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Ketamine

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81. Modulation of the antidepressant effects of ketamine by the mTORC1 inhibitor rapamycin. Full Text available with Trip Pro

Modulation of the antidepressant effects of ketamine by the mTORC1 inhibitor rapamycin. Twenty-four hours after administration, ketamine exerts rapid and robust antidepressant effects that are thought to be mediated by activation of the mechanistic target of rapamycin complex 1 (mTORC1). To test this hypothesis, depressed patients were pretreated with rapamycin, an mTORC1 inhibitor, prior to receiving ketamine. Twenty patients suffering a major depressive episode were randomized to pretreatment (...) with oral rapamycin (6 mg) or placebo 2 h prior to the intravenous administration of ketamine 0.5 mg/kg in a double-blind cross-over design with treatment days separated by at least 2 weeks. Depression severity was assessed using Montgomery-Åsberg Depression Rating Scale (MADRS). Rapamycin pretreatment did not alter the antidepressant effects of ketamine at the 24-h timepoint. Over the subsequent 2-weeks, we found a significant treatment by time interaction (F(8,245) = 2.02, p = 0.04), suggesting

2020 Neuropsychopharmacology

82. Evaluating global brain connectivity as an imaging marker for depression: influence of preprocessing strategies and placebo-controlled ketamine treatment. (Abstract)

Evaluating global brain connectivity as an imaging marker for depression: influence of preprocessing strategies and placebo-controlled ketamine treatment. Major depressive disorder (MDD) is associated with altered global brain connectivity (GBC), as assessed via resting-state functional magnetic resonance imaging (rsfMRI). Previous studies found that antidepressant treatment with ketamine normalized aberrant GBC changes in the prefrontal and cingulate cortices, warranting further investigations (...) of GBC as a putative imaging marker. These results were obtained via global signal regression (GSR). This study is an independent replication of that analysis using a separate dataset. GBC was analyzed in 28 individuals with MDD and 22 healthy controls (HCs) at baseline, post-placebo, and post-ketamine. To investigate the effects of preprocessing, three distinct pipelines were used: (1) regression of white matter (WM)/cerebrospinal fluid (CSF) signals only (BASE); (2) WM/CSF + GSR (GSR); and (3) WM

2020 Neuropsychopharmacology

83. Ketamine normalizes subgenual cingulate cortex hyper-activity in depression. (Abstract)

Ketamine normalizes subgenual cingulate cortex hyper-activity in depression. Mounting evidence supports the rapid antidepressant efficacy of the N-methyl-D-aspartate receptor antagonist, ketamine, for treating major depressive disorder (MDD); however, its neural mechanism of action remains poorly understood. Subgenual anterior cingulate cortex (sgACC) hyper-activity during rest has been consistently implicated in the pathophysiology of MDD, potentially driven in part by excessive hippocampal (...) gluatmatergic efferents to sgACC. Reduction of sgACC activity has been associated with successful antidepressant treatment. This study aimed to examine whether task-based sgACC activity was higher in patients with MDD compared to controls and to determine whether this activity was altered by single-dose ketamine. In Study 1, patients with MDD (N = 28) and healthy controls (N = 20) completed task-based functional magnetic resonance imaging using an established incentive-processing task. In Study 2, a second

2020 Neuropsychopharmacology

84. Enduring effects of adolescent ketamine exposure on cocaine- and sucrose-induced reward in male and female C57BL/6 mice. (Abstract)

Enduring effects of adolescent ketamine exposure on cocaine- and sucrose-induced reward in male and female C57BL/6 mice. Ketamine has shown promising antidepressant efficacy for adolescent treatment-resistant depression. However, the potential enduring consequences of ketamine exposure have not been thoroughly evaluated. Thus, we examined if juvenile ketamine treatment results in long-lasting changes for the rewarding properties of sucrose and cocaine in adulthood, across three separate (...) experiments. In Experiment 1, adolescent male and female C57BL/6 mice received ketamine (20 mg/kg) for 15 consecutive days (Postnatal Day [PD] 35-49). Twenty-one days later (PD70; adulthood) we examined their behavioral responsivity to sucrose (1%) on a two-bottle choice design, or cocaine (0, 5, 10 mg/kg) using the conditioned place preference (CPP) test. We found that juvenile ketamine-pretreatment increased preference for sucrose and environments paired with cocaine in male, but not female, adult mice

2020 Neuropsychopharmacology

85. Single and repeated ketamine infusions for reduction of suicidal ideation in treatment-resistant depression. (Abstract)

Single and repeated ketamine infusions for reduction of suicidal ideation in treatment-resistant depression. Repeated administration of subanesthetic intravenous ketamine may prolong the rapid decrease in suicidal ideation (SI) elicited by single infusions. The purpose of this secondary analysis was to evaluate reduction in SI with a single ketamine infusion compared with an active control, and prolonged suppression of SI with repeated and maintenance infusions. Thirty-seven participants (...) with treatment-resistant depression (TRD) and baseline SI first received a single ketamine infusion during a randomized, double-blind crossover with midazolam. Following relapse of depressive symptoms, participants received six open-label ketamine infusions administered thrice-weekly over 2 weeks. Antidepressant responders (≥50% decrease in Montgomery-Åsberg Depression Rating Scale [MADRS] scores) received four further open-label infusions administered once-weekly. Changes in SI were assessed

2020 Neuropsychopharmacology

86. Ketamine for rapid sequence intubation in adult trauma patients: A retrospective observational study. (Abstract)

Ketamine for rapid sequence intubation in adult trauma patients: A retrospective observational study. In the trauma population, ketamine is commonly used during rapid sequence induction. However, as ketamine has been associated with important side effects this study sought to compare in-hospital mortality in trauma patients after induction with ketamine versus other induction agents.We retrospectively identified adult trauma patients intubated in the pre-hospital phase or initially (...) in the trauma bay at two urban level-1 trauma centers during a two-year period using local trauma registries and medical records. In-hospital mortality was compared for patients intubated with ketamine versus other agents using logistic regression with adjustment for age, gender, Injury Severity Score (ISS), systolic blood pressure (SBP) < 90 mmHg, and pre-hospital Glasgow Coma Scale (GCS) score.A total of 343 trauma patients were included with a median ISS of 25 [17-34]. The most frequently used induction

2020 Acta Anaesthesiologica Scandinavica

87. The influence of subanaesthetic ketamine on regional cerebral blood flow in healthy dogs measured with 99mTc-HMPAO SPECT. Full Text available with Trip Pro

The influence of subanaesthetic ketamine on regional cerebral blood flow in healthy dogs measured with 99mTc-HMPAO SPECT. Subanaesthetic ketamine has recently been proven to be a highly effective and fast acting alternative treatment for several psychiatric disorders. The mechanisms responsible for ketamine's antidepressant effects remain unclear, but a possible explanation could be that ketamine interacts with regional cerebral blood flow (rCBF). Therefore, the effects of two subanaesthetic (...) ketamine doses on rCBF were evaluated. Twelve dogs were randomly assigned to one of the three treatment conditions (condition saline, condition 0.5 mg/kg ketamine or condition 2 mg/kg ketamine) and received in total five saline or ketamine infusions, with one week interval. Single Photon Emission Computed Tomography (SPECT) scans with the radiotracer 99mTc-hexamethylpropylene amine oxime were performed before the start of the infusions (baseline) and 24 hours after the first (single) and last (multiple

2018 PLoS ONE

88. Impact of repeated anesthesia with ketamine and xylazine on the well-being of C57BL/6JRj mice. Full Text available with Trip Pro

Impact of repeated anesthesia with ketamine and xylazine on the well-being of C57BL/6JRj mice. Within the scope of the 3Rs of Russel and Burch, the number of laboratory animals can be reduced by repeated use of an animal. This strategy only becomes relevant, if the total amount of pain, distress or harm the individual animal experiences does not exceed the severity of a single manipulation. For example, when using imaging techniques, an animal can be examined several times during a study (...) , but it has to be anesthetized each time imaging is performed. The severity of anesthesia is thought to be mild according to the Directive 2010/63/EU. However, the Directive does not differentiate between single and repeated anesthesia, although repeated anesthesia may have a greater impact on well-being. Hence, we compared the impact of single and repeated anesthesia (six times at an interval of three to four days) by injection of ketamine and xylazine (KX) on the well-being of adult female and male

2018 PLoS ONE

89. Correction: The Ketamine Analogue Methoxetamine and 3- and 4-Methoxy Analogues of Phencyclidine Are High Affinity and Selective Ligands for the Glutamate NMDA Receptor. Full Text available with Trip Pro

Correction: The Ketamine Analogue Methoxetamine and 3- and 4-Methoxy Analogues of Phencyclidine Are High Affinity and Selective Ligands for the Glutamate NMDA Receptor. [This corrects the article DOI: 10.1371/journal.pone.0059334.].

2018 PLoS ONE

90. Ketamine independently modulated power and phase-coupling of theta oscillations in Sp4 hypomorphic mice. Full Text available with Trip Pro

Ketamine independently modulated power and phase-coupling of theta oscillations in Sp4 hypomorphic mice. Reduced expression of Sp4, the murine homolog of human SP4, a risk gene of multiple psychiatric disorders, led to N-methyl-D-aspartate (NMDA) hypofunction in mice, producing behavioral phenotypes reminiscent of schizophrenia, including hypersensitivity to ketamine. As accumulating evidence on molecular mechanisms and behavioral phenotypes established Sp4 hypomorphism as a promising animal (...) the effects of a subanesthetic dosage of ketamine on theta abnormalities unique to Sp4 hypomorphism. Sp4 hypomorphic mice had markedly elevated theta power localized frontally and parietally, a more pronounced theta phase progression along the neuraxis, and a stronger frontal-parietal theta coupling. Acute subanesthetic ketamine did not affect theta power in wildtype animals but significantly reduced it in Sp4 hypomorphic mice, nearly completely neutralizing their excessive frontal/parietal theta power

2018 PLoS ONE

91. Sexual and bladder dysfunction in male ketamine abusers: A large-scale questionnaire study. Full Text available with Trip Pro

Sexual and bladder dysfunction in male ketamine abusers: A large-scale questionnaire study. To evaluate the prevalence of lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) in the illicit male ketamine abusers (KA).The male street KAs caught by policemen and patients visiting urologic clinics were invited to answer a structured questionnaire including demographic data, illicit drug use related details (duration, frequency, dosage and abstinence status), international prostate (...) (OR = 1.765). Subgroup analysis on male street KAs disclosed that abstinence ≧3 months is a protective factor for ED. Lower urinary tract symptoms (ICSI+ICPI ≧12) was prevalent in KAs and multivariate analysis disclosed that significant risk factors for LUTS (ICSI+ICPI ≧12) were age ≧30 years, duration ≧24 months and co-use of other illicit drugs.Male ED and LUTS were frequently observed in the ketamine abusers. We suggested that street ketamine abuse should be considered in young men presented with ED

2018 PLoS ONE

92. Using Neuroimaging to Decipher the Mechanism of Action of Ketamine: A Pathway to Novel Therapeutics? Full Text available with Trip Pro

Using Neuroimaging to Decipher the Mechanism of Action of Ketamine: A Pathway to Novel Therapeutics? 29560906 2019 02 27 2019 02 27 2451-9030 2 7 2017 10 Biological psychiatry. Cognitive neuroscience and neuroimaging Biol Psychiatry Cogn Neurosci Neuroimaging Using Neuroimaging to Decipher the Mechanism of Action of Ketamine: A Pathway to Novel Therapeutics? 549-551 S2451-9022(17)30146-5 10.1016/j.bpsc.2017.08.006 Nugent Allison C AC Experimental Therapeutics and Pathophysiology Branch

2017 Biological psychiatry. Cognitive neuroscience and neuroimaging

93. Prefrontal Connectivity and Glutamate Transmission: Relevance to Depression Pathophysiology and Ketamine Treatment Full Text available with Trip Pro

Prefrontal Connectivity and Glutamate Transmission: Relevance to Depression Pathophysiology and Ketamine Treatment Prefrontal global brain connectivity with global signal regression (GBCr) was proposed as a robust biomarker of depression, and was associated with ketamine's mechanism of action. Here, we investigated prefrontal GBCr in treatment-resistant depression (TRD) at baseline and following treatment. Then, we conducted a set of pharmacological challenges in healthy subjects to investigate (...) the glutamate neurotransmission correlates of GBCr.In study A, we used functional magnetic resonance imaging (fMRI) to compare GBCr between 22 TRD and 29 healthy control. Then, we examined the effects of ketamine and midazolam on GBCr in TRD patients 24h post-treatment. In study B, we acquired repeated fMRI in 18 healthy subjects to determine the effects of lamotrigine (a glutamate release inhibitor), ketamine, and lamotrigine-by-ketamine interaction.In study A, TRD patients showed significant reduction

2017 Biological psychiatry. Cognitive neuroscience and neuroimaging

94. Use of Intranasal Ketamine in Pediatric Patients in the Emergency Department. (Abstract)

Use of Intranasal Ketamine in Pediatric Patients in the Emergency Department. Ketamine is a safe and widely used sedative and analgesic in the pediatric emergency department (ED). The use of intranasal (IN) ketamine in exchange for the administration of intravenous sedatives or analgesics for procedural sedation in pediatric patients is not commonplace. The goal of this study was to evaluate provider perceptions and patient outcomes at varying doses of IN ketamine for anxiolysis, agitation (...) , or analgesia.From January 2018 to May 2018, we performed a prospective survey and chart review of pediatric patients receiving IN ketamine. The primary outcome was to determine provider satisfaction with using IN ketamine. Secondary objectives included comparing outcomes stratified by dose, adverse events, assessing for treatment failure, and ED length of stay (LOS). As a secondary comparison, patients receiving IN ketamine whom otherwise would have required procedural sedation with intravenous sedatives

2019 Pediatric Emergency Care

95. Comparison of Intranasal Dexmedetomidine and Oral Ketamine Versus Intranasal Midazolam Premedication for Children Undergoing Dental Rehabilitation. Full Text available with Trip Pro

Comparison of Intranasal Dexmedetomidine and Oral Ketamine Versus Intranasal Midazolam Premedication for Children Undergoing Dental Rehabilitation. Dental rehabilitation surgery is associated with significant fear and anxiety with subsequent psychological disturbances. Midazolam has been used frequently as a premedication. However, it may be associated with side effects. Dexmedetomidine and ketamine combination has been suggested as an effective premedication in improving preoperative sedation (...) and analgesia.This study compared the effects of combined intranasal dexmedetomidine and oral ketamine versus intranasal midazolam on anxiolysis and postoperative analgesia.Seventy-six children (aged two to six years) undergoing dental rehabilitation under general anesthesia were assigned randomly to one of the two groups (n = 38 each) receiving either intranasal dexmedetomidine at 2 µg/kg and oral ketamine at 3 mg/kg (Group DK) or intranasal midazolam at 0.2 mg/kg (group M) 30 minutes prior to the anesthesia

2019 Anesthesiology and pain medicine Controlled trial quality: uncertain

96. Dextromethorphan and memantine after ketamine analgesia: a randomized control trial. Full Text available with Trip Pro

Dextromethorphan and memantine after ketamine analgesia: a randomized control trial. Intravenous ketamine is often prescribed in severe neuropathic pain. Oral N-methyl-D-aspartate receptor (NMDAR) antagonists might prolong pain relief, reducing the frequency of ketamine infusions and hospital admissions. This clinical trial aimed at assessing whether oral dextromethorphan or memantine might prolong pain relief after intravenous ketamine.A multicenter randomized controlled clinical trial (...) included 60 patients after ketamine infusion for refractory neuropathic pain. Dextromethorphan (90 mg/day), memantine (20 mg/day) or placebo was given for 12 weeks (n=20 each) after ketamine infusion. The primary endpoint was pain intensity at one month. Secondary endpoints included pain, sleep, anxiety, depression, cognitive function and quality of life evaluations up to 12 weeks.At 1 month, dextromethorphan maintained ketamine pain relief (Numeric Pain Scale: 4.01±1.87 to 4.05±2.61, p=0.53

2019 Drug design, development and therapy Controlled trial quality: uncertain

97. Preemptive Effect of Intraurethral Instillation of Ketamine-lidocaine Gel on Postoperative Catheter-related Bladder Discomfort after Lumbar Spine Surgery. Full Text available with Trip Pro

Preemptive Effect of Intraurethral Instillation of Ketamine-lidocaine Gel on Postoperative Catheter-related Bladder Discomfort after Lumbar Spine Surgery. Catheter-related bladder discomfort (CRBD) is one of the main reasons of agitation after surgery, leading to urgency and frequency during recovery. Ketamine has been used as an effective drug for reducing the signs and severity of this problem. We hypothesized that intraurethral instillation of ketamine-lidocaine gel before urinary (...) catheterization can reduce the incidence of CRBD in the postoperative period.A total of 136 male patients, who underwent two-level laminectomy/discectomy were enrolled in this randomized clinical trial. Patients were randomized into the two groups before urinary catheterization. The ketamine group received urethral lubrication with 5 mL xylocaine jelly (2%) in conjunction with 2 mL (100 mg) ketamine. Patients in control group received urethral lubrication with 5 mL xylocaine jelly (2%) in conjunction with 2

2019 Asian journal of neurosurgery Controlled trial quality: uncertain

98. Comparison of intradermal Dexmedmotidine and subcutaneous Ketamine for post-surgical pain management in patients with abdominal hysterectomy. Full Text available with Trip Pro

Comparison of intradermal Dexmedmotidine and subcutaneous Ketamine for post-surgical pain management in patients with abdominal hysterectomy. Hysterectomy after cesarean section is the second most commonly used surgery for women in the United States. One of the most common problem after hysterectomy is pain. We decided to compare the effects of dexmedmotidine or ketamine on pain in patients by a double blind randomized clinical trial on 126 female candidates for abdominal hysterectomy in three (...) groups of 42 persons referred to Taleghani hospital in Arak. For the first group, 50 micrograms of intradermal dexmedmotidine were injected, while in the second group, patients were injected with 100 mg of subcutaneous ketamine and the third group received 5 cc normal saline. Data were next analyzed by SPSS version 19. The mean age and body mass index of the patients were not significantly different in the three groups. The mean scores of pain during recovery of patients in ketamine, dexmedmotidine

2019 European journal of translational myology Controlled trial quality: uncertain

99. [Ketamine as an adjunct to bupivacaine in infra-orbital nerve block analgesia after cleft lip repair]. Full Text available with Trip Pro

[Ketamine as an adjunct to bupivacaine in infra-orbital nerve block analgesia after cleft lip repair]. We conducted this study to investigate the safety and analgesic efficacy of the addition of Ketamine to Bupivacaine in bilateral extra-oral infra-orbital nerve block in children undergoing cleft lip surgeries.Sixty patients were randomly allocated into two groups (n=30), Group B received infra-orbital nerve block with 2mL of 0.25% Bupivacaine and Group BK received 0.5mg.kg-1 Ketamine for each (...) ) and in the first hour (h) postoperatively (1.40±0.17 vs. 0.67±0.14, p<0.003). Higher parent satisfaction scores were recorded in Group BK (p<0.04) without significant adverse effects.The addition of Ketamine to Bupivacaine has accentuated the analgesic efficacy of infra-orbital nerve block in children undergoing cleft lip repair surgeries.Copyright © 2018 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

2019 Revista brasileira de anestesiologia Controlled trial quality: uncertain

100. Association between dynamic resting-state functional connectivity and ketamine plasma levels in visual processing networks. Full Text available with Trip Pro

Association between dynamic resting-state functional connectivity and ketamine plasma levels in visual processing networks. Numerous studies demonstrate ketamine's influence on resting-state functional connectivity (rsFC). Seed-based and static rsFC estimation methods may oversimplify FC. These limitations can be addressed with whole-brain, dynamic rsFC estimation methods. We assessed data from 27 healthy subjects who underwent two 3 T resting-state fMRI scans, once under subanesthetic (...) suggesting that esketamine's influence on dynamic rsFC is highly stable in visual processing networks. Our findings may be reflective of ketamine's role as a model for psychosis, a disorder associated with alterations to visual processing and impaired inter-hemispheric connectivity. Ketamine is a highly effective antidepressant and studies have shown changes to sensory processing in depression. Dynamic rsFC in sensory processing networks might be a promising target for future investigations of ketamine's

2019 Scientific reports Controlled trial quality: uncertain

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