Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.833
Filtrar
1.
Anesth Prog ; 68(1): 3-9, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33827122

RESUMO

Precooperative children and patients with intellectual disabilities often require intramuscular (IM) sedation prior to the induction of general anesthesia (GA). Ketamine is an effective preinduction sedative but can produce significant adverse side effects. Dexmedetomidine, a sedative with sympatholytic and analgesic properties, may provide advantages when used in combination with ketamine. This retrospective study evaluated the efficacy and safety of IM ketamine with dexmedetomidine for preoperative sedation. We conducted a chart review of all patients (n = 105) treated for dental rehabilitation who received either IM ketamine and dexmedetomidine (study group, n = 74) or IM ketamine and midazolam (control group, n = 31) prior to induction of GA. No significant difference (p = .14) was observed in the time interval from IM administration to operating room entry (median [interquartile range]) between the study and control groups (5 [4-8] vs 5 [2-7] minutes). Patients who received IM dexmedetomidine exhibited significantly lower mean arterial pressures throughout the induction (p = .004) and had lower heart rates (p = .01) throughout the intraoperative period compared with patients who did not receive dexmedetomidine. The combination of dexmedetomidine and ketamine may provide effective and safe IM sedation prior to the induction of GA.


Assuntos
Dexmedetomidina , Ketamina , Criança , Dexmedetomidina/efeitos adversos , Humanos , Hipnóticos e Sedativos/efeitos adversos , Ketamina/efeitos adversos , Midazolam/efeitos adversos , Estudos Retrospectivos
2.
Medicine (Baltimore) ; 100(6): e24605, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33578565

RESUMO

ABSTRACT: Preoperative anxiety is a major problem in children leading to a poor outcome. Preanesthetic oral ketamine is generally used in children but has less bioavailability due to the first-pass effect. Even ketamine has an unpleasant taste. Preanesthetic inhaled ketamine is also reported effective and safe in children. The objectives of the study were to compare the effectiveness and safety of preanesthetic nebulized ketamine against preanesthetic oral ketamine for sedation and postoperative pain management in children.Children received 10 mg/kg oral ketamine (children received preanesthetic oral ketamine [OK cohort], n = 142), or nebulized with 3 mg/kg ketamine (children were preanesthetic nebulized with ketamine [NK cohort], n = 115), or received apple juice (children suspectable to preoperative ketamine and received apple juice only [OA cohort], n = 126) before anesthesia for elective surgery. Data regarding preoperative hemodynamic parameters, sedation score measurements, postoperative pain management, postoperative nausea and vomiting management, and postoperative complications were collected and analyzed.Preoperative hemodynamic parameters for oral and nebulized ketamine administration were stable. Nebulized ketamine was provided higher sedation than apple juice (P = .002, q = 4.859) and oral ketamine (P = .002, q = 3.526). Children of NK cohort had required fewer fentanyl consumption until discharge than those of OA (55.45 ±â€Š7.19 µG/ child vs 65.15 ±â€Š15.24 µG/ child, P < .0001, q = 9.859) and OK (55.45 ±â€Š7.19 µG/child vs 60.19 ±â€Š8.12 µG/child, P < .0001, q = 4.953) cohorts. Children of the NK cohort had consumed higher ondansetron syrup than those of the OA cohort but fewer than those of the OK cohort until discharge. Gastrointestinal side effects were reported in the OK cohort, and nose irritation and drowsiness were reported in the NK cohort.Like preanesthetic oral ketamine, preanesthetic inhaled ketamine also has safety for children. Preanesthetic inhaled ketamine can provide effective sedation in low doses during operation than preanesthetic oral ketamine.Level of evidence: III.


Assuntos
Analgésicos/administração & dosagem , Ketamina/administração & dosagem , Dor Pós-Operatória/prevenção & controle , Medicação Pré-Anestésica , Analgésicos/efeitos adversos , Antieméticos/administração & dosagem , Criança , Pré-Escolar , Procedimentos Cirúrgicos Eletivos , Feminino , Humanos , Ketamina/efeitos adversos , Masculino , Ondansetron/administração & dosagem , Náusea e Vômito Pós-Operatórios/induzido quimicamente , Náusea e Vômito Pós-Operatórios/prevenção & controle , Estudos Retrospectivos
4.
J Affect Disord ; 282: 160-164, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33418362

RESUMO

BACKGROUND: Dissociation is a treatment-emergent adverse event commonly associated with IV ketamine, often measured using the 23-item Clinician-Administered Dissociative States Scale (CADSS). The objective of this study was to develop a short form version of the CADSS for easier clinical use. METHODS: Retrospective data of 260 patients with treatment-resistant depression (TRD) receiving IV ketamine were randomly divided into two datasets. The first dataset (n = 130) was leveraged to develop a brief 6-item version of the CADSS (CADSS-6) based on items most sensitive to ketamine-induced dissociation. The CADSS-6 questions were then applied to the second dataset (n = 130) and the Spearman's correlation between the full-length CADSS and the CADSS-6 were assessed. RESULTS: The CADSS-6 was developed from questions 1, 2, 6, 7, 15, and 22 from the full length CADSS. There was a strong significant correlation between the CADSS-6 total score and the CADSS total score at infusions 1 (rs(106) = 0.92, p < 0.001), 2 (rs(100) = 0.91, p < 0.001), 3(rs(99) = 0.95, p < 0.001) and 4 (rs(102) = 0.94, p < 0.001). LIMITATIONS: The CADSS-6 was developed using a retrospective data; therefore, the scale remains unvalidated in this population. CONCLUSIONS: The CADSS-6 presented herein was sensitive to dissociation experienced by patients receiving IV ketamine. Overall, the CADSS-6 was strongly correlated at each infusion with the full-length CADSS. While future studies should look to validate the CADSS-6 in a TRD sample, this scale offers clinicians a brief assessment that can be used to characterize symptoms of dissociation.


Assuntos
Anestésicos , Transtorno Depressivo Maior , Transtorno Depressivo Resistente a Tratamento , Ketamina , Anestésicos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Transtornos Dissociativos/induzido quimicamente , Transtornos Dissociativos/diagnóstico , Transtornos Dissociativos/tratamento farmacológico , Humanos , Infusões Intravenosas , Ketamina/efeitos adversos , Estudos Retrospectivos
5.
Psychopharmacology (Berl) ; 238(4): 917-926, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33484298

RESUMO

Intravenous (IV) ketamine has been shown to have rapid and robust antidepressant effects in adults with treatment-resistant depression (TRD). Urological toxicity has been observed in chronic ketamine abusers as evidenced by dysuria, urgency, and hematuria. The foregoing observation provides the basis for evaluating whether ketamine-induced urological toxicity (KIUT) is associated with sub-anesthetic doses of ketamine (0.5-1.0 mg/kg) in adults with mood disorders. The overarching objective of this article is to identify potential mechanisms of KIUT which appears to be dose and frequency dependent. Available research indicates that high-frequency ketamine is associated with disruption of the urothelial barrier as well as direct ketamine toxicity (i.e., decreased expression of junction proteins) in KIUT of the bladder. Chronic and high-frequency ketamine use is also associated with bladder inflammation mediated via neurogenic and IgE inflammation. Other non-mutually exclusive causes are nerve hyperplasia, hypersensitivity, cell apoptosis, microvascular damage, and overexpression of carcinogenic genes. Notwithstanding the evidence of KIUT in ketamine abusers, there is no evidence that ketamine and/or esketamine treatment in adults with mood disorders is associated with KIUT. However, all patients receiving ketamine/esketamine for mood disorder treatment should be queried about genitourinary symptoms during acute and, where applicable, maintenance dosing.


Assuntos
Antidepressivos/uso terapêutico , Ketamina/administração & dosagem , Transtornos do Humor/tratamento farmacológico , Adulto , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Humanos , Ketamina/efeitos adversos
6.
J Affect Disord ; 278: 542-555, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33022440

RESUMO

BACKGROUND: 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. OBJECTIVES: This study aimed to assess the comparative efficacy and tolerability of racemic and esketamine for the treatment of unipolar and bipolar major depression. DESIGN: Systematic review and meta-analysis. DATA SOURCES: We searched PubMed, MEDLINE, Embase, PsycINFO, the Cochrane Central Register of Controlled Clinical Trials, and the Cochrane Database of Systematic Reviews for relevant studies published since database inception and December 17, 2019. STUDY ELIGIBILITY CRITERIA: We considered randomized controlled trials examining racemic or esketamine for the treatment of unipolar or bipolar major depression. OUTCOMES: Primary outcomes were response and remission from depression, change in depression severity, suicidality, retention in treatment, drop-outs, and drop-outs due to adverse events. ANALYSIS: 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. FINDINGS: 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 as lower dropouts (RR = 0.76 vs. RR = 1.37). CONCLUSIONS: Intravenous ketamine appears to be more efficacious than intranasal esketamine for the treatment of depression.


Assuntos
Transtorno Depressivo Maior , Ketamina , Antidepressivos/uso terapêutico , Depressão , Transtorno Depressivo Maior/tratamento farmacológico , Humanos , Ketamina/efeitos adversos
7.
Expert Opin Drug Saf ; 20(2): 123-138, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33327811

RESUMO

Introduction: Management of patients with acute agitation or aggressive behavior can pose a significant challenge to health-care providers in emergency departments. Areas covered: This article provides a comprehensive review of the pharmacologic properties, efficacy, and safety profiles of select intramuscular (IM) sedative agents (i.e., antipsychotics, benzodiazepines, and ketamine) for rapid tranquilization. Expert opinion: Using antipsychotics and benzodiazepines - whether a single agent or combined - will have similar efficacy in producing sedation. But there are differences in the time to sedation depending on which agent is used. Based upon the available studies, droperidol (5-10 mg IM) and midazolam (5-10 mg IM) have the fastest onset of sedation when either is used as a single agent. When combination therapy is used, using midazolam with an antipsychotic agent, instead of lorazepam, may result in faster sedative effect. QT prolongation and torsades de pointes are uncommon adverse drug effects of antipsychotic administration. Ketamine is often reserved as a second-line agent when antipsychotics and benzodiazepines fail to produce the desired tranquilization. However, ketamine (5 mg/kg IM) is more frequently associated with airway compromise requiring endotracheal intubation. A low-dose of ketamine (2 mg/kg IM) may reduce the risk of airway compromise while providing adequate sedation.


Assuntos
Agressão/efeitos dos fármacos , Delírio/tratamento farmacológico , Agitação Psicomotora/tratamento farmacológico , Doença Aguda , Antipsicóticos/administração & dosagem , Antipsicóticos/efeitos adversos , Benzodiazepinas/administração & dosagem , Benzodiazepinas/efeitos adversos , Serviço Hospitalar de Emergência , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Antagonistas de Aminoácidos Excitatórios/efeitos adversos , Humanos , Ketamina/administração & dosagem , Ketamina/efeitos adversos
9.
Psychiatr Danub ; 32(3-4): 325-333, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33370729

RESUMO

Major depressive disorder is the greatest burden of developed countries in the context of morbidity caused by mental disorders. Until recent, ketamine has been mostly used for anesthesia, analgesia, sedation and treatment of chronic pain syndromes. However, unique pharmacodynamic properties of ketamine have increased interests in it's use for treatment of depression. It is assumed that ketamine reverses synaptic chronic stress pathology within one day of administration by postsynaptic glutamate activation, providing synaptic connectivity restoration that last for days or weeks. Potential glutamatergic agents, in context of treatment of major depressive disorder are not entirely novel phenomenon. Considering the aforementioned, current neurobiological view of depression as a solely monoaminergic phenomenon should be reassessed in order to prompt discovery of putative antidepressant drugs of novel generation. Acute side effects, such as increased salivation, increase in heart rate, systemic arterial pressure and intracranial pressure necessitate careful monitoring during intravenous administration of ketamine, even in subanesthetic doses. However, major burden of ketamine administration lies in it's ability to produce psychotomimetic side effects and emergence delirium. Esketamine nasal spray has now been widely approved and is considered safe in terms of acute side effects, tolerability and consistent therapeutic benefit.


Assuntos
Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Ketamina/farmacologia , Ketamina/uso terapêutico , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/metabolismo , Interações Medicamentosas , Epigênese Genética/efeitos dos fármacos , Ácido Glutâmico/metabolismo , Humanos , Ketamina/efeitos adversos , Ketamina/química
10.
PLoS One ; 15(9): e0236430, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32956357

RESUMO

Rhesus macaques represent an important species for translational and pre-clinical research studies across a multitude of disease and injury models, including aging. Ketamine anesthesia is used in humans and non-human primates but may be associated with adverse effects, including neuromuscular reactions. The effects of aging on ketamine adverse effects is not well characterized. Urodynamic recordings and electromyography (EMG) studies were performed in aged (>20 years old) and adult (3.9-14.9 years old) female rhesus macaques under an equal and light plane of sedation by constant rate infusion (CRI) of ketamine. A total of 4 of 41 adult subjects (9.7%) showed clinical signs of ketamine-induced abnormal neuromuscular reactivity, whereas a larger portion of 14 of 26 aged subjects showed similar ketamine-induced neuromuscular reactivity (53.8%; P< 0.001). The ketamine CRI rate was 19.8±0.9 mg/kg/h in adults and lower in aged subjects at 16.5±1.4 mg/kg/h (P<0.05). The ketamine CRI rate was negatively correlated with age (r = -0.30, P<0.05, n = 64). The incidence of ketamine reactivity or CRI rate was not different between aged pre-and post-menopausal females. EMG recordings during neuromuscular reactivity showed coordinated activation of multiple muscles, suggesting a central nervous system (CNS) mechanism for ketamine-associated neuromuscular reactivity. The incidence of ketamine-induced neuromuscular reactivity is age related but not affected by the estrous cycle in female rhesus macaques. A coordinated activation of multiple muscles, innervated by different peripheral nerves, suggests that ketamine-induced neuromuscular reactivity originates in the CNS.


Assuntos
Envelhecimento , Anestésicos Dissociativos/efeitos adversos , Ketamina/efeitos adversos , Macaca mulatta/fisiologia , Músculos/efeitos dos fármacos , Envelhecimento/efeitos dos fármacos , Animais , Eletromiografia , Feminino , Músculos/inervação , Músculos/fisiologia
11.
Nat Commun ; 11(1): 4328, 2020 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-32859919

RESUMO

The general anesthetic ketamine has been repurposed by physicians as an anti-depressant and by the public as a recreational drug. However, ketamine use can cause extensive pathological changes, including ketamine cystitis. The mechanisms of ketamine's anti-depressant and adverse effects remain poorly understood. Here we present evidence that ketamine is an effective L-type Ca2+ channel (Cav1.2) antagonist that directly inhibits calcium influx and smooth muscle contractility, leading to voiding dysfunction. Ketamine prevents Cav1.2-mediated induction of immediate early genes and transcription factors, and inactivation of Cav1.2 in smooth muscle mimics the ketamine cystitis phenotype. Our results demonstrate that ketamine inhibition of Cav1.2 signaling is an important pathway mediating ketamine cystitis. In contrast, Cav1.2 agonist Bay k8644 abrogates ketamine-induced smooth muscle dysfunction. Indeed, Cav1.2 activation by Bay k8644 decreases voiding frequency while increasing void volume, indicating Cav1.2 agonists might be effective drugs for treatment of bladder dysfunction.


Assuntos
Ketamina/efeitos adversos , Transdução de Sinais/efeitos dos fármacos , Animais , Cálcio/metabolismo , Canais de Cálcio Tipo L/efeitos dos fármacos , Canais de Cálcio Tipo L/genética , Proliferação de Células , Cistite/induzido quimicamente , Modelos Animais de Doenças , Humanos , Rim/efeitos dos fármacos , Rim/patologia , Camundongos , Camundongos Knockout , Músculo Liso/efeitos dos fármacos , Músculo Liso/metabolismo , Músculo Liso/patologia , Oócitos , Receptores de N-Metil-D-Aspartato/efeitos dos fármacos , Bexiga Urinária/patologia , Xenopus
12.
Adv Pharmacol ; 89: 131-162, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32616205

RESUMO

Major depressive disorder (MDD) is a debilitating illness with significant morbidity and mortality, leading to attempted and completed suicides. It affects interpersonal relationships and also contributes to decreased productivity, causing financial burden to individuals and society. Patients often fail to respond to various antidepressant medication trials resulting in treatment-resistant depression (TRD). Current antidepressant medications work by modulating the monoaminergic systems and takes several weeks to establish a clinical response. Ketamine has been used extensively as an anesthetic agent since the 1970s, and more recent research has shown its rapid and robust effectiveness in TRD the subject of this review. Ketamine is a racemic mixture comprised of two enantiomers (R)-ketamine and (S)-ketamine and acts as an NMDA receptor antagonist. Most research studies have explored its antidepressant and antisuicidal effects by using it as an intravenous infusion or via the intranasal route due to increased bioavailability. Recently an intranasal esketamine spray was approved by the United States Food and Drug Administration (FDA) for TRD as an adjunct to standard antidepressant treatment in a supervised setting. Regarding its safety profile, multiple research studies have established the short-term safety and efficacy of ketamine in TRD. The cardiorespiratory and neuropsychiatric adverse events observed in these studies were mostly transient. However, ketamine is a scheduled agent with abuse potential, making its long-term use challenging and mandating further research.


Assuntos
Depressão/tratamento farmacológico , Ketamina/uso terapêutico , Antidepressivos/uso terapêutico , Humanos , Ketamina/administração & dosagem , Ketamina/efeitos adversos , Ketamina/metabolismo , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptores de N-Metil-D-Aspartato/metabolismo , Suicídio
13.
Adv Pharmacol ; 89: 237-259, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32616208

RESUMO

Major depressive disorder (MDD) is the leading cause of disability worldwide and reduces life expectancy. Achieving and sustaining remission from depression is challenging after initial improvement of an acute episode with an antidepressant, especially for patients whose depressive episodes have proven treatment-resistant in response to conventional antidepressant pharmacotherapy. While standard antidepressants are at least partly effective for the short-term treatment of acute depressive episodes of MDD, many patients relapse within 6 months of apparent clinical remission, with faster and higher rates observed in those with treatment-resistant depression (TRD). Efficacy of IV ketamine, a rapid-acting N-methyl d-aspartate (NMDA) receptor antagonist, in maintaining antidepressant effect was suggested in a few small, single center, open-label studies and case series. More recently, maintenance of antidepressant effects beyond the initial acute (induction) treatment period has been shown with esketamine nasal spray, an enantiomer of ketamine, in conjunction with an oral antidepressant in three phase 2/3 registration studies (SYNAPSE, SUSTAIN-1, SUSTAIN-2) of adult patients with TRD. In these studies the maintenance of efficacy of an intermittently-dosed esketamine treatment regimen was established in which twice-weekly dose administration during a 4-week induction period was followed initially by weekly administration and later by either weekly or every-other-week administration. During long-term maintenance therapy the antidepressant effect persisted in most patients with this regimen, despite their history of being resistant to conventional antidepressants prior to entering esketamine studies. These data suggest that the neurobiological changes induced by initial esketamine treatment, which putatively underlie its antidepressant effect, can be maintained using repeated administration.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Prevenção Secundária , Antidepressivos/farmacologia , Ensaios Clínicos como Assunto , Humanos , Ketamina/administração & dosagem , Ketamina/efeitos adversos , Ketamina/uso terapêutico
14.
Adv Pharmacol ; 89: 261-286, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32616209

RESUMO

A serious lack of effective pharmacotherapeutic interventions for posttraumatic stress disorder (PTSD) raises the urgent need for the development of novel treatments. Ketamine-a noncompetitive glutamate N-methyl-d-aspartate (NMDA) receptor antagonist in use for decades as an anesthetic and analgesic agent-has more recently been demonstrated to have rapid-onset antidepressant effects in patients with treatment-resistant depression (TRD). In the present review of ketamine as an emerging novel pharmacotherapeutic intervention for chronic PTSD, we discuss findings from the first proof-of-concept, randomized clinical trial (RCT) of single-dose intravenous ketamine in patients with chronic PTSD, as well as open-label studies and current practice. We introduce ongoing RCTs investigating the efficacy of repeated ketamine infusions in rapidly reducing symptoms and maintaining improvement in samples of individuals with PTSD stemming from civilian and military traumas. Additionally, we discuss mixed findings from published reports on ketamine administration in the acute aftermath of trauma. Studies in animal models of chronic stress have investigated molecular mechanisms underlying ketamine's effects, generating a shift in the conceptualization of PTSD as a disorder of impaired neural connectivity. We review animal studies examining the potential of ketamine to modify the expression of fear by altering memory reconsolidation or enhancing fear extinction, as well as others investigating ketamine administration prophylactically prior to stress exposure. We introduce the need for additional study in humans to evaluate whether ketamine might enhance the efficacy of psychotherapeutic interventions in individuals with chronic PTSD, harnessing a window of ketamine-induced neuroplasticity. While research on ketamine for PTSD is still in its early stages, it brings about the promise of novel and more effective treatments for this disabling condition.


Assuntos
Ketamina/uso terapêutico , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Animais , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Modelos Animais de Doenças , Humanos , Ketamina/administração & dosagem , Ketamina/efeitos adversos , Ketamina/farmacologia , Padrões de Prática Médica , Ensaios Clínicos Controlados Aleatórios como Assunto , Transtornos de Estresse Pós-Traumáticos/terapia
15.
Sci Rep ; 10(1): 9440, 2020 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-32528071

RESUMO

Ketamine is a valuable anaesthetic and analgesic that in recent years has gained notoriety as a recreational drug. Recently, ketamine has also been proposed as a novel treatment for depression and post-traumatic stress disorder. Beyond its anaesthetic actions, however, the effects of ketamine on brain activity have rarely been probed. Here we examined the cortical electroencephalography (EEG) response to ketamine of 12 sheep. Following ketamine administration, EEG changes were immediate and widespread, affecting the full extent of the EEG frequency spectrum measured (0-125 Hz). After recovery from sedation during which low frequency activity dominated, the EEG was characterised by short periods (2-3 s) of alternating low (<14 Hz) and high (>35 Hz) frequency oscillation. This alternating EEG rhythm phase is likely to underlie the dissociative actions of ketamine, since it is during this phase that ketamine users report hallucinations. At the highest intravenous dose used (24 mg/kg), in 5/6 sheep we observed a novel effect of ketamine, namely the complete cessation of cortical EEG activity. This persisted for up to several minutes, after which cortical activity resumed. This phenomenon is likely to explain the 'k-hole', a state of oblivion likened to a near death experience that is keenly sought by ketamine abusers.


Assuntos
Eletroencefalografia/efeitos dos fármacos , Ketamina/administração & dosagem , Ketamina/efeitos adversos , Psicotrópicos/administração & dosagem , Psicotrópicos/efeitos adversos , Anestésicos Dissociativos/administração & dosagem , Anestésicos Dissociativos/efeitos adversos , Animais , Encéfalo/efeitos dos fármacos , Alucinações/induzido quimicamente , Humanos , Ovinos
16.
Psychosomatics ; 61(5): 544-550, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32591212

Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Antipsicóticos/uso terapêutico , Infecções por Coronavirus/terapia , Delírio/tratamento farmacológico , Hipnóticos e Sedativos/efeitos adversos , Pneumonia Viral/terapia , Agitação Psicomotora/tratamento farmacológico , Medicamentos Indutores do Sono/uso terapêutico , Idoso , Analgésicos Opioides/efeitos adversos , Azepinas/uso terapêutico , Betacoronavirus , Depressores do Sistema Nervoso Central/uso terapêutico , Clordiazepóxido/efeitos adversos , Infecções por Coronavirus/complicações , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/psicologia , Delírio/etiologia , Delírio/fisiopatologia , Delírio/psicologia , Dexmedetomidina/efeitos adversos , Feminino , Guanfacina/uso terapêutico , Haloperidol/uso terapêutico , Humanos , Hidromorfona/efeitos adversos , Unidades de Terapia Intensiva , Ketamina/efeitos adversos , Melatonina/uso terapêutico , Midazolam/efeitos adversos , Oxicodona/efeitos adversos , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/fisiopatologia , Pneumonia Viral/psicologia , Propofol/efeitos adversos , Agitação Psicomotora/etiologia , Agitação Psicomotora/fisiopatologia , Agitação Psicomotora/psicologia , Respiração Artificial , Transtornos do Sono do Ritmo Circadiano/tratamento farmacológico , Transtornos do Sono do Ritmo Circadiano/etiologia , Transtornos do Sono do Ritmo Circadiano/fisiopatologia , Traqueostomia , Triazóis/uso terapêutico , Ácido Valproico/uso terapêutico
17.
Anesthesiology ; 133(1): 154-164, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32384291

RESUMO

BACKGROUND: Ketamine is often used for the management of refractory chronic pain. There is, however, a paucity of trials exploring its analgesic effect several weeks after intravenous administration or in association with magnesium. The authors hypothesized that ketamine in neuropathic pain may provide pain relief and cognitive-emotional benefit versus placebo and that a combination with magnesium may have an additive effect for 5 weeks. METHODS: A randomized, double-blind, crossover, placebo-controlled study (NCT02467517) included 20 patients with neuropathic pain. Each ketamine-naïve patient received one infusion every 35 days in a random order: ketamine (0.5 mg/kg)/placebo or ketamine (0.5 mg/kg)/magnesium sulfate (3g) or placebo/placebo.The primary endpoint was the area under the curve of daily pain intensity for a period of 35 days after infusion. Secondary endpoints included pain (at 7, 15, 21 and 28 days) and health-related, emotional, sleep, and quality of life questionnaires. RESULTS: Daily pain intensity was not significantly different between the three groups (n = 20) over 35 days (mean area under the curve = 185 ± 100, 196 ± 92, and 187 ± 90 pain score-days for ketamine, ketamine/magnesium, and placebo, respectively, P = 0.296). The effect size of the main endpoint was -0.2 (95% CI [-0.6 to 0.3]; P = 0.425) for ketamine versus placebo, 0.2 (95% CI [-0.3 to 0.6]; P = 0.445) for placebo versus ketamine/magnesium and -0.4 (95% CI [-0.8 to 0.1]; P = 0.119) for ketamine versus ketamine/magnesium. There were no significant differences in emotional, sleep, and quality of life measures. During placebo, ketamine, and ketamine/magnesium infusions, 10%, 20%, and 35% of patients respectively reported at least one adverse event. CONCLUSIONS: The results of this trial in neuropathic pain refuted the hypothesis that ketamine provided pain relief at 5 weeks and cognitive-emotional benefit versus placebo and that a combination with magnesium had any additional analgesic effect.


Assuntos
Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Ketamina/uso terapêutico , Sulfato de Magnésio/uso terapêutico , Neuralgia/tratamento farmacológico , Adulto , Idoso , Cognição/efeitos dos fármacos , Estudos Cross-Over , Método Duplo-Cego , Quimioterapia Combinada , Emoções , Antagonistas de Aminoácidos Excitatórios/efeitos adversos , Feminino , Humanos , Infusões Intravenosas , Ketamina/efeitos adversos , Sulfato de Magnésio/efeitos adversos , Masculino , Pessoa de Meia-Idade , Neuralgia/psicologia , Medição da Dor/efeitos dos fármacos , Resultado do Tratamento
18.
J Clin Psychiatry ; 81(3)2020 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-32412700

RESUMO

OBJECTIVE: To compare esketamine to placebo, each in addition to standard-of-care treatment, for rapidly reducing major depressive disorder symptoms, including suicidal ideation. METHODS: This phase 3, double-blind, multicenter study (ASPIRE I), conducted between June 2017 and December 2018, enrolled 226 adults having major depressive disorder based on Diagnostic and Statistical Manual of Mental Disorders fifth edition (DSM-5) criteria, active suicidal ideation with intent, and need for psychiatric hospitalization. Patients were randomized 1:1 to esketamine 84 mg or placebo nasal spray twice-weekly for 4 weeks, each with comprehensive standard-of-care treatment (initial psychiatric hospitalization and newly initiated or optimized oral antidepressant[s] therapy). Change from baseline to 24 hours post-first dose in Montgomery-Asberg Depression Rating Scale (MADRS) total score (primary endpoint) was analyzed using analysis of covariance (ANCOVA), and change in Clinical Global Impression of Severity of Suicidality Revised version (CGI-SS-r; key secondary endpoint) score was analyzed using ANCOVA on ranks with treatment difference estimated using the Hodges-Lehmann estimate. RESULTS: Greater improvement in MADRS total score was observed with esketamine + standard-of-care versus placebo + standard-of-care at 24 hours (least-squares mean difference [SE]: -3.8 [1.39]; 95% CI, -6.56 to -1.09; 2-sided P = .006), as well as at earlier (4 hours) and later time points during 4-week double-blind treatment. The difference between groups in the severity of suicidality was not statistically significant (median of treatment difference [95% CI]: 0.0 [-1.00 to 0.00]; 2-sided P = .107). The most common adverse events among esketamine-treated patients were dizziness, dissociation, headache, nausea, and somnolence. CONCLUSIONS: These findings demonstrate rapid and robust efficacy of esketamine nasal spray in reducing depressive symptoms in severely ill patients with major depressive disorder who have active suicidal ideation with intent. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03039192.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Ketamina/uso terapêutico , Ideação Suicida , Administração Intranasal , Adolescente , Adulto , Antidepressivos/administração & dosagem , Antidepressivos/efeitos adversos , Transtorno Depressivo Maior/psicologia , Método Duplo-Cego , Feminino , Humanos , Ketamina/administração & dosagem , Ketamina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Sprays Nasais , Adulto Jovem
19.
J Clin Psychiatry ; 81(3)2020 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-32316080

RESUMO

OBJECTIVE: To evaluate long-term safety and efficacy of esketamine nasal spray plus a new oral antidepressant (OAD) in patients with treatment-resistant depression (TRD). METHODS: This phase 3, open-label, multicenter, long-term (up to 1 year) study was conducted between October 2015 and October 2017. Patients (≥ 18 years) with TRD (DSM-5 diagnosis of major depressive disorder and nonresponse to ≥ 2 OAD treatments) were enrolled directly or transferred from a short-term study (patients aged ≥ 65 years). Esketamine nasal spray (28-mg, 56-mg, or 84-mg) plus new OAD was administered twice a week in a 4-week induction (IND) phase and weekly or every-other-week for patients who were responders and entered a 48-week optimization/maintenance (OP/MAINT) phase. RESULTS: Of 802 enrolled patients, 86.2% were direct-entry and 13.8% were transferred-entry; 580 (74.5%) of 779 patients who entered the IND phase completed the phase, and 150 (24.9%) of 603 who entered the OP/MAINT phase completed the phase. Common treatment-emergent adverse events (TEAEs) were dizziness (32.9%), dissociation (27.6%), nausea (25.1%), and headache (24.9%). Seventy-six patients (9.5%) discontinued esketamine due to TEAEs. Fifty-five patients (6.9%) experienced serious TEAEs. Most TEAEs occurred on dosing days, were mild or moderate in severity, and resolved on the same day. Two deaths were reported; neither was considered related to esketamine. Cognitive performance generally either improved or remained stable postbaseline. There was no case of interstitial cystitis or respiratory depression. Treatment-emergent dissociative symptoms were transient and generally resolved within 1.5 hours postdose. Montgomery-Åsberg Depression Rating Scale total score decreased during the IND phase, and this reduction persisted during the OP/MAINT phase (mean [SD] change from baseline of respective phase to endpoint: IND, -16.4 [8.76]; OP/MAINT, 0.3 [8.12]). CONCLUSIONS: Long-term esketamine nasal spray plus new OAD therapy had a manageable safety profile, and improvements in depression appeared to be sustained in patients with TRD. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02497287.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Ketamina/uso terapêutico , Administração Intranasal , Administração Oral , Adolescente , Adulto , Idoso , Antidepressivos/administração & dosagem , Cognição/efeitos dos fármacos , Quimioterapia Combinada , Feminino , Humanos , Ketamina/administração & dosagem , Ketamina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Sprays Nasais , Adulto Jovem
20.
Am J Emerg Med ; 38(7): 1544.e5-1544.e6, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32317201

RESUMO

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 and oriented. An X-ray demonstrated an acute comminuted nondisplaced right humeral head and neck fracture. Her pain improved after an additional 4 mg of morphine and placement of a sling. Prior to discharge, the patient developed confusion, difficulty finding words, amnesia to the event, and anterograde amnesia evidenced by repetitive questioning. A head CT and a CT angiogram of the patient's head and neck demonstrated no acute abnormalities and an EEG demonstrated no epileptiform activity. The patient 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.


Assuntos
Analgésicos/administração & dosagem , Analgésicos/efeitos adversos , Anemia/induzido quimicamente , Ketamina/administração & dosagem , Ketamina/efeitos adversos , Acidentes por Quedas , Idoso , Relação Dose-Resposta a Droga , Serviços Médicos de Emergência , Feminino , Humanos , Dor/tratamento farmacológico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...