Ketamine modulates the exploratory dynamics and homebase-related behaviors of adult zebrafish.

Anxiety can be a protective emotion when animals face aversive conditions, but is commonly associated with various neuropsychiatric disorders when pathologically exacerbated. Drug repurposing has emerged as a valuable strategy based on utilizing the existing pharmaceuticals for new therapeutic purposes. Ketamine, traditionally used as an anesthetic, acts as a non-competitive antagonist of the glutamate N-methyl-d-aspartate (NMDA) receptor, and shows potential anxiolytic and antidepressant effects at subanesthetic doses. However, the influence of ketamine on multiple behavioral domains in vertebrates is not completely understood. Here, we evaluated the potential modulatory effect of ketamine on the spatio-temporal exploratory dynamics and homebase-related behaviors in adult zebrafish using the open field test (OFT). Animals were exposed to subanesthetic concentrations of ketamine (0, 2, 20, and 40 mg/L) for 20 min and their locomotion-, exploration- and homebase-related behaviors were assessed in a single 30-min trial. Our data revealed that acute ketamine (20 and 40 mg/L) induced hyperlocomotion, as verified by the increased total distance traveled. All concentrations tested elicited circling behavior, a stereotyped-like response which gradually reduced across the periods of test. We also observed modulatory effects of ketamine on the spatio-temporal exploratory pattern, in which the reduced thigmotaxis and homebase activity, associated with the increased average length of trips, suggest anxiolytic-like effects. Collectively, our findings support the modulatory effects of ketamine on the spatio-temporal exploratory activity, and corroborate the utility of homebase-related measurements to evaluate the behavioral dynamics in zebrafish models.

The relationship between alcohol bingeing in the gestational period of wistar rats and the development of schizophrenia in the offspring adult life.

The incidence of schizophrenia in young adulthood may be associated with intrauterine factors, such as gestational alcohol consumption. This study investigated the relationship between a single high dose of alcohol during pregnancy in Wistar rats and the development of schizophrenia in the adult life of the offspring. On the 11th day of gestation, pregnant rats received either water or alcohol via intragastric gavage. Male and female offspring were subjected to behavioral tests at 30 days of age according to the maternal group. At 60 days of age, offspring received intraperitoneal injections of ketamine (ket) or saline (SAL). After the final ketamine administration, the adult offspring underwent behavioral tests, and their brain structures were removed for biochemical analysis. Alcohol binge drinking during pregnancy induces hyperlocomotion in both young female and male offspring, with males of alcohol-exposed mothers showing reduced social interactions. In adult offspring, ketamine induced hyperlocomotion; however, only females in the alcohol + ket group exhibited increased locomotor activity, and a decrease in the time to first contact was observed in the alcohol group. Cognitive impairment was exclusively observed in male animals in the alcohol group. Increased serotonin and dopamine levels were observed in male rats in the alcohol + ket group. Biochemical alterations indicate the effects of intrauterine alcohol exposure associated with ketamine in adult animals. These behavioral and biochemical changes suggest that the impact of prenatal stressors such as alcohol persists throughout the animals' lives and may be exacerbated by a second stressor in adulthood, such as ketamine.

Ketamine-induced cystitis: A case report and literature review.

Ketamine, a dissociative anesthetic drug, has gained popularity as a recreational substance, particularly among young adults. However, chronic ketamine abuse can lead to various complications including ketamine-induced cystitis. We present the case of a 46-year-old Caucasian male with a history of HIV infection and daily recreational ketamine use for 7 months, who was admitted to the emergency room with hypogastric pain and hematuria. Laboratory examinations and contrast-enhanced abdominal CT tomography revealed significant irregular circumferential thickening of both ureters, substantial bilateral pyeloureteral ectasia, and a bladder with markedly thickened walls. Bilateral flexible ureteropyeloscopy, bladder transurethral resection, and bladder fulguration were performed, and pathology confirmed the diagnosis of ketamine-induced cystitis. Treatment consisted of ketamine withdrawal, pain relief, and support from psychiatrists and urologists. The patient's symptoms improved and he was discharged without complications. This case highlights the importance of recognizing the potential adverse effects of recreational ketamine use and the need for a multidisciplinary approach to managing ketamine-induced cystitis. Further research is necessary to elucidate the precise mechanisms underlying this condition and develop effective prevention and treatment strategies.

Navigating the challenge of patient selection and scales to measure outcomes in ketamine trials for treatment-resistant depression.

The letter about the article "Ketamine for treatment-resistant major depressive disorder: Double-blind active-controlled crossover study" that discusses some points about methodology, outcome measures, and results.

Use of Ketamine in Patients with Multifactorial Neuropathic Pain: A Systematic Review and Meta-Analysis.

Neuropathic pain (NP) is a heterogeneous group of conditions characterized by the experience of a number of sensory disturbances including pain, burning sensations, paroxysms of stabbing pain, dysesthesias, allodynia, and hyperalgesia. The above-mentioned sensations may occur in a specific dermatome area or other delimited region of the body. The objective of this review was to analyze the evidence for ketamine in multifactorial neuropathic pain. The research group systematically searched the databases MEDLINE (via PubMed), EMBASE, SCOPUS, the Cochrane Central Register of Controlled Trials, the Cumulative Index to Nursing and Allied Health Literature (Cinahl), and the Web of Science. The findings of this review show that different forms of low doses of ketamine (LDK) do not present statistically significant changes for any of the scales included. In this study, the total symptom score [standardized mean difference (SMD) = -3.59, confidence interval (CI) = -4.16 to -3.02, and p < 0.00001], neuropathy impairment score (SMD = -1.42, CI = -3.68 to 0.84, and p = 0.22), and neuropathy symptom checklist (SMD = -0.09, CI = -0.15 to -0.02, and p = 0.01) were taken into account. For finality compared to the use of a placebo, the findings suggest that LDK does not exhibit significant differences in terms of pain reduction and functionality. Moreover, no specific dosages are identified to support the use of LDK in the reduction in NP.

Repeated subcutaneous esketamine on treatment-resistant depression: An open-label dose titration study.

BACKGROUND: Ketamine has gained prominence as one of the most effective therapeutic options in unipolar treatment-resistant depression (TRD). However, most studies related to the antidepressant action of ketamine used intravenous (IV) or intranasal (IN) administration. The subcutaneous (SC) route of administration is a promising alternative, as it results in plasma levels comparable to IV, causes fewer side effects, and is easier and cheaper to administer than both IV and/or IN routes. METHODS: In this context, we conducted an open-label clinical trial for investigating the efficacy and safety of 8 weekly sessions of SC esketamine in TRD patients (n = 30). RESULTS: At the end of the treatment, a partial response rate of 26.09 %, a response rate of 52.17 % and remission rate of 34.78 % were observed, assessed by Montgomery-Åsberg Depression Rating Scale. Moreover, the self-reported depressive symptoms, as measured by the Beck Depression Inventory II (BDI-II), significantly decreased from the baseline to the final session, and the improvements were sustained throughout the week. Follow-up evaluations (BDI-II) up to the sixth month consistently showed scores lower than the baseline. LIMITATIONS: The small sample size and the drop-out during the follow-up phase may limit the generalizability of the findings. Additionally, the absence of a control group necessitates cautious interpretation of causality. CONCLUSIONS: This groundbreaking study, which addresses SC esketamine treatment for TRD, reported promising response and remission rates, as well as sustained antidepressant effects. It highlights the need for further research to improve and expand our knowledge of this innovative, more accessible, and cost-effective therapeutic approach.

Ketamine for catatonia: A novel treatment for an old clinical challenge? A systematic review of the evidence.

INTRODUCTION: Catatonia, documented since the 19th century, remains a significant challenge in terms of recognition and treatment. Over the last two decades, ketamine has brought new perspectives to psychiatry, sparking widespread interest. Concurrently, catatonia has attracted heightened scientific attention. Preliminary evidence suggests the therapeutic potential of ketamine for catatonia. METHODS: We systematically searched Medline/PubMed, Embase, PsycINFO, Lilacs, and Cochrane Library databases, as well as Google Scholar, for studies with ketamine or its enantiomers as intervention for catatonia, with no restrictions to underlying diagnosis, date, language, or study design. RESULTS: Twenty articles were included, encompassing a total of 25 catatonic patients receiving ketamine or esketamine. Predominantly female (61.9 %), with a mean age of 44.4 years, patients mostly exhibited manifestations compatible with the retarded subtype of catatonia. Mood disorders were the most prevalent underlying diagnoses. Ketamine was primarily administered intravenously over a 40-minute period and in multiple-dosing schemes. Mean response and remission rates of catatonic manifestations for the whole sample were 80 % and 44 %, respectively, with no reports of worsening catatonic features or psychotic symptoms. Only one patient discontinued treatment due to intolerable dissociative effects. CONCLUSION: Challenging the conventional contraindication of ketamine in psychotic disorders, current evidence highlights its potential efficacy, particularly in treating catatonia. Pending further research, we advocate reevaluating this contraindication, as it may offer a promising therapeutic option, especially for challenging cases. Preliminary evidence suggests potentially greater benefits for catatonic patients with underlying mood disorders compared to primary psychotic disorders.

Successful treatment for serious depression with suicidal risk in a heart transplant patient.

INTRODUCTION: Major depressive disorder is related to unfavourable outcomes in patients with severe comorbidities. In transplant patients, major depression is associated with worse clinical outcomes. CASE REPORT: We present the case of a 55-year-old man with a heart transplant due to heart failure of ischaemic origin. Six months after the transplant he developed depressed mood, anhedonia and suicidal ideation with a score of 20/27 on the PHQ-9 depression screening scale. After receiving mirtazapine 30 mg/night for a week and persisting with a high suicide risk, it was decided to administer ketamine infusion for 24 h, with which a significant improvement in mood was observed, and the disappearance of suicidal ideation 24 h after the infusion. DISCUSSION: Depression in transplant patients is a factor associated with graft loss and post-transplant mortality, in addition to favouring other negative outcomes such as deep vein thrombosis. CONCLUSIONS: Ketamine infusion was shown to be an effective and safe option to treat major depression with suicidal risk in a heart transplant patient.

Anesthetic effects of the ketamine and midazolam association by intranasal or intramuscular route in domestic chickens: prospective, blinded, randomized and crossover study.

This prospective, blinded, randomized crossover study aimed to assess the anesthetic effects of the combination of 30 mg/kg ketamine and 2 mg/kg midazolam via intranasal (IN) or intramuscular (IM) routes in twelve domestic chickens. Physiological parameters (respiratory rate - RR, heart rate - HR, and cloacal temperature -Tºcloacal) were monitored throughout the experiment, along with recovery time and sedation level (S0: awake, no recumbency, responsive to stimuli; S1: blinking eyes, recumbency, relaxed, response to stimulus, mild movement; S2: open eyes, recumbency, relaxed, mild response to stimuli; S3: closed eyes, recumbency, relaxed, no movement). In the IM group, all birds reached S3, while in IN 5/12 reached S3, 4/12 reached at most S1, and 1/12 at most S2. IM administration showed higher sedation at 5, 10, 15, 20, 30, 35, 40, and 45 minutes (p<0.05). IN administration exhibited a shorter total recovery time (26.3±21.4 min vs. 92.9±33.4 min; p<0.001). No time, group, or time-group interaction effects were observed in HR and cloacal Tº, with a trend to a decrease in RR both groups (p<0.001). Increased incidences of vocalization and agitation was observed via IM (4/12 vs. 0/12; p=0.028), with no difference in salivation. Despite faster recovery with less agitation and vocalization, the ketamine and midazolam combination via IN provided less consistent sedation compared to the IM route in chickens.

Este estudo crossover randomizado objetivou avaliar os efeitos anestésicos da associação de 30 mg/kg de cetamina e 2 mg/kg de midazolam via intranasal (IN) ou intramuscular (IM) em doze galinhas. Além dos parâmetros fisiológicos (frequência respiratória ­ FR e cardíaca ­ FC e temperatura cloacal ­ Tºcloacal), registrou-se o tempo de recuperação e o grau de sedação ao longo do experimento (S0: acordada, sem decúbito, responsiva a estímulos; S1: olhos piscando, decúbito, relaxada, resposta a estímulo, movimentação leve; S2: olhos abertos, decúbito, relaxada, resposta leve a estímulos; S3: olhos fechados, decúbito, relaxada, sem movimentação. Pela via IM, todas as aves atingiram o grau S3, enquanto pela via IN 5/12 alcançaram S3, 4/12 atingiram no máximo S1 e 1/12 no máximo S2. A via IM apresentou maior sedação em 5, 10, 15, 20, 30, 35, 40 e 45 min (p<0,05). A via IN apresentou menor tempo total até recuperação (26,3±21,4 min vs. 92,9±33,4 min; p<0,001). Não foram observados efeitos de tempo, grupo e interação tempo-grupo na FC e na Tºcloacal com uma tendência de queda da FR nos dois grupos (p<0,001). Observou-se maior incidência de vocalização e agitação pela via IM (4/12 vs. 0/12; p=0,028), não havendo diferença para sialorreia. Apesar da recuperação mais rápida e com menos agitação e vocalização, a associação cetamina e midazolam via IN levou a uma sedação menos consistente que a via IM em galinhas.

Ketamine in fibromyalgia: a systematic review.

OBJECTIVE: Fibromyalgia (FM) subjects are treated with antidepressant agents; in most cases, these drugs lose efficacy or have adverse effects. Ketamine is an anesthetic drug used in FM in some studies. This article aims to systematically review the safety and efficacy of ketamine in fibromyalgia (FM) patients. MATERIALS AND METHODS: We systematically searched articles on FM and ketamine published at Pubmed from 1966 to 2021. This study was registered at PROSPERO. RESULTS: There were only 6 articles published in this field, with a total of 115 patients. The female sex was predominant (88 to 100%). The age varied from 23 to 53 years old. Disease duration ranged from 1 month to 28 years. The dosage of ketamine changed from 0.1 mg/kg-0.3-0.5 mg/kg in intravenous infusion (4/5) and subcutaneous application (1/5). Regarding outcomes, the Visual analog scale (VAS) before ketamine was from 59 to 100 mm and after treatment from 2 to 95 mm. Most short-term studies had a good response. Only the study with 8 weeks of follow-up did not observe a good response. Side effects were common; all appeared during the infusion and disappeared after a few minutes of the ketamine injection. CONCLUSIONS: The present study demonstrates the effectiveness and safety of ketamine in FM patients in the short term. Although, more studies, including long-term follow-up studies, are still needed.

Is the antidepressant effect of ketamine separate from its psychotomimetic effect? A review of rodent models.

Ketamine is an NMDA (N-methyl-d-aspartate) glutamate receptor antagonist, which has a myriad of dose-dependent pharmacological and behavioral effects, including anesthetic, sedative, amnestic, analgesic, and anti-inflammatory properties. Intriguingly, ketamine at subanesthetic doses displays a relevant profile both in mimicking symptoms of schizophrenia and also as the first fast-acting treatment for depression. Here, we present an overview of the state-of-the-art knowledge about ketamine as an antidepressant as well as a pharmacological model of schizophrenia in animal models and human participants. Ketamine's dual effect appears to arise from its mechanism of action involving NMDA receptors, with both immediate and downstream consequences being triggered as a result. Finally, we discuss the feasibility of a unified approach linking the glutamatergic hypothesis of schizophrenia to the promising preclinical and clinical success of ketamine in the treatment of refractory depression.

Hemodynamic response to sub-anesthetic doses of ketamine for postoperative pain: systematic review / Respuesta hemodinámica a dosis subanestésicas de ketamina en dolor posoperatorio: revisión sistemática

Abstract Introduction: Low-dose ketamine infusions have shown analgesic effectiveness for the management of postoperative pain. The impact of low-dose ketamine infusions on cardiovascular response is dose-dependent and requires a better knowledge about its effects on this population. Objective: To conduct a systematic review to describe changes in systolic, diastolic and mean arterial pressure, and heart rate 24, 48 and 72 hours after surgery. Methods: Randomized, controlled trials were reviewed in the Cochrane Library, PubMed, EMBASE, SciELO, Lilacs and grey literature on low-dose ketamine infusions for the study variables. The quality of the studies was assessed using the Cochrane's risk of bias tool. Results: Six randomized, controlled trials with 641 patients were included. Low-quality evidence was found suggestive of a lack of certainty of any significant differences in the systolic blood pressure variables at 24 hours (mean standard deviation -1.00, 95 % CI: -7.27 to 5.27). A statistically significant higher mean heart rate at 24 hours was identified in the low-dose ketamine infusion group, (mean standard deviation 1.64 95 % CI: 0.38 to 2.90) which did not reach clinical significance. A lower pain level and less use of opioids was identified in the low-dose ketamine infusion group. Conclusions: Low quality evidence was found, suggesting that low-dose ketamine infusions are not associated with significant changes in blood pressure or heart rate 24 - 48 hours after surgery. It is important to individualize cardiovascular risk for each case, before initiating treatment.

Resumen Introducción: Las infusiones en dosis bajas de ketamina han mostrado eficacia analgésica en el manejo del dolor posoperatorio. El impacto de las infusiones en dosis bajas de ketamina en la respuesta cardiovascular es dosisdependiente y requiere un mejor conocimiento de sus efectos en esta población. Objetivo: Realizar una revisión sistemática para describir los cambios en la presión arterial sistólica, presión arterial diastólica, presión arterial media, frecuencia cardiaca a las 24, 48 y 72 horas del posoperatorio. Métodos: Se revisaron ensayos controlados aleatorizados en Cochrane Library, PubMed, EM-BASE, SciELO, Lilacs y literatura gris de infusiones en dosis bajas de ketamina para las variables del estudio. La calidad de los estudios se evaluó usando la herramienta de riesgo de sesgos de Cochrane. Resultados: Se incluyeron seis ensayos controlados aleatorizados con 641 pacientes. Se encontró evidencia de baja calidad sugestiva de ausencia de certeza de diferencias significativas en las variables presión arterial sistólica a las 24 horas (diferencia de medias estandarizada -1,00, IC95 %: -7,27 a 5,27). Para las 24 horas se halló una media de frecuencia cardiaca mayor en el grupo de infusiones en dosis bajas de ketamina, estadísticamente significativa (diferencia de medias estandarizada 1,64 IC95 %: 0,38 a 2,90) sin alcanzar significancia clínica. Se encontró menor nivel de dolor y consumo de opioides en el grupo de infusiones en dosis bajas de ketamina. Conclusiones: Se encontró evidencia de baja calidad, sugestiva de que las infusiones en dosis bajas de ketamina no se asocian a cambios significativos en la presión arterial o frecuencia cardiaca a las 24-48 horas en el posoperatorio. Es importante individualizar el riesgo cardiovascular para cada caso previo al inicio del tratamiento.

Tratamiento Exitoso para la Depresión Grave con Riesgo Suicida en un Paciente Trasplantado de Corazón / Successful Treatment for Serious Depression with Suicidal Risk in a Heart Transplant Patient

RESUMEN Introducción: El trastorno depresivo mayor se relaciona con desenlaces desfavorables en pacientes con comorbilidades graves. En pacientes trasplantados, la depresión mayor se asocia con peores desenlaces clínicos. Reporte de caso: Se presenta el caso de un varón de 55 arios, con trasplante de corazón por insuficiencia cardiaca de origen isquémico, que 6 meses después del trasplante presentó ánimo deprimido, anhedonia e ideación suicida, con un puntaje de 20 sobre 27 en la escala para tamizar depresión PHQ-9. Luego de recibir mirtazapina 30 mg/noche durante 1 semana y persistir con alto riesgo suicida, se decidió administrar infusión de ketamina durante 24 h, con lo cual se observó mejoría significativa en el ánimo y desaparición de la ideación suicida 24 h tras la infusión. Discusión: La depresión en pacientes trasplantados es un factor asociado con la pérdida del injerto y la mortalidad postrasplante, además de favorecer otros desenlaces negativos como trombosis venosa profunda. Conclusiones: La infusión de ketamina se ha demostrado como una opción efectiva y segura para tratar la depresión mayor con riesgo suicida en un paciente trasplantado de corazón.

ABSTRACT Introduction: Major depressive disorder is related to unfavorable outcomes in patients with severe comorbidities. In transplant patients, major depression is associated with worse clinical outcomes. Case report: We present the case of a 55-year-old man with a heart transplant due to heart failure of ischemic origin. Six months after the transplant he developed depressed mood, anhedonia and suicidal ideation with a score of 20/27 on the PHQ-9 depression screening scale. After receiving mirtazapine 30 mg/night for a week and persisting with a high suicide risk, it was decided to administer ketamine infusion for 24hours, with which a significant improvement in mood was observed, and the disappearance of suicidal ideation 24 hours after the infusion. Discussion: Depression in transplant patients is a factor associated with graft loss and post-transplant mortality, in addition to favoring other negative outcomes such as deep vein thrombosis. Conclusions: Ketamine infusion was shown to be an effective and safe option to treat major depression with suicidal risk in a heart transplant patient.

Ketamine versus electroconvulsive therapy for major depressive episode: An updated systematic review and non-inferiority meta-analysis.

We conducted a systematic review and meta-analysis to investigate the comparative effectiveness of ketamine versus electroconvulsive therapy (ECT) for the treatment of major depressive episodes (MDEs). PubMed, EMBASE and Cochrane Library databases were systematically searched for randomized controlled trials (RCTs) comparing ketamine and ECT for MDE. The primary outcome was response rate, for which we prespecified a non-inferiority margin of -0.1, based on the largest and most recent RCT. Response was defined as a reduction of at least 50 % in the depression scale score. Six RCTs met the inclusion criteria, comprising 655 patients. In the overall population, ketamine was not non-inferior to ECT in response rate (RD -0.10; 95 % CI -0.26 to 0.05; p = 0.198; I2 = 72 %). The ECT group had a higher reduction in depression scores, but without difference in remission and relapse rates. Regarding safety outcomes, ketamine had better posttreatment cognition scores and reduced muscle pain rate compared with ECT, albeit with an increased rate of dissociative symptoms. In a subanalysis with only inpatients, ketamine was inferior to ECT in response rate (RD -0.15; 95 % CI -0.27 to -0.03; p = 0.014; I2 = 25 %), remission, and change in depression scores. These findings support the use of ECT over ketamine for inpatients. Further RCTs are warranted to clarify the comparative effect of these treatments for outpatients.

Effectiveness of Ketamine for the Treatment of Post-Traumatic Stress Disorder - A Systematic Review and Meta-Analysis.

Objective: Post-traumatic stress disorder (PTSD) is an enduring condition characterized by a chronic course and impairments across several areas. Despite its significance, treatment options remain limited, and remission rates are often low. Ketamine has demonstrated antidepressant properties and appears to be a promising agent in the management of PTSD. Method: A systematic review was conducted in PubMed/MEDLINE, Cochrane Library, Clinicaltrials.gov, Lilacs, Scopus, and Embase, covering studies published between 2012 and December 2022 to assess the effectiveness of ketamine in the treatment of PTSD. Ten studies, consisting of five RCTs, two crossover trials, and three non-randomized trials, were included in the meta-analysis. Results: Ketamine demonstrated significant improvements in PCL-5 scores, both 24 hours after the initial infusion and at the endpoint of the treatment course, which varied between 1 to 4 weeks in each study. Notably, the significance of these differences was assessed using the Two Sample T-test with pooled variance and the Two Sample Welch's T-test, revealing a statistically significant effect for ketamine solely at the endpoint of the treatment course (standardized effect size= 0.25; test power 0.9916; 95% CI = 0.57 to 17.02, p=0.0363). It is important to note that high heterogeneity was observed across all analyses. Conclusions: Our findings suggest that ketamine holds promise as an effective treatment option for PTSD. However, further trials are imperative to establish robust data for this intervention.

The effect of low dose intra-articular S(+) ketamine on osteoarthritis in rats: an experimental study.

BACKGROUND: This study aimed to investigate the analgesic impact of S(+)-ketamine on pain behavior and synovial inflammation in an osteoarthritis (OA) model. METHODS: Animals were grouped as follows: OA-Saline (n = 24) and OA-Ketamine (n = 24), OA induced via intra-articular sodium monoiodoacetate (MIA); a Non-OA group (n = 24) served as the control. On the 7th day post OA induction, animals received either saline or S(+)-ketamine (0.5 mg.kg-1). Behavioral and histopathological assessments were conducted up to day 28. RESULTS: S(+)-ketamine reduced allodynia from day 7 to 28 and hyperalgesia from day 10 to 28. It notably alleviated weight distribution deficits from day 10 until the end of the study. Significant walking improvement was observed on day 14 in S(+)-ketamine-treated rats. Starting on day 14, OA groups showed grip force decline, which was countered by S(+)-ketamine on day 21. However, S(+)-ketamine did not diminish synovial inflammation. CONCLUSION: Low Intra-articular (IA) doses of S(+)-ketamine reduced MIA-induced OA pain but did not reverse synovial histopathological changes. IRB APPROVAL NUMBER: 23115 012030/2009-05.

Subcutaneous ketamine reduces suicide risk and improves functioning in depression: A proof-of-concept study.

This investigation explores the efficacy of subcutaneous ketamine for mitigating depressive symptoms and suicidal ideation, addressing a crucial need for rapid-onset treatments in severe depression cases. It introduces an innovative approach to administering an NMDA receptor antagonist, significantly advancing psychopharmacological methods for treating suicidal behaviors as distinct entities, even within depressive episodes. The study's objective is to assess the impact of subcutaneous ketamine on diminishing suicidal thoughts and mood symptoms during depressive episodes through a naturalistic, prospective observational design. Conducted at Hospital de Clínicas de Porto Alegre, Brazil, between 2021 and 2023, the study involved 26 patients undergoing a current depressive episode. Of these, 23 completed the acute phase of treatment, and 18 were followed up for 6 months. The treatment regimen commenced with a ketamine dose of 0.5 mg/kg, which was adjusted according to individual responses under psychiatric supervision. The findings revealed substantial decreases in Columbia Suicide Severity Rating Scale scores following multiple ketamine sessions, with most patients achieving remission after approximately eight sessions. A notable reduction in depressive symptoms was also observed. A clear dose-response relationship was established, indicating that higher doses of ketamine were associated with more significant improvements in depressive symptoms, suicidal ideation, and overall functionality. Follow-up assessments suggested that these improvements were sustained over time. The subcutaneous administration of ketamine was generally well-tolerated, with minor and short-lived side effects. The study posits that subcutaneous ketamine may present a promising solution for treating severe depression accompanied by suicidal tendencies, particularly considering its positive influence on patient functionality and well-being. This method could offer a cost-effective and accessible treatment alternative, especially relevant in settings with limited resources. Given its potential in reducing long-term disability and economic viability, the study advocates for its broader application and further validation through larger, controlled trials. Trial Registration: ClinicalTrials.gov NCT05249309.

The effect of dexmedetomidine-ketamine combination versus dexmedetomidine on behavior of uncooperative pediatric dental patients: a randomized controlled clinical trial

Abstract Objective Uncooperative behavior in pediatric dentistry is one of the most common manifestations of dental anxiety. Managing anxious patients can be attained by moderate sedation. This study aimed to compare the effect of sedation by dexmedetomidine-ketamine combination (DEX-KET) versus dexmedetomidine (DEX) on behavior of uncooperative pediatric dental patients. Methodology In total, 56 uncooperative healthy children (3-5 years old) requiring dental treatment were divided randomly into two groups: Group I (study group), which received buccal dexmedetomidine (2 μg/kg) and ketamine (2 mg/kg), and Group II (control group), which received only buccal dexmedetomidine (4 μg/kg). Drugs effects were assessed in terms of hemodynamic parameters, patient's drug acceptance, child behavior, postoperative effect of sedation, amnesic effect, incidence of adverse events, as well as procedural induced stress measured by salivary secretory immunoglobulin A (s-IgA). Results Hemodynamic results did not reveal a statistically significant difference between the two study groups (P>0.05). There was a significant difference in patient's acceptance to sedative drug between both groups, favoring DEX (p=0.005). Children who received DEX-KET showed significantly better behavior than those who received DEX for local anesthesia (p=0.017) and during operative procedure (p=0.037). Adverse events, post-operative and amnesic effects of drugs were comparable in both groups (p>0.05). Moreover, the mean difference in the salivary s-IgA levels between initial and final value was not statistically significant between both groups (p=0.556). Conclusion Both DEX-KET combination and DEX alone are effective in providing hemodynamic stability. DEX-KET combination significantly improved the behavior of sedated children compared to DEX alone but the drug acceptance was decreased in the DEX-KET group. Both regimens did not have a negative effect on postoperative behavior of children and had comparable amnesic effect with no significant adverse events. Salivary s-IgA is not considered a potential stress biomarker in sedated children.

Randomized clinical trial comparing the efficacy and safety of ketamine and fentanyl for analgesia in pediatric orthopedic procedures / Ensaio clínico randomizado comparando a eficácia e a segurança da cetamina e do fentanil para analgesia em procedimentos ortopédicos pediátricos

ABSTRACT BACKGROUND AND OBJECTIVES: Bone fractures constitute a frequent cause of emergency care in the pediatric population. Opioid drugs are routinely used for analgesia during the hospitalization of children victims of trauma. Few studies have evaluated the importance of a multimodal approach to analgesia in this context. The aim of this study was to compare the analgesic effect and possible side effects of fentanyl compared to those of ketamine. METHODS: The study analyzed 50 children and adolescents, aged between 24 and 192 months, submitted to surgical treatment of upper limb fractures in a tertiary trauma care hospital. The participants were randomized into two groups: one that received Ketamine and the other Fentanyl. In the post-anesthetic recovery room (PARR), pain intensity and the occurrence of delirium were measured for a period of 30 minutes. The incidence of respiratory depression, nausea, vomiting and other side effects during the surgical procedure were assessed. RESULTS: The sample consisted mostly of male individuals (76.0%). The mean age of the participants was 90.1 months. The use of a low-flow oxygen cannula was necessary in 30.0% of the participants. The incidence of vomiting and laryngospasm was 2.0% among the participants, and 6.0% presented increased salivary secretion. The occurrence of pain, delirium and respiratory depression was not different between the two assessed groups, as well as the occurrence of nausea and laryngospasm. CONCLUSION: Ketamine is not an effective and safe option to opioids for analgesia in children undergoing surgical procedures to treat upper limb fractures.

RESUMO JUSTIFICATIVA E OBJETIVOS: As fraturas ósseas constituem causa frequente de atendimento de emergência na população pediátrica. Fármacos opioides são rotineiramente utilizados para analgesia durante a hospitalização de crianças vítimas de trauma. Poucos estudos avaliaram a importância de uma abordagem multimodal para analgesia nesse contexto. O objetivo deste estudo foi comparar o efeito analgésico e possíveis efeitos adversos do fentanil em relação aos da cetamina. MÉTODOS: Foram analisados 50 crianças e adolescentes, com idade entre 24 e 192 meses, submetidos ao tratamento cirúrgico das fraturas de membros superiores em um hospital terciário de atendimento ao trauma. Os participantes foram aleatorizados em dois grupos: um recebeu cetamina e outro fentanil. Na sala de recuperação pós-anestésica (SRPA), a intensidade da dor e a ocorrência de delirium foram mensuradas por um período de 30 minutos. A incidência de depressão respiratória, náuseas, vômitos e outros efeitos adversos durante o procedimento cirúrgico foram avaliados. RESULTADOS: A amostra foi composta, em sua maioria, por indivíduos do sexo masculino (76,0%). A média de idade dos participantes foi de 90,1 meses. O uso de cânula de oxigênio de baixo fluxo foi necessário em 30,0% dos participantes. A incidência de vômitos e laringoespasmo foi de 2,0% entre os participantes, sendo que 6,0% apresentaram aumento da secreção salivar. A ocorrência de dor, delirium e depressão respiratória não foi diferente entre os dois grupos avaliados, assim como a ocorrência de náuseas e laringoespasmo. CONCLUSAO: Acetamina não se mostrou uma opção eficaz e segura aos opioides para analgesia em crianças submetidas a procedimentos cirúrgicos para tratamento de fraturas de membros superiores.