Ketamine Treatment Research Articles

Differential effects of opioid receptor antagonism on the anti-dyskinetic and anti-parkinsonian effects of sub-anesthetic ketamine treatment in a preclinical model

Sub-anesthetic ketamine treatment has been shown to be an effective therapy for treatment-resistant depression and chronic pain. Our group has previously shown that sub-anesthetic ketamine produces acute anti-parkinsonian, and acute anti-dyskinetic effects in preclinical models of Parkinson's disease (PD). Ketamine is a multifunctional drug and exerts effects through blockade of N-methyl-d-aspartate receptors but also through interaction with the opioid system. In this report, we provide detailed pharmacokinetic rodent data on ketamine and its main metabolites following an intraperitoneal injection, and second, we explore the pharmacodynamic properties of ketamine in a rodent PD model with respect to the opioid system, using naloxone, a pan-opioid receptor antagonist, in unilateral 6-hydroxydopamine-lesioned male rats, treated with 6 mg/kg levodopa (l-DOPA) to establish a model of l-DOPA-induced dyskinesia (LID). As previously reported, we showed that ketamine (20 mg/kg) is highly efficacious in reducing LID and now report that the magnitude of this effect is resistant to naloxone (3 and 5 mg/kg). The higher naloxone dose of 5 mg/kg, however, led to an extension of the time-course of the LID, indicating that opioid receptor activation, while not a prerequisite for the anti-dyskinetic effects of ketamine, still exerts an acute modulatory effect. In contrast to the mild modulatory effect on LID, we found that naloxone added to the anti-parkinsonian activity of ketamine, further reducing the akinetic phenotype. In conclusion, our data show opioid receptor blockade differentially modulates the acute anti-parkinsonian and anti-dyskinetic actions of ketamine, providing novel mechanistic information to support repurposing ketamine for individuals with LID.

At-home, telehealth-supported ketamine treatment for depression: Findings from longitudinal, machine learning and symptom network analysis of real-world data

BackgroundImproving safe and effective access to ketamine therapy is of high priority given the growing burden of mental illness. Telehealth-supported administration of sublingual ketamine is being explored toward this goal. MethodsIn this longitudinal study, moderately-to-severely depressed patients received four doses of ketamine at home over four weeks within a supportive digital health context. Treatment was structured to resemble methods of therapeutic psychedelic trials. Patients receiving a second course of treatment were also examined. Symptoms were assessed using the Patient Health Questionnaire (PHQ-9) for depression. We conducted preregistered machine learning and symptom network analyses to investigate outcomes (osf.io/v2rpx). ResultsA sample of 11,441 patients was analyzed, demonstrating a modal antidepressant response from both non-severe (n = 6384, 55.8 %) and severe (n = 2070, 18.1 %) baseline depression levels. Adverse events were detected in 3.0–4.8 % of participants and predominantly neurologic or psychiatric in nature. A second course of treatment helped extend improvements in patients who responded favorably to initial treatment. Improvement was most strongly predicted by lower depression scores and age at baseline. Symptoms of Depressed mood and Anhedonia sustained depression despite ongoing treatment. LimitationsThis study was limited by the absence of comparison or control groups and lack of a fixed-dose procedure for ketamine administration. ConclusionsAt-home, telehealth-supported ketamine administration was largely safe, well-tolerated, and associated with improvement in patients with depression. Strategies for combining psychedelic-oriented therapies with rigorous telehealth models, as explored here, may uniquely address barriers to mental health treatment.

Analysis of the mechanism by which ketamine affects astrocytes in Parkinsonian rats through the PI3K/AKT axis.

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 oftimes of grid crossings andstanding, and the ATPaseactivity 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 mechanismof KET on PD is related to the inhibition of the PI3K/AKT axis.

Oral ketamine effects on dynamics of functional network connectivity in patients treated for chronic suicidality.

The underlying brain mechanisms of ketamine in treating chronic suicidality and the characteristics of patients who will benefit from ketamine treatment remain unclear. To address these gaps, we investigated temporal variations of brain functional synchronisation in patients with suicidality treated with ketamine in a 6-week open-label oral ketamine trial. The trial's primary endpoint was the Beck Scale for Suicide Ideation (BSS). Patients who experienced greater than 50% improvement in BSS scores or had a BSS score less than 6 at the post-treatment and follow-up (10 weeks) visits were considered responders and persistent responders, respectively. The reoccurring and transient connectivity pattern (termed brain state) from 29 patients (45.6 years ± 14.5, 15 females) were investigated by dynamic functional connectivity analysis of resting-state functional MRI at the baseline, post-treatment, and follow-up. Post-treatment patients showed significantly more (FDR-Q = 0.03) transitions among whole brain states than at baseline. We also observed increased dwelling time (FDR-Q = 0.04) and frequency (FDR-Q = 0.04) of highly synchronised brain state at follow-up, which were significantly correlated with BSS scores (both FDR-Q = 0.008). At baseline, persistent responders had higher fractions (FDR-Q = 0.03, Cohen's d = 1.39) of a cognitive control network state with high connectivities than non-responders. These findings suggested that ketamine enhanced brain changes among different synchronisation patterns and enabled high synchronisation patterns in the long term, providing a possible biological pathway for its suicide-prevention effects. Moreover, differences in cognitive control states at baseline may be used for precise ketamine treatment planning.

Experience from a single-center study on multimodal medication therapy for patients with complex regional pain syndrome.

Despite the application of various therapeutic methods, pain caused by complex regional pain syndrome (CRPS) is not sufficiently managed and often progresses to a chronic stage. For the systematic and effective treatment of CRPS, we developed an algorithm for multimodal medication therapy based on the established pathophysiology of CRPS to control CRPS-related pain. In this study, we present the outcomes of our novel algorithm for multimodal medication therapy for patients with CRPS, consisting of three major components: multimodal oral medication, intravenous ketamine, and intravenous lidocaine therapy. We retrospectively investigated patients with CRPS who received multimodal therapy. Pain severity scores were evaluated using a numerical rating scale at four time points (P1, pain at initial consultation; P2, pain after oral medication; P3, pain after ketamine treatment; and P4, pain after lidocaine treatment). The effect of the multimodal medication therapy algorithm on pain management was evaluated at each time point. In patients with CRPS, multimodal oral medication, intravenous ketamine, and intravenous lidocaine therapies led to significantly improved pain control (p< 0.05). Additionally, the combination of these three therapies (through the multimodal medication therapy algorithm) resulted in significant pain relief in patients with CRPS (p< 0.05). Our multimodal medication therapy algorithm effectively controlled pain in patients with CRPS. However, further prospective studies with large sample sizes and randomized controlled trials are needed for more accurate generalization.

Enteral Ketamine for Status Epilepticus in Children with Epilepsy

BackgroundApproximately 10% to 20% of children with epilepsy experience status epilepticus (SE), and children with seizure clustering are at higher risk. Ketamine is growing in use for SE. This study examines the efficacy and safety of enteral ketamine in the treatment of convulsive status epilepticus (CSE) characterized by refractory seizure clusters and nonconvulsive status epilepticus (NCSE) in children with epilepsy. MethodsPatient charts were reviewed retrospectively. Children with epilepsy aged one to 21 years presenting in SE and treated with enteral ketamine between September 1, 2021 and September 1, 2022 at a pediatric tertiary care center were identified. Resolution or reduction in seizure frequency within 48 hours, clinical presentation, endotracheal intubation, hospitalization duration, side effects, and readmission were assessed. ResultsNine patients aged two to 21 years were identified. Six patients presented in CSE characterized by recurrent seizures, and three patients presented in NCSE. Five patients had genetic epilepsies, including PCDH19- and MECP2-related epilepsy. Seven patients had resolution or reduction in seizures within 48 hours of ketamine initiation. Two patients were intubated. Hospitalization duration ranged from one to 34 days. Three patients reported side effects. Three patient readmissions with early ketamine treatment had equal or shorter hospitalizations. ConclusionsEnteral ketamine may prove an effective, well-tolerated option for treatment of convulsive and nonconvulsive SE in children with epilepsy, including genetic epilepsies, and may prevent intubation and shorten hospitalization time.

Ketamine-enhanced prolonged exposure therapy in veterans with PTSD: A randomized controlled trial protocol

BackgroundThe 2023 VA/DoD Clinical Practice Guideline for the Management of PTSD recommends individual, manualized trauma-focused such as Prolonged Exposure (PE) over pharmacologic interventions for the primary treatment of PTSD. Unfortunately, clinical trials of trauma-based therapies in the military and veteran population showed that 30% to 50% of patients did not demonstrate clinically meaningful symptom change. Ketamine, an FDA-approved anesthetic with potent non-competitive glutamatergic N-methyl-d-aspartate antagonistic properties, has demonstrated to enhance the recall of extinction learning and decrease fear renewal without interference of extinction training in preclinical studies. MethodsWe plan to conduct a single site RCT comparing three ketamine treatment vs. active placebo (midazolam) adjunct to PE therapy among Veterans with PTSD. Pharmacological phase will start simultaneously with PE session 1. Infusions will be administered 24 h. prior to PE session for the first 3 weeks. After PE is completed (session 10), patients will be assessed during a 3-month follow-up period at various time points. We estimate that out of 100 veterans, 80 will reach time point for primary outcome measure and will be considered for primary analysis. Secondary outcomes include severity of depression and anxiety scores, safety and tolerability of ketamine-enhanced PE therapy, cognitive performance during treatment and early improvement during PE related to the rate of dropouts during PE therapy. DiscussionResults of the proposed RCT could provide scientific foundation to distinguish the essential components of this approach, enhance the methodology, elucidate the mechanisms involved, and identify sub-PTSD populations that most likely benefit from this intervention.

Ketamine as Treatment for Cluster Headache: A Systematic Review of Literature and a Case Series.

Cluster headache is a severe and debilitating neurological condition characterized by intense, excruciating pain with a significant impact on patients' wellbeing. Although different treatment options are available, many patients continue to experience inadequate relief. Therefore, experimental strategies are increasingly studied. One of the more promising approaches is the use of ketamine. We present the currently available evidence and our own data. In this mixed-methods paper, we first summarize the available evidence of ketamine for treatment of cluster headache based on a systematic review of literature in MEDLINE, EMBASE and the Cochrane library of systematic reviews. As the level of evidence is quite limited, we report our own cohort study with ten patients treated with ketamine infusions for cluster headache. They were followed up to investigate the patients' experience of treatment success and quality of life. The search and review of literature identified four reports with a total of 68 patients. All were uncontrolled case series. The current literature suggests that ketamine might decrease cluster headache. However, as the applied regimes and reported outcomes are highly heterogeneous, further analysis was futile. Our own data show high patient satisfaction with ketamine treatment. Despite the limited evidence, ketamine might be considered a potential therapeutic approach for cluster headache. Therefore, further research including randomized controlled trials should be encouraged.

Rapid and sustained antidepressant effects of intravenous ketamine in treatment-resistant major depressive disorder and suicidal ideation: a randomized clinical trial

BackgroundMajor 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.MethodsThe 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.ResultsOne 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.ConclusionThe 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 registrationIRCT registration number: IRCT20210806052096N1; IRCT URL: https://www.irct.ir/trial/62243; Ethical code: IR.ZUMS.REC.1400.150; Registration date: 2022-04-09.

Ketamine-induced prevention of SD-associated late infarct progression in experimental ischemia

Spreading depolarizations (SDs) occur frequently in patients with malignant hemispheric stroke. In animal-based experiments, SDs have been shown to cause secondary neuronal damage and infarct expansion during the initial period of infarct progression. In contrast, the influence of SDs during the delayed period is not well characterized yet. Here, we analyzed the impact of SDs in the delayed phase after cerebral ischemia and the potential protective effect of ketamine. Focal ischemia was induced by distal occlusion of the left middle cerebral artery in C57BL6/J mice. 24 h after occlusion, SDs were measured using electrocorticography and laser-speckle imaging in three different study groups: control group without SD induction, SD induction with potassium chloride, and SD induction with potassium chloride and ketamine administration. Infarct progression was evaluated by sequential MRI scans. 24 h after occlusion, we observed spontaneous SDs with a rate of 0.33 SDs/hour which increased during potassium chloride application (3.37 SDs/hour). The analysis of the neurovascular coupling revealed prolonged hypoemic and hyperemic responses in this group. Stroke volume increased even 24 h after stroke onset in the SD-group. Ketamine treatment caused a lesser pronounced hypoemic response and prevented infarct growth in the delayed phase after experimental ischemia. Induction of SDs with potassium chloride was significantly associated with stroke progression even 24 h after stroke onset. Therefore, SD might be a significant contributor to delayed stroke progression. Ketamine might be a possible drug to prevent SD-induced delayed stroke progression.

Protocol for a randomised controlled trial of ketamine versus ketamine and behavioural activation therapy for adults with treatment-resistant depression in the community

IntroductionAlthough 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...

Analysis: Study design contributed to differences in ketamine‐ECT trials

Differences in study population characteristics and treatment modalities were largely responsible for the discordant findings between the two adequately powered trials that have compared ketamine treatment and electroconvulsive therapy (ECT) for major depressive disorder, an analysis has concluded. Remission rates with ECT treatment diverged significantly, at 63% in one of the studies and 22% in the other. Results of the analysis were published online Dec. 19, 2023 in the International Journal of Neuropsychopharmacology.

A retrospective analysis of iv ketamine outcome on hospitalisations in an unselected psychiatric sample.

This study aims to explore the outcome with iv ketamine treatment in a real-world clinical setting, primarily measured as posttreatment days hospitalised. The psychiatric medical records of 46 patients having received iv ketamine on a psychiatric treatment indication between 2015 and 2018 were retrospectively examined. Analysis comparing the number and duration of hospital admissions before and after ketamine treatment as well as logistic regression analysis to investigate clinical predictors of effectiveness, were performed. To assess patients' severity of depressed symptoms records were screened for MADRS-S scores. No significant difference between pre- and posttreatment hospital days (p = 0.170), or number of hospitalisations (p = 0.740) were found. The response rate was 31% and remission rate 21%. None of the predictors showed statistical significance in the logistic model. Iv ketamine treatment showed effectiveness in reducing depressive symptoms even with complex patients in a real-world clinical setting. However, this did not translate to a reduction in hospitalisation. Highlighting the multifaceted challenges posed when implementing iv ketamine treatment in clinical practice.

Evaluation of Ketamine after subacute low dosage Lipopolysaccharide-activated Microglia produced depressive-like phenotype in mice

Depression is a common mental illness, with an estimated 3.8% of global population affected. Peripheral administration of lipopolysaccharide (LPS) culminate in a distinct depressive-like behavioral syndrome, measured by increased duration of immobility in the forced swim test (FST) and anhedonia in sucrose preference tests (SPT). After 6 days of LPS stimulation, we established a depression model in C57BL/6 mice, where animals started to recover from the B/W loss brought on by the LPS and the significant immunological response that resulted in microglial activation in the brain. There was a modulation in the relative weight of the thymus and spleen observed under these experimental conditions. Ketamine having a quick onset of action reduces the emergence of depressive-like behaviour by modifying the intensity of Iba-1 in stressed mice by reducing swimming behaviour and boosting desire for sucrose. However, it did not result in an improvement in the number of microglia or CD11b cells activation in the hippocampus of C57BL/6 mice or in the relative weights of the spleen and thymus. In summary, these data emphasizes that Ketamine treatment improves depressive-like behavior and Iba-1 immunoreactivity, but the hyperactive in terms of number of microglia and CD11b expression were not modulated in the mouse hippocampus.

Neither Amphetamine nor Sub-Anesthetic Ketamine Treatment during Adolescence Impairs Devaluation in Rats Tested during Adulthood.

Much of the existing animal literature on the devaluation task suggests that prior repeated exposure to drugs of abuse during adulthood can impair goal-directed action, but the literature on human drug users is mixed. Also, the initiation of drug use often occurs during adolescence, but examinations of the effects of drug exposure during adolescence on behavior in the devaluation task are lacking. We examined whether repeated exposure during adolescence to amphetamine (3 mg/kg injections every-other day from post-natal day 27-45) or ketamine (twice daily 30 mg/kg injections from post-natal day 35-44) would impair behavior in a devaluation test when tested drug-free in adulthood. Rats were trained to press a left lever with a steady cue-light above it for one reinforcer and a right lever with a flashing cue-light above it for a different reinforcer. We tested whether any impairments in goal-directed action could be overcome by compensation between strategies by giving rats information based on lever-location and cue-lights during the test that was either congruent (allowing compensation) or incongruent (preventing compensation between strategies) with the configurations during training. Our results provided no evidence for impairment of goal-directed action during adulthood after adolescent amphetamine or ketamine exposure. We discuss possible reasons for this discrepancy with the prior literature, including (1) the age of exposure and (2) the pattern in the previous literature that most previous demonstrations of drug exposure impairing devaluation in laboratory animals may be attributed to either drug-associated cues present in the testing environment and/or accelerated habit learning in tasks that predispose laboratory animals towards habit formation with extended training (with training procedures that should resist the formation of habits in the current experiment). However, additional research is needed to examine the effects of these factors, as well a potential role for the particular doses and washout periods to determine the cause of our finding of no devaluation impairment after drug exposure.

Combining brief recall and ketamine treatment prevents stress-primed methamphetamine memory reinstatement via heightening mPFC GABA activity

This study aimed to assess whether brief recall of methamphetamine (MA) memory, when combined with ketamine (KE) treatment, may prevent stress-primed MA memory reinstatement. Combining 3-min recall and KE facilitated MA memory extinction and resistance to subsequent stress-primed reinstatement. Such combination also produced glutamate metabotropic receptor 5 (mGluR5) upregulation in animals’ medial prefrontal cortex (mPFC) γ-amino-butyric acid (GABA) neuron. Accordingly, chemogenetic methods were employed to bi-directionally modulate mPFC GABA activity. Following brief recall and KE-produced MA memory extinction, intra-mPFC mDlx-Gi-coupled-human-muscarinic-receptor 4 (hM4Di)-infused mice receiving compound 21 (C21) treatment showed eminent stress-primed reinstatement, while their GABA mGluR5 expression seemed to be unaltered. Intra-mPFC mDlx-Gq-coupled-human-muscarinic-receptor 3 (hM3Dq)-infused mice undergoing C21 treatment displayed MA memory extinction and resistance to stress-provoked reinstatement. These results suggest that combining a brief recall and KE treatment and exciting mPFC GABA neuron may facilitate MA memory extinction and resistance to stress-primed recall. mPFC GABA neuronal activity plays a role in mediating brief recall/KE-produced effects on curbing the stress-provoked MA seeking.

Electroencephalogram monitoring during ketamine antidepressant treatment: a pilot study

Introduction Depression is a major cause of disability world-wide. Up to a third of patients have a treatment-resistant form (TRD), presenting a major challenge. Ketamine has been introduced as a novel rapid-acting antidepressant effective in this population. However, at present, ketamine treatment is not routinely informed by any objective neural markers. Basic research has shown promising electroencephalogram (EEG) changes including a decrease in alpha power. However, clinical translation is lacking.ObjectivesAssess the feasibility of identifying EEG correlates of ketamine infusions in a routine outpatient setting with a low-cost, easily usable system.MethodsThe study was carried out at the Oxford Health Foundation Trust Ketamine Clinic (ethics reference 22/EM/0226). N=18 EEG recordings from N=12 patients were collected (5 women, mean age 44, range 33-62, IV dose 0.5-1mg/kg over 40min). 4-channel EEG was collected with a Muse-S headband at 256Hz, from 5min before to 55min after infusion start. 5s epochs were rejected if gyroscope data indicated head movement above 10 deg/s or if amplitude was above 200μV. A spectrogram (4s window, 3s overlap) as well as band-limited power (theta: 4-8Hz, alpha: 8-13Hz, beta: 13-25Hz) were computed. Significance of changes was found with a repeated measures analysis of variance (RM-ANOVA) on power in 5min segments together with post-hoc Tukey’s P-values.ResultsAcross the ketamine infusion recordings, there was a significant effect of time (F=3.65, P=0.0105) and Channel*Time interaction (F=3.80, P&lt;0.001) on the EEG spectrum. Effects were largest on temporal electrodes, particularly TP9 in the alpha and theta bands (Figure 1, Table 1).Table 1:Effect sizes (Cohen’s d) and FDR-corrected ANOVA P-values for ketamine effects on each EEG channel and frequency band. P&lt;0.05 was considered significant (bold). n.s. = not significant (P&gt;0.2). Channel / Band TP9AF7AF8TP10Theta1.16 (P=0.019)0.11 (n.s.)0.11 (n.s.)0.42 (P=0.113)Alpha1.41 (P&lt;0.001)0.12 (n.s.)0.17 (n.s.)0.605 (P=0.113)Beta1.19 (P=0.112)0.03 (n.s.)0.08 (n.s.)0.21 (n.s.)Image:ConclusionsIn a routine outpatient setting, sub-anaesthetic ketamine infusions in TRD patients were associated with decreased fronto-temporal EEG alpha and theta power. Future work should assess the potential of low-cost routine EEG, and alpha desaturation specifically, to inform individualised ketamine treatment.Disclosure of InterestNone Declared

Pretreatment Brain White Matter Integrity Associated With Neuropathic Pain Relief and Changes in Temporal Summation of Pain Following Ketamine

Neuropathic pain (NP) is a prevalent condition often associated with heightened pain responsiveness suggestive of central sensitization. Neuroimaging biomarkers of treatment outcomes may help develop personalized treatment strategies, but white matter (WM) properties have been underexplored for this purpose. Here we assessed whether WM pathways of the default mode network (DMN: medial prefrontal cortex [mPFC], posterior cingulate cortex, and precuneus) and descending pain modulation system (periaqueductal gray [PAG]) are associated with ketamine analgesia and attenuated temporal summation of pain (TSP, reflecting central sensitization) in NP. We used a fixel-based analysis of diffusion-weighted imaging data to evaluate WM microstructure (fiber density [FD]) and macrostructure (fiber bundle cross-section) within the DMN and mPFC-PAG pathways in 70 individuals who underwent magnetic resonance imaging and TSP testing; 35 with NP who underwent ketamine treatment and 35 age- and sex-matched pain-free individuals. Individuals with NP were assessed before and 1 month after treatment; those with ≥30% pain relief were considered responders (n = 18), or otherwise as nonresponders (n = 17). We found that WM structure within the DMN and mPFC-PAG pathways did not differentiate responders from nonresponders. However, pretreatment FD in the anterior limb of the internal capsule correlated with pain relief (r=.48). Moreover, pretreatment FD in the DMN (left mPFC-precuneus/posterior cingulate cortex; r=.52) and mPFC-PAG (r=.42) negatively correlated with changes in TSP. This suggests that WM microstructure in the DMN and mPFC-PAG pathway is associated with the degree to which ketamine reduces central sensitization. Thus, fixel metrics of WM structure may hold promise to predict ketamine NP treatment outcomes. PerspectiveWe used advanced fixel-based analyses of MRI diffusion-weighted imaging data to identify pretreatment WM microstructure associated with ketamine outcomes, including analgesia and markers of attenuated central sensitization. Exploring associations between brain structure and treatment outcomes could contribute to a personalized approach to treatment for individuals with NP.

The effect of music type in ketamine-assisted group therapy on treatment-resistant mental health conditions: a prospective observational study

Introduction Currently, Ketamine is the only safe, effective, and widely used psychedelic-like medicine in Canada. It has demonstrated notably efficacy in providing relief to those experiencing treatment resistant mental health conditions. Pairing Ketamine treatment with psychotherapy, known as Ketamine Assisted Therapy (KAT), has been shown to yield more enduring outcomes. Work by Greenway et al. has demonstrated that playing music following ketamine administration for patients with bipolar disorder can help the patient feel more in control and reduce discomfort (Greenway et al. International Clinical Psychopharmacology 2021; 36 218-220).ObjectivesThe primary objective is to evaluate and compare the subjective clinical efficacy of two different types of music during ketamine-assisted group therapy. This will be explored through various validated psychiatric questionnaires, including the PHQ-9, GAD-7, and PCL-5. The secondary objective is to compare the objective changes in brain activity between the two music types. This will be evaluated using EEG data collected from MUSE headband before and after each ketamine-assisted therapy session.Methods This study is a crossover trial of 32 participants undergoing ketamine-assisted therapy for treatment-resistant mental health conditions. Half of participants will undergo a KAT session with a “weightless” music playlist followed by a session with a “grounding” music playlist. The other half will do the same, in reverse order. All participants will complete several psychiatric questionnaires within 7 days of each session over email. Before and after each session, participants will play a simple game to test executive function while wearing a headband to measure EEG activity.ResultsThe absolute and relative changes to the scores of the questionnaires will be examined between participants and music conditions. The change in brain activity from pre-session to post-session will be compared between the different music conditions as well. As this is a crossover trial, any changes in outcomes due to order effects will be controlled for. Relevant demographic and medical factors will also be controlled for.ConclusionsTo date, no studies have explored the influence that different types of music have on patients experience with KAT in a group therapy setting. With the results of this study, we hope to fine tune and improve the use of music in future KAT administration.Disclosure of InterestNone Declared

Seizure-like reactions induced by propofol in dogs: prevalence and clinical insight

This study investigated the incidence of seizure-like reactions induced by propofol in dogs treated at the Veterinary Hospital of UNIUBE over three years, highlighting its low frequency and the scarcity of reports in veterinary literature. During the study period, the prevalence of these reactions was 0,02% among dogs receiving propofol as a sedative or anesthetic agent. One case was described and discussed: a three-year-old female dog presented the reaction during anesthetic induction for elective ovariohysterectomy, was treated with ketamine, and showed resolution of signs, allowing the surgery to proceed without complications. Although rare, seizure-like reaction can occur in healthy, young dogs. Several theories have been proposed to explain its mechanism, including propofol antagonism to glycine receptors, stimulation of subcortical dopaminergic areas, and toxicity of metabolites. Ketamine treatment was effective in stopping the crisis in this specific case. In conclusion, seizure-like reaction is a reality in veterinary surgical centers, and ketamine administration is an effective option for its treatment.