Ketamine Treatment Research Articles

Changes in synaptic markers after administration of ketamine or psychedelics: a systematic scoping review.

Ketamine and psychedelics have abuse liability. They can also induce "transformative experiences" where individuals experience enhanced states of awareness. This enhanced awareness can lead to changes in preexisting behavioral patterns which could be beneficial in the treatment of substance use disorders (SUDs). Preclinical and clinical studies suggest that ketamine and psychedelics may alter markers associated with synaptic density, and that these changes may underlie effects such as sensitization, conditioned place preference, drug self-administration, and verbal memory performance. In this scoping review, we examined studies that measured synaptic markers in animals and humans after exposure to ketamine and/or psychedelics. A systematic search was conducted following PRISMA guidelines, through PubMed, EBSCO, Scopus, and Web of Science, based on a published protocol (Open Science Framework, DOI: 10.17605/OSF.IO/43FQ9). Both in vivo and in vitro studies were included. Studies on the following synaptic markers were included: dendritic structural changes, PSD-95, synapsin-1, synaptophysin-1, synaptotagmin-1, and SV2A. Eighty-four studies were included in the final analyses. Seventy-one studies examined synaptic markers following ketamine treatment, nine examined psychedelics, and four examined both. Psychedelics included psilocybin/psilocin, lysergic acid diethylamide, N,N-dimethyltryptamine, 2,5-dimethoxy-4-iodoamphetamine, and ibogaine/noribogaine. Mixed findings regarding synaptic changes in the hippocampus and prefrontal cortex (PFC) have been reported when ketamine was administered in a single dose under basal conditions. Similar mixed findings were seen under basal conditions in studies that used repeated administration of ketamine. However, studies that examined animals during stressful conditions found that a single dose of ketamine counteracted stress-related reductions in synaptic markers in the hippocampus and PFC. Repeated administration of ketamine also counteracted stress effects in the hippocampus. Psychedelics generally increased synaptic markers, but results were more consistently positive for certain agents. Ketamine and psychedelics can increase synaptic markers under certain conditions. Heterogeneous findings may relate to methodological differences, agents administered (or different formulations of the same agent), sex, and type of markers. Future studies could address seemingly mixed results by using meta-analytical approaches or study designs that more fully consider individual differences.

Age, Dose, and Locomotion: Decoding Vulnerability to Ketamine in C57BL/6J and BALB/c Mice.

Ketamine has been abused as a psychedelic agent and causes diverse neurobehavioral changes. Adolescence is a critical developmental stage but vulnerable to substances and environmental stimuli. Growing evidence shows that ketamine affects glutamatergic neurotransmission, which is important for memory storage, addiction, and psychosis. To explore diverse biological responses, this study was designed to assess ketamine sensitivity in mice of different ages and strains. Male C57BL/6J and BALB/c mice were studied in adolescence and adulthood separately. An open field test assessed motor behavioral changes. After a 30-min baseline habituation, mice were injected with ketamine (0, 25, and 50 mg/kg), and their locomotion was measured for 60 min. Following ketamine injection, the travelled distance and speed significantly increased in C57BL/6J mice between both age groups (p < 0.01), but not in BALB/c mice. The pattern of hyperlocomotion showed that mice were delayed at the higher dose (50 mg/kg) compared to the lower dose (25 mg/kg) of ketamine treatment. Ketamine accentuated locomotor activation in adolescent C57BL/6J mice compared to adults, but not in the BALB/c strain. Here, we show that ketamine-induced locomotor behavior is modulated by dose and age. The discrepancy of neurobehaviors in the two strains of mice indicates that sensitivity to ketamine is biologically determined. This study suggests that individual vulnerability to ketamine's pharmacological responses varies biologically.

Sustaining the benefits of intravenous ketamine with behavioural activation therapy for depression: A case series

BackgroundDespite advances in treatments for depression, approximately one third of patients do not benefit from available therapies. Intravenous ketamine is a novel intervention that can yield rapid yet transient antidepressant effects. Behavioural activation (BA) therapy for depression has been shown to be effective in preventing relapse of major depressive episodes. In this pilot study, we examined whether antidepressant response achieved through repeated ketamine infusions could be maintained with BA. MethodsIn this case series, patients with treatment-resistant depression who met antidepressant response criteria in a clinical trial of repeated ketamine infusions subsequently completed 12–17 sessions of BA. Depressive symptoms were measured at each session with the Beck Depression Inventory-II (BDI-II). Secondary outcomes included changes in work and social adjustment, suicidal ideation, and anxiety. ResultsTen of the 13 participants who initiated BA completed the full course of psychotherapy. These participants showed significant improvement in self-reported depressive symptoms (p = 0.007) and work and social adjustment scores (p<0.001) with BA. The 6 participants who started BA therapy prior to relapse of depressive symptoms following cessation of ketamine sustained the clinical gains achieved with ketamine. LimitationsThe small sample size and lack of control group limit the conclusions. ConclusionsThe transient period of increased mood after repeated ketamine treatment offers a window of opportunity to intervene with psychotherapy such as BA. A better understanding of how to best integrate psychological treatments with pharmacological treatment, particularly the novel use of rapid-acting medications such as ketamine is an unmet clinical need and promising research area.

A systematic review of the print media representation of ketamine treatments for psychiatric disorders.

Public and patient expectations of treatment influence health behaviours and decision-making. We aimed to understand how the media has portrayed the therapeutic use of ketamine in psychiatry. We systematically searched electronic databases for print and online news articles about ketamine for psychiatric disorders. The top ten UK, USA, Canadian and Australian newspapers by circulation and any trade and consumer magazines indexed in the databases were searched from 2015 to 2020. Article content was quantitatively coded with a framework encompassing treatment indication, descriptions of prior use, references to research, benefits and harms, treatment access and process, patient and professional testimony, tone and factual basis. We found 119 articles, peaking in March 2019 when the United States Food and Drug Administration approved esketamine. Ketamine treatment was portrayed in an extremely positive light (n = 82, 68.9%), with significant contributions of positive testimony from key opinion leaders (e.g. clinicians). Positive research results and ketamine's rapid antidepressant effect (n = 87, 73.1%) were frequently emphasised, with little reference to longer-term safety and efficacy. Side-effects were frequently reported (n = 96, 80.7%), predominantly ketamine's acute psychotomimetic effects and the potential for addiction and misuse, and rarely cardiovascular and bladder effects. Not infrequently, key opinion leaders were quoted as being overly optimistic compared with the existing evidence base. Information pertinent to patient help-seeking and treatment expectations is being communicated through the media and supported by key opinion leaders, although some quotes go well beyond the evidence base. Clinicians should be aware of this and may need to address their patients' beliefs directly.

The Role of Ketamine in the Treatment of Bipolar Depression: A Scoping Review

Bipolar depression remains a clinical challenge with a quarter of patients failing to respond to initial conventional treatments. Although ketamine has been extensively studied in unipolar depression, its role in bipolar disorder remains inconclusive. The aim of our scoping review was to comprehensively synthesize the current clinical literature around ketamine use in bipolar depression. A total of 10 clinical studies (5 randomized controlled trials and 5 open label studies) were selected. The preliminary evidence, albeit weak, suggests that ketamine is a promising treatment and calls for further interest from the research community. Overall, ketamine treatment appeared to be tolerable with minimal risk for manic/hypomanic switching and showed some effectiveness across parameters of depression and suicidality. Moreover, ketamine is a potential treatment agent in patients with treatment-resistant bipolar depression with promising data extracted from extant controlled trials and real-world effectiveness studies. Future studies are needed to identify ketamine’s role in acute and maintenance treatment phases of bipolar depression. Moreover, future researchers should study the recurrence prevention and anti-suicidal effects of ketamine in the treatment of bipolar depression.

Sex-Dependent Attentional Impairments in a Subchronic Ketamine Mouse Model for Schizophrenia

BackgroundThe development of more effective treatments for schizophrenia targeting cognitive and negative symptoms has been limited, partly due to a disconnect between rodent models and human illness. Ketamine administration is widely used to model symptoms of schizophrenia in both humans and rodents. In mice, subchronic ketamine treatment reproduces key dopamine and glutamate dysfunction; however, it is unclear how this translates into behavioral changes reflecting positive, negative, and cognitive symptoms. MethodsIn male and female mice treated with either subchronic ketamine or saline, we assessed spontaneous and amphetamine-induced locomotor activity to measure behaviors relevant to positive symptoms, and used a touchscreen-based progressive ratio task of motivation and the rodent continuous performance test of attention to capture specific negative and cognitive symptoms, respectively. To explore neuronal changes underlying the behavioral effects of subchronic ketamine treatment, we quantified expression of the immediate early gene product, c-Fos, in key corticostriatal regions using immunofluorescence. ResultsWe showed that spontaneous locomotor activity was unchanged in male and female subchronic ketamine–treated animals, and amphetamine-induced locomotor response was reduced. Subchronic ketamine treatment did not alter motivation in either male or female mice. In contrast, we identified a sex-specific effect of subchronic ketamine on attentional processing wherein female mice performed worse than control mice due to increased nonselective responding. Finally, we showed that subchronic ketamine treatment increased c-Fos expression in prefrontal cortical and striatal regions, consistent with a mechanism of widespread disinhibition of neuronal activity. ConclusionsOur results highlight that the subchronic ketamine mouse model reproduces a subset of behavioral symptoms that are relevant for schizophrenia.

Ketamine Reduces the Surface Density of the Astroglial Kir4.1 Channel and Inhibits Voltage-Activated Currents in a Manner Similar to the Action of Ba2+ on K+ Currents.

A single sub-anesthetic dose of ketamine evokes rapid and long-lasting beneficial effects in patients with a major depressive disorder. However, the mechanisms underlying this effect are unknown. It has been proposed that astrocyte dysregulation of extracellular K+ concentration ([K+]o) alters neuronal excitability, thus contributing to depression. We examined how ketamine affects inwardly rectifying K+ channel Kir4.1, the principal regulator of K+ buffering and neuronal excitability in the brain. Cultured rat cortical astrocytes were transfected with plasmid-encoding fluorescently tagged Kir4.1 (Kir4.1-EGFP) to monitor the mobility of Kir4.1-EGFP vesicles at rest and after ketamine treatment (2.5 or 25 µM). Short-term (30 min) ketamine treatment reduced the mobility of Kir4.1-EGFP vesicles compared with the vehicle-treated controls (p < 0.05). Astrocyte treatment (24 h) with dbcAMP (dibutyryl cyclic adenosine 5'-monophosphate, 1 mM) or [K+]o (15 mM), which increases intracellular cAMP, mimicked the ketamine-evoked reduction of mobility. Live cell immunolabelling and patch-clamp measurements in cultured mouse astrocytes revealed that short-term ketamine treatment reduced the surface density of Kir4.1 and inhibited voltage-activated currents similar to Ba2+ (300 µM), a Kir4.1 blocker. Thus, ketamine attenuates Kir4.1 vesicle mobility, likely via a cAMP-dependent mechanism, reduces Kir4.1 surface density, and inhibits voltage-activated currents similar to Ba2+, known to block Kir4.1 channels.

Ketamin in therapy of pharmacoresistent depressions in patients with double diagnosis (naturalistic study)

Pharmacotherapy of depression based on a monoaminergic model in many cases is not enough effective. In this regard the ketamine treatment results of pharmacoresistant depression by subanaesthetic doses, including the patients with double diagnosis, are of interest. Method: in an open label naturalistic non-randomized trial, 12 patients with non-psychotic treatment-resistant depression (10 of whom had concomitant addictive disorder), 6 sessions of ketamine therapy (0.5 - 0.75 mg/kg intravenously) were undertaken. Clinical and psychometric (Beck scale, visual analogue scale and scale of general clinical impression) assessment were used. Statistical processing - general linear model and nonparametric criterion. Results: the effectiveness of therapy was noted in 11 of 12 respondents, and in 7 ones the improvement was qualified as significant. The total scores of the scales applied corresponded to 50% reduction of depressive symptoms (p0.05). Conclusions: ketamine proved to be an effective and safe method of the fast achieving therapeutic effect in patients with therapeutically-resistant depression. However insufficiently representative sample, the lack of a control group and the mechanism of randomization and the open nature of the study limit the wide extrapolation of the results.

Reinstating olfactory bulb-derived limbic gamma oscillations alleviates depression-like behavioral deficits in rodents

Although the etiology of major depressive disorder remains poorly understood, reduced gamma oscillations is an emerging biomarker. Olfactory bulbectomy, an established model of depression that reduces limbic gamma oscillations, suffers from non-specific effects of structural damage. Here, we show that transient functional suppression of olfactory bulb neurons or their piriform cortex efferents decreased gamma oscillation power in limbic areas and induced depression-like behaviors in rodents. Enhancing transmission of gamma oscillations from olfactory bulb to limbic structures by closed-loop electrical neuromodulation alleviated these behaviors. By contrast, silencing gamma transmission by anti-phase closed-loop stimulation strengthened depression-like behaviors in naive animals. These induced behaviors were neutralized by ketamine treatment that restored limbic gamma power. Taken together, our results reveal a causal link between limbic gamma oscillations and depression-like behaviors in rodents. Interfering with these endogenous rhythms can affect behaviors in rodent models of depression, suggesting that restoring gamma oscillations may alleviate depressive symptoms.

Oral Morphine versus Rectal Ketamine in Pain Management during Burn Wound Dressing: An Open Label Randomized Clinical Trial

Background: Oral morphine has been widely used to manage children’s pain during burn wound dressing. Rectal ketamine may also be safely administered to children.&#x0D; Objective: To evaluate and compare the efficacy of oral morphine vs. rectal racemic ketamine in management of pain during burn wound dressing in a pediatric population in a rural study population.&#x0D; Methods: This was a randomized open-label clinical trial done in a rural hospital in Uganda. Study participants were randomly assigned to one of the treatment groups, either oral morphine or rectal ketamine, with a ratio of 1:1. Overall, we enrolled 44 participants, with 22 in each treatment arm.&#x0D; Assessment of baseline vital signs, including pulse rate, blood pressure, respiratory rate, temperature, oxygen saturation (SPO2), pain assessment (using Face Legs Activity Cry Consolability [FLACC]), and sedation scores (using Richmond’s agitation and sedation scale [RASS]) among others was done. Study participants were followed up hourly for 8 hours for outcomes of interest: adequate pain management/adverse events.&#x0D; Results: The mean age of the study participants was 2.56 (±1.59) years. The overall mean intra-procedural pain difference score for children who received oral morphine was 2.7 (SD±2.2) compared to 0 (SD±0) among those who received rectal ketamine, and the mean difference of 2.7 was statistically significant (p &lt; 0.0001). Sialorrhea (hyper-salivation) was the only significant adverse event, with more occurrence in the rectal Ketamine treatment arm (n= 8, 36.3%) compared to 1 (5%) in the oral Morphine treatment arm, p = 0.009. There were no significant adverse effects noted in either treatment arm.&#x0D; Conclusion: The study showed the non-inferiority of rectal ketamine over oral morphine and concluded that administration of rectal ketamine was better at pain management and safety compared to oral morphine. Rectal ketamine is associated with an increased incidence of sialorrhea compared to oral morphine.

A comparative analysis of antidepressant and anti-suicidal effects of repeated ketamine infusions in elderly and younger adults with depression

ObjectivesThis study aims to investigate the differences in safety and antidepressant effects of multi-infusion ketamine treatment between elderly and young adults with depression. MethodsThe safety, antidepressant, and anti-suicidal effects of multi-infusion ketamine were compared between 19 elderly (≥50 years) and 116 younger (<50 years) adults with depression; all were treated with six ketamine infusions (0.5 mg/kg). Montgomery-Åsberg Depression Rating Scale (MADRS) was used to measure the depressive symptoms, and suicidal ideation was measured with Beck Scale for Suicide Ideation (SSI)-part 1, Hamilton Rating Scale for Depression (HAMD) item 3, and (MADRS) item 10. Dissociative and psychotomimetic symptoms were evaluated based on the Clinician-Administered Dissociative States Scale (CADSS) and the Brief Psychiatric Rating Scale (BPRS)-four items. ResultsMulti-Ketamine infusions resulted in a lower (trend) antidepressant response (37.1 % versus 57.8 %) and antidepressant remission (15.8 % versus 47.4 %) in elderly patients with depression compared with younger patients with depression (all ps > 0.05). Interestingly, elderly patients with depression had a higher MADRS score after six ketamine infusions compared with younger patients (p = 0.04). No significant differences in SSI-part 1 scores, HAMD item 3 scores, MADRS item 10 scores, CADSS scores, and BPRS-four items scores were found between the two groups at any assessment point (all ps > 0.05). ConclusionOur study shows that repeated-dose infusions of ketamine may be a feasible treatment strategy in elderly Chinese patients with depression; however, elderly patients with depression may be less responsive to ketamine compared with younger adults with depression.

Pain mediates the improvement of social functions of repeated intravenous ketamine in patients with unipolar and bipolar depression

ObjectivePrevious research has shown that ketamine can improve social functions. In addition, evidence also suggests that ketamine can alleviate pain. Herein, we propose that ketamine-induced improvements in pain and depression are partially mediated by a reduction in pain. We aimed to determine whether improvements in pain-mediated changes in psychological function were associated with ketamine treatment. MethodThis trial included unipolar or bipolar patients (n = 103) who received 6 intravenous infusions (0.5 mg/kg) of ketamine over 2 weeks. The severity of current depressive symptoms and social function were evaluated by the Montgomery-Åsberg Depression Scale (MADRS), Self-Rating Depression Scale (SDS) and Global Assessment Function (GAF), respectively, at baseline and on day 13 and day 26. At the same time points, the three dimensions of pain, including the sensory index, affective index and present pain intensity (PPI), were measured by the Simple McGill Pain Scale (SF-MPQ). ResultsThe mixed model results showed that ketamine plays an important role in improving the psychosocial functioning of patients. There was a significant decrease from baseline to the day 13 and day 26, indicating that the pain index of the patient improved significantly. Mediation analysis showed that for SDS score (coef = −5.171, 95 % CI[−6.317, −4.025]) and GAF score (coef = 1.021, 95 % CI[0.848, 1.194]), the overall effect of ketamine was observable. The overall indirect and direct effects of ketamine on social functioning were significant (SDS: direct: coef = −1949 to −2114; total indirect: from 0.594 to 0.664; GAF: from 0.399 to 0.427; total indirect: coef = 0.593 to 0.664). The MADRS total score and emotional index were important mediators of the association between ketamine treatment and improvements in subjective and objective social functioning. ConclusionDepressive symptom severity and the affective index of pain partially mediated improvements in social function after six repeated ketamine treatments among patients with bipolar or unipolar depressive disorder.

Ketamine Treatment for Alcohol Use Disorder: A Systematic Review.

Alcohol use disorder (AUD) is a chronic, recurrent condition that demonstrates significant heterogeneity in treatment response to first-line agents. Ketamine may have a therapeutic role in substance use disorders; however, research on this topic is limited. The objective of this systematic review is to qualitatively synthesize the current evidence of ketamine treatment for alcohol use disorder and evaluate its efficacy. A systematic review of Medline, PsycINFO, CINAHL, the Cochrane Library, and Google Scholar was performed to identify completed human studies in English or Spanish (from inception to July 2022) that assess the effectiveness of ketamine therapy for alcohol use disorder. This review was registered on the Open Science Framework. Data were descriptively summarized and presented in tables and tested via narrative synthesis methodology. The risk of bias was measured with Cochrane Collaboration tools and a case series quality assessment tool. A total of 11 studies with 854 adult patients in three different countries (the USA, the UK, and Russia) were analyzed. Sample sizes ranged from 5 to 211 people. Seven studies included patients with alcohol use disorder, one study focused on heavy drinkers, and three studies elaborated extensively on alcohol withdrawal. The overall proportion of patients achieving abstinence and reduced consumption was most favorable in people receiving combination ketamine and psychotherapy treatment. The results were mixed with respect to relapse, craving, and withdrawal. Ketamine may be an effective therapeutic modality for people with alcohol use disorders who fail to respond to FDA-approved first-line agents. More robust clinical trials are necessary to provide a more accurate assessment of efficacy, safety profile, and dosing strategies for ketamine utilization in alcohol use disorder.

Ketamine supresses REM sleep and markedly increases EEG gamma oscillations in the Wistar Kyoto rat model of treatment-resistant depression

Wistar–Kyoto (WKY) rats exhibit depression-like characteristics and decreased sensitivity to monoamine-based antidepressants, making them a suitable model of treatment-resistant depression (TRD). Ketamine has emerged recently as a rapidly acting antidepressant with high efficacy in TRD. Our aim was to determine whether subanaesthetic doses of ketamine can correct sleep and electroencephalogram (EEG) alterations in WKY rats and whether any ketamine-induced changes differentially affect WKY rats compared to Sprague-Dawley (SD) rats. Thus, we surgically implanted 8 SD and 8 WKY adult male rats with telemetry transmitters and recorded their EEG, electromyogram, and locomotor activity after vehicle or ketamine (3, 5 or 10 mg/kg, s.c.) treatment. We also monitored the plasma concentration of ketamine and its metabolites, norketamine and hydroxynorketamine in satellite animals. We found that WKY rats have an increased amount of rapid eye movement (REM) sleep, fragmented sleep-wake pattern, and increased EEG delta power during non-REM sleep compared to SD rats. Ketamine suppressed REM sleep and increased EEG gamma power during wakefulness in both strains, but the gamma increase was almost twice as large in WKY rats than in SD rats. Ketamine also increased beta oscillations, but only in WKY rats. These differences in sleep and EEG are unlikely to be caused by dissimilarities in ketamine metabolism as the plasma concentrations of ketamine and its metabolites were similar in both strains. Our data suggest an enhanced antidepressant-like response to ketamine in WKY rats, and further support the predictive validity of acute REM sleep suppression as a measure of antidepressant responsiveness.

Ketamine and psychotherapy for the treatment of psychiatric disorders: systematic review.

Ketamine is an effective short-term treatment for a range of psychiatric disorders. A key question is whether the addition of psychotherapy to ketamine treatment improves outcomes or delays relapse. To identify all studies combining psychotherapy with ketamine for the treatment of psychiatric disorders to summarise their effects and make recommendations for future research. The review protocol was prospectively registered with PROSPERO (registration number CRD42022318120). Potential studies were searched for in MEDLINE, Embase, PsycINFO, SCOPUS, the Cochrane library and Google Scholar. Eligible studies combined ketamine and psychotherapy for the treatment of psychiatric disorders and did not use case reports or qualitative designs. Key findings relating to psychotherapy type, diagnosis, ketamine protocol, sequencing of psychotherapy and study design are reported. Risk of bias was assessed using modified Joanna Briggs critical appraisal tools. Nineteen studies evaluating 1006 patients were included in the systematic review. A variety of supportive individual and group, manualised and non-manualised psychotherapies were used. The majority of studies evaluated substance use disorders, post-traumatic stress disorder and treatment-resistant depression. Ketamine protocols and sequencing of ketamine/psychotherapy treatment varied substantially between studies. Outcomes were largely positive for the addition of psychotherapy to ketamine treatment. The combination of psychotherapy and ketamine offers promise for the treatment of psychiatric disorders, but study heterogeneity prevents definitive recommendations for their integration. Larger randomised controlled trials using manualised psychotherapies and standardised ketamine protocols are recommended to clarify the extent to which the addition of psychotherapy to ketamine improves outcomes over ketamine treatment alone.

Repeated oral esketamine in patients with treatment resistant depression and comorbid posttraumatic stress disorder

IntroductionKetamine and its S-enantiomer esketamine are novel pharmacotherapeutic options for treatment resistant depression (TRD). There is growing evidence on the efficacy for other psychiatric disorders, including posttraumatic stress disorder (PTSD). It is hypothesized that psychotherapy may further potentiate the effects of (es)ketamine in psychiatric disorders. MethodsRepeated oral esketamine was prescribed once or twice weekly in five patients suffering from TRD and comorbid PTSD. We describe the clinical effects of esketamine and report data from psychometric instruments and patients’ perspectives. ResultsEsketamine treatment duration ranged from six weeks to a year. In four patients, we observed improvement in depressive symptoms, increased resilience and more receptiveness to psychotherapy. One patient experienced symptom worsening in response to a threatening situation during esketamine treatment, highlighting the need for a safe setting. Discussion(Es)ketamine treatment within a psychotherapeutic framework appears promising in patients with treatment resistant symptoms of depression and PTSD. Controlled trials are warranted to validate these results and to elucidate the optimal treatment methods.

Neurocognitive effects of subanesthetic serial ketamine infusions in treatment resistant depression

IntroductionKetamine treatment prompts a rapid antidepressant response in treatment-resistant depression (TRD). We performed an exploratory investigation of how ketamine treatment in TRD affects different cognitive domains and relates to antidepressant response. MethodsPatients with TRD (N = 66; 30 M/35F; age = 39.5 ± 11.1 years) received four ketamine infusions (0.5 mg/kg). Neurocognitive function and depressive symptoms were assessed at baseline, 24 h after the first and fourth ketamine infusion, and 5 weeks following end of treatment. Mixed effect models tested for changes in seven neurocognitive domains and antidepressant response, with post-hoc pairwise comparisons between timepoints, including follow-up. Relationships between change in neurocognitive function and antidepressant response over the course of treatment were tested with Pearson's correlation and mediation analyses. Associations between baseline neurocognitive performance and antidepressant response were tested with Pearson's correlation. ResultsSignificant improvements in inhibition, working memory, processing speed, and overall fluid cognition were observed after the first and fourth ketamine infusion. Improvements in processing speed and overall fluid cognition persisted through follow-up. Significant improvements in depressive symptoms reverted towards baseline at follow-up. Baseline working memory and change in inhibition were moderately correlated with antidepressant response, however, improvements in neurocognitive performance were statistically independent from antidepressant response. ConclusionAntidepressant ketamine leads to improved neurocognitive function, which persist for at least 5 weeks. Neurocognitive improvements observed appear independent of antidepressant response, suggesting ketamine may target overlapping but distinct functional brain systems.LimitationsResearch investigating repeated serial ketamine treatments is important to determine cognitive safety. This study is a naturalistic design and does not include placebo.

342. Pretreatment Hippocampal Subfield Volumes Predict Improved Neurocognitive Function Following Ketamine Treatment in Major Depression

342. Pretreatment Hippocampal Subfield Volumes Predict Improved Neurocognitive Function Following Ketamine Treatment in Major Depression

113. Static and Dynamic Functional Connectivity Changes From the Lateral Habenula Associate With Therapeutic Response to Ketamine Treatment in Major Depression

113. Static and Dynamic Functional Connectivity Changes From the Lateral Habenula Associate With Therapeutic Response to Ketamine Treatment in Major Depression

Perioperative use of ketamine infusion versus dexmedetomidine infusion for analgesia in obese patients undergoing bariatric surgery: a double-blinded three-armed randomized controlled trial

BackgroundBariatric surgery depends on the development of novel anesthetic techniques to reduce the incidence of complications and improve postoperative outcomes. Ketamine and dexmedetomidine have been used for perioperative analgesia and we hypothesized that they would decrease postoperative morphine requirements. The objective of this trial is to study whether choice of ketamine or dexmedetomidine infusion would affect postoperative total morphine consumption.MethodsNinety patients were equally randomized into three groups. The ketamine group received a bolus dose (0.3 mg/kg) of ketamine over 10 min, followed by an infusion of the same drug (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 of this drug (0.5 mg/kg/h). The control group received a saline infusion. All infusions were given till 10 min before the end of surgeries. Intraoperative fentanyl was given when patient developed hypertension and tachycardia despite adequate anesthesia and muscle relaxation. Postoperative pain was managed by a rescue dose of 4 mg of IV morphine, with a minimum interval of 6 h between morphine doses if the numerical rating scale (NRS) score was ≥ 4. The primary outcome was the total morphine dose, and the secondary outcomes were intraoperative fentanyl requirement, time to extubation, postoperative nausea and vomiting (PONV), NRS scores, and modified observer’s agitation/sedation scale (MOASS) scores.ResultsCompared with ketamine, dexmedetomidine decreased the need for fentanyl intraoperatively (160 ± 42 µg), shortened the time to extubation (3 ± 1 min), and improved MOASS and PONV scores. In turn, ketamine decreased postoperative NRS scores and the need for morphine (3 ± 3 mg).ConclusionsDexmedetomidine treatment was associated with lower fentanyl doses, a shorter time to extubation, and better MOASS and PONV scores. Ketamine treatment was associated with significantly lower NRS scores and morphine doses. These results indicated that dexmedetomidine effectively decreased intraoperative fentanyl requirement and the time to extubation, while ketamine decreased the need for morphine.Trial registrationThis trail was registered on the clinicaltrials.gov registry (NCT04576975) on October 6, 2020.