Ketamine offers promising new therapeutic options for difficult-to-treat depression. The efficacy of treatment response, including ketamine, has been intricately linked to EEG measures of vigilance. This research investigated the interplay between intravenous ketamine and alterations in brain arousal, quantified through EEG vigilance assessments in two distinct cohorts of depressed patients (original dataset: n = 24; testing dataset: n = 24). Clinical response was defined as a decrease from baseline of >33% on the Montgomery-Åsberg Depression Rating Scale (MADRS) 24 h after infusion. EEG recordings were obtained pre-, start-, end- and 24 h post- infusion, and the resting EEG was automatically scored using the Vigilance Algorithm Leipzig (VIGALL). Relative to placebo (sodium chloride 0.9%), ketamine increased the amount of low-vigilance stage B1 at end-infusion. This increase in B1 was positively related to serum concentrations of ketamine, but not to norketamine, and was independent of clinical response. In contrast, treatment responders showed a distinct EEG pattern characterized by a decrease in high-vigilance stage A1 and an increase in low-vigilance B2/3, regardless of whether placebo or ketamine had been given. Furthermore, pretreatment EEG differed between responders and non-responders with responders showing a higher percentage of stage A1 (53% vs. 21%). The logistic regression fitted on the percent of A1 stages was able to predict treatment outcomes in the testing dataset with an area under the ROC curve of 0.7. Ketamine affects EEG vigilance in a distinct pattern observed only in responders. Consequently, the percentage of pretreatment stage A1 shows significant potential as a predictive biomarker of treatment response.Clinical Trials Registration: https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-000952-17/CZ Registration number: EudraCT Number: 2013-000952-17.

• MeSH
• bdění MeSH
• depresivní porucha unipolární * farmakoterapie   MeSH
• elektroencefalografie MeSH
• ketamin * farmakologie   terapeutické užití   MeSH
• lidé MeSH
• mozek MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ketamin * MeSH

Ketamine exerts anti-inflammatory, neuroprotective and neuroplastic activity, therefore it may counteract the neurotoxic processes underlying postoperative delirium. However, the majority of studies in this field failed. We identified several pharmacological reasons why these studies may have failed, together with suggestions of how to remediate them. Among them, the interaction with intravenous general anesthetics exerting the opposite effect on GABA interneurons than ketamine may be of principal importance. We suggest biomarkers which may elucidate the influence of this interaction on the different steps of neuroplastic pathways. We hypothesize that administering ketamine before or after general anesthesia could both prevent the interactions and strengthen the effect of ketamine by timing surgery within the climax of ketamine-induced neuroplastic changes or by stabilizing AMPA receptors. It is vital to deal with these questions because the protocols of ongoing studies are based again on the administration of ketamine during general anesthesia (the major identified pitfall).

• Klíčová slova
• Anesthesia, Benzodiazepines, Ketamine, Neuroplastic, Neuroprotective, Pharmacological interaction, Postoperative delirium,
• MeSH
• anestetika celková * MeSH
• anestetika disociativní MeSH
• anestetika intravenózní MeSH
• celková anestezie MeSH
• ketamin * terapeutické užití   MeSH
• lidé MeSH
• pooperační delirium * farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• anestetika celková * MeSH
• anestetika disociativní MeSH
• anestetika intravenózní MeSH
• ketamin * MeSH

Depression is disabling and highly prevalent. Intravenous (IV) ketamine displays rapid-onset antidepressant properties, but little is known regarding which patients are most likely to benefit, limiting personalized prescriptions. We identified randomized controlled trials of IV ketamine that recruited individuals with a relevant psychiatric diagnosis (e.g., unipolar or bipolar depression; post-traumatic stress disorder), included one or more control arms, did not provide any other study-administered treatment in conjunction with ketamine (although clinically prescribed concurrent treatments were allowable), and assessed outcome using either the Montgomery-Åsberg Depression Rating Scale or the Hamilton Rating Scale for Depression (HRSD-17). Individual patient-level data for at least one outcome was obtained from 17 of 25 eligible trials [pooled n = 809]. Rates of participant-level data availability across 33 moderators that were solicited from these 17 studies ranged from 10.8% to 100% (median = 55.6%). After data harmonization, moderators available in at least 40% of the dataset were tested sequentially, as well as with a data-driven, combined moderator approach. Robust main effects of ketamine on acute [~24-hours; β*(95% CI) = 0.58 (0.44, 0.72); p < 0.0001] and post-acute [~7 days; β*(95% CI) = 0.38 (0.23, 0.54); p < 0.0001] depression severity were observed. Two study-level moderators emerged as significant: ketamine effects (relative to placebo) were larger in studies that required a higher degree of previous treatment resistance to federal regulatory agency-approved antidepressant medications (≥2 failed trials) for study entry; and in studies that used a crossover design. A comprehensive data-driven search for combined moderators identified statistically significant, but modest and clinically uninformative, effects (effect size r ≤ 0.29, a small-medium effect). Ketamine robustly reduces depressive symptoms in a heterogeneous range of patients, with benefit relative to placebo even greater in patients more resistant to prior medications. In this largest effort to date to apply precision medicine approaches to ketamine treatment, no clinical or demographic patient-level features were detected that could be used to guide ketamine treatment decisions.Review Registration: PROSPERO Identifier: CRD42021235630.

• MeSH
• antidepresiva terapeutické užití   MeSH
• bipolární porucha * farmakoterapie   MeSH
• deprese farmakoterapie   MeSH
• intravenózní podání MeSH
• ketamin * terapeutické užití   MeSH
• lidé MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• antidepresiva MeSH
• ketamin * MeSH

OBJECTIVE: Ketamine has been shown to be effective in treatment of episodes of major depressive disorder (MDD). This controlled study aimed to analyse the predictive and discriminative power of heart rate (HR) and heart rate variability (HRV) for ketamine treatment in MDD. METHODS: In 51 patients, HR and HRV were assessed at baseline before and during ketamine infusion and 24 hours post ketamine infusion. Montgomery-Åsberg Depression Rating Scale (MADRS) was used to assess changes of depressive symptoms. A 30% or 50% reduction of symptoms after 24 hours or within 7 days was defined as response. A linear mixed model was used for analysis. RESULTS: Ketamine infusion increased HR and HRV power during and after infusion. Responders to ketamine showed a higher HR during the whole course of investigation, including at baseline with medium effect sizes (Cohen's d = 0.47-0.67). Furthermore, HR and HRV power discriminated between responders and non-responders, while normalized low and high frequencies did not. CONCLUSION: The findings show a predictive value of HR and HRV power for ketamine treatment. This further underlines the importance of the autonomous nervous system (ANS) and its possible malfunctions in MDD. SIGNIFICANCE: The predictive power of HR and HRV markers should be studied in prospective studies. Neurophysiological markers could improve treatment for MDD via optimizing the choice of treatments.

• Klíčová slova
• Electrocardiogram, Heart rate variability, Ketamine, Major Depression, Prediction,
• MeSH
• antidepresiva terapeutické užití   MeSH
• depresivní porucha unipolární farmakoterapie   patofyziologie   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• ketamin terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prospektivní studie MeSH
• srdeční frekvence fyziologie   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• antidepresiva MeSH
• ketamin MeSH

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 larger effect under midazolam than saline (t(111) = 5.40, p < 0.0001), whereas there was no difference between ketamine (midazolam) versus ketamine (saline) (t(177) = 0.65, p = 0.51). Model-estimated rates of response (with 95% CI) yielded similar results: ketamine (midazolam), 45% (34-56%); ketamine (saline), 46% (34-58%); midazolam, 18% (6-30%); saline, 1% (0-11%). The response rate for ketamine was higher than the control condition for both saline (t(353) = 7.41, p < 0.0001) and midazolam (t(353) = 4.59, p < 0.0001). Studies that used midazolam as a comparator yielded smaller effects of ketamine than those which used saline, which was accounted for by greater improvement following midazolam compared to saline.

• MeSH
• antidepresiva terapeutické užití   MeSH
• bipolární porucha farmakoterapie   MeSH
• depresivní porucha unipolární farmakoterapie   MeSH
• dospělí MeSH
• ketamin terapeutické užití   MeSH
• klinické zkoušky jako téma MeSH
• lidé středního věku MeSH
• lidé MeSH
• midazolam terapeutické užití   MeSH
• solný roztok aplikace a dávkování   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• antidepresiva MeSH
• ketamin MeSH
• midazolam MeSH
• solný roztok MeSH

OBJECTIVES: Ketamine and other NMDA (N-methyl-D-aspartate) antagonists produce fast-acting antidepressant-like effects, although the underlying mechanism is unclear. Furthermore, high affinity NMDA antagonists such as ketamine are associated with psychotomimetic effects. To date the link between the antidepressant and psychotomimetic effects of ketamine has not been explored. We examined the relationship between the antidepressant and psychotomimetic effects of a single ketamine infusion in subjects diagnosed with major depressive disorder. METHODS: In a double-blind, cross-over, placebo-controlled, two weeks clinical trial we studied the effects of ketamine (0.54 mg/kg within 30 min) in a group of 27 hospitalized depressive patients. RESULTS: Higher intensity of psychotomimetic symptoms, measured using BPRS, during ketamine administration correlated with alleviation in mood ratings during the following week with maximum on day seven. Ketamine was superior to placebo in all visits (day 1, 4, and 7) assessed by MADRS with effect size (Cohen´s d) of 0.62, 0.57, and 0.44 respectively. There was no significant correlation between ketamine and nor-ketamine plasma levels and MADRS score change at any study time point. CONCLUSION: The substantial relationship between ketamine's antidepressant and psychotomimetic effects was found. This relationship could be mediated by the initial steps of ketamine's action, trough NMDA receptors, shared by both ketamine's clinical effects.

• MeSH
• antidepresiva terapeutické užití   MeSH
• depresivní porucha unipolární farmakoterapie   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• halucinogeny terapeutické užití   MeSH
• intravenózní infuze MeSH
• ketamin terapeutické užití   MeSH
• klinické křížové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• receptory N-methyl-D-aspartátu antagonisté a inhibitory   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• antidepresiva MeSH
• halucinogeny MeSH
• ketamin MeSH
• receptory N-methyl-D-aspartátu MeSH

OBJECTIVES: Ketamine, noncompetitive antagonist of N-methyl-D-aspartate (NMDA) receptors, has been used in the treatment of chronic neuropathic pain for almost 15 years. The aim of the study was to describe and evaluate side effects of this drug in the group of 32 patients with diabetic polyneuropathy and with postherpetic neuralgia. DESIGN AND PATIENTS: In total, 32 patients with postherpetic neuralgia and diabetic polyneuropathy were enrolled into our prospective study. The side effects were divided in two groups. First, the side effects observed within 30 minutes lasting intravenuous infusion of 10 mg of ketamine in 100 mL of normal saline. Second after 3 months of peroral treatment of 30 mg of ketamine five times daily. RESULTS: Sedation was observed in 15.6% of patients after the initial infusion and in 19% of patients in the course of the subsequent oral therapy. In total, 44% (infusion) and 22% (oral administration) of patients reported dizziness. A total of 25% of patients complained about drowsiness and 19% of patients reported dry mouth during oral therapy. In the observed 3-month treatment period, five patients (15.6%) withdrew from the treatment due to a failure of therapy and four patients (12.5%) due to untolerated side effects (dizziness, sedation, loss of appetite, nausea, and vomiting). CONCLUSIONS: Ketamine is evaluated as a nonoptimal, however, available NMDA blocker suitable for clinical use. Studying its effects in clinics can be expected to increase our knowledge necessary for the development of new, effective, and safe "antineuralgic drug."

• MeSH
• analgetika aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• časové faktory MeSH
• diabetické neuropatie farmakoterapie   MeSH
• dospělí MeSH
• intravenózní infuze MeSH
• ketamin aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• lidé MeSH
• měření bolesti MeSH
• mladiství MeSH
• následné studie MeSH
• nauzea chemicky indukované   MeSH
• neuralgie farmakoterapie   MeSH
• prospektivní studie MeSH
• rozvrh dávkování léků MeSH
• výběr pacientů MeSH
• zvracení chemicky indukované   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• analgetika MeSH
• ketamin MeSH

Effect of two anticonvulsants with different mechanism of action, i.e. alprazolam and ketamine, was tested in two types of seizure activity. The first one was induced by N-(3,5-dimethoxy-4-propoxyphenylethyl)-aziridine, the second one by pentylenetetrazol. While alprazolam alleviated both the minimal as well as major paroxysms, ketamine suppressed only major seizures. These effects are discussed in terms of the both N-methyl-D-aspartate and GABA receptors involvement.

• MeSH
• alprazolam terapeutické užití   MeSH
• antikonvulziva terapeutické užití   MeSH
• aziridiny MeSH
• ketamin terapeutické užití   MeSH
• konvulzíva MeSH
• krysa rodu Rattus MeSH
• pentylentetrazol MeSH
• potkani Wistar MeSH
• záchvaty chemicky indukované   farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• alprazolam MeSH
• antikonvulziva MeSH
• aziridiny MeSH
• ketamin MeSH
• konvulzíva MeSH
• N-((3,5-dimethoxy-4-propoxyphenyl)ethyl)aziridine MeSH Prohlížeč
• pentylentetrazol MeSH

The effects of two non-competitive NMDA antagonists--MK-801 and ketamine--were studied in a model of generalized seizures elicited by s.c. injection of strychnine (2 or 3 mg/kg) in adult rats. The animals were observed in isolation for 30 min after strychnine administration. Pretreatment with MK-801 (0.5 or 2 mg/kg i.p.) suppressed the tonic, but not the clonic phase of generalized seizures following both doses of strychnine. A similar action of ketamine (20 or 40 mg/kg i.p.) was indicated but it did not attain statistical significance. Strychnine-induced lethality was not changed significantly. A comparison with antiepileptic drugs demonstrated that only phenobarbital (10-80 mg/kg i.p.) was clearly effective against strychnine-induced seizures; carbamazepine (25 or 50 mg/kg i.p.) and partly phenytoin (30 or 60 mg/kg i.p.) were able to suppress the incidence of the tonic phase. Primidone (40 or 80 mg/kg i.p.) as well as the benzodiazpines bretazenil (0.1 or 1 mg/kg i.p.) and midazolam (two lower doses of 0.5 and 1 mg/kg i.p.) were without significant effect. The 2 mg/kg dose of midazolam was partly effective. Only phenobarbital, carbamazepine and the highest dose of midazolam prevented strychnine-induced lethality.

• MeSH
• antikonvulziva terapeutické užití   MeSH
• dizocilpinmaleát terapeutické užití   MeSH
• ketamin terapeutické užití   MeSH
• krysa rodu Rattus MeSH
• modely nemocí na zvířatech MeSH
• potkani Wistar MeSH
• strychnin toxicita   MeSH
• záchvaty chemicky indukované   farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• antikonvulziva MeSH
• dizocilpinmaleát MeSH
• ketamin MeSH
• strychnin MeSH