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121. Considerations on the Off-label Use of Ketamine as a Treatment for Mood Disorders (Full text)

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

2017 JAMA

122. Prehospital Analgesia With Intranasal Ketamine (PAIN-K): A Randomized Double-Blind Trial in Adults. (Full text)

Prehospital Analgesia With Intranasal Ketamine (PAIN-K): A Randomized Double-Blind Trial in Adults. We compare intranasal ketamine with intranasal placebo in providing pain reduction at 30 minutes when added to usual paramedic care with nitrous oxide.This was a randomized double-blind study of out-of-hospital patients with acute pain who reported a verbal numeric rating scale (VNRS) pain score greater than or equal to 5. Exclusion criteria were younger than 18 years, known ketamine intolerance (...) , nontraumatic chest pain, altered mental status, pregnancy, and nasal occlusion. Patients received usual paramedic care and were randomized to receive either intranasal ketamine or intranasal saline solution at 0.75 mg/kg. The primary outcome was the proportion of patients with VNRS score reduction greater than or equal to 2 at 30 minutes. Secondary outcomes were pain reduction at 15 minutes, patient-reported comfort, satisfaction scores, nitrous oxide consumption, and incidence of adverse events.One

2019 Annals of Emergency Medicine Controlled trial quality: predicted high

123. 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

124. Increased Reactivity of the Mesolimbic Reward System after Ketamine Injection in Patients with Treatment-resistant Major Depressive Disorder. (PubMed)

Increased Reactivity of the Mesolimbic Reward System after Ketamine Injection in Patients with Treatment-resistant Major Depressive Disorder. The antidepressant effect of ketamine is associated with increased activity in the reward circuitry of the brain and a suppression of circuitry that mediates perceptual processing of negative emotions. The duration of ketamine effect on these brain structures remains to be defined.As expected, ketamine administration led to an improvement in mood (...) and global vigilance. The improvement in mood was accompanied by an increased recruitment of the orbitofrontal cortex, ventral striatum, medial substantial nigra and ventral tegmental area, structures that are part of the reward circuitry.Responses in the mesolimbic structures (amygdala, medial substantial nigra and ventral tegmental area, orbitofrontal cortex) to negative stimuli were decreased after ketamine administration.The data are consistent with the premise that ketamine induces sustained changes

2019 Anesthesiology

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

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

2019 Medicine

126. 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

127. Oral Ketamine for Depression, 1: Pharmacologic Considerations and Clinical Evidence. (Full text)

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

2019 Journal of Clinical Psychiatry

128. 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

129. Oral Ketamine for Depression, 2: Practical Considerations. (Full text)

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

2019 Journal of Clinical Psychiatry

130. Off-label use of ketamine for treatment-resistant depression in clinical practice: European perspective. (Full text)

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

2019 British Journal of Psychiatry

131. Intraoperative ketamine for prevention of postoperative delirium or pain after major surgery in older adults: an international, multicentre, double-blind, randomised clinical trial. (Full text)

Intraoperative ketamine for prevention of postoperative delirium or pain after major surgery in older adults: an international, multicentre, double-blind, randomised clinical trial. Delirium is a common and serious postoperative complication. Subanaesthetic ketamine is often administered intraoperatively for postoperative analgesia, and some evidence suggests that ketamine prevents delirium. The primary purpose of this trial was to assess the effectiveness of ketamine for prevention (...) of postoperative delirium in older adults.The Prevention of Delirium and Complications Associated with Surgical Treatments [PODCAST] study is a multicentre, international randomised trial that enrolled adults older than 60 years undergoing major cardiac and non-cardiac surgery under general anaesthesia. Using a computer-generated randomisation sequence we randomly assigned patients to one of three groups in blocks of 15 to receive placebo (normal saline), low-dose ketamine (0·5 mg/kg), or high dose ketamine (1

2017 Lancet Controlled trial quality: predicted high

132. Epidemiologic characteristics and risk factors in patients with ketamine-associated lower urinary tract symptoms accompanied by urinary tract infection: A cross-sectional study. (Full text)

Epidemiologic characteristics and risk factors in patients with ketamine-associated lower urinary tract symptoms accompanied by urinary tract infection: A cross-sectional study. Young adults with longstanding ketamine abuse present with lower urinary tract symptoms (LUTSs), which may be accompanied by urinary tract infection (UTI). However, the morbidity and risk factors for ketamine-associated LUTS accompanied by UTI (KALAUTI) are still unknown. To ascertain these, we surveyed patients (...) with a history of ketamine abuse and LUTS at the time of their initial presentation.One hundred untreated patients with ketamine-associated LUTS were initially surveyed at 3 medical institutions. The patients' basic demographic and clinical information, KALAUTI status, and possible risk factors were obtained via a questionnaire and analyzed.Eighty-one patients were finally enrolled. Eight patients (9.88%) had a definitive diagnosis of KALAUTI and 16 (19.75%) had suspected KALAUTI. The diagnosis of KALAUTI

2019 Medicine

133. Microglial production of quinolinic acid as a target and a marker of the antidepressant effect of ketamine. (Full text)

Microglial production of quinolinic acid as a target and a marker of the antidepressant effect of ketamine. Major depressive disorder is a complex multifactorial condition with a so far poorly characterized underlying pathophysiology. Consequently, the available treatments are far from satisfactory as it is estimated that up to 30% of patients are resistant to conventional treatment. Recent comprehensive evidence has been accumulated which suggests that inflammation may be implied (...) in the etiology of this disease. Here we investigated ketamine as an innovative treatment strategy due to its immune-modulating capacities. In a murine model of LPS-induced depressive-like behavior we demonstrated that a single dose of ketamine restores the LPS-induced depressive-like alterations. These behavioral effects are associated with i/ a reversal of anxiety and reduced self-care, ii/ a decrease in parenchymal cytokine production, iii/ a modulation of the microglial reactivity and iv/ a decrease

2019 Brain, behavior, and immunity

134. Intraoperative Ketamine in Total Knee Arthroplasty Does Not Decrease Pain and Narcotic Consumption: A Prospective Randomized Controlled Trial. (PubMed)

Intraoperative Ketamine in Total Knee Arthroplasty Does Not Decrease Pain and Narcotic Consumption: A Prospective Randomized Controlled Trial. Multiple studies have demonstrated that ketamine, a glutamate receptor blocker, may decrease postoperative pain in abdominal and orthopedic surgeries. However, its role with spinal anesthesia and total knee arthroplasty (TKA) remains unknown. The purpose of this study is to determine the efficacy of subanesthetic dosing of ketamine during TKA (...) on postoperative pain and narcotic consumption.In this prospective, randomized, double-blinded clinical trial, we enrolled 91 patients undergoing primary TKA with spinal anesthesia in a single institution from 2017 to 2018. Patients were randomized to receive intraoperative ketamine infusion at a rate of 6 mcg/kg/min for 75 minutes or a saline placebo. All patients received spinal anesthesia and otherwise identical surgical approaches, pain management, and rehabilitation protocols. Patient-reported visual

2019 Journal of Arthroplasty Controlled trial quality: predicted high

135. FentAnyl or placebo with KeTamine for emergency department rapid sequence intubation: The FAKT study protocol. (PubMed)

FentAnyl or placebo with KeTamine for emergency department rapid sequence intubation: The FAKT study protocol. Some critically ill patients require rapid sequence intubation in the emergency department, and ketamine is one sedative agent employed, due to its relative haemodynamic stability. Tachycardia and hypertension are frequent side effects, and in less stable patients, shock can be unmasked or exacerbated. The use of fentanyl as a co-induction agent may lead to a smoother haemodynamic (...) profile post-induction, which may lead to reduced mortality in this critically ill cohort. This randomised controlled trial aims to compare the effect of administering fentanyl vs placebo in a standardised induction regimen with ketamine and rocuronium on (a) the percentage of patients in each group with a systolic blood pressure outside the range of 100-150 mm Hg within 10 minutes of induction, (b) the laryngoscopic view, and (c) 30-day mortality.Three hundred patients requiring rapid sequence

2019 Acta Anaesthesiologica Scandinavica Controlled trial quality: predicted high

136. Efficacy of the ketamine metabolite (2R,6R)-hydroxynorketamine in mice models of pain. (PubMed)

Efficacy of the ketamine metabolite (2R,6R)-hydroxynorketamine in mice models of pain. Ketamine has been shown to reduce chronic pain; however, the adverse events associated with ketamine makes it challenging for use outside of the perioperative setting. The ketamine metabolite (2R,6R)-hydroxynorketamine ((2R,6R)-HNK) has a therapeutic effect in mice models of depression, with minimal side effects. The objective of this study is to determine if (2R,6R)-HNK has efficacy in both acute and chronic (...) mouse pain models.Mice were tested in three pain models: nerve-injury neuropathic pain, tibia fracture complex regional pain syndrome type-1 (CRPS1) pain, and plantar incision postoperative pain. Once mechanical allodynia had developed, systemic (2R,6R)-HNK or ketamine was administered as a bolus injection and compared with saline control in relieving allodynia.In all three models, 10 mg/kg ketamine failed to produce sustained analgesia. In the neuropathic pain model, a single intraperitoneal

2019 Regional Anesthesia and Pain Medicine

137. 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

138. 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

139. Does the addition of fentanyl to ketamine improve haemodynamics, intubating conditions or mortality in emergency department intubation: A systematic review. (Full text)

Does the addition of fentanyl to ketamine improve haemodynamics, intubating conditions or mortality in emergency department intubation: A systematic review. Ketamine is an induction agent frequently used for general anaesthesia in emergency medicine. Generally regarded as haemodynamically stable, it can cause hypertension and tachycardia and may cause or worsen shock. The effects of ketamine may be improved by the addition of fentanyl to the induction regime. We conducted a systematic review (...) to identify evidence with regard to the effect of adding fentanyl to an induction regime of ketamine and a paralysing agent on post-induction haemodynamics, intubating conditions and mortality.We conducted a search of the Cochrane library, EMBASE, MEDLINE, PROQUEST, OpenGrey and clinical trial registries. Prominent authors were contacted in order to identify additional literature pertinent to the research question. Studies were included if they pertained to intubation of adult patients in the prehospital

2019 Acta Anaesthesiologica Scandinavica

140. 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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