patients with sepsis and 2) to compare adverse events between etomidate and ketamine in sepsis.This was an observational cohort study of the prospective National Emergency Airway Registry (NEAR) data set. Descriptive statistics were used to report (...) ] = 0.4 to 0.5). Sepsis patients had a greater risk of adverse events, and vasopressor therapy was required for 25% of patients after intubation. Postprocedure hypotension was higher between those intubated for sepsis with ketamine versus etomidate (74% vs. 50%, OR = 2.9, 95% CI = 1.9 to 4.5). After confounding by indication in the propensity score-adjusted analysis was accounted for, ketamine was associated with more postprocedure hypotension (OR = 2.7, 95% CI = 1.1 to 6.7). No difference

2020 Academic Emergency Medicine

94. Transient amnesia following prehospital low-dose ketamine administration. (Abstract)

Transient amnesia following prehospital low-dose ketamine administration. Low doses of ketamine have been shown to be safe and effective for pain relief. Adverse effects are generally mild and transient. A 69-year-old woman suffered a witnessed ground-level fall without report of head injury, loss of consciousness, or intoxication. She was in severe pain despite 10 mg of intravenous morphine and paramedics provided intravenous ketamine 16 mg (0.19 mg/kg). Upon arrival to the ED, she was alert (...) was admitted for observation and her mental status gradually improved overnight. She was discharged the following morning. Low dose ketamine is an important therapeutic option. Delayed or prolonged neuropsychiatric effects may be possible following combined ketamine and opioid analgesia. Clinicians utilizing low dose ketamine should be aware of this potential complication as it could result in the need for additional diagnostic testing and prolonged length of stay.Copyright © 2020 Elsevier Inc. All rights

2020 American Journal of Emergency Medicine

95. Neurocognitive performance of repeated versus single intravenous subanesthetic ketamine in treatment resistant depression. Full Text available with Trip Pro

Neurocognitive performance of repeated versus single intravenous subanesthetic ketamine in treatment resistant depression. Ketamine demonstrated rapid antidepressant effects in treatment-resistant depression (TRD). However, evaluation of ketamine's neurocognitive effect in TRD is unclear. We aim to (1) characterize baseline neurocognitive performance as a predictor of the change in severity of depressive symptoms over time, and (2) investigate the association of six versus single intravenous (...) (IV) ketamine and neurocognitive changes from baseline to the end of treatment.Subjects with TRD were randomized to receive either five IV midazolam followed by a single IV ketamine or six IV ketamine during a 12-day period. Depression symptom assessments occurred prior and 24 h after infusion days using the Montgomery-Åsberg Depression Rating Scale. Neurocognitive tasks were designed to test attention, memory, speed of processing, and set shifting using the CogState battery at baseline

2020 Journal of Affective Disorders

96. Changes in symptoms of anhedonia in adults with major depressive or bipolar disorder receiving IV ketamine: Results from the Canadian Rapid Treatment Center of Excellence. (Abstract)

Changes in symptoms of anhedonia in adults with major depressive or bipolar disorder receiving IV ketamine: Results from the Canadian Rapid Treatment Center of Excellence. Anhedonia is a trans-diagnostic, multidimensional phenotype that mediates patient outcomes and suicidality. Convergent evidence suggests that ketamine may be effective in targeting measures of anhedonia in adults with treatment resistant depression (TRD).This retrospective, post-hoc analysis included 203 (x̄ = 45 ± 14.6 years (...) of age) patients receiving four infusions of intravenous (IV) ketamine at a community-based clinic. The primary outcome measure was change in anhedonia severity, as measured by the Snaith-Hamilton Pleasure Scale (SHAPS). Secondary measures sought to determine if improvement on the SHAPS mediated the effect of repeated IV ketamine infusions on symptoms of depression and suicidal ideations, as measured by the Quick Inventory for Depression Symptomatology-Self Report 16-Item (QIDS-SR16) and anxiety

2020 Journal of Affective Disorders

97. The effect of intravenous, intranasal, and oral ketamine in mood disorders: A meta-analysis. Full Text available with Trip Pro

The effect of intravenous, intranasal, and oral ketamine in mood disorders: A meta-analysis. Ketamine is established as a rapid and effective treatment in adults with treatment-resistant depression (TRD). The availability of different formulations and routes of delivery invites the need for evaluating relative effect sizes.Effect size with respect to depression symptom reduction for each formulation and route of delivery was compared at discrete time-points (i.e., 24 h, 2-6 days, 7-20 days, 21 (...) -28 days) in adults with TRD. A random-effects meta-analysis was conducted to evaluate the effect size across intravenous, intranasal and oral routes of administration. Analysis was also conducted evaluating the effect size of racemic ketamine to esketamine.The pooled effect size for intranasal ketamine/esketamine at 24 h was g = 1.247 (n = 5, 95% CI: 0.591-1.903, p < 0.01). At 2-6 days, the pooled effect size for intravenous ketamine/esketamine was g = 0.949 (n = 14, 95% CI: -0.308-2.206, p

2020 Journal of Affective Disorders

98. Relationship between hippocampal volume and inflammatory markers following six infusions of ketamine in major depressive disorder. (Abstract)

Relationship between hippocampal volume and inflammatory markers following six infusions of ketamine in major depressive disorder. Evidences suggest that inflammatory marker-mediated neuroplasticity contributes critically to brain changes following antidepressant treatment. To date, no study has examined the relationship between changes in hippocampal volume, depressive symptoms, and inflammatory markers following repeated ketamine treatment.Forty-four patients with major depressive disorder (...) received six intravenous ketamine (0.5 mg/kg) infusions over 12 days. The Montgomery-Asberg Depression Rating Scale (MADRS) was used to assess depressive symptoms, and peripheral blood was collected to test multiple cytokines and tryptophan (TRP) metabolites at baseline, 24 h and 14 days after the sixth infusion (day 13 and day 26). Magnetic resonance imaging (MRI) scans were carried out at baseline and day13, and FreeSurfer software was used to process the T1 images and analyze hippocampal

2020 Journal of Affective Disorders

99. Long-term outcome in outpatients with depression treated with acute and maintenance intravenous ketamine: A retrospective chart review. (Abstract)

Long-term outcome in outpatients with depression treated with acute and maintenance intravenous ketamine: A retrospective chart review. Little is known about the long-term outcomes of repeated ketamine infusions for depression. We conducted a retrospective chart review to investigate outcomes of maintenance intravenous ketamine treatment at Massachusetts General Hospital.Eighty-five patients with treatment-resistant depression (TRD) who started intravenous ketamine from October 2018 to November (...) 2019 were examined. Symptom severity was evaluated with the 16-item Quick Inventory of Depressive Symptomatology-Self Report scale (QIDS-SR16) at every visit prior to administration. The initial ketamine dose was usually 0.5 mg/kg infused over 40 min. Intravenous ketamine was administered twice-weekly for three weeks in an induction phase, followed by maintenance with a variable administration schedule and dose. Response was defined as a ≥50% reduction in total QIDS-SR16 score from baseline.Forty

2020 Journal of Affective Disorders

100. Comparative efficacy of racemic ketamine and esketamine for depression: A systematic review and meta-analysis. Full Text available with Trip Pro

Comparative efficacy of racemic ketamine and esketamine for depression: A systematic review and meta-analysis. Ketamine appears to have a therapeutic role in certain mental disorders, most notably depression. However, the comparative performance of different formulations of ketamine is less clear.This study aimed to assess the comparative efficacy and tolerability of racemic and esketamine for the treatment of unipolar and bipolar major depression.Systematic review and meta-analysis.We searched (...) -outs due to adverse events.Evidence from randomized controlled trials was synthesized as rate ratios (RRs) for treatment response, disorder remission, adverse events, and withdrawals and as standardized mean differences (SMDs) for change in symptoms, via random-effects meta-analyses.24 trials representing 1877 participants were pooled. Racemic ketamine relative to esketamine demonstrated greater overall response (RR = 3.01 vs. RR = 1.38) and remission rates (RR = 3.70 vs. RR = 1.47), as well

2020 Journal of Affective Disorders

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