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Ketamine

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101. Role of Neuronal VEGF Signaling in the Prefrontal Cortex in the Rapid Antidepressant Effects of Ketamine. (PubMed)

Role of Neuronal VEGF Signaling in the Prefrontal Cortex in the Rapid Antidepressant Effects of Ketamine. The N-methyl-d-aspartate receptor antagonist ketamine produces rapid and sustained antidepressant actions even in patients with treatment-resistant depression. Vascular endothelial growth factor (VEGF) has been implicated in the effects of conventional monoamine-based antidepressants, but the role of VEGF in the rapid antidepressant actions of ketamine remains unclear. The authors examined (...) of ketamine that underlie its behavioral actions.The behavioral actions of systemic ketamine are blocked by forebrain excitatory neuron-specific deletion of either VEGF or Flk-1 or by intra-mPFC infusion of a VEGF neutralizing antibody. Moreover, intra-mPFC infusions of VEGF are sufficient to produce rapid ketamine-like behavioral actions, and these effects are blocked by neuron-specific Flk-1 deletion. The results also show that local knockdown of Flk-1 in mPFC excitatory neurons in adulthood blocks

2019 American Journal of Psychiatry

102. MSc BLOG – Ketamine for DEPR

MSc BLOG – Ketamine for DEPR MSc BLOG - Ketamine for DEPR - CEBM CEBM The Centre for Evidence-Based Medicine develops, promotes and disseminates better evidence for healthcare. Navigate this website MSc BLOG – Ketamine for DEPR July 6, 2018 Ketamine for Depression During my time working with patients we noticed that each patient receiving repeated ketamine infusions often has very different treatment experiences and dissociative side effects from one treatment to the next despite no changes (...) to their treatment regimes. It was wanting to examine this variation that lead me to the MSC in Evidence-Based Healthcare programme to learn the skills and knowledge necessary to investigate this and write it up as my dissertation . Hayley Trueman, Clinical practitioner within the ECT and ketamine clinic at the Warneford Hospital Oxford In patients receiving repeated IV ketamine treatment for depression, does an individual’s severity of depression affect the dissociative side effects experienced during treatment

2018 CEBM blog

103. Ketamine independently modulated power and phase-coupling of theta oscillations in Sp4 hypomorphic mice. (PubMed)

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

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2018 PLoS ONE

104. A Comparison of Headache Treatment in the Emergency Department: Prochlorperazine Versus Ketamine

A Comparison of Headache Treatment in the Emergency Department: Prochlorperazine Versus Ketamine Intravenous subdissociative-dose ketamine has been shown to be effective for pain management, but has not been specifically studied for headaches in the emergency department (ED). For this reason, we designed a study to compare standard treatment (prochlorperazine) with ketamine in patients with benign headaches in the ED.This study was a multicenter, double-blind, randomized, controlled trial (...) with a convenience sample of patients presenting to the ED with benign headaches. Patients were randomized to receive either prochlorperazine and diphenhydramine or ketamine and ondansetron. Patients' headache severity was measured on a 100-mm visual analog scale (VAS) at 0, 15, 30, 45, and 60 minutes. Nausea, vomiting, anxiety, and the need for rescue medications were also tracked. Patients were contacted at 24 to 48 hours posttreatment to rate their satisfaction and to determine whether they were still

2017 EvidenceUpdates

105. Starting ketamine for neuroprotection earlier than its current use as an anesthetic/antiepileptic drug late in refractory status epilepticus. (PubMed)

Starting ketamine for neuroprotection earlier than its current use as an anesthetic/antiepileptic drug late in refractory status epilepticus. Ketamine is currently being used as an anesthetic/antiepileptic drug in refractory status epilepticus. To validate its use, 2 clinical trials are recruiting patients. However, preclinical studies of its use in chemically induced status epilepticus in rodents have shown that it is remarkably neuroprotective, through N-methyl-d-aspartate-receptor blockade (...) , even when given after the onset of status epilepticus. Human studies have shown that status epilepticus-induced brain damage can be caused by a glutamate analogue and that it occurs in the same brain regions as in the animal studies. We therefore propose that ketamine be started early in the course of human status epilepticus as a neuroprotectant and that it be continued until epileptic discharges are eliminated. Using it as an anesthetic/antiepileptic drug late in the course of refractory status

2019 Epilepsia

106. Adjunctive ketamine and electroconvulsive therapy for major depressive disorder: A meta-analysis of randomized controlled trials. (PubMed)

Adjunctive ketamine and electroconvulsive therapy for major depressive disorder: A meta-analysis of randomized controlled trials. Adjunctive ketamine with electroconvulsive therapy (ECT) has been investigated for treating major depressive disorder (MDD), but the findings have been inconsistent.This is an updated meta-analysis of the efficacy and safety of ketamine augmentation of ECT in the treatment of MDD.Randomized controlled trials (RCTs) reporting on the efficacy and safety of ketamine (...) and ECT were identified and analyzed.Seventeen RCTs (n = 1,035) compared ketamine alone or ketamine plus other anesthetic drugs (n = 557) with other anesthetic agents (n = 478) in MDD patients who received ECT. Ketamine+other anesthetic drugs was superior in improving depressive symptoms over other anesthetic medications at early study time point, but not at post-ECT or end of study time points. Ketamine alone was not more efficacious in treating depressive symptoms than other anesthetic drugs

2019 Journal of Affective Disorders

107. Plasticity in the dynamic pain connectome associated with ketamine-induced neuropathic pain relief. (PubMed)

Plasticity in the dynamic pain connectome associated with ketamine-induced neuropathic pain relief. Therapeutic interventions for neuropathic pain (NP), such as the NMDA-antagonist ketamine, can vary widely in effectiveness; Here, we conducted a longitudinal functional MRI study to test the hypothesis that the pain relieving effect of ketamine is due to reversal of abnormalities in regional low frequency brain oscillations (LFOs) and abnormal cross-network functional connectivity (FC (...) ) of the dynamic pain connectome. We found that: 1) ketamine decreased regional LFOs in the posterior cingulate cortex (PCC) of the default mode network (DMN), 2) a machine learning algorithm demonstrated that treatment-induced brain changes could be used to make generalizable inferences about pain relief, 3) treatment responders exhibited a significant decrease in cross-network static FC between the PCC and regions of the sensorimotor (SM) and salience networks following treatment, 4) the degree of reduced

2019 Pain

108. Massive Iatrogenic Pediatric Ketamine Overdose With Serial Levels and Minimal Morbidity. (PubMed)

Massive Iatrogenic Pediatric Ketamine Overdose With Serial Levels and Minimal Morbidity. Ketamine is a dissociative anesthetic commonly used for procedural sedation owing to its perceived favorable safety profile. Despite its frequent use, overdoses of ketamine are rarely reported, and no cases with serum levels of ketamine or its metabolite have previously been reported. We report a case of an iatrogenic pediatric ketamine 20 mg/kg intramuscular overdose with serial ketamine and norketamine

2019 Pediatric Emergency Care

109. Assessment of Ketamine Adult Anesthetic Doses in Pediatrics using Pharmacokinetic Modeling and Simulations. (PubMed)

Assessment of Ketamine Adult Anesthetic Doses in Pediatrics using Pharmacokinetic Modeling and Simulations. Although few studies have used ketamine for induction and maintenance of pediatric anesthesia, official dosage recommendations are lacking. This study evaluates the outcomes of adult anesthetic doses in a pediatric population through pharmacokinetic modeling and computer simulations in an attempt to recommend an adequate ketamine dosing regimen. Ketamine plasma concentration-time data (...) in 19 children (age 8 months to 16 years; weight 5.5 to 67 kg) were analyzed according to a non-compartmental pharmacokinetic approach. The relationship between pharmacokinetic parameters and demographic covariates was mathematically characterized. A one-compartment open model was implemented to simulate the plasma profile following administration of 1-4.5 mg/kg IV bolus dose and 0.1-0.5 mg/kg/min continuous infusion of ketamine and to predict anesthesia onset and offset. Pharmacokinetic parameters

2019 Pharmacotherapy

110. Impact of midazolam vs. saline on effect size estimates in controlled trials of ketamine as a rapid-acting antidepressant. (PubMed)

Impact of midazolam vs. saline on effect size estimates in controlled trials of ketamine as a rapid-acting antidepressant. The goal of this study was to infer the effectiveness of midazolam as a comparator in preserving the blind in ketamine studies for mood disorders through patient-level analyses of efficacy trial outcomes. In this integrative data analysis (k = 9, N = 367 patients with mood disorders), clinical outcomes were compared across four groups: ketamine (midazolam-controlled (...) ), ketamine (saline-controlled), midazolam, and saline. Ketamine doses ranged from 0.5 to 0.54 mg/kg and midazolam doses ranged from 0.02 to 0.045 mg/kg. The baseline-to-Day 1 effect size was d = 0.7 (95% CI: 0.4-0.9) for ketamine (midazolam) versus midazolam and d = 1.8 (95% CI: 1.4-2.2) for ketamine (saline) versus saline. The effect of ketamine relative to control was larger in saline-controlled studies than in midazolam-controlled studies (t(276) = 2.32, p = 0.02). This was driven by a comparatively

2019 Neuropsychopharmacology

111. The influence of subanaesthetic ketamine on regional cerebral blood flow in healthy dogs measured with 99mTc-HMPAO SPECT. (PubMed)

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

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2018 PLoS ONE

112. Considerations on the Off-label Use of Ketamine as a Treatment for Mood Disorders (PubMed)

Considerations on the Off-label Use of Ketamine as a Treatment for Mood Disorders 28806440 2017 09 27 2018 12 07 1538-3598 318 9 2017 Sep 05 JAMA JAMA Considerations on the Off-label Use of Ketamine as a Treatment for Mood Disorders. 793-794 10.1001/jama.2017.10697 Wilkinson Samuel T ST Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut. The Yale Psychiatric Hospital, Yale New Haven Health, New Haven, Connecticut. Sanacora Gerard G Department of Psychiatry, Yale School (...) of Medicine, New Haven, Connecticut. The Yale Psychiatric Hospital, Yale New Haven Health, New Haven, Connecticut. eng L30 MH111000 MH NIMH NIH HHS United States T32 MH062994 MH NIMH NIH HHS United States Journal Article United States JAMA 7501160 0098-7484 0 Anesthetics, Dissociative 690G0D6V8H Ketamine AIM IM Advisory Committees Anesthetics, Dissociative adverse effects therapeutic use Chronic Disease drug therapy Humans Ketamine adverse effects therapeutic use Mood Disorders drug therapy Off-Label Use

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2017 JAMA

113. A preliminary study of anti-suicidal efficacy of repeated ketamine infusions in depression with suicidal ideation. (PubMed)

A preliminary study of anti-suicidal efficacy of repeated ketamine infusions in depression with suicidal ideation. Suicide is a tremendous public health crisis and is demanded urgent intervention. Previous studies found that ketamine intervention could rapidly reduce suicidal ideation in depression. However, the comparatively study in Chinese population remains absence. The current study aims to assess the anti-suicidal efficacy of repeated ketamine infusions for Chinese depressed suicidal (...) patients, especially distinguish between low suicidal ideation (SI) group and high SI group.Eighty-six unipolar and bipolar depressive patients with current suicidal ideation received six ketamine infusions during a 12-day period. Hamilton Depression Rating Scale (HAMD) and Beck Scale for Suicide Ideation (SSI) was measured at baseline, 4 h and 24 h after each infusion, and two-week naturalistically follow-up.Forty-nine (57.0%) patients relief of suicidal ideation after first infusion and 56 (65.1

2019 Journal of Affective Disorders

114. Off-label use of ketamine for treatment-resistant depression in clinical practice: European perspective. (PubMed)

Off-label use of ketamine for treatment-resistant depression in clinical practice: European perspective. SummaryKetamine therapy for treatment-resistant depression in European national health systems may only be considered after attempting all evidence-based antidepressant strategies outlined in clinical guidelines. This paper seeks to explain the ethical, regulatory and procedural framework for the off-label use of ketamine for treatment-resistant depression within a public healthcare

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2019 British Journal of Psychiatry

115. Oral Ketamine for Depression, 1: Pharmacologic Considerations and Clinical Evidence. (PubMed)

Oral Ketamine for Depression, 1: Pharmacologic Considerations and Clinical Evidence. Clinical evidence is accumulating to support the use of ketamine as a powerful, quick-acting intervention for depression. Ketamine has been administered by oral, sublingual, transmucosal, intravenous, intramuscular, subcutaneous, intranasal, and even rectal routes. Whereas intravenous ketamine is the best studied approach, common sense dictates that oral ketamine is the most practical. The bioavailability (...) of oral ketamine and interindividual variations thereof have been poorly studied; possibly only 20%-25% of an oral dose reaches the bloodstream. This is not necessarily a limitation because, as with other drugs that have poor oral bioavailability, compensation is possible by administering an appropriately higher dose, and interindividual variations can be addressed through individualized dose up-titration. A quarter- century of experience supports the use of oral ketamine for treating acute

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2019 Journal of Clinical Psychiatry

116. Oral Ketamine for Depression: A Systematic Review. (PubMed)

Oral Ketamine for Depression: A Systematic Review. Intravenous (IV) ketamine has rapid and robust antidepressant effects; however, poor accessibility of the IV route often limits its use. Numerous alternative routes of administration are being investigated. Oral ketamine is particularly appealing for its ease of use with the potential for high accessibility. The objective of the current systematic review, in accordance with PRISMA, is to determine the efficacy, safety, tolerability, and dose (...) range of oral ketamine for bipolar and unipolar depression.The MEDLINE/PubMed, EMBASE, and Google Scholar databases were systematically searched for relevant articles, written in English, published prior to July 2018 using relevant keywords for all variants of ketamine, oral, and depression.All clinical studies assessing oral ketamine for bipolar or unipolar depression were included. A total of 13 published articles were identified, of which 2 were proof-of-concept, randomized controlled trials

2019 Journal of Clinical Psychiatry

117. Oral Ketamine for Depression, 2: Practical Considerations. (PubMed)

Oral Ketamine for Depression, 2: Practical Considerations. The oral route of administration is probably the least expensive and most convenient way to administer ketamine in indicated contexts in depressed patients. Because only 20%-25% of orally administered ketamine reaches systemic circulation, oral doses of about 2.0-2.5 mg/kg may need to be administered to achieve equivalence to intravenously administered ketamine. In case reports, case series, standard operating practice in ketamine (...) facilities, and randomized controlled trials, oral ketamine has been administered through weight-based dosing and as fixed doses, and the dosing strategy has been one-size-fits-all or individualized through a dose discovery process. Administered doses have ranged from 0.25 to 7.0 mg/kg in weight-based dosing sessions and from 25 mg to 300 mg in fixed dosing sessions. This article reviews strategies for dosing with oral ketamine, dose discovery procedures, rates of dosing during a session, the frequency

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2019 Journal of Clinical Psychiatry

118. Retrospective Comparison of Intranasal Fentanyl and Inhaled Nitrous Oxide to Intravenous Ketamine and Midazolam for Painful Orthopedic Procedures in a Pediatric Emergency Department. (PubMed)

Retrospective Comparison of Intranasal Fentanyl and Inhaled Nitrous Oxide to Intravenous Ketamine and Midazolam for Painful Orthopedic Procedures in a Pediatric Emergency Department. To compare the efficacy and adverse events of 2 pharmacological strategies: intranasal fentanyl and nitrous oxide (FN) inhaled against intravenous ketamine and midazolam (KM) as procedural sedation and analgesia (PSA) in painful orthopedic procedures in the pediatric emergency department (ED

2019 Pediatric Emergency Care

119. The comparison of dexmedetomidine and ketamine for pediatric dental surgery: A meta-analysis of randomized controlled studies. (PubMed)

The comparison of dexmedetomidine and ketamine for pediatric dental surgery: A meta-analysis of randomized controlled studies. Dexmedetomidine and ketamine are used for the sedation of pediatric dental surgery. We conduct a systematic review and meta-analysis to compare the sedation of dexmedetomidine and ketamine for pediatric dental surgery.PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched. Randomized controlled trials (RCTs) assessing the influence (...) of dexmedetomidine versus ketamine on pediatric dental surgery are included. Two investigators independently have searched articles, extracted data, and assessed the quality of included studies. This meta-analysis is performed using the random-effect model.Four RCTs involving 163 children are included in the meta-analysis. Compared with ketamine for pediatric dental surgery, dexmedetomidine results in comparable sedation level (very low quality, 2 RCTs, n = 40; Std. MD = -0.26; 95% CI = -0.74 to 0.23; P = .31

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2019 Medicine

120. Ketamine Infusions for Chronic Pain: A Systematic Review and Meta-analysis of Randomized Controlled Trials. (PubMed)

Ketamine Infusions for Chronic Pain: A Systematic Review and Meta-analysis of Randomized Controlled Trials. IV ketamine is widely used to treat patients with chronic pain, yet the long-term impact remains uncertain. We synthesized evidence from randomized control trials to investigate the effectiveness of IV ketamine infusions for pain relief in chronic conditions and to determine whether any pain classifications or treatment regimens are associated with greater benefit.We searched Medline (...) , Embase, and Google Scholar, as well as the clinicaltrials.gov website from inception through December 16, 2017 for randomized control trials comparing IV ketamine to placebo infusions for chronic pain that reported outcomes for ≥48 hours after the intervention. Three authors independently screened the studies, pooled the data, and appraised risk of bias. Random-effects model was used to calculate weighted mean differences for pain scores and secondary outcomes. Our primary outcome was the lowest

2019 Anesthesia and Analgesia

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