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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.

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BACKGROUND: Ketamine has been considered as an adjunct for children who do not reach their predefined target sedation depth. However, there is limited evidence regarding the use of ketamine as a prolonged infusion (i.e., >24 hours) in the pediatric intensive care unit (PICU). OBJECTIVE: We sought to evaluate the safety and effectiveness of continuous ketamine infusion for >24 hours in mechanically ventilated children. METHODS: We conducted a prospective cohort study in a tertiary PICU from January 2020 to December 2022. The primary outcome was the incidence of adverse events (AEs) after ketamine initiation. The secondary outcome included assessing the median proportion of time the patient spent on the Richmond Agitation-Sedation Scale (RASS) goal after ketamine infusion. Patients were also divided into two groups based on the sedative regimen, ketamine-based or non-ketamine-based, to assess the incidence of delirium. RESULTS: A total of 269 patients were enrolled: 73 in the ketamine group and 196 in the non-ketamine group. The median infusion rate of ketamine was 1.4 mg/kg/h. Delirium occurred in 16 (22%) patients with ketamine and 15 (7.6%) patients without ketamine (p = 0.006). After adjusting for covariates, logistic regression showed that delirium was associated with comorbidities (odds ratio [OR] 4.2), neurodevelopmental delay (OR 0.23), fentanyl use (OR 7.35), and ketamine use (OR 4.17). Thirty-one (42%) of the patients experienced at least one AE following ketamine infusion. Other AEs likely related to ketamine were hypertension (n = 4), hypersecretion (n = 14), tachycardia (n = 6), and nystagmus (n = 2). There were no significant changes in hemodynamic variables 24 h after the initiation of ketamine. Regarding the secondary outcomes, patients were at their goal RASS level for a median of 76% (range 68-80.5%) of the time in the 24 hours before ketamine initiation, compared with 84% (range 74.5-90%) of the time during the 24 h after ketamine initiation (p < 0.001). The infusion rate of ketamine did not significantly affect concomitant analgesic and sedative infusions. The ketamine group experienced a longer duration of mechanical ventilation and a longer length of stay in the PICU and hospital than the non-ketamine group. CONCLUSION: The use of ketamine infusion in PICU patients may be associated with an increased rate of adverse events, especially delirium. High-quality studies are needed before ketamine can be broadly recommended or adopted earlier in the sedation protocol.

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Schizophrenia is a chronic, debilitating mental illness that has not yet been completely understood. In this study, we aimed to investigate the effects of different doses of ketamine, a non-competitive NMDA receptor antagonist, on the positive- and negative-like symptoms of schizophrenia. We also explored whether these effects are related to changes in the immunoreactivity of GAD67, TH, and PPAR-γ in brain structures. To conduct the study, male mice received ketamine (20-40 mg/kg) or its vehicle (0.9 % NaCl) intraperitoneally for 14 consecutive days. We quantified stereotyped behavior, the time of immobility in the forced swimming test (FST), and locomotor activity after 7 or 14 days. In addition, we performed ex vivo analysis of the immunoreactivity of GAD, TH, and PPAR-γ, in brain tissues after 14 days. The results showed that ketamine administration for 14 days increased the grooming time in the nose region at all tested doses. It also increased immobility in the FST at 30 mg/kg doses and decreased the number of rearing cycles during stereotyped behavior at 40 mg/kg. These behavioral effects were not associated with changes in locomotor activity. We did not observe any significant alterations regarding the immunoreactivity of brain proteins. However, we found that GAD and TH were positively correlated with the number of rearing during the stereotyped behavior at doses of 20 and 30 mg/kg ketamine, respectively. GAD was positively correlated with the number of rearing in the open field test at a dose of 20 mg/kg. TH was inversely correlated with immobility time in the FST at a dose of 30 mg/kg. PPAR-γ was inversely correlated with the number of bouts of stereotyped behavior at a dose of 40 mg/kg of ketamine. In conclusion, the behavioral alterations induced by ketamine in positive-like symptoms were reproduced with all doses tested and appear to depend on the modulatory effects of TH, GAD, and PPAR-γ. Conversely, negative-like symptoms were associated with a specific dose of ketamine.

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Infections during pregnancy are associated with an increased risk of neuropsychiatric disorders with developmental etiologies, such as schizophrenia and autism spectrum disorders (ASD). Studies have shown that the animal model of maternal immune activation (MIA) reproduces a wide range of phenotypes relevant to the study of neurodevelopmental disorders. Emerging evidence shows that (R)-ketamine attenuates behavioral, cellular, and molecular changes observed in animal models of neuropsychiatric disorders. Here, we investigate whether (R)-ketamine administration during adolescence attenuates some of the phenotypes related to neurodevelopmental disorders in an animal model of MIA. For MIA, pregnant Swiss mice received intraperitoneally (i.p.) lipopolysaccharide (LPS; 100 µg/kg/day) or saline on gestational days 15 and 16. The two MIA-based groups of male offspring received (R)-ketamine (20 mg/kg/day; i.p.) or saline from postnatal day (PND) 36 to 50. At PND 62, the animals were examined for anxiety-like behavior and locomotor activity in the open-field test (OFT), as well as in the social interaction test (SIT). At PND 63, the prefrontal cortex (PFC) was collected for analysis of oxidative balance and gene expression of the cytokines IL-1ß, IL-6, and TGF-ß1. We show that (R)-ketamine abolishes anxiety-related behavior and social interaction deficits induced by MIA. Additionally, (R)-ketamine attenuated the increase in lipid peroxidation and the cytokines in the PFC of the offspring exposed to MIA. The present work suggests that (R)-ketamine administration may have a long-lasting attenuation in deficits in emotional behavior induced by MIA, and that these effects may be attributed to its antioxidant and anti-inflammatory activity in the PFC.

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BACKGROUND: ECT is considered the fastest and most effective treatment for TRD. Ketamine seems to be an attractive alternative due to its rapid-onset antidepressant effects and impact on suicidal thoughts. This study aimed to compare efficacy and tolerability of ECT and ketamine for different depression outcomes (PROSPERO/CRD42022349220). METHODS: We searched MEDLINE, Web of Science, Embase, PsycINFO, Google Scholar, Cochrane Library and trial registries, which were the ClinicalTrials.gov and the World Health Organization's International Clinical Trials Registry Platform, without restrictions on publication date. SELECTION CRITERIA: randomized controlled trials or cohorts comparing ketamine versus ECT in patients with TRD. RESULTS: Eight studies met the inclusion criteria (of 2875 retrieved). Random-effects models comparing ketamine and ECT regarding the following outcomes were conducted: a) reduction of depressive symptoms severity through scales, g = -0.12, p = 0.68; b) response to therapy, RR = 0.89, p = 0.51; c) reported side-effects: dissociative symptoms, RR = 5.41, p = 0.06; nausea, RR = 0.73, p = 0.47; muscle pain, RR = 0.25, p = 0.02; and headache, RR = 0.39, p = 0.08. Influential & subgroup analyses were performed. LIMITATIONS: Methodological issues with high risk of bias in some of the source material, reduced number of eligible studies with high in-between heterogeneity and small sample sizes. CONCLUSION: Our study showed no evidence to support the superiority of ketamine over ECT for severity of depressive symptoms and response to therapy. Regarding side effects, there was a statistically significant decreased risk of muscle pain in patients treated with ketamine compared to ECT.

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Depression in older adults with multiple medical comorbidities can contribute to clinical deterioration, and increased mortality. Electroconvulsive therapy (ECT) is the first-line treatment for these patients. This study aimed to evaluate the effectiveness and safety of subcutaneous (SC) ketamine as an alternative to ECT. We reviewed the medical records of all consecutive older inpatients with severe depression and multiple medical comorbidities who were referred for ECT but treated with SC ketamine over 1 year in our institution. Demographic data, DSM-5 diagnosis, MÅDRS score, and CGI score were analyzed. Twelve patients aged 67-94 years were included. All patients were rated as severely ill, 83% were women, with a mean of 12.6 (SD, 1.4) medical comorbidities. Remission was achieved in 75% of the intention-to-treat population and 100% of treatment completers. The number of sessions ranged from 1 to 6, and days until remission from 1 to 16. Patients remained without relapse for 8-28 months. SC ketamine was safe and well tolerated, and most adverse events were mild and transient. Although limited by the retrospective open-label design of the study and small sample size, our findings provide a potential new indication for ketamine: treatment of severe depression, not necessarily resistant to antidepressants, in older patients with multiple medical comorbidities, at risk of clinical deterioration, and referral for ECT. SC ketamine was highly effective in this population, with no relapse and good tolerance. Randomized controlled trials are needed to adequately test the use of ketamine in this specific group.

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Different anesthetic combinations are used for orchiectomy in cats. This study aimed to evaluate the anesthetic and cardiopulmonary effects on the physiological variables of ketamine (10 mg/kg), midazolam (0.2 mg/kg) and methadone (0.3 mg/kg), combined with local anesthesia, in cats undergoing orchiectomy (n = 19 cats). The time for lateral recumbency, degree of sedation, muscle relaxation and nociception were recorded preoperatively. The propofol rescue dose was recorded. The time to head up and quality of recovery were evaluated postoperatively. The time for lateral recumbency was 5 ± 2 minu-tes. Fifteen minutes after the administration of the ketamine-midazolam-methadone combination, a greater sedative effect, muscle relaxation and less response to noxious stimulation were observed. Propofol was administered to twelve cats under local anesthesia, at a total dose of 1.5 ± 0.8 mg/kg. Surgery was started 28 ± 5 minutes after the administration of ketamine--midazolam-methadone combination. There were no differences in the physiological variables evaluated over the other evalu-ation times (p > 0.05). The recovery quality scores were adequate, and the time to head up was 51 ± 10 minutes. Under the conditions of this study, the ketamine-midazolam-methadone combination did not allow local anesthesia for orchiectomy. Many cats required propofol rescue prior to surgery. This combination promoted minimal changes in physiological variables and prolonged anesthetic recovery.(AU)

Diferentes combinações anestésicas são usadas para orquiectomia em gatos. O objetivo deste estudo foi avaliar o efeito anestésico e as alterações promovidas nas variáveis fisiológicas pela cetamina (10 mg/kg), midazolam (0.2 mg/kg) e metadona (0.3 mg/kg), combinados com anestesia local, em gatos submetidos à orquiectomia (n = 19 gatos). O tempo para adoção do decúbito lateral, grau de sedação, relaxamento muscular e nocicepção foram registrados no pré-operatório. A dose de resgate de propofol foi registrada. O tempo para o gato erguer a cabeça e a qualidade da recuperação foram avaliados no pós-operatório. O tempo para adoção do decúbito lateral foi de 5 ± 2 minutos. Quinze minutos após a administração da associação cetamina-midazolam-metadona, observou-se maior efeito sedativo e relaxamento muscular, e menor resposta à estimulação nociva. O propofol foi administrado em doze gatos para realização de anestesia local, utilizando a dose total de 1.5 ± 0.8 mg/kg. A cirurgia foi iniciada 28 ± 5 minutos após a administração de cetamina-midazolam-metadona. Não houve diferença nas variáveis fisiológicas avaliadas em relação aos demais tempos de avaliação (p > 0.05). Os escores de qualidade de recuperação foram adequados e o tempo para o gato erguer a cabeça foi de 51 ± 10 minutos. Nas condições deste estudo, cetamina-midazolam-metadona não permitiu a realização da anestesia local para orquiectomia. Muitos gatos precisaram de resgate com propofol antes de iniciar a cirurgia. Essa associação promoveu alterações mínimas nas variáveis fisiológicas e longa recuperação anestésica.(AU)

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