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2.
Clin Neuropharmacol ; 47(3): 97-100, 2024.
Article in English | MEDLINE | ID: mdl-38743603

ABSTRACT

OBJECTIVE: Ketamine and esketamine have been used in the field of psychiatry to alleviate conditions such as major depressive disorder. Our objective was to evaluate the current literature on the use of ketamine for symptoms of social withdrawal in autism spectrum disorder (ASD) and autism-like conditions. METHODS: A comprehensive search of PubMed and Web of Science was conducted to identify literature involving the use of ketamine to treat symptoms of autism and social withdrawal. Patients with comorbid disorders were also included. RESULTS: Two original studies were found, showing mixed results on the use of ketamine for ASD. The use of esketamine found no statistically significant results, whereas the use of intravenous ketamine was shown to alleviate symptoms of social withdrawal especially in the short term. Neither study reported a significant amount of serious adverse events. Five case reports were also included, showing decreased depressive symptoms and evidence of increased social condition. CONCLUSIONS: Research on the use of ketamine for ASD and ASD-related conditions is limited. Evidence of improved social condition exists, but further studies should be conducted to increase sample power and test various doses and methods of administration.


Subject(s)
Ketamine , Ketamine/therapeutic use , Humans , Autism Spectrum Disorder/drug therapy , Autistic Disorder/drug therapy
4.
BMJ Open ; 14(5): e084844, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38692731

ABSTRACT

INTRODUCTION: Although short-term benefits follow parenteral ketamine for treatment-resistant major depressive disorder (TR-MDD), there are challenges that prevent routine use of ketamine by clinicians. These include acute dissociative effects of parenteral ketamine, high relapse rates following ketamine dosing and the uncertain role of psychotherapy. This randomised controlled trial (RCT) seeks to establish the feasibility of evaluating repeated oral doses of ketamine and behavioural activation therapy (BAT), compared with ketamine treatment alone, for TR-MDD. We also aim to compare relapse rates between treatment arms to determine the effect size of adding BAT to oral ketamine. METHODS AND ANALYSIS: This is a prospectively registered, two-centre, single-blind RCT. We aim to recruit 60 participants with TR-MDD aged between 18 and 65 years. Participants will be randomised to 8 weeks of oral ketamine and BAT, or 8 weeks of oral ketamine alone. Feasibility will be assessed by tracking attendance for ketamine and BAT, acceptability of treatment measures and retention to the study follow-up protocol. The primary efficacy outcome measure is the Montgomery-Asberg Depression Rating Scale (MADRS) measured weekly during treatment and fortnightly during 12 weeks of follow-up. Other outcome measures will assess the tolerability of ketamine and BAT, cognition and activity (using actigraphy). Participants will be categorised as non-responders, responders, remitters and relapsed during follow-up. MADRS scores will be analysed using a linear mixed model. For a definitive follow-up RCT study to be recommended, the recruitment expectations will be met and efficacy outcomes consistent with a >20% reduction in relapse rates favouring the BAT and ketamine arm will be achieved. ETHICS AND DISSEMINATION: Ethics approval was granted by the New Zealand Central Health and Disability Ethics Committee (reference: 2023 FULL18176). Study findings will be reported to participants, stakeholder groups, conferences and peer-reviewed publications. TRIAL REGISTRATION NUMBER: UTN: U1111-1294-9310, ACTRN12623000817640p.


Subject(s)
Depressive Disorder, Treatment-Resistant , Ketamine , Humans , Ketamine/administration & dosage , Ketamine/therapeutic use , Depressive Disorder, Treatment-Resistant/therapy , Depressive Disorder, Treatment-Resistant/drug therapy , Adult , Single-Blind Method , Middle Aged , Depressive Disorder, Major/therapy , Depressive Disorder, Major/drug therapy , Male , Female , Randomized Controlled Trials as Topic , Behavior Therapy/methods , Young Adult , Adolescent , Treatment Outcome , Prospective Studies , Aged
6.
BMC Anesthesiol ; 24(1): 185, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38789968

ABSTRACT

BACKGROUND: Despite the implementation of various postoperative management strategies, the prevalence of postoperative fatigue syndrome (POFS) remains considerable among individuals undergoing laparoscopic radical gastrectomy. While the N-methyl-D-aspartic acid receptor antagonist esketamine has demonstrated efficacy in enhancing sleep quality and alleviating postoperative pain, its impact on POFS remains uncertain. Consequently, the objective of this study is to ascertain whether perioperative administration of esketamine can effectively mitigate the occurrence of POFS in patients undergoing laparoscopic radical gastrectomy. METHODS: A total of 133 patients diagnosed with gastric cancer were randomly assigned to two groups, namely the control group (Group C) (n = 66) and the esketamine group (Group E) (n = 67), using a double-blind method. The Group C received standardized anesthesia, while the Group E received esketamine in addition to the standardized anesthesia. The primary outcome measure assessed was the Christensen fatigue score at 3 days after the surgical procedure, while the secondary outcomes included the disparities in postoperative fatigue, postoperative pain, sleep quality, and adverse reactions between the two groups. RESULTS: In the group receiving esketamine, the fatigue scores of Christensen on the third day after surgery were significantly lower compared to the Group C (estimated difference, -0.70; 95% CI, -1.37 to -0.03; P = 0.040). Additionally, there was a significant decrease in the occurrence of fatigue in the Group E compared to the Group C on the first and third days following surgery (P < 0.05). Also, compared to individuals who had distal gastrectomy, those who had entire gastrectomy demonstrated a higher degree of postoperative tiredness reduction with esketamine. Furthermore, the Group E exhibited reduced postoperative pain and improved sleep in comparison to the Group C. Both groups experienced similar rates of adverse events. CONCLUSIONS: The use of esketamine during the perioperative period can improve POFS after laparoscopic radical gastrectomy, without adverse reactions. TRIAL REGISTRATION: Registered in the Chinese Clinical Trial Registry (ChiCTR2300072167) on 05/06 /2023.


Subject(s)
Gastrectomy , Ketamine , Laparoscopy , Pain, Postoperative , Postoperative Complications , Stomach Neoplasms , Humans , Ketamine/administration & dosage , Ketamine/therapeutic use , Stomach Neoplasms/surgery , Male , Female , Double-Blind Method , Laparoscopy/methods , Middle Aged , Gastrectomy/methods , Postoperative Complications/prevention & control , Pain, Postoperative/drug therapy , Pain, Postoperative/prevention & control , Fatigue/prevention & control , Aged
7.
Psychiatry Res ; 337: 115949, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38795698

ABSTRACT

Ketamine, a N-methyl-D-aspartate (NMDA) antagonist, is used for treatment-resistant depression (TRD). Recent studies have shown that there are increased levels of pro-inflammatory cytokines in individuals with major depressive disorder (MDD) and those with higher levels of oxidative stress markers have a decreased or null response to conventional antidepressants. Glutathione (GSH) as an antioxidant adjuvant to ketamine has not been well studied. This double-blind study with 30 patients divided into 2 groups of 15 each, aimed to determine if GSH, added to standard ketamine infusion (GSH+K), rendered better outcomes in MDD patients versus patients receiving ketamine infusions with a normal saline placebo (K+NS). There were significant drops in BDI-II scores from day 1 to day 14, PHQ- scores from day 1 to day 14 and PHQ-9 scores day 14 to day 28, suggesting the overall treatment was effective. There were no statistically significant differences between the groups over time. However, a sustained improvement in depressive symptoms was observed for 14 days post-infusion in both groups.


Subject(s)
Depressive Disorder, Major , Glutathione , Ketamine , Humans , Ketamine/administration & dosage , Ketamine/pharmacology , Ketamine/therapeutic use , Depressive Disorder, Major/drug therapy , Female , Male , Adult , Double-Blind Method , Middle Aged , Drug Therapy, Combination , Antidepressive Agents/administration & dosage , Anti-Inflammatory Agents/administration & dosage , Depressive Disorder, Treatment-Resistant/drug therapy , Treatment Outcome , Infusions, Intravenous , Psychiatric Status Rating Scales
8.
Cell Mol Biol (Noisy-le-grand) ; 70(5): 204-208, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38814215

ABSTRACT

Parkinson's disease (PD) remains the most common neurodegenerative disease worldwide, seriously affecting the normal life of patients. Currently, there is no effective clinical cure for PD. In this study, the research team explored the effect of ketamine (KET) on PD, which can lay a reliable foundation for future KET treatment of PD. First, the research team established a PD rat model with 6-hydroxydopamine (6-OHDA). The detection showed that the maximum angle of the inclined plate stay, the number of times of grid crossings and standing, and the ATPase activity in brain tissue were significantly lower in PD rats than in control rats, while the positive rate of α-synuclein in brain tissue was increased, showing typical pathological manifestations of PD. After using KET to intervene in PD rats, the behavioral and brain pathological changes were significantly alleviated, and the inflammation and oxidative stress damage of brain tissue were effectively reduced, suggesting the potential therapeutic effects of KET on PD. Furthermore, the use of KET inhibited the PI3K/AKT axis in the brain tissue of PD rats and promoted autophagy. Moreover, the significant suppression of the PI3K/AKT axis by KET was also demonstrated in the PD cell model established through lipopolysaccharide (LPS) inducement of astrocyte cell line HA1800. It is suggested that the mechanism of KET on PD is related to the inhibition of the PI3K/AKT axis.


Subject(s)
Astrocytes , Ketamine , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Rats, Sprague-Dawley , Signal Transduction , Animals , Ketamine/pharmacology , Ketamine/therapeutic use , Phosphatidylinositol 3-Kinases/metabolism , Astrocytes/drug effects , Astrocytes/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/drug effects , Male , Rats , Autophagy/drug effects , Oxidative Stress/drug effects , Parkinson Disease/drug therapy , Parkinson Disease/metabolism , Parkinson Disease/pathology , Brain/drug effects , Brain/metabolism , Brain/pathology , Disease Models, Animal , Oxidopamine , Lipopolysaccharides , Humans
9.
BMC Psychiatry ; 24(1): 341, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38714931

ABSTRACT

BACKGROUND: Major depressive disorder (MDD) is the most disabling and burdensome mental disorder, negatively affecting an individual's quality of life and daily functioning. the current study was conducted with the aim of investigating the clinical effects of intravenous ketamine on symptoms of MDD and suicidal ideation. METHODS: The current randomized clinical trial was carried out on 64 patients diagnosed with treatment-resistant major depressive disorder between April and August 2022. The participants were randomly assigned to two groups: the intervention group received a dose of 0.5 mg/kg of ketamine, while the control group received normal saline. The Montgomery-Asberg Depression Scale and Beck's Suicidal Ideation Scale were utilized to assess depression and suicidal ideation, respectively. RESULTS: One hour after the administration of ketamine treatment, there was a notable and significant improvement in both depression symptoms (35.16 ± 8.13 vs. 14.90 ± 10.09) and suicidal ideation (6.74 ± 6.67 vs. 0.42 ± 1.52). Moreover, there were statistically significant differences in depression scores between the two groups at one hour, four hours, one day, three days, one week, one month, and two months after the administration of ketamine (p-value < 0.001). However, ketamine recipients frequently experienced side effects such as increased heart rate, headache, dizziness, and dissociative syndrome symptoms. CONCLUSION: The observed rapid onset of action and sustained effect demonstrate the potential of ketamine to provide relief from depressive symptoms in a shorter timeframe compared to traditional treatment approaches. These findings contribute to the growing body of evidence supporting the use of ketamine as a valuable therapeutic option for patients with treatment-resistant depression. IRCT REGISTRATION: IRCT registration number: IRCT20210806052096N1; IRCT URL: https://www.irct.ir/trial/62243 ; Ethical code: IR.ZUMS.REC.1400.150; Registration date: 2022-04-09.


Subject(s)
Antidepressive Agents , Depressive Disorder, Major , Depressive Disorder, Treatment-Resistant , Ketamine , Suicidal Ideation , Humans , Ketamine/therapeutic use , Ketamine/administration & dosage , Male , Female , Depressive Disorder, Major/drug therapy , Adult , Depressive Disorder, Treatment-Resistant/drug therapy , Antidepressive Agents/therapeutic use , Antidepressive Agents/administration & dosage , Middle Aged , Administration, Intravenous , Psychiatric Status Rating Scales , Treatment Outcome
10.
Ulus Travma Acil Cerrahi Derg ; 30(5): 309-315, 2024 May.
Article in English | MEDLINE | ID: mdl-38738674

ABSTRACT

BACKGROUND: This study aimed to evaluate the histopathological and biochemical effects of ketamine on penile tissues following ischemia-reperfusion injury induced by priapism. METHODS: Twenty-four male rats were randomized into three groups. Group 1 served as the control group. Group 2 underwent the priapism model to induce ischemia-reperfusion injury. Group 3, the treatment group, experienced a similar ischemia-reperfusion model as Group 2; additionally, 50 mg/kg of ketamine was administered intraperitoneally just before reperfusion. Blood biochemical analyses and penile histopathological evaluations were performed. RESULTS: In Group 3, significant improvements were observed in all histopathological scores, including desquamation, edema, inflammation, and vasocongestion compared to Group 2 (p<0.001). Blood biochemical analyses showed that the malondialdehyde (MDA) levels were recorded as 10 in Group 2, with a significant decrease in Group 3 (p=0.013). Similarly, proinflammatory cytokine levels, including interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), were found to be suppressed in Group 3 compared to Group 2 (p=0.003, p=0.022, and p=0.028, respectively). Antioxidant enzyme activities, such as glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD), were higher in Group 3 compared to Group 2 (p=0.016 and p=0.024, respec-tively). CONCLUSION: Ketamine is an effective anesthetic agent in alleviating the effects of penile ischemia-reperfusion injury.


Subject(s)
Disease Models, Animal , Ketamine , Malondialdehyde , Penis , Priapism , Reperfusion Injury , Animals , Ketamine/administration & dosage , Ketamine/pharmacology , Ketamine/therapeutic use , Male , Priapism/drug therapy , Priapism/etiology , Rats , Penis/drug effects , Penis/blood supply , Penis/pathology , Reperfusion Injury/drug therapy , Reperfusion Injury/metabolism , Malondialdehyde/metabolism , Tumor Necrosis Factor-alpha/blood , Tumor Necrosis Factor-alpha/metabolism , Random Allocation , Anesthetics, Dissociative/administration & dosage , Interleukin-1beta/metabolism , Interleukin-1beta/blood
11.
Psychiatry Res ; 335: 115890, 2024 May.
Article in English | MEDLINE | ID: mdl-38579458

ABSTRACT

This systematic review and meta-analysis aimed to evaluate the impact of intraoperative and/or postoperative esketamine application on the prevention of postpartum depression (PPD). PubMed, Embase, and Web of Science were thoroughly searched for eligible randomized controlled trials (RCTs) regarding the application of esketamine for postnatal depression prevention. Nine RCTs including 1277 participants were involved in the final analysis. It was found that intraoperative and/or postoperative administration of esketamine significantly reduced the PPD incidence and the Edinburgh Postnatal Depression Scores in the early postoperative period. Meanwhile, esketamine lowered the occurrence of postoperative nausea and vomiting with no influence on other psychiatric symptoms.


Subject(s)
Depression, Postpartum , Ketamine , Female , Humans , Depression, Postpartum/prevention & control , Ketamine/therapeutic use , Postoperative Nausea and Vomiting , Postoperative Period
12.
PLoS One ; 19(4): e0301848, 2024.
Article in English | MEDLINE | ID: mdl-38640139

ABSTRACT

Ketamine has been shown to produce analgesia in various acute and chronic pain states; however, abuse liability concerns have limited its utility. The ketamine metabolite (2R,6R)-hydroxynorketamine (HNK) has been shown to produce antidepressant-like effects similar to ketamine without abuse liability concerns. (2R,6R)-HNK produces sustained analgesia in models of chronic pain, but has yet to be evaluated in models of acute pain. The present study evaluated the efficacy of acute (2R,6R)-HNK administration (one injection) in assays of pain-stimulated (52- and 56-degree hot plate test and acetic acid writhing) and pain-depressed behavior (locomotor activity and rearing) in male and female C57BL/6 mice. In assays of pain-stimulated behaviors, (2R,6R)-HNK (1-32 mg/kg) failed to produce antinociception in the 52- and 56-degree hot plate and acetic acid writhing assays. In assays of pain-depressed behaviors, 0.56% acetic acid produced a robust depression of locomotor activity and rearing that was not blocked by pretreatment of (2R,6R)-HNK (3.2-32 mg/kg). The positive controls morphine (hot plate test) and ketoprofen (acetic acid writhing, locomotor activity, and rearing) blocked pain-stimulated and pain-depressed behaviors. Finally, the effects of intermittent (2R,6R)-HNK administration were evaluated in 52-degree hot plate and pain-depressed locomotor activity and rearing. Intermittent administration of (2R,6R)-HNK also did not produce antinociceptive effects in the hot plate or pain-depressed locomotor activity assays. These results suggest that (2R,6R)-HNK is unlikely to have efficacy in treating acute pain; however, the efficacy of (2R,6R)-HNK in chronic pain states should continue to be evaluated.


Subject(s)
Acute Pain , Chronic Pain , Ketamine , Ketamine/analogs & derivatives , Mice , Male , Female , Animals , Ketamine/pharmacology , Ketamine/therapeutic use , Acute Pain/drug therapy , Mice, Inbred C57BL , Acetates
13.
Discov Med ; 36(183): 714-720, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38665020

ABSTRACT

BACKGROUND: Spinal cord injury (SCI) is usually caused by external direct or indirect factors, and with a high morbidity and mortality rate. The aim of this study was to observe the effects of Dexmedetomidine (DEX) combined with Esketamine (ESK) on pain behavior and potential analgesic mechanisms in rats with SCI. The goal was to provide a reliable multimodal analgesic medication regimen for SCI. METHODS: Thirty rats were divided into five groups with six rats in each group: Sham group, SCI group, DEX group, ESK group, and DEX+ESK group. The SCI model in rats was constructed, and the motor function of hind limbs of rats was measured using Basso Beattie Bresnahan (BBB) locomotor rating scale and inclined plate test. The levels of interleukin 18 (IL-18), interleukin 1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) in the spinal cord were determined by enzyme-linked immunosorbent assay (ELISA). The expressions of substance P (SP), neurokinin-1 receptor (NK-1R), B cell lymphoma-2 (Bcl-2), and Bcl2-associated X protein (Bax) in the rats' spinal cord were measured by Western blot assay. The viability of spinal astrocytes was evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. RESULTS: After 7 days, the BBB scores were significantly higher in the DEX, ESK, and DEX+ESK groups compared to the SCI group (p < 0.01). Additionally, the DEX+ESK group had significantly higher scores than both the DEX and ESK groups (p < 0.01). The maximum angle of the DEX (p < 0.05), ESK (p < 0.05), and DEX+ESK groups (p < 0.01) were higher than the SCI group, and the maximum angle of DEX+ESK group was higher than DEX and ESK groups (p < 0.05). The levels of IL-18, IL-1ß, and TNF-α in the DEX, ESK, and DEX+ESK groups were lower than the SCI group (p < 0.01), while the DEX+ESK group had significantly lower IL-18, IL-1ß, and TNF-α levels than the DEX and ESK groups (p < 0.01). The levels of SP (p < 0.01) and NK-1R (p < 0.05) were lower in the DEX, ESK, and DEX+ESK groups compared to the SCI group, and the levels of SP and NK-1R were lower in the DEX+ESK group compared to the DEX and ESK groups (p < 0.01). The DEX and ESK groups suppressed the activity of spinal astrocytes (p < 0.01), however, the DEX+ESK group had larger effects on spinal astrocytes than the ESK group (p < 0.05). CONCLUSIONS: Treatment using DEX combined with ESK improves the motor function, inhibits inflammation and astrocyte activity, and exerts analgesic effects on rats with SCI. These findings can serve as a reference for the selection of multi-modal analgesics.


Subject(s)
Dexmedetomidine , Ketamine , Rats, Sprague-Dawley , Spinal Cord Injuries , Animals , Dexmedetomidine/pharmacology , Dexmedetomidine/therapeutic use , Spinal Cord Injuries/drug therapy , Spinal Cord Injuries/pathology , Spinal Cord Injuries/metabolism , Rats , Ketamine/pharmacology , Ketamine/therapeutic use , Male , Analgesics/pharmacology , Analgesics/therapeutic use , Spinal Cord/drug effects , Spinal Cord/pathology , Spinal Cord/metabolism , Substance P/metabolism , Disease Models, Animal , Tumor Necrosis Factor-alpha/metabolism , Receptors, Neurokinin-1/metabolism , Interleukin-1beta/metabolism
14.
J Affect Disord ; 355: 342-354, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38570038

ABSTRACT

BACKGROUND: Electrophysiologic measures provide an opportunity to inform mechanistic models and possibly biomarker prediction of response. Serotonergic psychedelics (SPs) (i.e., psilocybin, lysergic acid diethylamide (LSD)) and ketamine represent new investigational and established treatments in mood disorders respectively. There is a need to better characterize the mechanism of action of these agents. METHODS: We conducted a systematic review investigating the spectral signatures of psilocybin, LSD, and ketamine in persons with major depressive disorder (MDD), treatment-resistant depression (TRD), and healthy controls. RESULTS: Ketamine and SPs are associated with increased theta power in persons with depression. Ketamine and SPs are also associated with decreased spectral power in the alpha, beta and delta bands in healthy controls and persons with depression. When administered with SPs, theta power was increased in persons with MDD when administered with SPs. Ketamine is associated with increased gamma band power in both healthy controls and persons with MDD. LIMITATIONS: The studies included in our review were heterogeneous in their patient population, exposure, dosing of treatment and devices used to evaluate EEG and MEG signatures. Our results were extracted entirely from persons who were either healthy volunteers or persons with MDD or TRD. CONCLUSIONS: Extant literature evaluating EEG and MEG spectral signatures indicate that ketamine and SPs have reproducible effects in keeping with disease models of network connectivity. Future research vistas should evaluate whether observed spectral signatures can guide further discovery of therapeutics within the psychedelic and dissociative classes of agents, and its prediction capability in persons treated for depression.


Subject(s)
Depressive Disorder, Major , Hallucinogens , Ketamine , Humans , Psilocybin/therapeutic use , Ketamine/pharmacology , Ketamine/therapeutic use , Lysergic Acid Diethylamide/therapeutic use , Depressive Disorder, Major/drug therapy , Depression , Healthy Volunteers , Hallucinogens/adverse effects
15.
Emerg Med Pract ; 26(5): 1-24, 2024 May.
Article in English | MEDLINE | ID: mdl-38639638

ABSTRACT

Ketamine has been in use since its development as a dissociative anesthetic in the 1960s, but it was largely confined to the operating theater or austere environments until used by emergency physicians to facilitate painful procedures in children. As the unique effects of ketamine across its dose-response curve were understood, new applications emerged. In low doses, ketamine has found an important role alongside or instead of opioids in the management of severe pain, and methods to slow its absorption allow higher, more effective doses while attenuating psychoperceptual effects. Ketamine's unique anesthetic properties have inspired its use as an induction agent for intubation without a paralytic and for the rapid, safe control of dangerously agitated patients. Emerging uses for ketamine in acute care include treatment for status epilepticus and alcohol withdrawal syndrome; however, its most important rising indication may be as an emergency treatment of depression and suicidality.


Subject(s)
Alcoholism , Ketamine , Substance Withdrawal Syndrome , Child , Humans , Ketamine/therapeutic use , Ketamine/pharmacology , Substance Withdrawal Syndrome/drug therapy , Anesthetics, Dissociative/therapeutic use , Pain/drug therapy , Emergency Service, Hospital
16.
Medicina (Kaunas) ; 60(4)2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38674325

ABSTRACT

Background and Objectives: Thoracic epidural catheterization (TEC) can be both uncomfortable and fearful for patients when performed awake with the thought that the procedure may be painful. The aim of this study was to assess the effect of low-dose intravenous ketamine administration on pain and anxiety during the TEC procedure. Materials and Methods: Sixty patients were randomly divided into two groups to receive intravenous (IV) placebo (Group P) and IV low-dose (0.15 mg/kg) ketamine (LDK) (Group K) 3 min before the procedure in a double-blind manner. A visual analog scale (VAS) was used to measure anxiety (VAS-A) and pain (VAS-P) scores. Vital parameters were monitored before premedication (T1), 20 min after premedication (T2), during skin anesthesia (T3), during TEC (T4), and 5 min after TEC (T5). VAS-A values were recorded at T1, T3, T4, and T5 periods, and VAS-P levels were noted at T3, T4, and T5 periods. Results: During TEC (T4), both VAS-P and VAS-A were significantly lower in Group K (p < 0.001). The mean VAS-A value was 10.6 mm lower, and the mean VAS-P value was 9 mm lower in Group K than in Group P at the T4 time point. Additionally, the mean VAS-P value was 7.7 mm lower in Group K compared to Group P at the T3 time point (p < 0.001). Both groups showed a statistically significant difference in VAS-A measurements when compared at their respective time points (p < 0.001). However, only Group P demonstrated a statistically significant difference in VAS-P measurements (p < 0.001). VAS-P values remained stable in Group K. The number of patients who did not recall the procedure was significantly higher in Group K (p < 0.001). Furthermore, the number of patients who would consent to the same procedure in the future was significantly higher in Group K (p = 0.007). Conclusions: A preprocedural LDK (0.15 mg/kg) can effectively prevent anxiety and pain experienced by patients during the TEC procedure. Administration of LDK may provide a more comfortable procedure process without causing ketamine-induced side effects (hemodynamic, respiratory, and psychological).


Subject(s)
Anxiety , Ketamine , Pain Measurement , Humans , Ketamine/administration & dosage , Ketamine/therapeutic use , Male , Female , Double-Blind Method , Anxiety/prevention & control , Anxiety/drug therapy , Adult , Middle Aged , Pain Measurement/methods , Analgesics/therapeutic use , Analgesics/administration & dosage , Catheterization/methods , Catheterization/adverse effects , Pain/drug therapy , Pain/prevention & control , Pain/psychology , Anesthesia, Epidural/methods
17.
BMC Psychiatry ; 24(1): 315, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38658886

ABSTRACT

BACKGROUND: Breast cancer is the most common malignant tumor in females worldwide. During disease development, breast cancer patients suffer anxious and depressed, which may lead to worse quality of life or even higher mortality. Esketamine has been regarded as an antidepressant in breast cancer patients with mild or moderate depression. Here, we wonder whether the administration of esketamine could reduce the postoperative depressive symptom score of breast cancer patients who have no preoperative depression. METHODS: A total of 64 patients treated with unilateral modified radical mastectomy were randomly divided into an experimental group (esketamine group, Group E) and a control group (Group C), with 32 cases in each one. After anesthesia induction, Group C received 0.2 ml/kg of normal saline intravenously and Group E was administered 0.2 mg/kg intravenous esketamine. The primary outcome was the Patient Health Questionnaire-9 (PHQ-9) scores. The secondary outcomes included the Visual Analogue Scale (VAS) scores for pain, inflammatory markers, perioperative-related indicators, and the incidence of postoperative delirium, nausea and vomiting. RESULTS: The PHQ-9 score on postoperative day (POD) 1 in Group E declined from the preoperative level, while the score in Group C was higher than before, and the former was far lower than the latter (P = 0.047). There is no statistically significant difference in PHQ-9 scores between Group E and Group C on POD 3, 7, and 30. Moreover, the postoperative leukocyte level of Group E was higher than that of Group C, and the difference was statistically significant (P = 0.030). CONCLUSIONS: A single subanesthetic dose of esketamine can result in lower postoperative score on subthreshold depressive symptoms compared to the Group C on POD 1, without increasing the occurrence of postoperative adverse reactions. TRIAL REGISTRATION: Registration number: Chinese Clinical Trial Registry ChiCTR2200057028. Date of registration: 26/02/2022.


Subject(s)
Breast Neoplasms , Depression , Ketamine , Mastectomy, Modified Radical , Humans , Ketamine/administration & dosage , Ketamine/therapeutic use , Female , Middle Aged , Double-Blind Method , Breast Neoplasms/surgery , Adult , Postoperative Complications/prevention & control , Antidepressive Agents/therapeutic use , Antidepressive Agents/administration & dosage
18.
Neurosci Lett ; 831: 137791, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38670523

ABSTRACT

The antidepressant effects of ketamine and esketamine are well-documented. Nonetheless, most of the underlying molecular mechanisms have to be uncovered yet. In the last decade, metabolomics has emerged as a useful means to investigate the metabolic phenotype associated with depression as well as changes induced by antidepressant treatments. This mini-review aims at summarizing the main findings from preclinical and clinical studies that used metabolomics to investigate the metabolic effects of subanesthetic, antidepressant doses of ketamine and esketamine and their relationship with clinical response. Both animal and human studies report alterations in several metabolic pathways - including the tricarboxylic acid cycle, glycolysis, the pentose phosphate pathway, lipid metabolism, amino acid metabolism, the kynurenine pathway, and the urea cycle - following the administration of ketamine or its enantiomers. Although more research is needed to clarify commonalities and differences in molecular mechanisms of action between the racemic compound and its enantiomers, these findings comprehensively support an influence of ketamine and esketamine on mitochondrial and cellular energy production, membrane homeostasis, neurotransmission, and signaling. Metabolomics may thus represent a promising strategy to clarify molecular mechanisms underlying treatment-resistant depression and related markers of clinical response to ketamine and esketamine. This body of preclinical and clinical evidence, if further substantiated, has the potential to guide clinicians towards personalized approaches, contributing to new paradigms in the clinical management of depression.


Subject(s)
Antidepressive Agents , Ketamine , Metabolomics , Ketamine/pharmacology , Ketamine/therapeutic use , Humans , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Metabolomics/methods , Animals , Depression/drug therapy , Depression/metabolism
19.
Eur Psychiatry ; 67(1): e33, 2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38572583

ABSTRACT

BACKGROUND: Amygdala subregion-based network dysfunction has been determined to be centrally implicated in major depressive disorder (MDD). Little is known about whether ketamine modulates amygdala subarea-related networks. We aimed to investigate the relationships between changes in the resting-state functional connectivity (RSFC) of amygdala subregions and ketamine treatment and to identify important neuroimaging predictors of treatment outcomes. METHODS: Thirty-nine MDD patients received six doses of ketamine (0.5 mg/kg). Depressive symptoms were assessed, and magnetic resonance imaging (MRI) scans were performed before and after treatment. Forty-five healthy controls underwent one MRI scan. Seed-to-voxel RSFC analyses were performed on the amygdala subregions, including the centromedial amygdala (CMA), laterobasal amygdala (LBA), and superficial amygdala subregions. RESULTS: Abnormal RSFC between the left LBA and the left precuneus in MDD patients is related to the therapeutic efficacy of ketamine. There were significant differences in changes in bilateral CMA RSFC with the left orbital part superior frontal gyrus and in changes in the left LBA with the right middle frontal gyrus between responders and nonresponders following ketamine treatment. Moreover, there was a difference in the RSFC of left LBA and the right superior temporal gyrus/middle temporal gyrus (STG/MTG) between responders and nonresponders at baseline, which could predict the antidepressant effect of ketamine on Day 13. CONCLUSIONS: The mechanism by which ketamine improves depressive symptoms may be related to its regulation of RSFC in the amygdala subregion. The RSFC between the left LBA and right STG/MTG may predict the response to the antidepressant effect of ketamine.


Subject(s)
Amygdala , Antidepressive Agents , Depressive Disorder, Major , Ketamine , Magnetic Resonance Imaging , Humans , Ketamine/pharmacology , Ketamine/administration & dosage , Ketamine/therapeutic use , Depressive Disorder, Major/drug therapy , Depressive Disorder, Major/diagnostic imaging , Depressive Disorder, Major/physiopathology , Amygdala/drug effects , Amygdala/diagnostic imaging , Amygdala/physiopathology , Male , Female , Adult , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Antidepressive Agents/administration & dosage , Middle Aged , Treatment Outcome
20.
Ann Intern Med ; 177(4): JC44, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38560909

ABSTRACT

SOURCE CITATION: Guo J, Zhao F, Bian J, et al. Low-dose ketamine versus morphine in the treatment of acute pain in the emergency department: a meta-analysis of 15 randomized controlled trials. Am J Emerg Med. 2024;76:140-149. 38071883.


Subject(s)
Acute Pain , Ketamine , Humans , Acute Pain/drug therapy , Analgesics/adverse effects , Analgesics/therapeutic use , Emergency Service, Hospital , Ketamine/adverse effects , Ketamine/therapeutic use , Morphine/therapeutic use , Pain Measurement
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