Ketamine Infusion Research Articles

Sleep alterations in treatment-resistant depression patients undergoing ketamine treatment.

This study examines self-reported sleep alterations in treatment-resistant depression (TRD) inpatients following intravenous ketamine administration. This is a post-hoc analysis of a naturalistic observational study, which enrolled 28 inpatients with treatment-resistant major depressive disorder and analyzed self-reported sleep changes (items 1-4; 'insomnia', 'nighttime restlessness', 'early morning waking', 'hypersomnia') in Inventory of Depressive Symptomatology 30-item (IDS SR-30) in responders and non-responders stratified per Montgomery-Åsberg Depression Rating Scale (MADRS) during short-term ketamine treatment. Responders, as well as non-responders, did not experience significant changes in IDS SR-30 sleep items ('insomnia', 'nighttime restlessness', 'early morning waking', 'hypersomnia') (p's > 0.05) at 7-day follow-up after eight intravenous ketamine infusions as compared to baseline. Neither responders, nor non-responders reported any significant alterations in sleep patterns during ketamine infusions. These findings are not in line with current literature, as so far modest improvements in sleep during ketamine treatment have been reported. Results should be interpreted with caution, primarily due to the small sample size.

Comparison of intravenous dexmedetomidine versus ketamine-dexmedetomidine combination on spinal block characteristics in patients undergoing lower limb orthopaedic surgery - A randomised clinical trial.

One major limitation of the spinal block remains the inability to extend the duration of the block intraoperatively unless planned before with spinal or epidural catheters and/or intrathecal additives. This study was designed to compare the effects of intravenous dexmedetomidine versus low-dose ketamine-dexmedetomidine combination infusion on spinal anaesthesia in lower limb orthopaedic surgeries. This randomised study was conducted in 60 patients scheduled for unilateral lower limb surgeries under spinal anaesthesia. Patients were randomised into Group D (n = 30) (0.5 µg/kg of intravenous (IV) dexmedetomidine bolus followed by maintenance infusion at 0.5 µg/kg/h) and Group LKD (n = 30) (IV bolus of 0.5 µg/kg of dexmedetomidine and 0.2 mg/kg of ketamine, followed by maintenance infusions of dexmedetomidine and ketamine at 0.5 µg/kg/h and 0.2 mg/kg/h, respectively). Ramsay Sedation Scale score of 3-4 was maintained. The t-test or the Wilcoxon-Mann-Whitney U test was used to compare the parameters between groups. The mean sacral segment 1 (S1) regression time was 390.3 [standard deviation (SD):84.38] [95% confidence interval (CI): 360.13, 420.53] versus 393.23 (SD: 93.01) (95% CI: 363.04, 423.43) min in Group D versus Group LKD respectively ((P = 0.701). The number of episodes of hypotension was significantly higher in Group D (19 patients) compared to Group LKD (nine patients) (P = 0.001). Pre- and postoperative stress markers (24 h) and the incidence of postoperative nausea and shivering were comparable between the two groups (P > 0.05). Tramadol requirement in the postoperative period was significantly less in Group LKD compared to Group D (P = 0.003). The duration of S1 regression was similar between group dexmedetomidine (Group D) and group low-dose ketamine and dexmedetomidine (Group LKD).

Effect of propofol infusion vs ketamine plus dexmedetomidine infusion on the amplitude of motor evoked potential in pediatric patients undergoing tethered spinal cord surgeries; a randomized, double blind controlled study

Background & objective: The use of intraoperative neurophysiologic monitoring (IOM) has increased over the past two decades for the detection and prevention of iatrogenic neurologic injuries. Motor evoked potentials (MEP) are extremely sensitive to changes in physiological variables and inhalational agents reduce MEPs in a dose dependent manner. So IV anesthetics (propofol or ketamine) and opioids (fentanyl or remifentanil), are frequently used in spinal surgeries under MEPs monitoring. We compared the effects of propofol and fentanyl to those of ketamine, dexmedetomidine, and fentanyl in terms of minimizing their effects on MEP amplitude and hemodynamic stability during surgery Methodology: This double blind, randomized, prospective study was conducted on 46 children, who were randomly allocated into 2 groups Ketamine–dexmedetomidine group: (n = 23) Maintenance throughout the procedure, by infusing Dexmedetomidine (0.4 -0.6 μg/.kg /.hr) ketamine, (1 -2m/.kg/.hr.) and giving bolus of fentanyl, (1-2μg/.kg/ ). Propofol-group:(n = 23) Maintenance throughout the procedure, By infusing propofol (100 ug L/kg/min) and giving bolus of fentanyl, (1-2μg/.kg/ ), with keeping mean arterial blood pressure changes within 25% of the baseline in both groups. Results: Right and left quadriceps muscle measurements were insignificantly different between both groups at base line and were significantly higher in Group KD than Group P at skin incision, surgical manipulation and surgical closure. Right and left adductor hallucis muscle measurements were insignificantly different between both groups at base line and were significantly higher in Group KD than Group P at 5 mins, 10 mins, 15 mins, skin incision, surgical manipulation and surgical closure (P value <0.001). Intraoperative fentanyl consumption was significantly lower in Group KD than Group P. Conclusion: The combination of dexmedetomidine and ketamine infusion is efficacious, safe, and has minimal effect on evoked potentials compared with the propofol-based TIVA group during spine pediatrics surgery. In addition, this combination increases the reliability and accuracy of MEP monitoring with hemodynamic stability and adequate post-operative pain relief. Using dexmedetomidine and ketamine infusions during pediatric spine surgery might successfully replace the typical propofol-based TIVA, although more studies are required . Registration: ClinicalTrials.gov registration number NCT05591001. Keywords: Motor evoked potential, dexmedetomidine, ketamine, propofol. Citation: Saleh AH, Hammad SH, Hassan PF. Effect of propofol infusion vs ketamine plus dexmedetomidine infusion on the amplitude of motor evoked potential in pediatric patients undergoing tethered spinal cord surgeries; a randomized, double blind controlled study. Anaesth. pain intensive care 2024;28(4):692−699; DOI: 10.35975/apic.v28i4.2218 Received: May 08, 2023; Reviewed: February 02, 2024; Accepted: July 03, 2924

Non-improvement predicts subsequent non-response to repeated-dose intravenous ketamine for depression: a re-analysis of a 2-week open-label study in patients with unipolar and bipolar depression

There is insufficient evidence to guide dose and frequency optimization with repeated-dose ketamine for depression. This study assessed the value of symptomatic non-improvement after the first few ketamine infusions as a predictor of overall non-response in depression for early decision-making to discontinue treatment. A total of 135 individuals with major depressive disorder or bipolar disorder experiencing a current major depressive episode were administered six repeated doses of intravenous ketamine. Depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline, 4 h after the first infusion, and 24 h after each infusion. Improvement, partial response, and response were defined as a reduction rate of ≥ 20%, 30%, and 50% in MADRS scores, respectively. This study examined the relationship between improvement (as opposed to non-improvement after each infusion or consecutive non-improvements after the first few infusions) and partial response and response after the sixth infusion. This analysis was summarized using sensitivity, specificity, and other diagnostic test parameters. The sensitivities of improvement at 24 h post-infusion 4 and improvement at 24 h post-infusion 3, vs. three consecutive non-improvements, as predictors for overall partial response and response exceeded 90%. No significant reduction in depressive symptoms was seen in non-improvers following the remaining infusions after the above-identified point. Our study suggests that non-improvement after four infusions, or more conservatively three consecutive non-improvements after three infusions, could serve as a signal of overall non-response to repeated-dose intravenous ketamine for depression and that subsequent treatments would not be warranted.

Ketamine Infusion Treatment (KIT): Emerging Role of PACU RNs in the Care of Veterans with Treatment-Refractory Depression (TRD) and Severe Suicidal Ideation (SI)

Ketamine Infusion Treatment (KIT): Emerging Role of PACU RNs in the Care of Veterans with Treatment-Refractory Depression (TRD) and Severe Suicidal Ideation (SI)

Efficacy of Continuous Infusion Ketamine for Analgosedation in the Medical Intensive Care Unit: A Propensity-Weighted Analysis

Background: Few randomized controlled trials have evaluated the use of ketamine vs opiate-based analgosedation. Methods: A retrospective cohort analysis of 169 mechanically ventilated patients admitted to the medical intensive care unit (MICU) at an academic medical center was conducted to evaluate efficacy of ketamine vs opiate-based analgosedation by comparing the percentage of time within target sedation range. The primary outcome was percentage of time within target sedation range (RASS -1 to +1) within first 72 hours of primary sedation initiation. Secondary outcomes including percentage of time under-sedated, over-sedated, and in coma; use of concomitant analgesic, sedative, and antipsychotic agents; presence of delirium; percentage of CPOT scores at goal; and hemodynamic effects were also evaluated. Results: After weighting, the mean percentage of time at RASS goal for ketamine patients was 43.0% compared to 41.4% for opiate-based sedation patients. Ketamine was not significantly non-inferior to opiate-based sedation for the mean percentage of time at RASS goal (P = .11). The median percentage of CPOT scores at goal was 13.3% higher in the ketamine group (P = .042). Patients in the ketamine group received significantly less additional sedative agents than the patients in the opiate-based sedation group. Conclusion: A similar percent of time at RASS goal was found for the ketamine analgosedation group compared to the opiate-based sedation group, although this did not reach statistical signicance for non-inferiority due to lack of statistical power. This study found a higher percentage of CPOT scores within goal with less additional sedative agents required compared to an opiate-based sedation regimen.

Transient peripheral blood transcriptomic response to ketamine treatment in children with ADNP syndrome

Activity-dependent neuroprotective protein (ADNP) syndrome is a rare neurodevelopmental disorder resulting in intellectual disability, developmental delay and autism spectrum disorder (ASD) and is due to mutations in the ADNP gene. Ketamine treatment has emerged as a promising therapeutic option for ADNP syndrome, showing safety and apparent behavioral improvements in a first open label study. However, the molecular perturbations induced by ketamine remain poorly understood. Here, we investigated the longitudinal effect of ketamine on the blood transcriptome of 10 individuals with ADNP syndrome. Transcriptomic profiling was performed before and at multiple time points after a single low-dose intravenous ketamine infusion (0.5 mg/kg). We show that ketamine triggers immediate and profound gene expression alterations, with specific enrichment of monocyte-related expression patterns. These acute alterations encompass diverse signaling pathways and co-expression networks, implicating upregulation of immune and inflammatory-related processes and down-regulation of RNA processing mechanisms and metabolism. Notably, these changes exhibit a transient nature, returning to baseline levels 24 hours to 1 week after treatment. These findings enhance our understanding of ketamine’s molecular effects and lay the groundwork for further research elucidating its specific cellular and molecular targets. Moreover, they contribute to the development of therapeutic strategies for ADNP syndrome and potentially, ASD more broadly.

Ketamine Infusion for Reducing Post-Operative Pain and Opioid Use in Gynecological Surgery

This analysis aimed to evaluate the efficacy of ketamine infusion for reducing post-operative pain and opioid use in gynecological surgeries. A comprehensive review of recent studies revealed that ketamine consistently demonstrates significant pain-reducing and opioid-sparing effects across various surgical contexts, including gynecological procedures. Sub-anesthetic doses of ketamine were found to be effective and well-tolerated. However, optimal dosing regimens and timing of administration specific to gynecological surgeries require further investigation. The analysis recommends conducting large-scale, procedure-specific trials to establish tailored protocols for different gynecological surgeries. Additionally, long-term follow-up studies are needed to assess the impact on chronic pain development and persistent opioid use. This analysis is significant for refining pain management strategies in gynecological surgeries, potentially improving patient outcomes and addressing opioid-related concerns. It underscores the need for more flexible regulations to facilitate ketamine's clinical use in this context.

A randomized controlled pilot study of daily intravenous ketamine over three days for treatment-resistant depression

BackgroundStudies have confirmed the rapid antidepressant action of ketamine in depressive episodes. Nevertheless, a standardized procedure for the delivery of ketamine infusion in individuals suffering from treatment-resistant depression, particularly in terms of infusion frequency and total dosage, remains undetermined. In addition, an efficacious ketamine regimen for persistent pain management involved a continuous 10-day infusion period with no notable adverse effects. Consequently, the primary objective of this study was to evaluate the antidepressant capacity of consecutive ketamine infusions spanning over three successive days, the duration of therapeutic response, and the overall safety profile of the treatment.MethodsIn this randomized controlled trial, participants aged 18–64 with treatment-resistant depression were randomized to receive either intravenous ketamine or midazolam (used as an active placebo) for 40 min daily over three consecutive days. Statistical analysis using repeated measures ANOVA was employed to assess the changes in the total score of the Montgomery–Åsberg Depression Rating Scale (MADRS) and the clinical global impression-Severity from the initial assessment to 10 and 31 days post-infusion. Additionally, the duration of response and remission was evaluated using Kaplan–Meier survival analysis.ResultsOut of 33 randomized participants, 20 underwent the treatment as planned. By day 10th, the ketamine group had a mean reduction in MADRS score of 12.55 (95% CI = 6.70–18.09), whereas the midazolam group had a decrease of 17.22 (95% CI = 11.09–23.36). This pattern continued to day 31, with ketamine showing a mean score decrease of 13.73 (95% CI = 7.54–19.91) and midazolam a fall of 12.44 (95% CI = 5.61–19.28). Both treatments were well tolerated, with dissociative symptoms in the ketamine group being temporary and ceasing by the end of each infusion.ConclusionIntravenous ketamine given for three consecutive days did not show a notable antidepressant advantage when compared to the active placebo midazolam, highlighting the need for further research into effective treatments schedules for treatment-resistant depression.Trial registrationNCT05026203, ClinicalTrials.gov, registered on 24/08/2021.

Treatment-emergent symptoms during short-term ketamine administration in treatment-resistant bipolar depression: A retrospective cross-sectional descriptive study

Symptoms that emerge during pharmacological treatment of bipolar depression are frequently observed, underscoring the necessity for comprehensive treatment monitoring. This observational study sought to observe the correlation of eight intravenous ketamine infusions with treatment-emergent depressive symptoms in treatment-resistant bipolar depression patients who maintained their baseline psychotropic and chronic somatic treatments. Depressive symptoms were evaluated using the Inventory of Depressive Symptomatology Self-Report 30 (IDS-SR30). Treatment-emergent symptoms TES were defined as symptoms absent at baseline but present at the conclusion of the study. The most common TES included decreased appetite, increased weight, hypersomnia, and diurnal mood variation. Conversely, feelings of sadness, altered perceptions of the future, decreased interest in sex, and physical discomfort were absent in all patients. Notably, 13.6 % of patients reported thoughts of death or suicide. Larger-scale studies, integrating clinician-rated and patient-reported outcome measures, are essential to deepen our understanding of treatment-emergent symptoms. Establishing regulatory or professional definitions for treatment-emergent symptoms is warranted to improve the robustness of future research endeavors.

Effects of Low-Dose Ketamine Infusion on the Positive and Negative Domains of Hopelessness and Suicidal Thoughts

Effects of Low-Dose Ketamine Infusion on the Positive and Negative Domains of Hopelessness and Suicidal Thoughts

Thalamocortical functional connectivity and rapid antidepressant and antisuicidal effects of low-dose ketamine infusion among patients with treatment-resistant depression.

Previous studies have shown an association between the thalamocortical dysconnectivity and treatment-resistant depression (TRD). Whether a single subanesthetic dose of ketamine may change thalamocortical connectivity among patients with TRD is unclear. Whether these changes in thalamocortical connectivity is associated with the antidepressant and antisuicidal effects of ketamine treatment is also unclear. Two resting-state functional MRIs were collected in two clinical trials of 48 patients with TRD (clinical trial 1; 32 receiving ketamine, 16 receiving a normal saline placebo) and 48 patients with TRD and strong suicidal ideation (clinical trial 2; 24 receiving ketamine, 24 receiving midazolam), respectively. All participants underwent rs-fMRI before and 3 days after infusion. Seed-based functional connectivity (FC) was analyzed in the left/right thalamus. FCs between the bilateral thalamus and right middle frontal cortex (BA46) and between the left thalamus and left anterior paracingulate gyrus (BA8) increased among patients in the ketamine group in clinical trials 1 and 2, respectively. FCs between the right thalamus and bilateral frontal pole (BA9) and between the right thalamus and left rostral paracingulate gyrus (BA10) decreased among patients in the ketamine group in clinical trials 1 and 2, respectively. However, the associations between those FC changes and clinical symptom changes did not survive statistical significance after multiple comparison corrections. Whether ketamine-related changes in thalamocortical connectivity may be associated with ketamine's antidepressant and antisuicidal effects would need further investigation. Clinical trials registration: UMIN Clinical Trials Registry (UMIN-CTR): Registration number: UMIN000016985 and UMIN000033916.

Blood pressure changes during ketamine infusion for the treatment of depression

ObjectiveThis study aimed to examine blood pressure changes during ketamine infusion for depression and exploring the factors associated with these changes. MethodThis study is a retrospective chart-review of patients with depression undergoing ketamine infusion at Yale Psychiatry Hospital during a 7-year period. Blood pressure (BP) was recorded every 10 min during the infusion. Surges in systolic and diastolic blood pressure (SBP, DBP), along with severe hypertension events, were analyzed in relation to patient demographics. ResultsA total of 138 patients received a total of 2342 infusions. SBP and DBP peaked at 40 min after the start of the infusion with a mean change of 16.0 (SD: 11.2) and 11.0 mmHg (SD: 8.45) respectively. Severe hypertension was observed in 17 patients (12.5%) and 23 infusion sessions (0.98%), occuring more frequently during the first three infusions (43.4%). Age (OR = 1.04 [1.02,1.05], p-value <0.001) was significantly associated with a surge in SBP and all patients with a past medical history of hypertension experienced a BP surge during their infusions. ConclusionKetamine infusions can cause significant blood pressure increases, particularly in older and hypertensive patients, highlighting the need for careful cardiovascular monitoring to mitigate risks during treatment.

Opioid-Free Anesthesia with a Mixture of Dexmedetomidine, Ketamine and Lidocaine in Severely Obese Patients Undergoing Laparoscopic Cholecystectomy

Abstract Background Opioids have historically been a first-line therapy for surgical pain control. They were considered optimum and the mainstay for balanced anesthesia but recently the concerns about their side effects were raised. The concept of opioid free anesthesia (OFA) was introduced to provide a safer alternative that would provide benefits to selective group of patients as well as enhance recovery after surgery. Methods The current study compares the use of a mixture of dexmedetomidine and ketamine infusion with traditional fentanyl infusion intra-operative on many variables both intra-operative and post- operative in laparoscopic surgeries. Number of patients who will need rescue narcotics after extubation and total nalbuphine consumption, hemodynamic events (bradycardia, hypotension and hypertension), time to extubation, time to reach Alderete score of 9, post-operative hypoxemia, vomiting, pain scores were recorded and compared with the traditional balanced anesthesia (TBA). Results Forty patients were enrolled in the study, 20 patients in each group. The 2 groups, TBA and OFA, were comparable in demographic data (age, sex, body mass index (BMI), lean body weight (LBW)) and duration of surgery. There was significant decrease in pain scores, number of patients who will need rescue narcotics after extubation and nalbuphine consumption in the OFA group that extended to 24 h post-operative. TBA group showed statistically significant less time needed for extubation (P-value 0.018) and reaching Aldrete score of 9 (P-value 0.02). Conclusions OFA has a better profile than TBA as regard to post-operative pain score and opioid consumption post-operative but they have relative increase in time to extubation and time to reach Aldrete score of 9, and they were equally safe regarding post operative hypoxia and hemodynamics.

Peri-Operative Use of Ketamine Infusion versus Dexmedetomidine Infusion for Analgesia in Obese Patients Undergoing Bariatric Surgery: A Double-Blinded Three-Armed Randomized Controlled Trial

Abstract Background The development of different techniques in bariatric surgeries has required the development of novel anesthetic techniques to reduce the incidence of complications and improve post-operative patient outcomes. Ketamine and dexmedetomidine have been used for their peri-operative analgesic profiles in different studies. Methods Ninety patients were studied and randomized equally into three groups. The Ketamine group received a bolus dose (0.3 mg/kg) of ketamine over 10 min followed by an infusion (0.3 mg/kg/h). The Dexmedetomidine group received a bolus dose (0.5 mcg/kg) of dexmedetomidine over 10 min followed by an infusion (0.5 mcg/kg/h). The control group received normal saline infusion. The total morphine dose was the primary outcome, and intra-operative fentanyl requirements, time to extubation, post-operative nausea and vomiting (PONV), Numerical Rating Scale (NRS) scores, and Modified Observer’s Agitation/Sedation Scale (MOASS) scores were secondary outcomes of the study. Results The Dexmedetomidine group showed decreased intra-operative fentanyl requirements (160.000 ± 42.345 µcg), less time to extubation (3.700 ± 0.925 min), and better scores on MOASS than the other groups. Post-operative NRS scores and the morphine requirement in the Ketamine group (1.867 ± 2.921 mg) were lower than in the other groups. The Dexmedetomidine group showed the lowest scores for PONV. Conclusions The Dexmedetomidine group showed lower total fentanyl doses, a significantly shorter time to extubation, better MOASS scores, and lower PONV. The Ketamine group showed significantly lower NRS scores and morphine doses than the other two groups. Dexmedetomidine was effective on the reduction of intraoperative fentanyl requirement with early extubation, and ketamine was effective on the reduction of postoperative pain. Trial Registration This trial has been registered on clinicaltrials.gov registry (NCT04576975) since 06/10/2020.

Ketamine plus Cervical Sympathetic Blockade (CSB) Seems to be Significantly More Effective in Reducing the Symptoms of PTSD and Depression than CSB alone in a PTSD Cohort

Purpose: A significant number of Americans have symptoms of Post-Traumatic Stress Disorder (PTSD) and depression. Cervical sympathetic block (CSB) combined with sub-anesthetic ketamine infusions (KI) have been shown to reduce the symptoms of PTSD and depression via a synergistic effect. We aim to report a significant improvement of PTSD and depressive symptoms by concordant use of CSB and KI as compared to CSB alone. Methods: 26 consecutive patients were recruited to study the effects of KI and bilateral CSB vs bilateral CSB alone on sleep via a WHOOP band analysis. Patients were randomized to receive CSB alone vs KI and CSB. Patients received KI and CSB via clinic protocol. Results: Patients (n=11) that received CSB only, demonstrated a PCL reduction of 56.1% and BDI reduction of 59.5%. Patients (n=12) that received CSB and KI together, demonstrated a PCL reduction of 76.9% and a BDI reduction of 83.7%. Conclusion: Bilateral CSB combined with KI seems to be more effective in treating PTSD and depression symptoms as compared to bilateral CSB alone. Considering the size of the study, a larger scale evaluation would be necessary to confirm our findings.

Retrospective case-control non-inferiority analysis of ultrasound-guided erector spinae plane block in dogs undergoing mini-hemilaminectomy for intervertebral disc disease.

Veterinary medicine has seen significant advancements in locoregional anaesthesia and pain management, including the emergence of the erector spinae plane (ESP) block. However, limited clinical evidence exists on its efficacy and safety. This study compares ultrasound-guided ESP block (ESP group) with an intraoperative intravenous ketamine infusion analgesic protocol (CRI group) in dogs undergoing thoracolumbar mini-hemilaminectomy, focusing on intraoperative opioid consumption, cardiovascular response to surgical stimulation (CR), postoperative pain scores (PS), and postoperative opioid consumption. Retrospective, case-control, non-inferiority study conducted in a single centre. Data collected included demographics, bupivacaine dose, ESP block operator, intraoperative recorded variables (haemodynamic variables, CR, complications, rescue analgesia), pre- and postoperative analgesia, 24-hour PS and opioid administration, first food intake post-extubation and postoperative complications. Univariate and multiple regression analyses were applied. One-hundred dogs were included, 75 in the ESP group and 25 in the CRI group. Univariate analysis revealed no significant differences between treatment groups in terms of CR, PS, postoperative rescue analgesia, intraoperative and postoperative opioid consumption, or time to first meal intake. However, the multivariate regression analysis indicated that dogs receiving ketamine infusion had higher CR suspected to be nociception-related (p = 0.036), and higher postoperative opioid consumption (p = 0.013). Our study suggests that ultrasound-guided ESP block is as effective as intraoperative ketamine infusion providing perioperative analgesia in dogs undergoing thoracolumbar mini-hemilaminectomy for intervertebral disc disease. ESP group showed significantly lower CR suspected to be nociception-related intraoperatively and lower postoperative opioid consumption within the initial 24 hours.

Ketamine vs Electroconvulsive Therapy for Treatment-Resistant Depression

The ELEKT-D: Electroconvulsive Therapy (ECT) vs Ketamine in Patients With Treatment Resistant Depression (TRD) (ELEKT-D) trial demonstrated noninferiority of intravenous ketamine vs ECT for nonpsychotic TRD. Clinical features that can guide selection of ketamine vs ECT may inform shared decision-making for patients with TRD. To evaluate whether selected clinical features were associated with differential improvement with ketamine vs ECT. This secondary analysis of an open-label noninferiority randomized clinical trial was a multicenter study conducted at 5 US academic medical centers from April 7, 2017, to November 11, 2022. Analyses for this study, which were not prespecified in the trial protocol, were conducted from May 10 to Oct 31, 2023. The study cohort included patients with TRD, aged 21 to 75 years, who were in a current nonpsychotic depressive episode of at least moderate severity and were referred for ECT by their clinicians. Eligible participants were randomized 1:1 to receive either 6 infusions of ketamine or 9 treatments with ECT over 3 weeks. Association between baseline factors (including 16-item Quick Inventory of Depressive Symptomatology Self-Report [QIDS-SR16], Montgomery-Asberg Depression Rating Scale [MADRS], premorbid intelligence, cognitive function, history of attempted suicide, and inpatient vs outpatient status) and treatment response were assessed with repeated measures mixed-effects model analyses. Among the 365 participants included in this study (mean [SD] age, 46.0 [14.5] years; 191 [52.3%] female), 195 were randomized to the ketamine group and 170 to the ECT group. In repeated measures mixed-effects models using depression levels over 3 weeks and after false discovery rate adjustment, participants with a baseline QIDS-SR16 score of 20 or less (-7.7 vs -5.6 points) and those starting treatment as outpatients (-8.4 vs -6.2 points) reported greater reduction in the QIDS-SR16 with ketamine vs ECT. Conversely, those with a baseline QIDS-SR16 score of more than 20 (ie, very severe depression) and starting treatment as inpatients reported greater reduction in the QIDS-SR16 earlier in course of treatment (-8.4 vs -6.7 points) with ECT, but scores were similar in both groups at the end-of-treatment visit (-9.0 vs -9.9 points). In the ECT group only, participants with higher scores on measures of premorbid intelligence (-14.0 vs -11.2 points) and with a comorbid posttraumatic stress disorder diagnosis (-16.6 vs -12.0 points) reported greater reduction in the MADRS score. Those with impaired memory recall had greater reduction in MADRS during the second week of treatment (-13.4 vs -9.6 points), but the levels of MADRS were similar to those with unimpaired recall at the end-of-treatment visit (-14.3 vs -12.2 points). Other results were not significant after false discovery rate adjustment. In this secondary analysis of the ELEKT-D randomized clinical trial of ECT vs ketamine, greater improvement in depression was observed with intravenous ketamine among outpatients with nonpsychotic TRD who had moderately severe or severe depression, suggesting that these patients may consider ketamine over ECT for TRD.

Baseline monocyte count predicts symptom improvement during intravenous ketamine therapy in treatment-resistant depression: a single-arm open-label observational study.

Neuroinflammatory processes in depression are associated with treatment resistance to conventional antidepressants. Ketamine is an effective new therapeutic option for treatment-resistant depression (TRD). Its well-established immunomodulatory properties are hypothesized to mediate its antidepressant effect. In this context, higher levels of inflammation may predict a better treatment response. However, conclusive evidence for this hypothesis is lacking. We thus investigated whether standard peripheral inflammatory cell markers and C-reactive protein (CRP) levels could predict symptom improvement during intravenous ketamine therapy in TRD patients. 27 participants with TRD were treated with six weight-adjusted intravenous ketamine infusions (0.5 mg/kg bodyweight) over three weeks. Baseline assessments included CRP, absolute monocyte count (AMC), and absolute neutrophil count (ANC). Depression severity was measured using the Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline (D1), after the first (D3) and before the last ketamine infusion (D18). Raters were blinded for the baseline laboratory assessments. 13 participants responded to ketamine treatment, and 8 participants partially responded. Baseline AMC showed a strong negative correlation with MADRS change at D3 (r=-0.57, p=0.002) and at D18 (r =-0.48, p=0.010), indicating that a high baseline AMC was associated with greater symptom improvement. A generalized linear model confirmed the association of baseline AMC with symptom improvement during ketamine treatment when additionally accounting for age, sex, and body mass index. Specifically, baseline AMC demonstrated predictive value to discriminate responders and partial responders from non-responders, but lacked discriminative ability between partial responders and responders. Baseline ANC correlated with the MADRS changes at D3 (r=-0.39, p=0.046), while CRP values did not correlate at all. Our prospective single-arm open-label observational study demonstrated that baseline AMC reliably predicted symptom improvement during intravenous ketamine treatment in TRD patients. AMC could therefore serve as a simple and easily accessible marker for symptom improvement during ketamine therapy in daily clinical practice. Future studies with larger sample sizes and a more detailed longitudinal assessment of AMC subtypes are needed to better understand the specific relationship between monocytes and the neuromodulatory effects of ketamine.

Use of Early Ketamine Sedation and Association With Clinical and Cost Outcomes Among Mechanically Ventilated Patients With COVID-19: A Retrospective Cohort Study.

To describe the utilization of early ketamine use among patients mechanically ventilated for COVID-19, and examine associations with in-hospital mortality and other clinical outcomes. Retrospective cohort study. Six hundred ten hospitals contributing data to the Premier Healthcare Database between April 2020 and June 2021. Adults with COVID-19 and greater than or equal to 2 consecutive days of mechanical ventilation within 5 days of hospitalization. The exposures were early ketamine use initiated within 2 days of intubation and continued for greater than 1 day. Primary was hospital mortality. Secondary outcomes included length of stay (LOS) in the hospital and ICUs, ventilator days, vasopressor days, renal replacement therapy (RRT), and total hospital cost. The propensity score matching analysis was used to adjust for confounders. Among 42,954 patients, 1,423 (3.3%) were exposed to early ketamine use. After propensity score matching including 1,390 patients in each group, recipients of ketamine infusions were associated with higher hospital mortality (52.5% vs. 45.9%, risk ratio: 1.14, [1.06-1.23]), longer median ICU stay (13 vs. 12 d, mean ratio [MR]: 1.15 [1.08-1.23]), and longer ventilator days (12 vs. 11 d, MR: 1.19 [1.12-1.27]). There were no associations for hospital LOS (17 [10-27] vs. 17 [9-28], MR: 1.05 [0.99-1.12]), vasopressor days (4 vs. 4, MR: 1.04 [0.95-1.14]), and RRT (22.9% vs. 21.7%, RR: 1.05 [0.92-1.21]). Total hospital cost was higher (median $72,481 vs. $65,584, MR: 1.11 [1.05-1.19]). In a diverse sample of U.S. hospitals, about one in 30 patients mechanically ventilated with COVID-19 received ketamine infusions. Early ketamine may have an association with higher hospital mortality, increased total cost, ICU stay, and ventilator days, but no associations for hospital LOS, vasopressor days, and RRT. However, confounding by the severity of illness might occur due to higher extracorporeal membrane oxygenation and RRT use in the ketamine group. Further randomized trials are needed to better understand the role of ketamine infusions in the management of critically ill patients.